Effect of α-adrenergic stimulation on regional contractile function and myocardial blood flow with and without ischemia

Background. The effect of α-adrenergic receptor activation on regional contractile function and transmural myocardial blood flow is controversial. Accordingly, the effects of selective α₁-(methoxamine) and α₂- (BHT 933) receptor stimulation on regional contractile function and transmural myocardial blood flow distribution were studied in 15 anesthetized open-chest dogs. Methods and Results. The α-adrenergic agonists were separately infused into the cannulated left circumflex coronary artery during control and ischemic conditions in the same animal. Mean coronary perfusion pressure was held constant by a servocontrolled pump in an extracorporeal circuit. Ischemia was created by reducing coronary perfusion pressure to the level at which percent systolic wall thickening (%WT) decreased by 54%. Contractile function during control conditions was unchanged, whereas under ischemic conditions a further significant decrease in %WT of 27% occurred with either α₁- or α₂-receptor stimulation without any change in the anterior (control) wall function. Both α₁- and α2-receptor stimulations during control conditions resulted in a relatively uniform transmural decrease in blood flow with no change in the subendocardial-to-subepicardial blood flow ratio. With α₁-stimulation during ischemia (n=13), there was a tendency toward decreased subepicardial blood flow with no change in subendocardial flow, resulting in an increased subendocardial-to-subepicardial blood flow ratio (0.61±0.23 to 0.82±0.40, p<0.05). α₂-Receptor stimulation during ischemia (n=12) produced a significant decrease in subepicardial blood flow (0.45±0.20 to 0.35±0.12 ml/min/g, p<0.01) with no change in subendocardial blood flow, also resulting in an increased subendocardial-to-subepicardial blood flow ratio. Conclusions. These results indicate that selective vasoconstriction in outer wall layers during ischemia mediated by either α₁- or α₂-receptors can cause a decrease in regional contractile function despite unchanged subendocardial blood flow and improved subendocardial-to-subepicardial flow ratio. This suggests an adverse effect of α-adrenergic vasoconstriction during ischemia in this coronary perfusion pressure-controlled canine model.