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Biomedical subjects

J E Doherty

Publications and source records attributed to J E Doherty.

At least 37 records · Page 2Linked to original sources
PubMed1982

Adrenergic and cholinergic mechanisms in digitalis inotropy.

In anesthetized dogs, the effects of peripheral cardiac nerves upon cardiotonic steroid-induced contractile force increases were determined by comparing the effects seen with cardiac nerves intact, cardiac denervation, stellate ganglia removed or vagi sectioned. Additionally, structure-activity relationships among four cardiotonic steroids were determined by comparing the contractile force effects of bolus i.v. injections of digitoxigenin (the genin), digitoxigenin-galactose (genin-neutral sugar combination), digitoxigenin-aminogalactose (ASI-222, genin-aminosugar combination) and digoxin. The effects of these drugs upon cardiac rate, mean blood pressure and cardiac contractile force were recorded. Cardiotonic steroids differ in their interaction with cardiac nerves. Digitoxigenin, in addition to its direct contractile force effect on the myocardium, modulates contractile force through adrenergic mechanisms. In contrast, both digoxin and ASI-222 influence their direct inotropic responses through cholinergic mechanisms. Neither adrenergic nor cholinergic mechanisms significantly affect the peak inotropic response of digitoxigenin-galactose. Our data indicate that alterations in both the aglycone and the sugar moieties can significantly alter the contribution of the autonomic nervous system to the contractile force response.

Animals↗
PubMed1981

Digoxin uptake into peripheral autonomic cardiac nerves: possible mechanism of digitalis-induced antiarrhythmic and toxic electrophysiologic actions.

It is generally accepted that certain cardiac rhythm disturbances are due to imbalances between the sympathetic and parasympathetic nervous systems. We have provided evidence that digoxin is concentrated in the peripheral nervous system of the heart as well as in the central nervous system. Previous findings have indicated that cardiac glycosides may directly or indirectly affect autonomic neurotransmitters. Therefore the uptake of digoxin into the peripheral cardiac nervous system may play an important role in both the antiarrhythmic and toxic electrophysiologic actions of digoxin.

Animals↗
PubMed1981

Ventricular arrhythmia before and after aorto-coronary bypass surgery.

The influence of aorto-coronary bypass surgery (ACBS) on ventricular arrhythmia was examined in 57 patients. Six-hour Holter monitoring was done on the day prior to and 3 mth after ACBS. None of the patients were on any antiarrhythmic drugs during these recordings. Ventricular arrhythmia was classified into three groups: Group I (45 patients) had an average of less than 10 premature ventricular contractions (PVCs) per hour, Group II (7 patients), 11-30 PVCs per hour and Group III (5 patients), greater than 30 PVCs per hour. There was no significant change in the number of patients in each group after ACBS. Complex PVCs were present in 8 patients preoperatively and in 9 patients after ACBS. The number of diseased vessels and the extent of left ventricular wall motion abnormality noted preoperatively, had no effect on ventricular arrhythmia following surgery. These data show that ACBS, when performed to relieve angina, does not have a significant effect on the prevalence of PVCs and does not prevent or reduce the occurrence of complex PVCs.

Adult↗
PubMed1981

Systolic time intervals in the experimental animal with aortic outflow obstruction. Effect of digoxin.

This study shows significant changes occurring in systolic time intervals in an experimental animal model of aortic outflow obstruction with cardiac hypertrophy. The left ventricular ejection time is markedly prolonged and the preejection period/left ventricular ejection time ratio shortened. These changes are in the opposite direction of those usually observed with left ventricular dysfunction in man but similar to those described in man with aortic stenosis. Furthermore, the changes observed in systolic time intervals after digoxin in this experimental model are not comparable to those reported in man with normal or abnormal left ventricular function. Hence, the use of systolic time intervals, including digitalis effect, to evaluate the functional state of the left ventricle in aortic outflow obstruction are probably unreliable.

Animals↗
PubMed1980

The long-term suppression of ventricular arrhythmia by oral acebutolol in patients with coronary artery disease.

The short-term efficacy of oral acebutolol was evaluated in 20 patients with coronary artery disease and frequent premature ventricular contractions (PVCs) by serial 24-hour Holter monitoring before and while the patients were receiving an average daily dose of 1,100 mg. of acebutolol for four weeks. Fifty-five percent of the 20 patients showed a greater than 70% PVC reduction from baseline values. The only serious side effect during short-term therapy was mild, reversible cardiac decompensation in one patient. The long-term safety and continued efficacy of acebutolol was then evaluated over the next 11 months in nine of the 11 patients showing greater than 70% PVC reduction at four weeks. Two-thirds of these nine patients continued to show greater than 80% PVC reduction from baseline values at 12 months. One patient developed alopecia during long-term therapy. The majority of patients not responding well to acebutolol at four weeks had an actual increase in PVCs on acebutolol therapy. We conclude that acebutolol produces long-term, effective reduction in PVCs without serious toxicity in the majority of patients with ventricular ectopy. However, this drug appears to either produce an excellent response or no response with regard to PVC control in most instances.

Acebutolol↗
PubMed1980

Digoxin-quinidine interaction. Changes in canine tissue concentration from steady state with quinidine.

Tissue concentrations of tritiated digoxin inthe dog are altered by simultaneous administration of quinidine. Serum levels rise as tissue concentration decreases significantly in all tissue except brain tissue, where an increase of 51 percent is noted over that of the control digitalized state. The digitalis toxicity associated with digoxin-quinidine interaction appears to be associated with rising brain levels of digoxin and falling levels in the myocardium. These findings suggest a neurally mediated form of toxicity with this interaction related to a change in the space of distribution. The question of possible loss of inotropic effect associated with diminished myocardial digoxin concentration requires further study.

Animals↗
PubMed1980

Effect of sanguinarine on ventricular refractoriness.

The purpose of this study was to determine the effect of the Na+K+ATPase inhibitor sanguinarine on the refractory period of the porcine ventricle. Measurements of ventricular refractoriness and strength-interval curves were obtained before and after 0.5 to 4.0 mg/kg sanguinarine. The ventricular refractory period was found to be prolonged at all doses studied from a control of 276 +/- 12 msec to 318 +/- 24 msec at 4.0 mg/kg (p < 0.01). The strength-interval curve was shifted to increased values for ventricular refractoriness from 0.5 to 16.0 ma. No depression of arterial pressure or left ventricular dp/dt was observed. This study shows that sanguinarine prolongs ventricular refractoriness. This property may be useful in the treatment of ventricular arrhythmias.

Alkaloids↗
PubMed1979

Evaluation of warning arrhythmias before paroxysmal ventricular tachycardia during acute myocardial infarction in man.

In order to determine the relationship of paroxysmal ventricular tachycardia (PVT) to any antecedent (premonitory) ventricular arrhythmias during the early phases of acute myocardial infarctions, 24-hour Holter monitoring was begun on 52 male patients an average of 12.6 hours after the onset of prolonged chest pain that was documented as acute infraction. Twenty-four patients had PVT and 28 did not. We analyzed in detail the incidence of frequency of premature ventricular complexes (PVCs), prematurity and pairing during the 10 minutes immediately preceding PVT from a continuous 10-minute rhythm strip. There was no positive correlation between PVT and the number or complexity of PVCs in the 10 minutes immediately before ventricular tachycardia. These findings suggest that there is no consistent pattern or frequency of ventricular arrhythmia that could be identified as premonitory for PVT during the immediate pre-PVT period, even during the acute phase of myocardial infarction in man.

Acute Disease↗
PubMed1978

How and when to use the digitalis serum levels.

The indications for measuring serum digoxin levels are suspicion of digitalis intoxication and the need to know the status of digitalization. Pitfalls of interpretation include time of serum sample relative to time of last digitalis dose, age of patient, atrial arrhythmia, electrolyte disturbances, disease state of the patient, recent radioisotopes "on board," abnormal absorption or metabolism, and laboratory error. The serum digoxin level is a useful clinical tool but only when employed with good judgment. Not every patient receiving digitalis requires the measurement of a blood level.

Decision Making↗
PubMed1978

Effect of digitalis on human ventricular refactoriness.

In order to evaluate the effect of digitalis on the effective refractory period of the human ventricle, 14 patients were studied with atrial or ventricular pacing and with the introduction of ventricular extra-stimuli. The ventricular effective refractory period (VERP) was recorded before and after 1.0 to 1.25 mg ouabain given intravenously and the results compared with similar changes in the Q-T interval. During atrial pacing (eight patients) at rates of 70 to 110 beats per minute, ouabain reduced the mean ventricular effective refractory period from 290 +/- 13 ms to 260 +/- 16 ms (P less than 0.01) and the mean Q-T interval was reduced from 372 +/- 18 ms to 359 +/- 19 ms (P less than 0.01); the mean VERP/Q-T ratio was 0.79 +/- 0.04 before ouabain and 0.73 +/- 0.04 after ouabain (P less than 0.01). Utilising ventricular drive pacing (six patients) the mean ventricular effective refractory period was reduced from 245 +/- 16 ms to 226 +/- 13 ms (P less than 0.01) and the mean Q-T interval reduced from 382 +/- 18 ms to 360 +/- 29 ms (P less than 0.01). There was no significant change in the mean VERP/Q-T ratio (0.63 +/- 0.04 before vs 0.63 +/- 0.04 after ouabain). The results demonstrate that clinically effective doses of ouabain produce a significant reduction of the effective refractory period of the human ventricle. This change is accompanied by a reduction in the VERP/Q-T ratio during atrial pacing.

Adult↗