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Biomedical subjects

W J Powell

Publications and source records attributed to W J Powell.

At least 73 records · Page 4Linked to original sources

The neurogenic vasoconstrictor effect of digitalis on coronary vascular resistance.

The coronary vasoconstrictor properties of digitals were evaluated in 61 anesthetized, openchest dogs after coronary sinus cannulation and under conditions of a constant heart rate (atrioventricular pacing) and near-constant blood pressure. The contribution of alpha adrenergic receptor stimulation to the digitalis-induced increase in coronary vascular resistance (CVR) was examined. With Na pentobarbital anesthesia (16 dogs), intravenous acetylstrophanthidin (0.5 mg) caused a significant (P<0.05) rise in CVR from 1 through 9 min after injection. The peak increase was +11+/-2% SE of the control of 1.8+/-0.2 mm Hg/cm(3)/min. The mean time to peak effect was 3 min, and to recovery was 21 min. Prior alpha adrenergic receptor blockade with phenoxybenzamine in 11 animals reduced (P<0.05) the acetylstrophanthidin-induced peak of CVR and substantially decreased (P<0.05) the time to recovery (5 min). Intravenous digoxin (1.0 mg) with Na pentobarbital anesthesia (five dogs) had no significant effect on CVR. However, with chloralose and urethane anesthesia (nine dogs) the same dose of digoxin produced a significant rise in CVR from 3 through 30 min. The peak increase was +20+/-3% of control (1.4+/-0.1 mm Hg/cm(3)/min). One-third the dose of intravenous digoxin (0.35 mg) produced a 9.5+/-1.0% increase in CVR (five additional dogs). Myocardial oxygen consumption did not change significantly in nine dogs after intravenous digoxin. In 10 additional dogs pretreated with phenoxy-benzamine and in 7 dogs pretreated with mecamylamine, the increase in CVR did not occur after 1.0 mg of intravenous digoxin. Thus there is a coronary vasoconstrictor effect of intravenous acetylstrophanthidin and digoxin, of rapid onset, which is mediated through alpha adrenergic receptor stimulation.

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The central nervous system as a site of action for the coronary vasoconstrictor effect of digoxin.

Digitalis is known to have a vasoconstrictor effect in the coronary circulation. Recent studies have demonstrated that the coronary vasoconstrictor effects of acetylstrophanthidin and digoxin are neurally mediated via alpha adrenergic fibers. In the present study, experiments were done in 20 dogs anesthetized with chloralose and urethane to study the central nervous system as a possible site of action for this vasoconstrictor effect of digoxin. After the intravenous administration of 1.0 mg digoxin, cerebrospinal fluid concentrations of digoxin rose to a peak of 2.3+/-0.4 (SEM) ng/ml at 15 min, temporally corresponding to the peak in coronary vascular resistance change of +20.0+/-2.5% of control in the paced canine heart. Submicrogram digoxin injections into the lateral cerebral ventricle produced a significant increase in coronary vascular resistance, the latter injection producing a peak increase in coronary vascular resistance of 12.4+/-1.2% of control. Cross-perfusion experiments, where the isolated head of the operative dog was perfused from a donor dog receiving digoxin, thus keeping digoxin levels in the remainder of the operative dog very low, showed a similar degree of coronary vasoconstriction. Thus, the central nervous system appears to be an important site of action for the early coronary vasoconstrictor effect of digoxin.

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Improvement in myocardial function and coronary blood flow in ischemic myocardium after mannitol.

The purpose of this study was to evaluate the effect of hyperosmolality on the performance of, and the collateral blood flow to, ischemic myocardium. The myocardial response to mannitol, a hyperosmolar agent which remains extracellular, was evaluated in anesthetized dogs. Mannitol was infused into the aortic roots of 31 isovolumic hearts and of 15 dogs on right heart bypass, before and during ischemia. Myocardial ischemia was produced by temporary ligation of either the proximal or mid-left anterior descending coronary artery. Mannitol significantly improved the depressed ventricular function curves which occurred with left anterior descending coronary artery occlusion. Mannitol also significantly lessened the S-T segment elevation (epicardial electrocardiogram) occurring during myocardial ischemia in the isovolumic hearts and this reduction was associated with significant increases in total coronary blood flow (P < 0.005) and with increased collateral coronary blood flow to the ischemia area (P < 0.005).THUS, INCREASES IN SERUM OSMOLALITY PRODUCED BY MANNITOL RESULT IN THE FOLLOWING BENEFICIAL CHANGES DURING MYOCARDIAL ISCHEMIA: (a) improved myocardial function, (b) reduced S-T segment elevation, (c) increased total coronary blood flow, and (d) increased collateral coronary blood flow.

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