Functional consequences and intracoronary localization of alpha-adrenergic stimulation of the canine coronary circulation

Although alpha-adrenergic stimulation can increase coronary vascular resistance, it remains unknown whether the vasoconstriction can override intrinsic coronary regulatory influences to produce ischemia. Methoxamine, 2 to 4 mg, was infused into the circumflex coronary artery of 23 chloralose-anesthetized open chest dogs, and resulted in a 68% increase in coronary vascular resistance. The functional consequence of this increased coronary vascular resistance was assessed by gated radionuclide ventriculography and ST-T wave changes on the electrocardiogram.In six dogs (Croup 1), aortic pressure changed trivially (<5 mm Hg) to allow distinction between direct effects of the flow reduction and indirect effects of increased aortic pressure. In this group, coronary blood flow decreased 33% from a control value of 44 ± 10 ml/min (p < 0.001) and left ventricular ejection fraction decreased from 0.54 ± 0.12 to 0.46 ± 0.10 (p < 0.025). In eight dogs (Group II) in which aortic pressure increased by more than 5 mm Hg, left ventricular ejection fraction decreased from 0.46 ± 0.07 to 0.39 ± 0.09 (p < 0.002). Pressure gradients were measured between the aorta and a distal coronary artery branch to calculate small and large vessel resistances separately in four other dogs (Group III). The resistance of small coronary arteries accounted for 92% of the total increase in coronary vascular resistance produced by methoxamine. In five other dogs (Group IV), intracoronary methoxamine, 2 mg, produced ST-T wave changes suggestive of ischemia as it increased coronary vascular resistance by 33%.In conclusion, this study demonstrated that methoxamine caused functionally significant vasoconstriction of small coronary arteries as shown by the decreased left ventricular ejection fraction and ST-T wave changes. These findings suggest that alpha-adrenergic vasoconstriction can override coronary regulatory influences to cause ischemia