Electrocardiographic findings in dogs with motor vehicle-related trauma.

Motor vehicle-related injury is the most common form of trauma incurred by dogs, and cardiac arrhythmias are a well-recognized complication. Although posttraumatic arrhythmias are often observed, little is known regarding their frequency. This study utilized continuous ambulatory electrocardiography (i.e., Holter monitoring) to describe the cardiac rhythm disturbances in 30 dogs sustaining trauma in motor vehicle accidents. Ventricular ectopy was identified by Holter monitoring in 29 of 30 dogs, although the initial electrocardiogram (EKG) only documented ventricular ectopic complexes (VECs) in four dogs. Ventricular ectopy was infrequent in most dogs (i.e., 62% of the dogs had less than 100 VECs per day for the entire study), but 16% developed frequent arrhythmias (greater than 4,000 VECs per day). In all cases, the VECs were observed within 24 hours of injury. Forty-three percent of dogs had at least one episode of ventricular tachycardia, including several dogs that had an overall infrequent rate of VECs (i.e., less than 100 or 100 to 1,000 VECs per day). Although baseline EKGs are useful in identifying arrhythmias in most dogs, the length of the recording should be increased to improve the likelihood of observing an abnormal EKG event. Most importantly, additional EKGs should be obtained or continuous EKG monitoring should be performed in dogs that display clinical signs that could be attributed to ventricular arrhythmias.

Effect of amlodipine on echocardiographic variables in cats with systemic hypertension.

Left ventricular hypertrophy signals a poor prognosis in hypertensive humans. Cardiac disease is common in cats with systemic hypertension. The aims of this study were to characterize the echocardiographic findings of cats with systemic hypertension and to determine if reducing the degree of hypertension is associated with resolution of cardiac hypertrophy. Echocardiographic examinations were performed on 19 cats with naturally occurring systemic hypertension. Fourteen of these cats were subsequently studied after a minimum of 3 months of treatment with the antihypertensive agent amlodipine. Hypertensive cats had a significantly thicker interventricular septum in both systole and diastole, thicker left ventricular free wall in both systole and diastole, and larger left atrium compared to the published normal values and 74% (14/19) of the cats met criteria for left ventricular hypertrophy (diastolic septal or free-wall thickness > 0.60 cm). Systolic blood pressure was lower after treatment (217 +/- 25 mm Hg, range: 180-275 mm Hg; and 142 +/- 27 mm Hg, range: 90-200 mm Hg). No difference was found in any of the echocardiographic measurements between the untreated and treated cats, although more cats had ventricular hypertrophy before treatment (11/14) than after initiating amlodipine (6/14; P = .006). Ventricular hypertrophy is common in hypertensive cats and may resolve after the initiation of amlodipine.

Polyamine analogue antidiarrheals: a structure-activity study.

The syntheses of a group of spermine polyamine analogues and their evaluation as antidiarrheals are described. Each compound was assessed in a rodent castor oil-induced diarrhea model for its ability to reduce stool output and weight loss in a dose-dependent manner. The spermine pharmacophore is shown to be an excellent platform from which to construct antidiarrheals. The activity of the compounds is very dependent on both the nature of the terminal alkyl groups and the geometry of the methylene spacers separating the nitrogens. The toxicity profile is also quite dependent on these same structural features. On the basis of subcutaneous dose-response data and toxicity profiles, two compounds, N(1),N(12)-diisopropylspermine and N(1),N(12)-diethylspermine, were taken forward into more complete evaluation. These measurements included formal acute and chronic toxicity trials, drug and metabolic tissue distribution studies, and assessment of the impact of these analogues on tissue polyamine pools. Finally, the remarkable activity of N,N'-bis[3-(ethylamino)propyl]-trans-1,4-cyclohexanediamine underscores the need to further explore this framework as a pharmacophore for the construction of other antidiarrheal agents.

Performance of serologic tests used to detect heartworm infection in cats.

OBJECTIVE: To compare heartworm serum antibody (Ab) and antigen (Ag) test results, using commercial laboratories and in-house heartworm test kits, with necropsy findings in a population of shelter cats. DESIGN: Prospective study. ANIMALS: 330 cats at an animal shelter. PROCEDURE: Between March and June 1998, 30 ml of blood was collected from the cranial and caudal venae cavae of 330 cats that were euthanatized at a local animal shelter. Results of heartworm Ab and Ag serologic tests for heartworm infection were compared with necropsy findings in this population of cats, using commercial laboratories and in-house test kits to measure serum Ab and Ag concentrations. RESULTS: On necropsy, adult Dirofilaria immitis were found in 19 of 330 (5.8%) cats. Combining results from serum Ab and Ag tests achieved higher sensitivities than using serum Ab and Ag test results alone (i.e., maximum sensitivities of 100% vs 89.5%, respectively, whereas use of serum Ag and Ab test results alone achieved higher specificities compared with the use of a combination of serum Ab and Ag results (i.e., maximum specificities of 99.4% vs 92.9%, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of our findings, if a cat has clinical signs that suggest heartworm disease despite a negative heartworm serum Ab test result, an alternative heartworm Ab test, a heartworm Ag test, thoracic radiography, or two-dimensional echocardiography should be performed.

Bartonella vinsonii subsp. berkhoffii and related members of the alpha subdivision of the Proteobacteria in dogs with cardiac arrhythmias, endocarditis, or myocarditis.

Cardiac arrhythmias, endocarditis, or myocarditis was identified in 12 dogs, of which 11 were seroreactive to Bartonella vinsonii subspecies berkhoffii antigens. Historical abnormalities were highly variable but frequently included substantial weight loss, syncope, collapse, or sudden death. Fever was an infrequently detected abnormality. Cardiac disease was diagnosed following an illness of short duration in most dogs, but a protracted illness of at least 6 months' duration was reported for four dogs. Valvular endocarditis was diagnosed echocardiographically or histologically in eight dogs, two of which also had moderate to severe multifocal myocarditis. Four dogs lacking definitive evidence of endocarditis were included because of seroreactivity to B. vinsonii antigens and uncharacterized heart murmurs and/or arrhythmias. Alpha proteobacteria were not isolated from the blood by either conventional or lysis centrifugation blood culture techniques. Using PCR amplification and DNA sequencing of a portion of the 16S rRNA gene, B. vinsonii was identified in the blood or heart valves of three dogs. DNA sequence alignment of PCR amplicons derived from blood or tissue samples from seven dogs clustered among members of the alpha subdivision of the Proteobacteria and suggested the possibility of involvement of one or more alpha proteobacteria; however, because of the limited quantity of sequence, the genus could not be identified. Serologic or molecular evidence of coinfection with tick-transmitted pathogens, including Ehrlichia canis, Babesia canis, Babesia gibsonii, or spotted fever group rickettsiae, was obtained for seven dogs. We conclude that B. vinsonii subsp. berkhoffii and closely related species of alpha proteobacteria are an important, previously unrecognized cause of arrhythmias, endocarditis, myocarditis, syncope, and sudden death in dogs.

Two-dimensional echocardiographic anatomy of the snake heart (Python molurus bivittatus).

Two-dimensional echocardiography was performed on Burmese pythons (Python molurus bivittatus) to determine an optimal echocardiographic imaging technique for snakes and to describe the echocardiographic anatomy of the snake heart. Five snakes immobilized with tiletamine/zolazepam and maintained on isoflurane in oxygen were imaged in dorsal recumbency. The portion of the snake's body containing the heart was submerged in warm water to reduce the artifact created by air trapped between and under the scales. Imaging in sagittal planes demonstrated the caudal vena cava, sinus venous valve, right atrium, various portions of the ventricle, horizontal septum, the left aortic arch, and pulmonary artery. Transverse imaging depicted the spatial relationship of the left and right aortic arches and pulmonary artery and the horizontal septum. Basic knowledge of cardiac blood flow in the reptile was necessary to understand the echocardiographic anatomy.

Polyamine analogue antiarrhythmics.

A group of polyamine analogues was assessed for their ability to prevent isoproterenol-induced ventricular fibrillation and death in a desoxycorticosterone acetate (DOCA)/saline rodent model. The compounds tested included polyamine antimetabolites and putrescine mimics. A structure-activity analysis revealed that tetraamines that are dicationic at physiological pH with their terminal nitrogens incorporated into pyridine rings are the most active analogues. It is clear from this study that there was no correlation between the compounds' ability to diminish polyamine metabolism and their effects on the electrical properties of the heart. In fact, the most potent polyamine antimetabolites were among the least effective antiarrhythmics. The most active of the compounds investigated, N1, N3-bis(4-pyridyl)-1,3-diaminopropane, PYR(3,3,3), was shown to both prevent isoproterenol-induced arrhythmias in DOCA/saline-treated rodents and reverse the progression of arrhythmic events that would otherwise culminate in ventricular fibrillation and death. Electrocardiographic tracings demonstrated that PYR(3,3,3) and propranolol both protect from and reverse the progression of arrhythmic events to ventricular fibrillation. In addition, cardiac pathologies from rats treated with both drugs are similar, but are substantially different from the control (isoproterenol)-treated animals. (c) 1998 The Italian Pharmacological Society.

Calcium channel blockers in veterinary medicine.

Calcium channel blockers are becoming increasingly popular in veterinary medicine for the treatment of systemic hypertension, cardiac arrhythmias, and hypertrophic cardiomyopathy. Calcium is vital to many cellular functions and thus stringent regulation of intracellular calcium concentrations is required. Pharmacologic manipulation of the regulatory mechanisms has the potential to alter cellular function in all body systems. In human medicine, calcium channel blockers are being evaluated for, among other things, use in treating glaucoma, deep vein thrombosis, and pulmonary hypertension, in renal transplantation, and for prevention of reperfusion injury. The potentially beneficial effects of these drugs have often been overshadowed by adverse effects including hypotension, inappetence, bradycardia, conduction abnormalities, and decreased cardiac output. With the introduction of sustained-release formulations (diltiazem) and 2nd generation calcium channel blockers (amlodipine) many of these effects have been attenuated or eliminated. This paper will review the functions of calcium and the calcium channels as well as discussing the classes and current and potential uses of the various calcium channel blockers.

Amlodipine: a randomized, blinded clinical trial in 9 cats with systemic hypertension.

The efficacy of amlodipine (AML) was tested in hypertensive cats in a placebo-controlled, randomized, blinded clinical trial. Five cats were randomized to receive 0.625 mg AML once daily and 4 cats to receive placebo (PLA) once daily. The average systolic blood pressure (SBP) recorded by the Doppler method on day 0 was 212 +/- 21 mm Hg in the AML group and 216 +/- 32 mm Hg in the PLA group. On day 7, the cats receiving AML had a significantly lower average daily SBP (160 +/- 30 mm Hg) but SBP in the PLA group was unchanged (207 +/- 31 mm Hg). On day 7, all cats receiving PLA and one cat receiving AML were crossed over to the other group because of inadequate response. Blood pressure did not decrease adequately in 3 cats by day 14 (7 days of PLA and 7 days AML) and the treatment code was broken. Each of these cats was subsequently administered 1.25 mg AML daily. Cats requiring 1.25 mg AML once daily (6.1 kg +/- 0.7 kg) weighed significantly more than cats that responded to 0.625 mg AML once daily (4.1 +/- 0.7 kg). The average daily SBP recorded in the 6 cats that completed the study was significantly lower after 16 weeks of treatment (152 +/- 14 mm Hg) compared to day 0 (221 +/- 24 mm Hg). Three cats were euthanized before completion of the study. All 3 cats were responders to AML on day 7. SBPs measured 24 hours after AML administration were similar to the average daily SBP, suggesting that AML effectively controlled SBP for a 24-hour period. AML was shown to be an effective once-daily antihypertensive agent when administered to cats at a dosage of 0.18 +/- 0.03 mg/kg sid.

Fluid therapy in the cardiac patient.

Correcting fluid deficits and preventing fluid overload in patients with cardiac disease can be challenging. The purpose of the fluid therapy, the projected duration of the therapy, and the type of heart disease affecting the patient play important roles in the decision-making process. In addition, the distinction between patients who are not symptomatic (NYHA Class I) and those who are symptomatic (NYHA Classes II to IV) for their cardiac disease should be made early in fluid therapy planning.

Treatment of systemic hypertension in cats with amlodipine besylate.

Amlodipine besylate, a calcium channel blocker, was used to treat (mean +/- standard deviation [SD], 127 +/- 68 days) 12 cats with systemic hypertension. Amlodipine was administered orally at a dosage of 0.625 mg per cat (range, 0.08 to 0.23 mg/kg body weight; mean dose +/- SD, 0.17 +/- 0.04 mg/kg body weight) once daily as a single agent. Average indirect systolic blood pressure measurements in the 12 cases decreased significantly from 198 to 155 mmHg during amlodipine treatment. Significant changes in body weight and serum creatinine and potassium concentrations were not detected. Amlodipine appears to be a safe and effective oral treatment for systemic hypertension in cats when used chronically once daily as a single agent.

Systolic time intervals and their derivatives for evaluation of cardiac function.

Systolic time intervals provide a noninvasive indication of global left ventricular performance, are relatively sensitive, and are easily obtained from an M-mode echocardiogram. This paper defines systolic time intervals (preejection period, left ventricular ejection time, and total electromechanical systole) and their derivatives (preejection period/left ventricular ejection time and velocity of circumferential fiber shortening). Their utility and weaknesses, as well as the effects of heart rate, loading conditions, cardiac contractility, and drug therapies on systolic time intervals are discussed. Normal values for systolic time intervals for the dog and cat are provided.

Treatment of membranoproliferative glomerulonephritis and nephrotic syndrome in a dog with a thromboxane synthetase inhibitor.

A 2-year-old spayed female Whippet with membranoproliferative glomerulonephritis and nephrotic syndrome was treated with a specific thromboxane synthetase inhibitor (3-methyl-2[3-pyridyl]-1-indoleoctanoic acid), resulting in decreased proteinuria and resolution of ascites and edema. Glomerular histology, however, appeared unaffected by treatment. Discontinuation of treatment for 10 weeks resulted in increased proteinuria and decreased serum albumin concentrations that were again attenuated when treatment was reinitiated. Thromboxane synthetase inhibitors have been used successfully to treat experimentally induced glomerulonephritis in several species and this treatment appears to hold promise for naturally occurring glomerulonephritis in dogs.

Efficacy of digoxin for treatment of cats with dilated cardiomyopathy.

The role of digoxin in treatment of cats with dilated cardiomyopathy and other forms of myocardial failure is unclear. We evaluated the chronotropic and inotropic effects of digoxin by comparing baseline, noninvasive indices of cardiac performance with those obtained after 9 +/- 1.3 (mean +/- SEM) days of digoxin treatment in 6 cats with heart failure attributable to dilated cardiomyopathy. Two-dimensionally directed, M-mode echocardiography and electrocardiography were used to determine left ventricular shortening fraction, preejection period (PEP), ejection time (LVET), PEP to LVET ratio, velocity of circumferential fiber shortening, electromechanical systole, heart rate, and PR interval. Treatment consisted of administration of furosemide (mean dosage, 2.4 mg/kg of body weight/day), digoxin in tablet form (approximately 0.01 mg/kg, q 48 h), aspirin (80 mg, q 48 h), and a commercial low-salt diet. In addition, 2 cats were administered short-term, low-dose fluids IV, and 2 were given taurine supplementation at rates of 500 and 1,000 mg/day. Other off-loading or inotropic agents were not administered. Therapeutic or toxic serum digoxin concentration was achieved in all cats. Significant (P less than 0.05) improvement was detected in mean values for shortening fraction, PEP, PEP to LVET ratio, and velocity of circumferential fiber shortening. Mean electromechanical systole and LVET did not change significantly. Improvement, as assessed by indices of cardiac function, was documented in 4 of the 6 cats treated with digoxin, including the 2 cats given taurine supplementation. In the cats given taurine, positive inotropic effect was observed prior to the time when taurine-induced improvement in ventricular function is detectable.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of compensated heart failure on digoxin pharmacokinetics in cats.

To evaluate the effects of compensated heart failure (HF) on digoxin pharmacokinetic properties in cats, 6 cats with dilated cardiomyopathy were compared with 6 clinically normal (control) cats. Digoxin tablets were administered at a dosage of 0.01 mg/kg of body weight, q 48 h for approximately 10 days, until presumed steady state was reached. Both groups were treated concomitantly with aspirin, furosemide, and a commercial low-salt diet. Retrospectively, control and HF cats were calculated to be at 95% and 97% steady state, respectively. At the time blood samples were collected, HF cats were clinically compensated. Serum digoxin concentration [( DXN]) was determined by radioimmunoassay on samples drawn immediately before and 1, 2, 4, 8, 12, 24, 34, and 48 hours after digoxin administration. Measured and calculated values (peak, 8-hour, and mean [DXN]; elimination half-life [t1/2]; oral clearance; and hours during which [DXN] was in the toxic range) were not significantly different between control and HF cats. To predict individual propensity for digoxin intoxication, serum creatinine and urea concentrations and sulfobromophthalein dye retention were measured in control and HF cats prior to the onset of treatment with digoxin. There was no statistically significant correlation between serum creatinine and urea concentrations when compared with sulfobromophthalein dye retention nor between any of these values and digoxin peak, 8-hour, and mean concentrations or t1/2, oral clearance, or hours during which [DXN] was in the toxic range. Mean serum creatinine and urea nitrogen concentrations were significantly greater (P less than 0.01) and sulfobromophthalein dye retention approached significant prolongation (P less than 0.06) in HF cats, compared with that in control cats.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of aspirin, furosemide, and commercial low-salt diet on digoxin pharmacokinetic properties in clinically normal cats.

Steady-state serum digoxin concentration ([digoxin]) was measured for 48 hours in 6 healthy cats after they were treated with digoxin tablets (0.01 mg/kg of body weight, q 48 h) for 10 days and again after concurrent treatment of identical duration with orally administered digoxin, aspirin (80 mg, q 48 h), furosemide (2 mg/kg, q 12 h), and a commercial low-salt diet. The concurrent treatment substantially altered digoxin pharmacokinetic properties, with a resultant increase in peak (mean +/- SEM; from 2.1 +/- 0.35 to 3.3 +/- 0.6 ng/ml), 8-hour (from 1.4 +/- 0.35 to 2.5 +/- 0.64 ng/ml), and 48-hour mean (from 1.1 +/- 0.22 to 2.2 +/- 0.57 ng/ml) serum [digoxin]; an increase in the number of hours during which serum [digoxin] was in the toxic range (from 3 +/- 1.7 to 24.7 +/- 9.8 h); and a decrease in oral clearance (from 0.15 +/- 0.04 to 0.08 +/- 0.02 L/h.kg). Of these differences, all but the 8-hour serum [digoxin] were significant at P less than 0.05. Similar sampling procedures were performed in 3 cats after administration of digoxin alone (0.01 mg/kg, q 48 h) until steady-state conditions were reached (10 days) and again after an additional 10 days of treatment. Differences were not noticed in digoxin pharmacokinetic properties. Eight-hour serum [digoxin] was shown to correlate closely with the mean serum [digoxin] at steady-state conditions when digoxin was administered every 48 hours. Variation in digoxin pharmacokinetic properties was noticed between cats.(ABSTRACT TRUNCATED AT 250 WORDS)