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Arterial blood pressure values in dogs naturally infected with

Arterial blood pressure values in dogs naturally infected with

Babesia canis

Babesia canis

Marin Torti

Marin Torti11*, *, Mihaela ČerlekMihaela Čerlek22, , Vesna MatijatkoVesna Matijatko11, , Mirna BrkljačićMirna Brkljačić11, , Ivana Kiš

Ivana Kiš11, , Iva MayerIva Mayer11, , Dalibor PotočnjakDalibor Potočnjak11, and , and Vladimir MrljakVladimir Mrljak11

1

1Clinic for Internal Diseases, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, CroatiaClinic for Internal Diseases, Faculty of Veterinary Medicine, University of Zagreb, Zagreb, Croatia 2

2Veterinarian, Zagreb, CroatiaVeterinarian, Zagreb, Croatia

________________________________________________________________________________________ ________________________________________________________________________________________

TORTI, M., M. ČERLEK, V. MATIJATKO, M. BRKLJAČIĆ, I. KIŠ, I. MAYER, TORTI, M., M. ČERLEK, V. MATIJATKO, M. BRKLJAČIĆ, I. KIŠ, I. MAYER, D. POTOČNJAK, V. MRLJAK

D. POTOČNJAK, V. MRLJAK: Arterial blood pressure values in dogs naturally Arterial blood pressure values in dogs naturally infected with

infected with Babesia canisBabesia canis. Vet. arhiv 84, 563-574, 2014. ABSTRACT

Babesiosis is a signifi cant disease of domestic and wild animals caused by haemoprotozooan parasites Babesiosis is a signifi cant disease of domestic and wild animals caused by haemoprotozooan parasites of the

of the Babesia Babesia genus. The aim of the present study was to compare arterial blood pressure values in healthy genus. The aim of the present study was to compare arterial blood pressure values in healthy dogs and dogs naturally infected with

dogs and dogs naturally infected with Babesia canis Babesia canis ((B. canisB. canis), and to compare arterial blood pressure values ), and to compare arterial blood pressure values

in dogs with complicated and uncomplicated babesiosis. An additional aim was to determine if hypotension is in dogs with complicated and uncomplicated babesiosis. An additional aim was to determine if hypotension is an important contributing factor in development of complicated babesiosis and whether it affects the outcome an important contributing factor in development of complicated babesiosis and whether it affects the outcome of the disease. Fifty dogs were included in this study, and were divided into two groups: healthy dogs (20 dogs) of the disease. Fifty dogs were included in this study, and were divided into two groups: healthy dogs (20 dogs) and dogs with babesiosis (30 dogs). The group of dogs with babesiosis was subdivided into a subgroup of dogs and dogs with babesiosis (30 dogs). The group of dogs with babesiosis was subdivided into a subgroup of dogs with complicated (12 dogs) and a subgroup of dogs with uncomplicated babesiosis (18 dogs). Babesiosis was with complicated (12 dogs) and a subgroup of dogs with uncomplicated babesiosis (18 dogs). Babesiosis was diagnosed by demonstrating the presence of

diagnosed by demonstrating the presence of B. canis B. canis in Romanowsky stained blood smears. The study showed in Romanowsky stained blood smears. The study showed that dogs with babesiosis had lower blood pressure (systolic arterial pressure = 120 ± 96.76, diastolic arterial that dogs with babesiosis had lower blood pressure (systolic arterial pressure = 120 ± 96.76, diastolic arterial pressure = 68 ± 59.1, mean arterial pressure = 83 ± 65.08) compared to healthy dogs (systolic arterial pressure = pressure = 68 ± 59.1, mean arterial pressure = 83 ± 65.08) compared to healthy dogs (systolic arterial pressure = 145 ± 44.02; diastolic arterial pressure = 92 ± 32.96; mean arterial pressure = 106 ± 22.38). Furthermore, blood 145 ± 44.02; diastolic arterial pressure = 92 ± 32.96; mean arterial pressure = 106 ± 22.38). Furthermore, blood pressure was higher in dogs with uncomplicated babesiosis (systolic arterial pressure = 162 ± 51.96, diastolic pressure was higher in dogs with uncomplicated babesiosis (systolic arterial pressure = 162 ± 51.96, diastolic arterial pressure = 95 ± 48.38, mean arterial pressure = 116 ± 41.33) compared to healthy dogs (systolic arterial arterial pressure = 95 ± 48.38, mean arterial pressure = 116 ± 41.33) compared to healthy dogs (systolic arterial pressure = 145 ± 44.02; diastolic arterial pressure = 92 ± 32.96; mean arterial pressure = 106 ± 22.38), and pressure = 145 ± 44.02; diastolic arterial pressure = 92 ± 32.96; mean arterial pressure = 106 ± 22.38), and lower in dogs with complicated babesiosis (systolic arterial pressure = 90 ± 69.38, diastolic arterial pressure lower in dogs with complicated babesiosis (systolic arterial pressure = 90 ± 69.38, diastolic arterial pressure = 48 ± 15.86, mean arterial pressure = 60 ± 22.38) compared to dogs with uncomplicated babesiosis (systolic = 48 ± 15.86, mean arterial pressure = 60 ± 22.38) compared to dogs with uncomplicated babesiosis (systolic arterial pressure = 162 ± 51.96, diastolic arterial pressure = 95 ± 48.38, mean arterial pressure = 116 ± 41.33). arterial pressure = 162 ± 51.96, diastolic arterial pressure = 95 ± 48.38, mean arterial pressure = 116 ± 41.33). The results of this study confi rm that hypotension is present in complicated forms of canine babesiosis caused The results of this study confi rm that hypotension is present in complicated forms of canine babesiosis caused by

by B. canisB. canis. Serial blood pressure measurements should be carried out in order to estimate the infl uence of blood . Serial blood pressure measurements should be carried out in order to estimate the infl uence of blood

pressure changes on the course and outcome of the disease. pressure changes on the course and outcome of the disease.

Key words:

Key words: arterial blood pressure, systolic blood pressure, diastolic blood pressure, mean arterial arterial blood pressure, systolic blood pressure, diastolic blood pressure, mean arterial pressure, dog, babesiosis

pressure, dog, babesiosis

________________________________________________________________________________________ ________________________________________________________________________________________

*Corresponding author:

Marin Torti, DVM, Assistant, Clinic for Internal Diseases, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova Marin Torti, DVM, Assistant, Clinic for Internal Diseases, Faculty of Veterinary Medicine, University of Zagreb, Heinzelova 55, 10000 Zagreb, Croatia, Phone: +385 1 2390 355, Fax: +385 1 2441 390, E-mail: marin.torti@vef.hr

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Introduction Introduction

Babesiosis is a signifi cant disease of domestic and wild animals transmitted by Babesiosis is a signifi cant disease of domestic and wild animals transmitted by ticks, which is caused by haemoprotozooan parasites of the

ticks, which is caused by haemoprotozooan parasites of the Babesia Babesia genus (genus (TABOADA TABOADA and MERCHANT, 1991

and MERCHANT, 1991). In dogs, babesiosis is caused by three different species of large ). In dogs, babesiosis is caused by three different species of large

babesia:

babesia: Babesia canis Babesia canis ((B. canisB. canis), ), Babesia Babesia spp. (spp. (CocoCoco) and ) and Babesia caballiBabesia caballi ( (B. caballiB. caballi) ) ((BIRKENHEUER et al., 2004; LEHTINEN et al., 2008BIRKENHEUER et al., 2004; LEHTINEN et al., 2008). Apart from the large babesia, the ). Apart from the large babesia, the following small babesia can also cause canine babesiosis:

following small babesia can also cause canine babesiosis: Babesia gibsoni Babesia gibsoni ((B. gibsoniB. gibsoni), ), Babesia conradae

Babesia conradae ((B. conradaeB. conradae), ), Theileria annaeTheileria annae ( (T. annaeT. annae) () (ZAHLER et al., 2000ZAHLER et al., 2000) ) and

and Theileria equiTheileria equi ( (T. equiT. equi) () (CRIADO-FORNELIO et al., 2003CRIADO-FORNELIO et al., 2003). Based on biological and ). Based on biological and antigenic differences it has been suggested that

antigenic differences it has been suggested that B. canisB. canis can be divided into three distinct can be divided into three distinct subspecies:

subspecies: B. canis canisB. canis canis, , B. canis vogeliB. canis vogeli and and B. canis rossi B. canis rossi ((UILENBERG, 1989UILENBERG, 1989). Since ). Since additional molecular biological studies have shown that these three groups of parasites do additional molecular biological studies have shown that these three groups of parasites do not cluster in a single clade, which therefore suggest they are not subspecies (

not cluster in a single clade, which therefore suggest they are not subspecies (CARRET et CARRET et al., 1999; UILENBERG, 2006

al., 1999; UILENBERG, 2006), classical nomenclature (), classical nomenclature (B. canisB. canis, , B. rossiB. rossi and and B. vogeliB. vogeli) will ) will

be used, as suggested by

be used, as suggested by SCHETTERS (1997), CARRET et al. (1999), PASSOS et al. (2005) SCHETTERS (1997), CARRET et al. (1999), PASSOS et al. (2005)

and

and SCHETTERS (2005) SCHETTERS (2005). Canine babesiosis caused by . Canine babesiosis caused by B. canisB. canis has been reported to be a has been reported to be a signifi cant cause of morbidity and mortality in Croatia, especially in the area of the City signifi cant cause of morbidity and mortality in Croatia, especially in the area of the City of Zagreb (

of Zagreb (CACCIO et al., 2002; MATIJATKO et al., 2007; BRKLJAČIĆ et al., 2010CACCIO et al., 2002; MATIJATKO et al., 2007; BRKLJAČIĆ et al., 2010). ).

On the basis of the clinical picture, canine babesiosis can be described as uncomplicated On the basis of the clinical picture, canine babesiosis can be described as uncomplicated and complicated (

and complicated (LOBETTI, 1998; JACOBSON, 2006LOBETTI, 1998; JACOBSON, 2006). Complications of canine babesiosis ). Complications of canine babesiosis can develop singularly or in combination, as part of the multiple organ dysfunction can develop singularly or in combination, as part of the multiple organ dysfunction syndrome (MODS), which is the consequence of a generalized and uncontrolled systemic syndrome (MODS), which is the consequence of a generalized and uncontrolled systemic infl ammatory response (

infl ammatory response (JACOBSON and CLARK, 1994JACOBSON and CLARK, 1994). Complicated babesiosis can be ). Complicated babesiosis can be classifi ed as “protozoal sepsis”, and it is similar to other septic conditions characterized classifi ed as “protozoal sepsis”, and it is similar to other septic conditions characterized by systemic infl ammatory response syndrome (SIRS) and MODS (

by systemic infl ammatory response syndrome (SIRS) and MODS (BONE et al., 1992; BONE et al., 1992; JACOBSON et al., 2002

JACOBSON et al., 2002).).

One of the key factors that affects tissue perfusion is arterial blood pressure, which is One of the key factors that affects tissue perfusion is arterial blood pressure, which is maintained within the physiological values by various regulatory mechanisms (

maintained within the physiological values by various regulatory mechanisms (EGNER, EGNER, 2002

2002). Peripheral baroreceptors are the fi rst mechanism of blood pressure regulation. They ). Peripheral baroreceptors are the fi rst mechanism of blood pressure regulation. They act via cardiovascular refl ex and arterial tonus. If changes implemented by the action of act via cardiovascular refl ex and arterial tonus. If changes implemented by the action of the peripheral baroreceptors do not restore blood pressure to physiological value, the the peripheral baroreceptors do not restore blood pressure to physiological value, the renin-angiotensin-aldosterone system is activated, together with prostaglandins, atrial renin-angiotensin-aldosterone system is activated, together with prostaglandins, atrial natriuretic peptide and antidiuretic hormones. Arterial blood pressure values differ natriuretic peptide and antidiuretic hormones. Arterial blood pressure values differ between dog breeds, and small breeds have higher blood pressure values compared to between dog breeds, and small breeds have higher blood pressure values compared to large breeds. The average values in dogs are 133 mmHg for systolic, and 75 mmHg large breeds. The average values in dogs are 133 mmHg for systolic, and 75 mmHg for diastolic arterial blood pressure (

for diastolic arterial blood pressure (BODEY and MICHELL, 1996BODEY and MICHELL, 1996). It is known that ). It is known that physiological oscillations (from 10 to 15 mmHg) in arterial blood pressure occur physiological oscillations (from 10 to 15 mmHg) in arterial blood pressure occur between measurements, and therefore it is generally accepted that a mean value of 3 to 5 between measurements, and therefore it is generally accepted that a mean value of 3 to 5

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measurements should be calculated to improve the accuracy (

measurements should be calculated to improve the accuracy (ERHARD and HENKE, 2002; ERHARD and HENKE, 2002; STEPIEN, 2005

STEPIEN, 2005). Pathological changes in arterial blood pressure values are: increased ). Pathological changes in arterial blood pressure values are: increased blood pressure (hypertension) or decreased blood pressure (hypotension), and as such they blood pressure (hypertension) or decreased blood pressure (hypotension), and as such they can signifi cantly infl uence the functioning of various organs and promote the progression can signifi cantly infl uence the functioning of various organs and promote the progression of the disease, which in the end can increase mortality.

of the disease, which in the end can increase mortality.

Hypotension in dogs is defi ned as a systolic arterial blood pressure value lower Hypotension in dogs is defi ned as a systolic arterial blood pressure value lower than 90 mmHg, or a mean arterial blood pressure value lower than 80 mmHg ( than 90 mmHg, or a mean arterial blood pressure value lower than 80 mmHg (BRADY BRADY and OTTO, 2001

and OTTO, 2001). There are many causes of hypotension, and it develops because of ). There are many causes of hypotension, and it develops because of the interplay of various factors on peripheral arterial resistance, heart frequency and/ the interplay of various factors on peripheral arterial resistance, heart frequency and/ or cardiac output. Primary goals of treatment are patient stabilization and correction of or cardiac output. Primary goals of treatment are patient stabilization and correction of hypotension (

hypotension (ERHARD and HENKE, 2002; WADDEL, 2005ERHARD and HENKE, 2002; WADDEL, 2005). Hypotension is commonly ). Hypotension is commonly reported in septic dogs (

reported in septic dogs (DE LAFORCADE and ROZANSKI, 2001DE LAFORCADE and ROZANSKI, 2001), and has been reported in ), and has been reported in canine babesiosis caused by

canine babesiosis caused by B. rossiB. rossi ( (JACOBSON et al., 2000JACOBSON et al., 2000), an experimental study of ), an experimental study of canine babesiosis caused by

canine babesiosis caused by B. canisB. canis ( (SCHETTERS et al., 2009SCHETTERS et al., 2009), and a study of septic shock ), and a study of septic shock in canine babesiosis caused by

in canine babesiosis caused by B. canisB. canis ( (MATIJATKO et al., 2009MATIJATKO et al., 2009).).

The aim of this study was to compare arterial blood pressure values in healthy dogs The aim of this study was to compare arterial blood pressure values in healthy dogs and dogs naturally infected with

and dogs naturally infected with B. canisB. canis, and also to compare arterial blood pressure , and also to compare arterial blood pressure values in dogs with complicated and uncomplicated babesiosis, in order to determine values in dogs with complicated and uncomplicated babesiosis, in order to determine if hypotension is an important contributing factor in the development of complicated if hypotension is an important contributing factor in the development of complicated babesiosis and whether it affects the outcome of the disease.

babesiosis and whether it affects the outcome of the disease.

Materials and methods Materials and methods

Fifty dogs were included in this study. They were divided into two groups: group Fifty dogs were included in this study. They were divided into two groups: group 1 consisted of 30 dogs naturally infected with

1 consisted of 30 dogs naturally infected with B. canisB. canis and group 2 of 20 healthy dogs. and group 2 of 20 healthy dogs. Group 1 was further divided into groups with complicated and uncomplicated babesiosis. Group 1 was further divided into groups with complicated and uncomplicated babesiosis. All the dogs were clinically examined, and the blood samples for haematological and All the dogs were clinically examined, and the blood samples for haematological and biochemical parameters were taken from the cephalic vein. In each dog blood pressure biochemical parameters were taken from the cephalic vein. In each dog blood pressure was measured at admission.

was measured at admission.

Babesiosis was diagnosed by demonstrating

Babesiosis was diagnosed by demonstrating B. canisB. canis in Romanowsky stained blood in Romanowsky stained blood smears. Group 2 was used as healthy controls.

smears. Group 2 was used as healthy controls.

The blood samples were placed in tubes with ethylenediaminetetraacetic acid (EDTA) The blood samples were placed in tubes with ethylenediaminetetraacetic acid (EDTA) for haematological analysis and in tubes with no anticoagulant, which were centrifuged at for haematological analysis and in tubes with no anticoagulant, which were centrifuged at 1200 x g prior to biochemical analysis. White blood cell count (WBC), platelet count and 1200 x g prior to biochemical analysis. White blood cell count (WBC), platelet count and haematocrit (HCT) were determined using an automatic haematology analyser (System haematocrit (HCT) were determined using an automatic haematology analyser (System 9120; Serono Baker Diagnostic) while serum creatinine, alanine aminotranspherase 9120; Serono Baker Diagnostic) while serum creatinine, alanine aminotranspherase (ALT), alkaline phosphatase (AP), creatine phosphokinase (CPK), glucose and serum (ALT), alkaline phosphatase (AP), creatine phosphokinase (CPK), glucose and serum bilirubin were determined using a biochemical autoanalyser, Olympus AU 600 (Olympus bilirubin were determined using a biochemical autoanalyser, Olympus AU 600 (Olympus Diagnostica, Hamburg). Analyses were performed using standard methods and the Diagnostica, Hamburg). Analyses were performed using standard methods and the

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original reagents of the manufacturer (Olympus Diagnostica, Hamburg). The animal was original reagents of the manufacturer (Olympus Diagnostica, Hamburg). The animal was classifi ed as having the complicated form of the babesiosis if one of the following criteria classifi ed as having the complicated form of the babesiosis if one of the following criteria were fulfi lled: renal dysfunction (serum creatinine more than 180 μmol/L - reference were fulfi lled: renal dysfunction (serum creatinine more than 180 μmol/L - reference values 44-140 μmol/L), liver dysfunction (alanine aminotranspherase, ALT, more than values 44-140 μmol/L), liver dysfunction (alanine aminotranspherase, ALT, more than 176 U/L - reference value less than 88 U/L, and alkaline phosphatase, AP, more than 360 176 U/L - reference value less than 88 U/L, and alkaline phosphatase, AP, more than 360 U/L - reference value less than 156 U/L), central nervous system dysfunction (a modifi ed U/L - reference value less than 156 U/L), central nervous system dysfunction (a modifi ed Glasgow coma scale score less than 9) (

Glasgow coma scale score less than 9) (SHORES, 1989; WELZL SHORES, 1989; WELZL et al.et al., 2001, 2001), respiratory ), respiratory system dysfunction (radiographic signs of pulmonary oedema, dyspnoea or blood/tinged system dysfunction (radiographic signs of pulmonary oedema, dyspnoea or blood/tinged frothy nasal discharge), muscular involvement (creatine phosphokinase, CPK, more frothy nasal discharge), muscular involvement (creatine phosphokinase, CPK, more than 600 U/L - reference value less than 160 U/L). We included bilirubin values greater than 600 U/L - reference value less than 160 U/L). We included bilirubin values greater than 100 μmol/L (reference value 1.7-8.6 μmol/L) as an additional criterion for liver than 100 μmol/L (reference value 1.7-8.6 μmol/L) as an additional criterion for liver dysfunction (

dysfunction (WEISER, 1992WEISER, 1992). If two or more of the aforementioned criteria were fulfi lled ). If two or more of the aforementioned criteria were fulfi lled the animal was classifi ed as MODS positive and included in the complicated babesiosis the animal was classifi ed as MODS positive and included in the complicated babesiosis group.

group.

One dose (6 mg/kg) of imidocarb dipropionat (Imizol

One dose (6 mg/kg) of imidocarb dipropionat (Imizol®®, Schering-Plough) was , Schering-Plough) was

administered to all the dogs subcutaneously on the day of admission. Additional treatment administered to all the dogs subcutaneously on the day of admission. Additional treatment consisted of various fl uids (hydroxyethyl starch and crystalloids), whole blood transfusion, consisted of various fl uids (hydroxyethyl starch and crystalloids), whole blood transfusion, and in dogs that were dyspnoeic or had radiographic signs of pulmonary oedema, oxygen and in dogs that were dyspnoeic or had radiographic signs of pulmonary oedema, oxygen supplementation was administered, via intranasal tubes or oxygen cage.

supplementation was administered, via intranasal tubes or oxygen cage.

Blood pressure was determined non-invasively by an oscillometric technique: we Blood pressure was determined non-invasively by an oscillometric technique: we used a PM-9000Vet Veterinary Portable Multi-Parameter Patient Monitor (Grady Medical used a PM-9000Vet Veterinary Portable Multi-Parameter Patient Monitor (Grady Medical Systems, Inc., Temecula, CA, USA) and standard dog cuffs. Each dog was placed in Systems, Inc., Temecula, CA, USA) and standard dog cuffs. Each dog was placed in right lateral recumbency, and the cuff was placed on the distal left forelimb, immediately right lateral recumbency, and the cuff was placed on the distal left forelimb, immediately proximal to the carpus, over the radial artery. The cuff size was selected so that its width proximal to the carpus, over the radial artery. The cuff size was selected so that its width was approximately 40% of the limb circumference. Five measurements of systolic arterial was approximately 40% of the limb circumference. Five measurements of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) were recorded (

were recorded (JACOBSON et al., 2000JACOBSON et al., 2000). Hypotension was defi ned as MAP lower than 80 ). Hypotension was defi ned as MAP lower than 80 mmHg, and refractory hypotension was defi ned as hypotension (SAP less than 90 mmHg) mmHg, and refractory hypotension was defi ned as hypotension (SAP less than 90 mmHg) that persisted despite adequate volume repletion (

that persisted despite adequate volume repletion (BRADY and OTTO, 2001BRADY and OTTO, 2001).).

Arterial blood pressure values in healthy dogs and dogs with babesiosis, as well as Arterial blood pressure values in healthy dogs and dogs with babesiosis, as well as in dogs with uncomplicated and complicated babesiosis, were compared using the in dogs with uncomplicated and complicated babesiosis, were compared using the Mann-Whitney U test, and P values of <0.05 were considered to be signifi cant.

Whitney U test, and P values of <0.05 were considered to be signifi cant.

Results Results

Out of 30 dogs with confi rmed babesiosis, 12 developed a complicated form and 18 Out of 30 dogs with confi rmed babesiosis, 12 developed a complicated form and 18 an uncomplicated form of babesiosis. In two dogs with complicated babesiosis, single an uncomplicated form of babesiosis. In two dogs with complicated babesiosis, single organ dysfunction was present (acute hepatic failure), while in rest of the dogs (10) organ dysfunction was present (acute hepatic failure), while in rest of the dogs (10) MODS developed.

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In dogs that developed MODS, one dog had four organ system involvement, fi ve dogs In dogs that developed MODS, one dog had four organ system involvement, fi ve dogs had three organ system involvement, while in four dogs two organ system involvement was had three organ system involvement, while in four dogs two organ system involvement was present. Within MODS, the most common feature noted was acute renal dysfunction (10 present. Within MODS, the most common feature noted was acute renal dysfunction (10 dogs), while central nervous system dysfunction was the rarest complication (1 dog). The dogs), while central nervous system dysfunction was the rarest complication (1 dog). The most frequent combination of organ system dysfunction within MODS was acute renal most frequent combination of organ system dysfunction within MODS was acute renal dysfunction and muscle involvement (7 dogs), followed by acute renal dysfunction and dysfunction and muscle involvement (7 dogs), followed by acute renal dysfunction and liver dysfunction (5 dogs), acute renal dysfunction and ARDS (3 dogs), liver dysfunction liver dysfunction (5 dogs), acute renal dysfunction and ARDS (3 dogs), liver dysfunction and muscle involvement (2 dogs), ARDS and muscle involvement (2 dogs), and fi nally and muscle involvement (2 dogs), ARDS and muscle involvement (2 dogs), and fi nally liver dysfunction and ARDS (1 dog) (Table 1). All the dogs with uncomplicated forms of liver dysfunction and ARDS (1 dog) (Table 1). All the dogs with uncomplicated forms of babesiosis survived, while nine out of twelve dogs with complicated forms of babesiosis babesiosis survived, while nine out of twelve dogs with complicated forms of babesiosis died. Mortality was signifi cantly higher (P<0.05) in cases of complicated babesiosis died. Mortality was signifi cantly higher (P<0.05) in cases of complicated babesiosis compared to uncomplicated babesiosis.

compared to uncomplicated babesiosis.

Arterial blood pressure values in healthy dogs and dogs with babesiosis are shown Arterial blood pressure values in healthy dogs and dogs with babesiosis are shown in Table 2. In 11/12 dogs with complicated babesiosis hypotension was present. None of in Table 2. In 11/12 dogs with complicated babesiosis hypotension was present. None of the 18 dogs with uncomplicated babesiosis were hypotensive. A statistically signifi cant the 18 dogs with uncomplicated babesiosis were hypotensive. A statistically signifi cant difference (P<0.05) was noted in blood pressure values of healthy dogs and dogs with difference (P<0.05) was noted in blood pressure values of healthy dogs and dogs with babesiosis. Arterial blood pressure in dogs with uncomplicated babesiosis was higher babesiosis. Arterial blood pressure in dogs with uncomplicated babesiosis was higher when compared to healthy dogs, as well as dogs with complicated babesiosis.

when compared to healthy dogs, as well as dogs with complicated babesiosis.

Table 1. Overview of complications in dogs with developed complicated babesiosis and their Table 1. Overview of complications in dogs with developed complicated babesiosis and their

number number Renal

Renal failure

failure Hepatic Hepatic failurefailure dysfunctiondysfunctionCNS CNS damagedamageMuscle Muscle dysfunctiondysfunctionRespiratory Respiratory numbernumberTotal Total 1. 1. ++ -- -- ++ -- 22 2. 2. -- ++ -- -- -- 11 3. 3. ++ -- -- ++ ++ 33 4. 4. ++ ++ -- -- -- 22 5. 5. ++ -- -- ++ ++ 33 6. 6. -- ++ -- -- -- 11 7. 7. ++ -- -- ++ -- 22 8. 8. ++ ++ -- -- -- 22 9. 9. ++ ++ -- ++ -- 33 10. 10. ++ ++ -- ++ -- 33 11. 11. ++ ++ ++ -- ++ 44 12. 12. ++ -- -- ++ -- 22 Total number Total number 1010 77 11 77 33

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Table 2. Arterial blood pressure values in healthy dogs and dogs with babesiosis. Table 2. Arterial blood pressure values in healthy dogs and dogs with babesiosis.

SAP/DAP/MAP

(min-max) (mean ± 2 SD) (SAP) (mean ± 2 SD) (DAP) (mean ± 2 SD) (MAP)

Healthy dogs 123-193/ 59-117/ 70-134 145 ± 44.02* 92 ± 32.96* 106 ± 22.38* Dogs with babesiosis 60-202/ 34-129/ 42-143 120 ± 96.76* 68 ± 59.1* 83 ± 65.08* Uncomplicated babesiosis 146-202/ 55-124/ 75-143 162 ± 51.96* 95 ± 48.38* 116 ± 41.33* Complicated babesiosis 60-193/ 34-59/ 42-73 90 ± 69.38* 48 ± 15.86* 60 ± 22.38* Reference values - 133 75 104

(SAP) Systolic arterial blood pressure. (DAP) Diastolic arterial blood pressure. (MAP) Mean arterial pressure. (SAP) Systolic arterial blood pressure. (DAP) Diastolic arterial blood pressure. (MAP) Mean arterial pressure. (*) Signifi cant difference (P<0.05) between healty dogs and dogs with babesiosis. Reference values for SAP and (*) Signifi cant difference (P<0.05) between healty dogs and dogs with babesiosis. Reference values for SAP and DAP according to Bodey and Michell (1996).

DAP according to Bodey and Michell (1996).

Discussion Discussion

Arterial blood pressure is present in the arterial part of circulation, and is often defi ned Arterial blood pressure is present in the arterial part of circulation, and is often defi ned as the product of cardiac output and peripheral resistance (

as the product of cardiac output and peripheral resistance (EGNER, 2002EGNER, 2002). In sepsis, ). In sepsis, hypotension commonly occurs, and is one of the criteria used to defi ne the progression hypotension commonly occurs, and is one of the criteria used to defi ne the progression of infl ammatory response, from severe sepsis to septic shock (

of infl ammatory response, from severe sepsis to septic shock (BONE et al., 1992BONE et al., 1992). The ). The release of pro-infl ammatory mediators and vasodilators plays a crucial role in the genesis release of pro-infl ammatory mediators and vasodilators plays a crucial role in the genesis of hypotension in sepsis (

of hypotension in sepsis (PARRATT, 1997PARRATT, 1997).).

Babesiosis is a widespread disease of various species of animals, with the severity of Babesiosis is a widespread disease of various species of animals, with the severity of the disease ranging from mild to fatal. Complications of babesiosis can occur individually the disease ranging from mild to fatal. Complications of babesiosis can occur individually or in combination, and although they are different, the mechanism which promotes them or in combination, and although they are different, the mechanism which promotes them is uniform (

is uniform (JACOBSON and CLARK, 1994; JACOBSON and LOBETTI, 1996; LOBETTI et al., JACOBSON and CLARK, 1994; JACOBSON and LOBETTI, 1996; LOBETTI et al., 1996; WELZL et al., 2001; JACOBSON, 2006

1996; WELZL et al., 2001; JACOBSON, 2006). This mechanism is the consequence of poorly ). This mechanism is the consequence of poorly

regulated infl ammatory response and is similar in various conditions, such as bacterial regulated infl ammatory response and is similar in various conditions, such as bacterial sepsis, babesiosis, malaria, multiple trauma and burns (

sepsis, babesiosis, malaria, multiple trauma and burns (JACOBSON and CLARK, 1994JACOBSON and CLARK, 1994). ). All these conditions are similar in clinical presentation, and are characterized by All these conditions are similar in clinical presentation, and are characterized by multi-system signs, caused by dysfunction of different organ multi-systems (

system signs, caused by dysfunction of different organ systems (JACOBSON, 2006JACOBSON, 2006).). In our study, 10/12 dogs with a complicated form of babesiosis (83%) developed In our study, 10/12 dogs with a complicated form of babesiosis (83%) developed MODS. MODS as a complication of babesiosis was fi rst described in the study by MODS. MODS as a complication of babesiosis was fi rst described in the study by WELZLWELZL

et al. (2001)

et al. (2001), in canine babesiosis caused by , in canine babesiosis caused by B. rossiB. rossi. Later, the development of MODS was . Later, the development of MODS was also reported in canine babesiosis caused by

also reported in canine babesiosis caused by B. canisB. canis ( (MÁTHÉ et al., 2006; MATIJATKO MÁTHÉ et al., 2006; MATIJATKO et al., 2009; MATIJATKO et al., 2010

et al., 2009; MATIJATKO et al., 2010). Within MODS, the most frequent complication was ). Within MODS, the most frequent complication was

acute renal dysfunction (83%), followed by liver dysfunction (58%), muscle involvement acute renal dysfunction (83%), followed by liver dysfunction (58%), muscle involvement

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(58%), ARDS (33%) and central nervous system dysfunction (8%). These results are (58%), ARDS (33%) and central nervous system dysfunction (8%). These results are similar to the results of other studies of MODS in canine babesiosis (

similar to the results of other studies of MODS in canine babesiosis (WELZL et al., 2001; WELZL et al., 2001; MATIJATKO et al., 2010

MATIJATKO et al., 2010).).

The high occurrence of renal dysfunction in our study (83%) can be explained by The high occurrence of renal dysfunction in our study (83%) can be explained by the fact that the patients which developed renal dysfunction had signifi cantly lower the fact that the patients which developed renal dysfunction had signifi cantly lower arterial blood pressure (P<0.05), compared to uncomplicated babesiosis. It is a arterial blood pressure (P<0.05), compared to uncomplicated babesiosis. It is a well-known fact that hypotension is one of the main causes of poor tissue perfusion, which known fact that hypotension is one of the main causes of poor tissue perfusion, which is especially detrimental to renal tissue (

is especially detrimental to renal tissue (BONE et al., 1992; BAGSHAW and BELLOMO, BONE et al., 1992; BAGSHAW and BELLOMO, 2006; ALDRICH, 2007

2006; ALDRICH, 2007). Another possible cause of renal damage is rhabdomiolysis. Renal ). Another possible cause of renal damage is rhabdomiolysis. Renal

dysfunction caused by myoglobin release due to rhabdomiolysis has been documented dysfunction caused by myoglobin release due to rhabdomiolysis has been documented in canine babesiosis (

in canine babesiosis (JACOBSON and LOBETTI; 1996, MATIJATKO et al., 2009JACOBSON and LOBETTI; 1996, MATIJATKO et al., 2009), and has ), and has been confi rmed in our study as well, because all dogs with muscle damage also had renal been confi rmed in our study as well, because all dogs with muscle damage also had renal dysfunction (Table 1).

dysfunction (Table 1).

Hypoxia can be the single cause of diffuse hepatocyte swelling and resultant hepatic Hypoxia can be the single cause of diffuse hepatocyte swelling and resultant hepatic dysfunction in dogs with babesiosis (

dysfunction in dogs with babesiosis (LOBETTI, 2000LOBETTI, 2000). Uncomplicated babesiosis has ). Uncomplicated babesiosis has been suggested to be a consequence of haemolysis (

been suggested to be a consequence of haemolysis (JACOBSON and CLARK, 1994JACOBSON and CLARK, 1994), but ), but recent publications showed that both uncomplicated and complicated babesiosis appear recent publications showed that both uncomplicated and complicated babesiosis appear to be the result of host infl ammatory responses (

to be the result of host infl ammatory responses (MATIJATKO et al., 2007; SCHETTERS MATIJATKO et al., 2007; SCHETTERS et al., 2009

et al., 2009). Although haemolysis and consequent anaemia occur in canine babesiosis, ). Although haemolysis and consequent anaemia occur in canine babesiosis,

it is unlikely that they are the main features of babesiosis that lead to tissue hypoxia. it is unlikely that they are the main features of babesiosis that lead to tissue hypoxia. Therefore, hypotension could not be excluded as a contributing factor of hepatic tissue Therefore, hypotension could not be excluded as a contributing factor of hepatic tissue hypoxia that could result in hepatic dysfunction.

hypoxia that could result in hepatic dysfunction.

Regarding blood pressure (Table 2), this study showed that dogs with babesiosis Regarding blood pressure (Table 2), this study showed that dogs with babesiosis have lower blood pressure (SAP = 120 ± 96.76, DAP = 68 ± 59.1, MAP = 83 ± 65.08) have lower blood pressure (SAP = 120 ± 96.76, DAP = 68 ± 59.1, MAP = 83 ± 65.08) compared to healthy dogs (SAP = 145 ± 44.02; DAP = 92 ± 32.96; MAP = 106 ± 22.38). compared to healthy dogs (SAP = 145 ± 44.02; DAP = 92 ± 32.96; MAP = 106 ± 22.38). Furthermore, blood pressure was higher in dogs with uncomplicated babesiosis (SAP = Furthermore, blood pressure was higher in dogs with uncomplicated babesiosis (SAP = 162 ± 51.96, DAP = 95 ± 48.38, MAP = 116 ± 41.33) compared to healthy dogs (SAP = 162 ± 51.96, DAP = 95 ± 48.38, MAP = 116 ± 41.33) compared to healthy dogs (SAP = 145 ± 44.02; DAP = 92 ± 32.96; MAP = 106 ± 22.38), and lower in dogs with complicated 145 ± 44.02; DAP = 92 ± 32.96; MAP = 106 ± 22.38), and lower in dogs with complicated babesiosis (SAP = 90 ± 69.38, DAP = 48 ± 15.86, MAP = 60 ± 22.38) compared to dogs babesiosis (SAP = 90 ± 69.38, DAP = 48 ± 15.86, MAP = 60 ± 22.38) compared to dogs with uncomplicated babesiosis (SAP = 162 ± 51.96, DAP = 95 ± 48.38, MAP = 116 ± with uncomplicated babesiosis (SAP = 162 ± 51.96, DAP = 95 ± 48.38, MAP = 116 ± 41.33).

41.33).

High blood pressure in dogs with babesiosis has already been documented, namely High blood pressure in dogs with babesiosis has already been documented, namely by

by JACOBSON et al. (2000)JACOBSON et al. (2000) and and LOBETTI et al. (2012) LOBETTI et al. (2012). In the study by . In the study by JACOBSON et al. JACOBSON et al. (2000)

(2000) one animal (out of 10) had high blood pressure, while in the study by one animal (out of 10) had high blood pressure, while in the study by LOBETTI et LOBETTI et

al. (2012)

al. (2012) fi ve individual animals were hypertensive. The higher blood pressure values in fi ve individual animals were hypertensive. The higher blood pressure values in

dogs with uncomplicated babesiosis can be explained by activation of the compensatory dogs with uncomplicated babesiosis can be explained by activation of the compensatory anti-infl ammatory response, because of which fl uids are translocated from the interstitial anti-infl ammatory response, because of which fl uids are translocated from the interstitial to vascular space, with the resultant increase in arterial blood pressure (

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2000; SCHETTERS et al., 2009

2000; SCHETTERS et al., 2009). It can be hypothesized that activation of compensatory ). It can be hypothesized that activation of compensatory

mechanisms (primarily of the sympathetic nervous system and mechanisms (primarily of the sympathetic nervous system and renin-angiotensin-aldosterone system) results in increased cardiac output and stroke volume, and, at least aldosterone system) results in increased cardiac output and stroke volume, and, at least in the beginning, increased vascular tone. Contrary to these fi ndings,

in the beginning, increased vascular tone. Contrary to these fi ndings, SCHETTERS et al. SCHETTERS et al. (2009)

(2009) reported hypotension despite haemodilution. reported hypotension despite haemodilution.

Hypotension has been documented in canine babesiosis caused by

Hypotension has been documented in canine babesiosis caused by B. rossiB. rossi ( (JACOBSON JACOBSON et al., 2000

et al., 2000) and ) and B. canis B. canis ((MATIJATKO et al. 2009, SCHETTERS et al. 2009MATIJATKO et al. 2009, SCHETTERS et al. 2009). In the study of ). In the study of canine babesiosis caused by

canine babesiosis caused by B. rossiB. rossi by by JACOBSON et al. (2000)JACOBSON et al. (2000) it was established that it was established that blood pressure values were lower in dogs that died compared to the values of dogs that blood pressure values were lower in dogs that died compared to the values of dogs that survived, but that the differences were not statistically signifi cant. In complicated forms survived, but that the differences were not statistically signifi cant. In complicated forms of canine babesiosis, due to the overwhelming and uncontrolled infl ammatory response of canine babesiosis, due to the overwhelming and uncontrolled infl ammatory response and the absence of a compensatory anti-infl ammatory response, blood pressure values are and the absence of a compensatory anti-infl ammatory response, blood pressure values are lower and hypotension develops.

lower and hypotension develops.

Hypotension in canine babesiosis is most probably the result of vasodilatation, the Hypotension in canine babesiosis is most probably the result of vasodilatation, the decrease in intravascular volume caused by increased vascular permeability and decreased decrease in intravascular volume caused by increased vascular permeability and decreased myocardial function. The degree of changes in the aforementioned mechanisms infl uences myocardial function. The degree of changes in the aforementioned mechanisms infl uences the severity of the disease

the severity of the disease ((JACOBSON et al., 1999; LOBETTI, 2000JACOBSON et al., 1999; LOBETTI, 2000).).

Hypotension is well documented in dogs with complicated forms of babesiosis, as Hypotension is well documented in dogs with complicated forms of babesiosis, as was established in our study as well, and is considered relevant when associated with was established in our study as well, and is considered relevant when associated with poor tissue perfusion

poor tissue perfusion ((LITTMAN and DROBATZ, 1995LITTMAN and DROBATZ, 1995). Also, it is questionable if a single ). Also, it is questionable if a single blood pressure measurement is a reliable predictor of the progression of the disease. In blood pressure measurement is a reliable predictor of the progression of the disease. In human medicine, the study of septic shock has shown that MAP at admission did not human medicine, the study of septic shock has shown that MAP at admission did not differ between survivors and non-survivors, but blood pressure values taken 24 hours differ between survivors and non-survivors, but blood pressure values taken 24 hours after admission had prognostic value (

after admission had prognostic value (BERNARDIN et al., 1996BERNARDIN et al., 1996).).

Finally, the results of this study confi rm that hypotension is present in complicated Finally, the results of this study confi rm that hypotension is present in complicated forms of canine babesiosis caused by

forms of canine babesiosis caused by B. canisB. canis. However, serial blood pressure . However, serial blood pressure measurements should be carried out, in order to estimate the infl uence of blood pressure measurements should be carried out, in order to estimate the infl uence of blood pressure changes on the course and outcome of the disease. Early recognition of hypotension, changes on the course and outcome of the disease. Early recognition of hypotension, coupled with the timely start of treatment, may infl uence disease progression, and possibly coupled with the timely start of treatment, may infl uence disease progression, and possibly prevent development of MODS and septic shock.

prevent development of MODS and septic shock. _______

Acknowledgements

This research was supported partially by the Ministry of Science, Education and Sports of the Republic of This research was supported partially by the Ministry of Science, Education and Sports of the Republic of Croatia (Project No. 053-0532266-2220).

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Received: 26 September 2013 Accepted: 11 July 2014

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TORTI, M., M. ČERLEK, V. MATIJATKO, M. BRKLJAČIĆ, I. KIŠ, I. MAYER, TORTI, M., M. ČERLEK, V. MATIJATKO, M. BRKLJAČIĆ, I. KIŠ, I. MAYER, D. POTOČNJAK, V. MRLJAK

D. POTOČNJAK, V. MRLJAK: Vrijednosti arterijskog krvnog tlaka u pasa prirodno invadiranih vrstom Babesia canisBabesia canis. Vet. arhiv 84, 563-574, 2014.

SAŽETAK

Babezioza predstavlja značajnu bolest domaćih i divljih životinja uzrokovanu protozoama roda

Babesia. Cilj je istraživanja bio usporediti vrijednosti arterijskog krvnog tlaka u zdravih pasa, pasa oboljelih od nekompliciranog i pasa oboljelih od kompliciranog oblika babezioze uzrokovane vrstom Babesia canis.

Dodatni je cilj bio utvrditi doprinosi li hipotenzija razvoju kompliciranog oblika babezioze i utječe li na ishod bolesti. Istraživanje je obuhvatilo 50 pasa koji su bili podijeljeni u dvije skupine: zdrave pse (20 pasa) i pse prirodno zaražene vrstom B. canis (30 pasa). Skupina prirodno infi ciranih pasa dodatno je bila podijeljena

na dvije podskupine: skupinu pasa oboljelu od kompliciranog oblika (12 pasa) i skupinu pasa oboljelu od nekompliciranog oblika (18 pasa). Babezioza je dokazana nalazom parazita u razmascima periferne krvi obojenima po Romanowskom. Istraživanje je pokazalo da psi oboljeli od babezioze imaju niži arterijski krvni tlak (sistolički arterijski tlak = 120 ± 96,76, dijastolički arterijski tlak = 68 ± 59,1, srednji arterijski tlak = 83 ± 65,08) u odnosu na zdrave pse (sistolički arterijski tlak = 145 ± 44,02; dijastolički arterijski tlak = 92 ± 32,96; srednji arterijski tlak = 106 ± 22,38). Arterijski krvni tlak bio je viši u pasa oboljelih od nekompliciranog oblika babezioze (sistolički arterijski tlak = 162 ± 51,96, dijastolički arterijski tlak = 95 ± 48,38, srednji arterijski tlak = 116 ± 41,33) u odnosu na zdrave pse (sistolički arterijski tlak = 145 ± 44,02; dijastolički arterijski tlak = 92 ± 32,96; srednji arterijski tlak = 106 ± 22,38), i nizak u pasa oboljelih od kompliciranog oblika babezioze (sistolički arterijski tlak = 90 ± 69,38, dijastolički arterijski tlak = 48 ± 15,86, srednji arterijski tlak = 60 ± 22,38) u odnosu na pse oboljele od nekompliciranog oblika babezioze (sistolički arterijski tlak = 162 ± 51,96, dijastolički arterijski tlak = 95 ± 48,38, srednji arterijski tlak = 116 ± 41,33). Rezultati istraživanja potvrđuju da je hipotenzija prisutna u pasa oboljelih od kompliciranog oblika babezioze uzrokovanog vrstom Babesia canis.

Serijska mjerenja arterijskog krvnog tlaka potrebna su kako bi se mogao procijeniti utjecaj promjena arterijskog krvnog tlaka na tijek i ishod bolesti.

Ključne riječi: arterijski krvni tlak, sistolički krvni tlak, dijastolički krvni tlak, srednji arterijski krvni tlak, pas, babezioza

Gambar

Table 1. Overview of complications in dogs with developed complicated babesiosis and their Table 1
Table 2. Arterial blood pressure values in healthy dogs and dogs with babesiosis.

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