The inotropic effect of digoxin on an isolated rat heart in hypercapnia and (or) hypoxia

Abstract

The explanation for the increased frequency of troubles with digoxin therapy in patients with chronic pulmonary diseases is debated. The reported effects of hypoxia in vivo on myocardial levels of digoxin are contradictory, and there have been few studies on the effects of hypercapnia. In the past, it has been shown in rat myocardial tissue at rest in vitro that hypoxia decreased and hypercapnia acidosis increased the digoxin uptake. We performed a new study in vitro in an isolated beating rat heart perfused at constant flow (37 °C) and stimulated at a constant frequency (6 Hz). The performances were recorded with an intraventricular balloon equipped with a tip-manometer catheter. The action of digoxin was studied by recording systolic pressure (PS) and diastolic pressure (PD), the left ventricular developed pressure (LVDP = PS − PD), the (dP/dt)max, and the ratio (dP/dt)max/PS. First, the heart was perfused for 30 min with a modified Tyrode's solution perfusate aerated with carbogen (pH = 7.40; [Formula: see text]; [Formula: see text]) (1 mmHg = 133.32 Pa). Various parameters of contractions were recorded (initial control values). Then the heart was perfused for 15 min with Tyrode's solution aerated either with a hypoxic gas mixture (pH = 7.41; [Formula: see text]; [Formula: see text]), a hypercapnic gas mixture (pH = 7.08; [Formula: see text]; [Formula: see text]), or a hypoxic–hypercapnic gas mixture (pH = 7.09; [Formula: see text]; [Formula: see text]). Control hearts were continuously perfused with Tyrode's solution aerated with carbogen. During heart perfusion with hypercapnic, hypoxic, or hypoxic–hypercapnic Tyrode's solution, a decrease in LVDP and (dP/dt)max was observed. Finally, the heart was perfused with the same Tyrode's solution plus 1.75 × 10−5 M digoxin. The increase in myocardial contractility produced by digoxin was enhanced by hypercapnia and abolished by hypoxia. The addition of hypercapnia to hypoxia in Tyrode's solution seems to enhance the depressor action of the hypoxia.Key words: isolated heart, digoxin, hypoxia, hypercapnia, myocardial contractility.