The Effect of Pharmacologic Agents Upon the Dynamics of Anoxic Perfused Rat Hearts 1

Abstract

Knowledge of the response of the hypoxic heart to positive inotropic agents is important in determining modes of therapy that might be beneficial in patients with ischemic heart disease. Shortly after coronary occlusion an ischemic segment of myocardium can respond to positive inotropic agents (1). Hypoxic isolated cat papillary muscles can also respond to positive inotropic interventions (2). In dogs made hypoxic, acetyl strophanthidin has an attenuated effect on overall cardiac function (3). It was recently shown that, during anoxia, hearts with elevated endogenous glycogen stores develop higher rates of anaerobic ATP formation, and that these hearts are partially protected against mechanical deterioration (4). This observation raises the possibility that the glycogen-rich heart might also respond better to positive inotropic agents during hypoxia than hearts with normal glycogen stores.

The present experiments were conducted to study whether anoxic myocardium, with known depressed ATP stores, would be responsive to positive inotropic agents. The responsiveness of hearts from normal rats and reserpinized rats with high glycogen stores were studied.

Methods. Hearts of male Wistar rats, 200-250 g, were perfused retrograde through the aorta at a constant perfusion pressure, using a double perfusion apparatus as described and diagramed previously (5, 6). A needle was inserted into the perfusion line just above the heart so that saline, or a pharmacologic agent could be delivered from a Harvard constant infusion pump. The perfusion medium contained 143 mM sodium, 126 mM chloride, 25 mM bicarbonate, 6 mM potassium, 1.2 mM magnesium sulfate, 1.2 mM phosphate, 1.2 mM calcium, 0.4 mM sodium EDTA and 5 mM glucose. In aerobic experiments, oxygenated perfusion (95% O₂, 5% CO₂ gassing mixture) was conducted for 25 min. In anoxic experiments hearts were perfused for 15 min under aerobic conditions and then an anoxic perfusion medium [95% N₂, 5% CO₂ (pO₂ 3-7 mm Hg)] was abruptly switched into the system for 5 min.