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Biomedical subjects

B W Keene

Publications and source records attributed to B W Keene.

At least 37 records · Page 2Linked to original sources
PubMed1990

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)

Animals↗
PubMed1990

Endomyocardial biopsy in cats.

A technique for transvenous endomyocardial biopsy of the right ventricle was developed and evaluated for safety and efficacy in anesthetized healthy cats positioned in left lateral recumbency. At least 6 endomyocardial biopsy specimens were obtained from the right ventricle or interventricular septum of 11 cats. In 4 cats, the right jugular vein was torn during attempts to pass the introducing catheter into the right ventricle; however, in only 1 cat did this preclude catheter passage. This cat's heart was biopsied via the left jugular vein. Except for damage to the jugular vein, complications were infrequent, and the biopsy procedure was well tolerated by all cats.

Animals↗
PubMed1990

Modified transvenous endomyocardial biopsy technique in dogs.

A technique for transvenous endomyocardial biopsy of the right ventricle was developed and evaluated for safety and efficacy in healthy dogs and dogs with dilated cardiomyopathy positioned in lateral recumbency. This technique allowed acquisition of multiple biopsy specimens from the right ventricle of each of 22 hemodynamically normal dogs and 40 of 42 dogs with congestive heart failure. In 2 dogs with dilated cardiomyopathy, transvenous access to the right ventricle could not be achieved, but left ventricular biopsy was performed without complication. Complications were infrequent, and dogs recovered to at least their baseline status within 48 hours. Evaluation of the efficacy and complication rate of the procedure with each of the 2 biopsy instruments currently available identified no differences between them.

Animals↗
PubMed1989

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)

Animals↗
PubMed1989

Inability to detect parasympathetic autonomic neuropathy in experimental canine diabetes mellitus in an electrocardiographic study.

Resting electrocardiography was used to evaluate parasympathetic control of the heart rate and heart rate variability in 25 adult alloxan-diabetic dogs and 34 nondiabetic controls. The duration of diabetes (mean +/- SEM) was 3.0 +/- 0.3 yr. Such long-term diabetes had no apparent effect on resting heart rate, maximum R to R interval variation, or percentage of subjects exhibiting respiratory sinus arrhythmia. In addition, despite significant differences in glycemic control between experimental groups, no differences in the above electrocardiographic parameters were demonstrated. Electrocardiographic indices of autonomic function were not significantly correlated with glycosylated hemoglobin concentration, age, or duration of diabetes. Up to 40% of diabetic humans develop autonomic neuropathy (diabetic autonomic neuropathy), with virtually all studies showing higher heart rates and greater heart rate variability in diabetics as compared to nondiabetic controls. The absence of electrocardiographic indicators of autonomic neuropathy in this study suggests that the dog is less susceptible to the development of diabetic autonomic neuropathy than is the diabetic human and therefore may be a poor model for many studies.

Animals↗
PubMed1988

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)

Administration, Oral↗
PubMed1988

Electrocardiographic abnormalities associated with tetanus in two dogs.

Bradycardia, sinus arrest, and second-degree atrioventricular block developed in 2 dogs with tetanus. Clinical signs attributable to bradycardia were not apparent. Administration of atropine resulted in resolution of the arrhythmias. Both dogs responded well to supportive treatment; the bradycardia resolved within 4 days of onset without specific treatment. Tetanus should be included in the differential diagnosis when increased neuromuscular excitability and bradycardia are evident, as is found in toxicity with acetylcholinesterase inhibitors, increased intracranial pressure, and other neurologic disorders.

Animals↗
PubMed1988

Pathophysiologic mechanism of cardiac dysfunction in experimentally induced heartworm caval syndrome in dogs: an echocardiographic study.

In dogs with experimentally induced heartworm infection, the onset of caval syndrome (CS) was characterized by a murmur, loudest over the tricuspid valve, and a large worm mass in the right ventricular lumen detectable during diastole by use of M-mode echocardiography. Two-dimensional echocardiography indicated that the worm mass was located in the right atrium and venae cavae and was "flowing" into the right ventricle during rapid diastolic filling. Paradoxical septal motion and vigorous right ventricular cranial wall motion also were observed. Other echocardiographic changes included decreased size of the left atrium and ventricle, aortic root, and ratio of left-to-right ventricular diastolic luminal diameter, compared with values obtained 6 months after experimentally induced heartworm infection. Right ventricular end diastolic diameter increased considerably. Most echocardiographic indices of left ventricular function (fractional shortening, velocity of circumferential fiber shortening, ejection fraction, and preejection period) were not altered appreciably, but estimates of cardiac index and stroke volume were markedly decreased. Electrocardiography revealed ventricular and supraventricular premature complexes in 7 of the 8 dogs studied, evidence of right ventricular enlargement in 6 of the 8 dogs studied, and increased mean heart rate, compared with that measured 6 months after inoculation of infective larvae, before the onset of CS. Cardiac catheterization was performed in 3 days at the onset of CS. Severe pulmonary arterial and right ventricular hypertension and decreased cardiac index (compared with values obtained before inoculation) were observed. Evidence of right ventricular inflow obstruction was not detected. Mean aortic blood pressure decreased with the onset of CS, but right ventricular end diastolic pressure increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Sensitivity and specificity of isolated perfused guinea pig heart to test for drug-induced lengthening of QTc.

INTRODUCTION: The purpose of this study was to determine the sensitivity and specificity for predicting the liability of a compound to lengthen QTc using isolated, perfused guinea pig hearts (Langendorff preparation). METHODS: QTc (Fridericia correction) was calculated from bipolar transventricular electrograms. Hearts were exposed to escalating concentrations of 26 compounds thought to lengthen, and 13 compounds thought not to lengthen, QTc in humans. RESULTS: In this preparation, QTc was found to lengthen in 26 of 26 compounds thought to be positive (sensitivity 1.00) and not to lengthen or to lengthen insignificantly in 13 of 13 compounds thought to be negative (specificity 1.0) in man. Probucol and ontazolast could not be studied because of limited solubility. Successful experiments were conducted on over 98% of guinea pigs anesthetized. DISCUSSION: We believe that the isolated perfused guinea pig heart is an in vitro preparation that could be utilized early in preclinical testing for identifying a liability to lengthen QTc in humans, but we do not believe--as is true also for other in vitro methods--that the concentration at which the liability is demonstrated in vitro necessarily predicts the concentration at which a liability exists in man.

Animals↗
PubMedDate not supplied

Effects of atropine and glycopyrrolate on esophageal, gastric, and tracheal pH in anesthetized dogs.

Atropine, glycopyrrolate, or saline solution was administered before anesthesia in a blinded, controlled study of 40 dogs scheduled to undergo surgery. Effects of treatment on esophageal, gastric, and tracheal pH were measured with an intraluminal pH meter. Preanesthetic administration of atropine and glycopyrrolate had no effect on esophageal, gastric, or tracheal pH but did result in increased heart rate. Thoracotomy procedures resulted in decreased intraluminal esophageal pH and increased heart rate. Esophageal pH at the level of the thoracic inlet decreased over the duration of surgery.

Anesthesia↗
PubMedDate not supplied

Asystole associated with iohexol myelography in a dog.

This is a report of a 10-year-old female neutered Doberman Pinscher with a clinical diagnosis of myelopathy. The dog was anesthetized using oxymorphone, thiopental, and halothane in oxygen for a cerebrospinal tap and a myelogram. Iohexal injection into the subarachnoid space by lumbar puncture was uneventful. Additional iohexal was given into the cerebeliomedullary cistern. Immediately following iohexal administration into the cerebellomedullary cistern, several electrocardiographic changes occurred. Two extended periods of asystole responded to intravenous glycopyrrolate administration. A slow multiform ventricular escape rhythm was established after the second dose of glycopyrrolate. Ultimately, atrial activity with apparent AV dissociation resumed, atrial fibrillation developed, and the rhythm converted to normal sinus rhythm. The dog had a normal cardiac examination the following day. Two days later, the dog was anesthetized using a similar anesthetic regimen with maintenance on isoflurane in oxygen for a hemilaminectomy. The dog recovered uneventfully from surgery and was discharged 2 days later.

Animals↗
PubMedDate not supplied

Investigation of caval syndrome in dogs experimentally infected with Dirofilaria immitis.

Nine of 16 dogs inoculated with 200 infective heartworm larvae developed caval syndrome (CS) of heartworm disease (HWD). There was no difference between dogs that did and did not develop CS with regard to total heartworm burden, burden relative to body weight, or female heartworm burden, indicating that factors other than worm mass are involved in the pathogenesis of CS. Male dogs were twice as frequently affected as females, although this finding was not statistically significant. Dogs afflicted with CS exhibited radiographic, pathologic, and hemodynamic evidence of chronic HWD. In a model of single heartworm exposure, these findings strongly support the theory that CS develops due to retrograde migration of adult worms from the pulmonary arteries and right ventricle to the right atrium and venae cavae. Pulmonary artery pressures were dramatically and significantly greater in dogs with CS (60 +/- 18 torr) as compared to non-CS (30 +/- 4 torr) dogs with equal worm burdens.

Animals↗
PubMedDate not supplied

Fanconi's syndrome in a dog with primary hypoparathyroidism.

An 11-year-old castrated male mixed breed dog was referred for evaluation of muscle twitching, polyuria, polydipsia, anorexia, and periocular alopecia. Primary hypoparathyroidism was diagnosed by documenting decreased serum concentrations of parathyroid hormone and ionized calcium. Neurological, gastrointestinal, and dermatological signs resolved after calcium repletion. Initially, 1,25-dihydroxycholecalciferol PO was required to correct the hypocalcemia. Dihydrotachysterol, in combination with oral calcium supplementation, was used for long-term maintenance of normal serum calcium concentration. Aminoaciduria, glucosuria, and hyperchloremic metabolic acidosis were consistent with a diagnosis of Fanconi's syndrome. This diagnosis was further supported by the presence of hypokalemia and increased urinary fractional excretion of sodium, potassium, calcium, phosphorus, and magnesium. Renal tubular dysfunction resolved after oral supplementation with calcium and vitamin D3. Fanconi's syndrome in this dog may have been caused by decreased serum concentration of 1,25-dihydroxycholecalciferol, which was secondary to decreased parathyroid hormone production.

Animals↗
PubMedDate not supplied

Orthodromic reciprocating tachycardia and heart failure in a dog with a concealed posteroseptal accessory pathway.

A 4-month-old male Labrador Retriever was presented for recurrent bouts of pulmonary edema associated with tachycardia. Initial physical examination and echocardiography were unremarkable, and the electrocardiogram revealed only an intraventricular conduction disturbance. Subsequent recordings showed paroxysmal supraventricular tachycardia (SVT) (340 beats/min), which consistently produced pulmonary edema. The supraventricular tachycardia was unresponsive to adenosine, esmolol, and propranolol; was variable and transiently responsive to various vagal maneuvers and precordial thumps; and was always responsive to IV diltiazem. Multiple life-threatening episodes of SVT occurred, however, despite the chronic administration of oral diltiazem, propranolol, and procainamide. Diastolic cardiac dysfunction was documented by Doppler echocardiography and was thought to contribute to the development of pulmonary edema. A subsequent electrophysiologic study confirmed the presence of an atrioventricular posteroseptal accessory pathway that participated in orthodromic reciprocating tachycardia. This pathway was determined to conduct only in the retrograde direction ("concealed accessory pathway"). Intraoperative IV procainamide titration terminated the arrhythmia, which could not be reinduced when procainamide blood concentration approximated 20 micrograms/dL. Increasing the oral procainamide dose to achieve such plasma concentrations was successful in eliminating orthodromic reciprocating tachycardia, preventing heart failure, and returning Doppler indices of diastolic function to normal.

Animals↗
PubMedDate not supplied

Pharmacokinetic and pharmacodynamic properties of conventional and CD-formulated diltiazem in cats.

The i.v. and apparent steady-state kinetics of diltiazem HCI (DLT) and slow-absorption long-acting diltiazem (CD) given p.o. were investigated in cats. The effects of p.o. diltiazem on heart rate and PR interval were also studied. Plasma diltiazem concentrations were determined by ultraviolet high-performance liquid chromatography (UV-HPLC), using verapamil as the internal standard. Heart rate and PR interval determinations were evaluated over a 24-hour period for the PO formulations and compared with values under diltiazemfree conditions. The mean systemic clearance and apparent volume of distribution of i.v. diltiazem were 15.0 mL/min/kg and 2.70 L/kg, respectively. The elimination half-life of diltiazem after i.v. and p.o. DLT administration were approximately 120 minutes. In contrast, the terminal half-life of CD was 460 minutes. The mean apparent bioavailability of DLT p.o. was 71%, which was significantly higher than that observed with CD (36%). Heart rate and PR intervals in cats receiving the 2 formulations at steady-state were not different from those measured in the drug-free state. We conclude that DLT at 1 mg/kg p.o. tid and CD at 10 mg/kg p.o. sid provide plasma concentrations that are known to have pharmacodynamic effects in other species.

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