Biomedical subjects

E L Carey

Publications and source records attributed to E L Carey.

4 recordsLinked to original sources

PubMed1995

Contraction of isolated porcine coronary arteries is inhibited by high concentrations of propranolol.

Isometric tension responses of isolated porcine coronary artery rings were studied in the presence of concentrations of propranolol higher than those necessary to block effects mediated by beta-adrenergic receptors. Propranolol (50-300 microM) inhibited contractions induced by 30 mM KCl and by histamine, norepinephrine, and acetylcholine in a concentration-dependent, noncompetitive fashion. The (+) propranolol isomer and the racemic mixture were equipotent inhibitors of contraction. Propranolol inhibition was partly reversed by increased extracellular Ca++. These effects of propranolol thus appeared to be independent of beta-blockade and could be relevant to some of the drug's observed but still unexplained in vivo actions.

Acetylcholine↗

PubMed1985

Spectrum of antiarrhythmic response to encainide.

Encainide is effective in suppressing non-life-threatening ventricular arrhythmias; however, inconsistent results have been noted in patients with more serious ventricular arrhythmias. Thirty-seven patients with drug-resistant ventricular arrhythmias were studied. Patients in group I (n = 11) has sustained ventricular tachycardia and those in group II (n = 26) had nonsustained ventricular arrhythmias. In group I, 8 patients had remote myocardial infarction, congestive heart failure and sustained ventricular tachycardia requiring repeated cardioversion (group Ia). None of these patients responded to encainide treatment, but 6 did have an antiarrhythmic response (complete in 3 and only partial in 3) to other investigational antiarrhythmic agents. Three patients in group I, all without ischemic heart disease (group Ib), had an excellent antiarrhythmic response to encainide, as did 21 of 26 patients in group II. In 4 of 5 patients in group II who did not respond, the dosage was limited due to the development of sinus pauses, atrioventricular block or bundle branch block, and in 3 of these 4 patients preexisting conduction disease was evident (PR longer than 0.2 second or QRS longer than 0.12 second). Diplopia occurred while taking the maximal oral dosage in the fifth patient. At 21.5 months of follow-up, 14 of the original 24 patients who responded to encainide continue to receive it; 3 have died (all due to natural progression of left ventricular dysfunction) and encainide was discontinued in 7: in 2 because of syncope, in 2 because of new-onset atrial fibrillation, in 1 patient because of exercise-induced polymorphic ventricular tachycardia, in 1 because of diplopia and in 1 because of skin exanthem.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilides↗

PubMed1984

Increased vascular beta2-adrenoceptor responsiveness in autonomic dysfunction.

Responsiveness to the vasopressor, vasodepressor and chronotropic effects of several sympathomimetic amines was assessed in 12 patients with severe autonomic dysfunction and in 8 age-matched control subjects. The patients with autonomic dysfunction showed a profound increase in responsiveness to both isoproterenol and phenylephrine as compared with control subjects. The mean bolus dose of isoproterenol required to increase heart rate by 25 beats/min was 0.9 + 0.2 microgram in the patients and 5.4 + 2.1 micrograms in the control subjects. The dose of isoproterenol required to reduce mean blood pressure by 25 mm Hg was 0.3 + 0.2 and 5.2 + 1.8 micrograms, respectively. Thus, although there is a 6-fold increase in responsiveness to the chronotropic effect of isoproterenol in autonomic dysfunction, the responsiveness to the drug's depressor effect is increased 17-fold. This enhanced depressor sensitivity is quite marked, even with oral beta-adrenoceptor agonists. Beta-adrenoceptor agonists must be used with caution in conditions associated with autonomic dysfunction if dangerous hypotension is to be avoided.

Aged↗

PubMed1984

Encainide and its metabolites. Comparative effects in man on ventricular arrhythmia and electrocardiographic intervals.

To assess the relative contributions of encainide and its putatively active metabolites, O-demethyl encainide (ODE) and 3 methoxy-O-demethyl encainide (3MODE), to the drug's pharmacologic effects, we compared intravenous infusions and sustained oral therapy in two phenotypically distinct groups of patients, extensive and poor metabolizers of encainide. Unlike poor metabolizers, extensive metabolizers had appreciable quantities of both metabolites detectable in plasma and had fourfold shorter elimination half-lives for encainide. By quantitating electrocardiogram intervals, arrhythmia frequency, and plasma concentrations, we found that, in poor metabolizers, arrhythmia suppression and ventricular complex (QRS) prolongation were correlated positively with encainide concentrations (r greater than or equal to 0.570, P less than 0.014). In these two subjects, antiarrhythmic concentrations of encainide (greater than 265 ng/ml) were at least fivefold higher than those sustained in the six extensive metabolizers during steady state oral therapy. In extensive metabolizers, encainide concentrations were uncorrelated with effects. Arrhythmia suppression and QRS prolongation in extensive metabolizers correlated best with ODE (r greater than or equal to 0.816, P less than 0.001); QTc change correlated positively with both 3MODE and ODE. Arrhythmia suppression paralleled QRS prolongation; the relationship between them appeared similar in both phenotypic groups. In most patients, extensive metabolizers, encainide effects during oral therapy are mediated by metabolites, probably ODE.

Aged↗