Biomedical subjects

J C Hartman

Publications and source records attributed to J C Hartman.

24 records · Page 2Linked to original sources

PubMed1989

Effects of nisoldipine on coronary collateral perfusion and hemodynamics in chronically instrumented dogs.

The effect of a new dihydropyridine slow-channel calcium blocking agent, nisoldipine, on hemodynamics and myocardial blood flow in normal and collateral-dependent areas distal to a chronic coronary artery occlusion were studied in chronically instrumented, conscious dogs. Nisoldipine produced significant and dose-related decreases in arterial blood pressure, an elevation of heart rate and large increases in coronary blood flow velocity. In dogs with an Ameroid constrictor previously implanted to enhance coronary collateral development, this agent produced large increases in perfusion distal to a chronic coronary artery occlusion. In addition, despite a reduction in arterial pressure, nisoldipine preserved renal cortical, intestinal and skeletal muscle blood flow while increasing tissue flow within liver and cerebral cortex. Thus, nisoldipine increases oxygen supply to collateral-dependent myocardium in the presence of reduced driving pressure for collateral perfusion.

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PubMed1988

Cyclical carotid artery flow reduction in conscious dogs: effect of a new thromboxane receptor antagonist.

Under sterile conditions, dogs were instrumented for continuous measurement of hemodynamics, and an Ameroid constrictor was positioned around the left carotid artery to produce slowly progressive narrowing of the vessel. In the awake, unsedated state, carotid cyclical blood flow reduction abruptly appeared on day 5.1 +/- 0.6 (mean +/- S.E.M.) at a frequency of 6.7 +/- 0.6 cycles per 30 minutes and usually remained present for only 1 day. The vessel was totally occluded on day 7.9 +/- 0.8. No focal neurologic deficit was observed. Following administration of the new thromboxane receptor antagonist, BM 13.505 (4-[2-(4-chlorobenzene-sulfonamide)-ethy]-benzene acetic acid), 50 and 100 micrograms/kg intravenously, the cyclical reduction in carotid blood flow was abolished for 30 +/- 5 and 45 +/- 15 minutes, respectively. No changes in systemic hemodynamics were observed over the course of the experiment. It is concluded that slowly progressive constriction of the carotid artery may provide an in vivo model for the study of perfusion deficits present in transient ischemic attacks. In addition, the results support the hypothesis that platelet aggregation plays a major role in cyclical carotid flow reduction, and the phenomenon can be eliminated by treatment with a new thromboxane receptor antagonist, BM 13.505.

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PubMed1988

Induction of cyclic flow reduction in the coronary, carotid, and femoral arteries of conscious, chronically instrumented dogs. A model for investigating the role of platelets in severely constricted arteries.

Under sterile conditions, dogs were instrumented for continuous measurement of hemodynamics, and an Ameroid constrictor was positioned around either the left carotid, left femoral, or left anterior descending coronary artery to produce slowly progressive narrowing of the vessel. Cyclic flow reduction (CFR) developed in the carotid artery in seven of nine dogs on day 5.1 +/- 0.8 (mean +/- S.E.M.) at a frequency of 6.7 +/- 0.6 cycles per 30 min. This phenomenon was abolished for 30 +/- 5 and 45 +/- 15 min with intravenous administration of 50 and 100 micrograms/kg, respectively of the thromboxane receptor antagonist, BM 13.505, 4-[2-(4-chloro-benzene-sulfonamide)-ethyl]-benzene acetic acid. Total carotid artery occlusion occurred on day 7.9 +/- 0.8. CFR developed in the femoral artery in one of three dogs on day 4 at a frequency of 7 cycles per 30 min and was abolished for 82 min after BM 13.505 (50 micrograms/kg i.v.). The vessel became totally occluded on day 7. Finally, CFR developed in the left anterior descending coronary artery in three of five dogs on day 9.3 +/- 4.9 at a frequency of 6.2 +/- 0.9 cycles per 30 min. CFR was abolished for 37 min after BM 13.505 (50 micrograms/kg i.v.) and for several hours after an oral dose of aspirin (650 mg). Total coronary occlusion was observed on day 17.4 +/- 2.6. The present results demonstrate that CFR can be induced in various arteries in conscious, chronically instrumented dogs by slowly progressive narrowing via Ameroid constrictors. This phenomenon may serve as a model for transient ischemic attack, claudication, and unstable angina. Because the conscious state is maintained, drug interactions with anesthetics are avoided. The usefulness of inhibitors of platelet aggregation in this model documents the potential benefit of such compounds in various vascular disease states.

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PubMed1988

Hemodynamic and electrocardiographic actions of the new intracellular calcium antagonist, KT-362, in the conscious dog.

Effects of the intracellular calcium antagonist, KT-362, on systemic and coronary hemodynamics and the electrocardiogram were evaluated in chronically instrumented, awake dogs during intravenous infusion or bolus administration. Both methods of administration resulted in systemic hypotension, tachycardia and decreases in left ventricular pressure and peak positive left ventricular dP/dt. KT-362 produced a transient increase in mean coronary blood flow velocity only during bolus injection, while subendocardial segment shortening was depressed only by drug infusion. Prolongation of QRS duration and the QT interval (corrected for change in heart rate, QTc) also occurred during drug infusion. The results suggest that the hemodynamic effects of intracellular calcium antagonism by KT-362 are qualitatively similar to those of other calcium channel blocking agents which inhibit extracellular calcium influx. In contrast, the actions of KT-362 on cardiac conduction may be different from those of other slow channel calcium blocking agents.

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PubMed1987

Antiarrhythmic, electrophysiologic and hemodynamic effects of ACC-9358.

The antiarrhythmic, electrophysiologic and hemodynamic effects of a new antiarrhythmic agent, ACC-9358, were evaluated. In anesthetized dogs, ACC-9358 converted ouabain-induced ventricular tachycardia to normal sinus rhythm at a cumulative dose equal to encainide or flecainide and less than disopyramide. In 24-hr coronary artery ligated dogs, ACC-9358 suppressed spontaneous ventricular arrhythmias for up to 6 hr after oral or i.v. administration. The antiarrhythmic effect and plasma concentrations of ACC-9358 correlated well for both oral (r = 0.88) and i.v. (r = 0.87) administration. ACC-9358, flecainide and disopyramide were equieffective in converting crush-stimulation-induced atrial flutter in anesthetized dogs to normal sinus rhythm. In alpha-chloralose-anesthetized, closed-chest dogs, ACC-9358 slowed impulse conduction through the atria, atrioventricular node, His-Purkinje system and ventricles and prolonged atrial functional refractory period. In conscious dogs, ACC-9358 increased heart rate, reduced stroke volume and had no effect on mean arterial pressure, systemic vascular resistance or cardiac output. In alpha-chloralose-anesthetized dogs, ACC-9358-induced sinus tachycardia was unaffected by propranolol but was blocked by hexamethonium or vagotomy. In isolated cat ventricular muscle, the IC50 for the negative inotropic effect of ACC-9358 was significantly greater than flecainide or disopyramide. These results indicate that ACC-9358 is a potent, broad-spectrum, long-acting, orally and intravenously active class Ic antiarrhythmic agent that 1) may be devoid of active metabolites, 2) exerts little or no vascular effects and 3) has less direct cardiodepressant activity than flecainide or disopyramide.

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PubMed1980

Thermodynamic technique for the quantification of regional blood flow.

A method is described to quantify regional blood flow by thermal analysis. A weak temperature field is established in a tissue and for a thermal steady state, unidirectional heat flux and the associated temperature gradient are measured simultaneously across a small fixed segment of the tissue. This information is evaluated with probe calibrations for homogeneous isotropic fluids, with data from ancillary measurements in the nonperfused tissue and with values of specific heat and density of blood to express local blood flow in heat transfer [effective thermal conductivity (W. degrees C-1 . cm-1 x 10(-3) and/or in perfusion (ml . min-1 . cm-3)] terms. The technique measures local perfusion in small tissue volumes and is usable in acute or chronic experiments. Its accuracy is not a function of the absolute steady-state temperature of the tissue or of its metabolic heat production.

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