Isolated Dog Heart Preparation Research Articles

Effects of UL-FS 49 on the chrono- and inotropic responses to cardiotonic agents in isolated dog heart preparations

Effects of UL-FS 49 on the chrono- and inotropic responses to cardiotonic agents in isolated dog heart preparations

The Effects of Nimodipine on Cocaine Toxicity

The response to nimodipine as an inhibitor of cocaine toxicity was investigated in pentobarbital-anesthetized dogs and in isolated dog heart preparations at constant heart rates. Nimodipine (10 micrograms/kg) markedly decreased peripheral and coronary vascular resistance and increased cardiac output, cardiac work, and coronary blood flow. When corrected for the change in afterload, nimodipine had a positive inotropic response, as measured by +/- maximal dP/dt, in the cocaine-depressed animal. Thus, cocaine toxicity was partially reversed by nimodipine. In the isolated heart preparation, nimodipine resulted in further cardiac depression similar to that seen with other calcium channel antagonists.

Pharmacological analysis of positive chronotropic and inotropic responses to etilefrine in isolated dog heart preparations.

Positive chronotropic and inotropic responses to etilefrine (alpha-[(ethylamino)methyl]-m-hydroxybenzyl alcohol), an orally active cardiovascular agent, were investigated in isolated dog right atrial and left ventricular preparations. Intravenous administration of etilefrine to a support dog increased heart rate and mean systemic blood pressure, and increased sinus rate and atrial contractile force in the isolated right atrium perfused with blood from the support dog. Etilefrine injected intra-arterially to isolated atria and ventricles induced dose-dependent positive chronotropic and inotropic effects. Etilefrine was about 100 times less potent than isoproterenol. The effects of etilefrine in isolated atria were significantly inhibited by treatment with atenolol, but were not significantly inhibited by ICI 118,551. The effects of etilefrine were partially inhibited by imipramine. These results indicate that etilefrine is a highly selective beta-1 adrenoceptor agonist and suggest a moderate catecholamine-releasing activity by tyramine-like action in the blood-perfused dog heart.

Cardiac responses to VIP and VIP-ergic-cholinergic interaction in isolated dog heart preparations

Whereas i.v. administration of vasoactive intestinal peptide (VIP) to support dogs increased heart rate and decreased systemic blood pressure, sinus rate and contractile force increased in isolated right atria perfused with blood from the support dogs. VIP injected intraarterially into isolated atria induced dose-dependent positive chronotropic and inotropic effects. Intracardiac parasympathetic nerve stimulation attenuated the positive cardiac responses to VIP, but neither propranolol, imipramine, nor tetrodotoxin influenced the responses to VIP. VIP given to isolated left ventricles also increased the contractile force in a dose-dependent manner. However, VIP induced a greater maximum atrial contractility than ventricular contractility. This may indicate that VIP receptor density in the ventricle was lower than in the atrium, as it has recognized that VIP-ergic nerves innervate the right atrium more densely than the left ventricle. We therefore suggest that the positive cardiac responses to VIP, together with the VIP-ergic innervation in dog hearts and vagal activation, attenuate the VIP-mediated responses at site(s) in the cyclic AMP cascade.

Myocardial oxygen transport during leftward shifts of the oxygen dissociation curve by carbamylation or hypothermia.

An isolated dog heart preparation was used to study the effect of left-shifting the O2 dissociation curve by carbamylation or hypothermia. The two interventions had a similar effect on the variables of O2 delivery. There were significant decreases in myocardial O2 consumption, coronary sinus PO2, and O2 extraction. There was no compensatory increase in O2 transport. Coronary flow autoregulation was somewhat blunted by hypothermia but not by carbamylation. We conclude that an increase in hemoglobin-O2 affinity is capable of limiting myocardial O2 delivery and that increases in convective O2 transport play a minor role at best in the coronary adaptation to small decreases in P50.

The influence of postischemic reperfusion on the recovery of ischemic lesions of the left ventricle (author's transl)

In an isolated dog heart preparation the influence of normothermic ischemic arrest and recovery of the ventricular function during the period of post-ischemic reperfusion were investigated. If ischemic arrest has caused a depression of ventricular function, the functional recovery of the myocardium cannot be improved significantly by a prolonged reperfusion of the empty beating heart.

The effect of a decrease in blood pressure, associated with extracorporeal blood pumping on myocardial metabolism in the isolated dog heart preparation

A fall in systolic blood pressure was associated with the use of a blood pump for extracorporeal circulation in dogs. The change in systolic blood pressure was negatively correlated to an increase in arterial lactate and glucose levels and positively with a decrease in free fatty acid levels. The changes in arterial levels of these major metabolic sybstrates resulted in a shift in myocardial metabolism whereby myocardial utilization of carbohydrate (glucose and lactate) was enhanced while free fatty acid utilization was markedly diminished.

Myoglobin function in the isolated fluorocarbon-perfused dog heart.

An isolated dog heart preparation perfused with hemoglobin-free fluorocarbon suspension has been developed to study the role of myoglobin in myocardial function. The coronary vasculature was perfused at constant flow, with oxygen consumption determined from arteriovenous PO2 differences. Muscle function was assessed by measurement of pressures generated in a latex balloon placed in the left ventricle. The perfusate consisted of 20% perfluorotributylamine and 80% Ringer's lactate with 16 mM glucose. Steady-state oxygen consumption decreased from 0.30 to 0.11 ml/min per gram dry weight left ventricle, as perfusate PO2 decreased from 690 to 150 mmHg. Left ventricular pressure generation and oxygen consumption were determined before and after addition of 8 mM sodium nitrite, which changed functional ferrous myoglobin to high-spin ferric myoglobin. Over the range of perfusate PO2 studied, nitrite addition did not alter mechanical performance or myocardial oxygen consumption. These data suggest that those conditions necessary for substantial myoglobin-facilitated diffusion of oxygen in the myocardium are not present in the isolated fluorocarbon-perfused dog heart.

The effect of adenosine on myocardial metabolism and oxygen consumption in the isolated dog heart preparation

The effects of adenosine on myocardial metabolism and oxygen consumption were examined in the isolated supported dog heart preparation (ISHP) perfused at a constant coronary blood flow. Heart rate was controlled by right atrial pacing. Coronary arterial and venous blood samples were collected and oxygen content, lactate, glucose and free fatty acid levels were determined. From arterialvenous differences and coronary blood flow, oxygen consumption and substrate uptake were determined. A 3 min intracoronary infusion of adenosine (50 and 100 μg/min) produced a significant dose-dependent decrease in MV̇O 2 while increasing glucose uptake and decreasing the uptake of lactate. The decrease in oxygen consumption, the increase in glucose uptake and the decrease in the uptake of lactate were all found to be dependent on the initial MV̇O 2 . These findings suggest that, in addition to its putative role as a regulator of coronary vascular resistance, adenosine might also exert important metabolic effects on the heart.

The cardiodynamic and metabolic effects of glucagon.

The cardiac effects of a continuous infusion of glucagon at the rate of 10 mug/min were studied in the Starling heart-lung preparation, modified to measure coronary flow and myocardial oxygen consumption. A maximal increase in myocardial contractility, as reflected by maximal rate of rise of left ventricular pressure, dp/dt, of 31% was observed at a total dose of glucagon of 50 mug and was accompanied by an increase in heart rate and in myocardial oxygen consumption of 59% and 57%, respectively. At a total dose of glucagon of 100 mug, there was an additional and comparable increase only in heart rate and myocardial oxygen consumption of 11.2% and 6.4% respectively. Similarly, at a total dose of glucagon of 150 mug, only heart rate and myocardial oxygen consumption increased additionally by increments of 2.6% and 2.9% respectively. These effects occurred at constant aortic pressure and left ventricular volume. Further infusion of glucagon led to an additional increase only in myocardial oxygen consumption of 4.2%. When the increase in heart rate was largely prevented by prior treatment with veratramine, an increase in dp/dt, not significantly different from the maximal increase obtained with glucagon alone, was accompanied by much lower and closely comparable increases in heart rate and in myocardial oxygen consumption of 15% and 19%, respectively. Coronary flow increased more markedly when glucagon was administered alone and it paralleled the increase in myocardial oxygen consumption. It may be concluded from this study that, in the isolated dog heart preparation, glucagon increases contractility, heart rate and myocardial oxygen consumption and that the increase in myocardial oxygen consumption is related more closely to the increase in heart rate than to the increase in contractility, but a minor increment is referable to a calorigenic action. The increase in coronary flow is of a secondary nature, resulting from the increase in myocardial metabolic demands.

Left ventricular pressure-volume relationships and myocardial oxygen consumption in the isolated heart.

An isolated dog-heart preparation, in which absolute volumes were known, was employed to determine left ventricular pressure-volume relationships and myocardial oxygen consumption. Loading was varied from the extreme of zero pressure change to zero volume change during systole. Maximum peak systolic pressures were developed by isovolumetric, and maximum stroke volumes by isobaric contractions. When the load was varied to allow both pressure and volume to change in systole, the peak systolic pressures and the simultaneously determined ventricular volumes could be plotted as a "peak systolic pressure-volume line." Moderate changes in diastolic volume had little effect on the position of the line, and the mechanical work of the heart appeared to depend on the nature of the load rather than the diastolic volume. Epinephrine and digitalis glycosides did not affect diastolic pressure-volume relationships. Heart rate affected the diastolic pressure-volume curve only at rapid rates, where changes in the rate of relaxation produced apparent differences in compliance. Myocardial oxygen consumption is shown to be correlated with peak systolic pressure or volume, and is not mainly determined by either diastolic volume or stroke work.

Studies on the potassium content of the heart muscle receiving k-strophanthin and the influence of potassium on the respiration of heart muscle.

We have several reports on the effect of cardiac glycosides on the potassium content of heart muscle. In dogs, Calhoun and Harrison (1) observed a marked decrease in muscle potassium after toxic and fatal doses of digitalis and no significant change after therapeutic doses. Cattel and Goodell (2), who used the excised frog sartorius, and Wood and Moe (3), who studied isolated dog heart preparations, confirmed the observation that large doses of the drugs caused loss of potassium. However, Wedd (4) reported that the therapeutic action of digitalis was not the result of a lowering of the potassium content, and that when potassium loss did occur it represented a toxic effect of the drug afterwards. Hagen (5), who used the isolated rabbit hearts, and Boyer and Poindexter (6), who studied cat hearts, found that calculated therapeutic doses of digitalis caused a uniform and significant increase, whereas toxic doses produced a marked decrease in potassium. Recently, Holland and his collaborators (7), who used the isolated guinea pig hearts, and Hajdu (8), who studied isolated frog hearts, reported therapeutic doses of digitalis caused a decrease in potassium.On the other hand, the effect of digitalis on the respiratory activity of heart muscle in vitro has attracted considerable attention. Levy and her collaborators (9), Wollenberger (10), and Finkelstein and Bodansky (11) found that mammalian heart slices showed an increased oxygen utilization in the presence of calculated therapeutic concentrations of cardiac glycosides. However, an experiment (10) with homogenized tissue showed no effect of the glycosides on the oxygen uptake. In this connection, the possibility arises that intact cells are necessary for the demonstration of the accelerating effect of the glycosides.Kleinzeller (12), Pressman and Lardy (13), Harman and Feigelson (14), and Korff and his collaborators (15) reported that potassium in a certain concentration produced a beneficial effect on the respiratory activity of the hamogenate or mitochondria of mammalian tissue. Then, the enhancing effect of digitalis on the respiration of heart muscle slice may have some relation with the changing effect of the drug on the potassium content of the tissue.In the present study, effects of κ-strophanthin on the potassium content of heart muscle, and those of potassium on the respiration of homogenate and intracellular components were observed, and a relation between them was calculated.In addition, some fundamental experiments were made on the preparation and respiration of intracellular components of heart muscle, as there were not a sufficient number of studies on such subjects.