Blood-perfused Dog Heart Research Articles

A comparison of the cardiovascular actions of thalicarpine and its moieties.

In the anesthetized rhesus monkey, thalicarpine (10 mg/kg), a dimeric alkaloid consisting of benzisoquinoline (veraisoquin, 10 mg/kg) and aporphine (N-methyl-laurotetanine, 10 mg/kg) moieties, depressed mean arterial pressure and force of contraction, but increased carotid artery blood flow and heart rate. N-methyl-laurotetanine depressed all four parameters, whereas veraisoquin increased the first three parameters. All three compounds produced an immediate negative inotropic and chronotropic response in isolated, blood-perfused dog hearts. After veraisoquin, heart rate and force of contraction increased above control levels within 5 min. Thalicarpine was the only agent which caused a persistent decrease in coronary perfusion pressure in this preparation. Many of the cardiovascular actions of thalicarpine can be ascribed to the aporphine moiety, but some appear to require the intact dimeric molecule.

Cardiovascular and central nervous system effects of parenterally administered single doses of procarbazine (NSC-77,213)

Experiments were undertaken to determine the initial pharmacologic changes elicited by iv administration of procarbazine in the rhesus monkey (25–400 mg/kg) and the isolated, blood-perfused dog heart (25–400 mg/kg). In unanesthetized animals somnolence and synchronization of the electroencephalogram were noted after all doses. These effects were reversible within 15 min to 3 hr at doses up to 200 mg/kg. Over a 4 hr period, mean arterial blood pressure gradually decreased 10–40 mmHg, and some animals developed intermittent periods of ventricular ectopic beats. Two of 3 animals given 400 mg/kg died from severe hypotension and respiratory distress. In pentobarbital-anesthetized animals, procarbazine suppressed or eliminated cortical electroencephalogram activity for varying periods of time. All doses initially increased carotid artery blood flow, but by 15–30 min after injection mean arterial blood pressure had decreased below control levels. Within 6 hr, 6 of 9 animals given 100–400 mg/kg died from severe hypotension and respiratory arrest. All doses of procarbazine exerted positive inotropic and chronotropic responses in the isolated heart. These actions could be attenuated by pretreatment with reserpine (0.1 mg/kg) or dl-propranolol (0.125 mg), but not by d-propranolol (0.125 mg). The present results indicate that parenterally administered procarbazine causes both central nervous system and cardiovascular alterations.

Hypoxia and acidosis in the blood-perfused dog heart

In hypoxic perfused hearts where glucose is present in abundance, there is an early loss of cellular potassium and inorganic phosphate. Glucose uptake is increased 3-fold over the control values. Lactate uptake becomes changed to production when oxygen uptake decreases below 1.2 ml./minute/100 grams wet wt. Total energy production is slightly decreased in the range of oxygen uptake from 1.2 ml. to 0.4 ml./minute/100 grams wet wt. Cellular glycogen seems to be spared if there is enough exogenous glucose present. Edema becomes severe during the second hour of hypoxia.

Insignificance of activation pathway on myocardial oxygen consumption.

Activation pathway per se is not a prime determinant of myocardial oxygen consumption, as indicated in studies in an isolated empty blood perfused dog heart, a preparation in which changes in end-diastolic volume and pressure are precluded.

The cardiovascular actions of ellipticine

Initial toxicity studies have revealed that ellipticine, a potential anticancer drug, produces alterations in the cardiovascular system. The effects of this agent on the intact cardiovascular system of dogs and monkeys were found to be dose dependent. Intravenous administration of 27–40 mg/kg produced irreversible cardiovascular and respiratory depression. At lower doses, 10–18 mg/kg in the dog and 5–20 mg/kg in the monkey, reversible hypotension and bradycardia were observed initially followed by a slight but persistent hypertension. In the isolated blood-perfused dog heart high doses of ellipticine (37.5 mg) produced a prolonged depression of both force of contraction and heart rate. In contrast to this action lower doses of ellipticine (6.25–18.75 mg) caused a brief decrease in rate and force which was followed by recovery of both parameters to above control levels. The maximum increase in both force of contraction and heart rate occurred at a dose of 12.5 mg. These cardiac actions could be prevented by pretreatment with dl-propranolol and reserpine, but not d-propranolol. Thus, ellipticine, by itself or through catecholamine release, appeared to stimulate beta receptors in the isolated heart and presumably in the intact animal. Higher doses, however, produced nonspecific depression of cardiac function in both preparations.

The effect of diphenylhydantoin on conduction in isolated, blood-perfused dog hearts: Sasynuik, B. I. and Dresel, P. E., J. Pharmacol. Exp. Therap. 161: 191–196, 1968. (Dept. Pharmacol. Therap. Univ. of Manitoba, Winnipeg, Canada.)

The effect of diphenylhydantoin on conduction in isolated, blood-perfused dog hearts: Sasynuik, B. I. and Dresel, P. E., J. Pharmacol. Exp. Therap. 161: 191–196, 1968. (Dept. Pharmacol. Therap. Univ. of Manitoba, Winnipeg, Canada.)

Influence of developed tension on myocardial potassium balance in the dog heart.

Experiments were carried out to determine the effect of changing preload on myocardial potassium balance. A blood-perfused dog heart was employed. Changes in the pressure recorded from a balloon in the left ventricle were assumed to reflect directional changes in myocardial wall tension. Developed tension was altered by changing the volume of the balloon. Net potassium balance was calculated as the product of the coronary A-V plasma potassium difference and coronary plasma flow. When the ventricle was developing little tension, it usually gained potassium. When diastolic volume and thus developed tension was increased, a net loss of myocardial potassium occurred. In some experiments the hemodynamic response of the ventricle to the increase in diastolic volume suggested that the contractility of the heart was increasing while the heart was losing potassium.

EFFECTS OF AMODIAQUIN AND QUINIDINE ON CARDIAC CONDUCTION

The effects of the antiarrhythmia agents amodiaquin and quinidine on conduction times through the atrium and the specialized conducting tissue to the ventricular myocardium have been determined from records obtained with needle electrodes suitably placed in isolated blood perfused dog hearts. Quinidine slowed conduction through each portion of the total pathway when very low concentrations were infused but had a preferential depressant effect on atrial conduction at slightly higher concentrations. Amodiaquin slowed conduction in the atrioventricular node to a greater extent than in the other parts of the common pathway at all concentrations tested. The major effect of each drug on extra-atrial conduction occurred at the atrioventricular node and at the Purkinje–myocardial junction. Amodiaquin did not induce bigeminal rhythm in the isolated heart.