Relationships between cardiac hyperactivity, oxygen tension, and release of vasodilator material in coronary autoregulation of guinea-pig hearts

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Abstract
Increases in cardiac activity induce autoregulatory coronary vasodilation. The intermediate steps which trigger this process are thought to be myocardial hypoxia which induces the release of vasodilator mediator(s). The present study examines the relationships between mechanical activity, oxygen tension, and release of vasodilator material in isolated perfused hearts. Guinea-pig isolated hearts were perfused in series, the effluent from donor hearts being regassed prior to entry to recipient hearts. Histamine (1 .mu.g) and isoproterenol (10 ng) increased the rate and tension of donor hearts and produced predominant coronary vasodilator responses which were followed by the appearance of vasodilator material in the recipient (falls in perfusion pressure, 9.8 .+-. 1.1 and 9.1 .+-. 2.5 mmHg) (1 mmHg = 133.322 Pa). Exposure of donor hearts to hypoxia also caused vasodilation and release of vasodilator material (fall in pressure, 11.4 .+-. 1.6 mmHg). Pacing-induced tachycardia (6 Hz) of donor hearts promoted the release of vasodilator material, the fall in recipient heart pressure being 11.5 .+-. 1.8 mmHg. This was abolished by .beta.-adrenoceptor blockade and when donor hearts were from reserpine-pretreated guinea pigs. In was concluded that pacing released endogenous catecholamines which in turn released the vasodilator material. Pacing per se did not cause vasodilatation or release of the vasodilator. The PO2 of perfusates from donor hearts was reduced by pacing at 5 Hz (25.7 .+-. 5.2 mmHg) and by isoproterenol (10 ng, 32.0 .+-. 3.7 mmHg), indicative of an elevated oxygen extraction. The isoproterenol-induced falls in PO2 were abolished by .beta.-adrenoceptor blockade. However, the pacing-induced falls in PO2 persisted, the values occurring before ((25.7 .+-. 5.2 mmHg) and after propranolol (45.7 .+-. 4.5 mmHg) and before (32.1 .+-. 1.1 mmHg) and after practolol (27.3 .+-. 4.1 mmHg) not differing significantly (p > 0.05). These falls in perfusate Po2 were not accompanied by coronary vasodilation or release of vasoactive material. Perfusate PO2 changes could therefore be dissociated from the coronary vasodilatation and vasoactive material release, suggesting that hypoxia may not be a prerequisite for the metabolic autoregulatory vasodilatation in response to myocardial hyperactivity induced by cardiac stimulants.