c-kit+ precursors support postinfarction myogenesis in the neonatal, but not adult, heart.

We examined the myogenic response to infarction in neonatal and adult mice to determine the role of c-kit(+) cardiovascular precursor cells (CPC) that are known to be present in early heart development. Infarction of postnatal day 1-3 c-kit(BAC)-EGFP mouse hearts induced the localized expansion of (c-kit)EGFP(+) cells within the infarct, expression of the c-kit and Nkx2.5 mRNA, myogenesis, and partial regeneration of the infarction, with (c-kit)EGFP(+) cells adopting myogenic and vascular fates. Conversely, infarction of adult mice resulted in a modest induction of (c-kit)EGFP(+) cells within the infarct, which did not express Nkx2.5 or undergo myogenic differentiation, but adopted a vascular fate within the infarction, indicating a lack of authentic CPC. Explantation of infarcted neonatal and adult heart tissue to scid mice, and adoptive transfer of labeled bone marrow, confirmed the cardiac source of myogenic (neonate) and angiogenic (neonate and adult) cells. FACS-purified (c-kit)EGFP(+)/(αMHC)mCherry(-) (noncardiac) cells from microdissected infarcts within 6 h of infarction underwent cardiac differentiation, forming spontaneously beating myocytes in vitro; cre/LoxP fate mapping identified a noncardiac population of (c-kit)EGFP(+) myocytes within infarctions, indicating that the induction of undifferentiated precursors contributes to localized myogenesis. Thus, adult postinfarct myogenic failure is likely not due to a context-dependent restriction of precursor differentiation, and c-kit induction following injury of the adult heart does not define precursor status.

Episodic syncope caused by ventricular flutter in a tiger (Panthera tigris).

A captive, 9-yr-old castrated male tiger (Panthera tigris) from an exotic cat sanctuary and rescue facility was observed to have three collapsing episodes within a 2-wk interval prior to being examined by veterinarians. No improvement in clinical signs was noted after empiric treatment with phenobarbital. During a more complete workup for epilepsy, ventricular flutter was observed on electrocardiogram (ECG). The arrhythmia resolved with a single intravenous bolus of lidocaine. Cardiac structure and function were unremarkable on echocardiogram and cardiac troponin I levels were within normal limits for domestic felids. No significant abnormalities were noted on abdominal ultrasound. Complete blood count and biochemistry panel were unremarkable, and heartworm antigen and Blastomyces urine antigen enzyme-linked immunosorbent assays were negative. Antiarrhythmic treatment with sotalol was initiated. On follow-up ECG performed 1 mo later, no significant arrhythmias were noted, and clinical signs have completely resolved.

Measurement of plasma cardiac troponin I concentration by use of a point-of-care analyzer in clinically normal horses and horses with experimentally induced cardiac disease.

OBJECTIVE: To compare cardiac troponin I (cTnI) concentrations determined by use of a point-of-care analyzer with values determined by use of a bench-top immunoassay in plasma samples obtained from clinically normal horses with and without experimentally induced cardiac disease, and to establish a reference range for plasma equine cTnI concentration determined by use of the point-of-care analyzer. ANIMALS: 83 clinically normal horses, 6 of which were administered monensin to induce cardiac disease. PROCEDURES: A blood sample was collected from each of the 83 clinically normal horses to provide plasma for analysis by use of the point-of-care analyzer; some of the same samples were also analyzed by use of the immunoassay. All 83 samples were used to establish an analyzer-specific reference range for plasma cTnI concentration in clinically normal horses. In 6 horses, blood samples were also collected at various time points after administration of a single dose of monensin (1.0 to 1.5 mg/kg) via nasogastric intubation; plasma cTnI concentration in those samples was assessed by use of both methods. RESULTS: The analyzer-specific reference range for plasma cTnI concentration in clinically normal horses was 0.0 to 0.06 ng/mL. Following monensin treatment in 5 horses, increases in plasma cTnI concentration determined by use of the 2 methods were highly correlated (Pearson correlation, 0.83). Peak analyzer-determined plasma cTnI concentrations in monensin-treated horses ranged from 0.08 to 3.68 ng/mL. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with and without experimentally induced cardiac disease, the point-of-care analyzer and bench-top immunoassay provided similar values of plasma cTnI concentration.

Clinical findings and serum cardiac troponin I concentrations in horses after intragastric administration of sodium monensin.

Six adult horses were administered sodium monensin, 1.0-1.5 mg/kg, via gastric gavage. Anorexia and/or diarrhea occurred within 24 hr after monensin administration in all 6 horses. Cardiac disease and dysfunction were evaluated by both elevations in heart rate, echocardiography, and an increase in serum concentrations of cardiac troponin I (cTnI), occurred in 4 horses. The development and severity of cardiac disease was likely affected by the monensin dose, vehicle (water or corn oil) mixed with monensin, and/or whether the monensin was administered to fed or fasted horses. Initial increases in cTnI concentrations occurred between 24 and 72 hr after monensin administration. The 2 horses with the highest cTnI concentrations died or were euthanized within 5 days after monensin administration and had severe cardiac disease. One horse had increased cTnI concentrations from day 2 to day 16, but no apparent change in ventricular contractile function was evident on echocardiography. The fourth diseased horse did not return to cTnI reference intervals until day 27 after monensin administration, and the ventricular function was still abnormal just before euthanasia 9 months later. Cardiac troponin I measurements could be useful in managing farm outbreaks of accidental monensin feeding by the early identification of horses with cardiac disease.

The R9H phospholamban mutation is associated with highly penetrant dilated cardiomyopathy and sudden death in a spontaneous canine model.

Causative mutations for familial dilated cardiomyopathy (DCM) have been identified in the phospholamban gene. There are many poorly understood aspects about familial DCM (variable penetrance, expression) which may be studied in natural animal models. We characterized genetic aspects of familial DCM in a canine model with a high incidence of sudden death. A missense G > A mutation in exon 1 of the phospholamban gene that changed an amino acid from arginine to histidine was identified in affected dogs. This variant was predicted to be deleterious. We describe a spontaneous canine model of familial DCM and sudden death with the R9H mutation. In comparison to a reported human family, the variant was highly penetrant and resulted in sudden death. Genetic penetrance of this mutation may be influenced by genetic or environmental modifiers. The dog provides an excellent model in which to study complex aspects of familial DCM.

Septicemia and cardiovascular infections in horses.

This article first reviews cardiovascular infections, including endocarditis, myocarditis, vasculitis, and pericarditis. It then addresses what is known at this stage about the effects of sepsis on the cardiovascular system. Some information is provided from current human literature to familiarize the reader with the diagnostics and therapeutics that may eventually be used in equine practice as well.

Use of CPR in hemorrhagic shock, a dog model.

INTRODUCTION: Cardiopulmonary resuscitation was designed for sudden cardiac events usually triggered by thrombotic phenomena. Despite this, it is routinely used in trauma resuscitations as per the American Heart guidelines. There is no data supporting the use of chest compressions in hemorrhagic shock. An evidence-based cardiopulmonary resuscitation (CPR) protocol has been developed for dogs. We sought to determine the effects and outcomes of chest compressions in hemorrhagic shock in a canine model. METHODS: Eighteen dogs were randomized to three treatment groups-chest compressions only after hemorrhagic shock (CPR), CPR with fluid resuscitation after hemorrhagic shock (CPR + FLU), and fluid resuscitation alone after hemorrhagic shock (FLU). Under anesthesia, dogs were hemorrhaged until pulse was lost; they were maintained pulseless for 30 minutes and then resuscitated over 20 minutes. Vital signs and laboratory values were recorded at determined intervals. Echocardiography was performed throughout the study. Upon termination of the study, kidney, liver, heart, and brain tissue histology was evaluated for end organ damage. Statistical significance was p < 0.05 with a Bonferroni correction for multiple comparisons. RESULTS: Blood loss and mean time to loss of pulse were similar between the groups. Dogs in the CPR group had significantly lower mean arterial pressure and higher pulse at all points compared to CPR + FLU and FLU (p < 0.05). Ejection fraction was lower in the CPR group at 5 and 10 minutes compared to the other groups (p < 0.05). Vital signs and laboratory results between CPR + FLU and FLU were equivalent. Two of six dogs in the CPR group died, while no dogs died in the CPR + FLU or FLU groups. Dogs in the CPR group were found to have more episodes of end organ damage. CONCLUSION: There was no benefit to chest compressions in the hypovolemic animals. Chest compressions in addition to fluid did not reverse signs of shock better than fluid alone. Further research is needed to define if there is a role of CPR in the trauma patient with hemorrhagic shock.

Rupture of the gastrocnemius muscle in six foals.

Rupture of the gastrocnemius muscle and subsequent disruption of the reciprocal mechanism of the hind limb was diagnosed in 6 foals examined at 7 hours to 3 weeks of age. In 2 foals, the musculoskeletal injury was detected as an ancillary finding to clinical signs of neurologic dysfunction ascribed to hypoxic ischemic insult during delivery, whereas in the other 4 foals, musculoskeletal injury, manifested as inability to rise or stand unsupported, was the chief complaint at admission. Five foals had a history of dystocia and assisted delivery. Common clinical signs were inability to rise, disruption of the reciprocal mechanism, swelling in the caudal aspect of the thigh, instability of the stifle joint, and stifle joint effusion. For mild gastrocnemius injury, exercise restriction via forced recumbency, with minimal or no bandaging, may be sufficient treatment. For more severe disruption of the muscle, limb stabilization via splinting and intensive nursing and monitoring are necessary. Four foals had important concurrent problems, including musculoskeletal deformations (joint contractures), hypoxic ischemic disease, and failure of passive transfer and associated problems (ie, sepsis, polyarthritis, and pneumonia). Moderate to severe gastrocnemius muscle injury is difficult to treat successfully, and the long-term prognosis for athletic function should be regarded as guarded.

Idiopathic pericarditis and cardiac tamponade in two cows.

Idiopathic pericarditis is an uncommon diagnosis in cattle with cardiac tamponade. Two cows were examined for clinical signs of right-sided congestive heart failure, including tachycardia, venous distention, and peripheral edema. Muffled heart sounds were detected in one of the cows. Echocardiography in both cows revealed voluminous anechoic pericardial effusion and compression of the right atrium and right ventricle. Cytologic analysis of the pericardial fluid revealed hemorrhagic inflammation but no evidence of a septic or neoplastic condition such as traumatic reticulopericarditis or lymphoma, respectively. Pericardial drainage and lavage accompanied by treatment with anti-inflammatory drugs were curative in both cows. It is important to differentiate cows with idiopathic pericarditis from cows with more common septic pericarditis because the prognosis for the former disease appears to be good with appropriate treatment.

Myonecrosis and cutaneous infarction associated with Salmonella serovar Infantum infection in a horse.

A 5-year-old Quarter Horse mare was referred for evaluation of oral ulcers, limb edema, weight loss, and weakness. There was marked diffuse swelling extending from the stifle region to the tarsal region of the left hind limb, and the horse had a left hind limb lameness. Firm swellings ranging from 2 to 15 cm in diameter and consisting of nodules, plaques, and discrete masses were palpated on both sides of the neck, over the right shoulder region, over the left elbow region, and over the left caudoventral aspect of the abdomen. Laboratory abnormalities included hypoproteinemia, neutrophilia, and hyperfibrinogenemia. Results of ultrasonographic examination of the left hind limb and masses were suggestive of muscle edema, necrosis, and hemorrhage. Histologic examination of a biopsy specimen from a subcutaneous mass revealed necrotizing, suppurative myositis. The horse's condition gradually deteriorated, and the horse was euthanatized. Necropsy revealed myonecrosis, cutaneous infarcts, hepatic abscesses, and cholangitis. Salmonella serovar Infantum was cultured from liver and muscle lesions, and a diagnosis of Salmonella myonecrosis was made.

Cardiomyocyte calcium cycling in a naturally occurring German shepherd dog model of inherited ventricular arrhythmia and sudden cardiac death.

OBJECTIVE: To further characterize arrhythmic mechanisms in German shepherd dogs (GSDs) affected with inherited ventricular arrhythmias by evaluating intracellular calcium cycling and expression of calcium handling genes. ANIMALS: Twenty five GSDs, 9 backcross dogs, and 6 normal mongrel dogs (controls) were studied. The GSDs and backcross dogs were from a research colony of inherited ventricular arrhythmias. The control research dogs were purchased. METHODS: Action potentials (APs) and pseudo-electrocardiograms (ECG) were recorded from left ventricular (LV) wedge preparations of GSDs and normal dogs. Midmyocardial (Mid) LV cells from GSDs and normal mongrels were isolated by enzymatic digestion. Cells were either field stimulated or voltage clamped and calcium transients were measured by confocal microscopy using the indicator Fluo-3AM. Expression of calcium handling genes was measured by quantitative RT-PCR. RESULTS: Mean calcium transient decay (tau) was not different between affected GSDs and control dogs, but striking cell-to-cell variability for tau was observed within affected GSDs and between affected GSDs and controls (P < 0.0001 each); within-dog variability accounted for 75% of total variability. Calcium sparks and afterdepolarizations occurred in GSD but not control cells. ATP2A2/SERCA2a expression was significantly reduced (P = 0.0063) in affected GSDs and inversely correlated (P = 0.0006) with severity of ventricular arrhythmias. CONCLUSIONS: German shepherd dogs with inherited ventricular arrhythmias have electrophysiologic abnormalities in calcium cycling associated with reduced ATP2A2/SERCA2a expression. These animals provide a unique opportunity to study calcium remodeling at the genetic and molecular level in familial ventricular arrhythmias.

An accessory bypass tract masked by the presence of atrial fibrillation in a horse.

Accessory bypass tracts are rarely documented in horses. Here, we present a case of an accessory bypass tract which was initially masked by the presence of atrial fibrillation. Evidence of ventricular pre-excitation was recognized after cardioversion to normal sinus rhythm and the horse was diagnosed with Wolff-Parkinson-White Syndrome. In people, atrial fibrillation in the presence of an accessory bypass tract is considered dangerous due to the risk of sudden cardiac death. Although we did not consider this horse safe to ride, he continues to compete successfully and has not had recurrence of clinically significant tachyarrhythmias.