Progressive vasomotor changes in ischaemic myocardium

Under certain conditions, a progressive increase in vascular resistance occurs within ischaemic myocardium during the first three hours after coronary artery stenosis. Measurements of vasodilator reserve in the ischaemic region demonstrated that this is at least partly due to an increase in vascular smooth muscle tone. Two hypotheses were suggested as an explanation: release of vasoconstrictors within the ischaemic area, or a decreasing release of vasodilators. Potential coronary constrictors considered included norepinephrine, PGF2 alpha, thromboxane A2, and high K+. Each of these substances was eliminated as the source of the vasoconstriction by pharmacological studies on ischaemic canine hearts. Measurement of adenosine release from isolated guinea pig hearts provided support for the possibility that the vasoconstriction results from a decreasing release of metabolic vasodilators. Throughout the period of ischaemia, both blood flow and myocardial function were far below the levels that could have been achieved in the presence of the stenosis. We conclude that during moderate ischaemia, myocardial function and blood flow are linked in a positive feedback cycle which promotes reduced ventricular function and coronary blood flow.