Influence of Acute Renal Failure on Coronary Vasoregulation in Dogs

Abstract

Impaired renal function is associated with an increased risk for cardiovascular events and death, but the pathophysiology is poorly defined. The hypothesis that coronary blood flow regulation and distribution of ventricular blood flow could be compromised during acute renal failure (ARF) was tested. In two separate groups (n = 14 each) of dogs with ARF, (1) coronary autoregulation (pressure-flow relations), vascular reserve (reactive hyperemia), and myocardial blood flow distribution (microspheres) and (2) coronary vessel responses to intracoronary infusion of select endothelium-dependent and -independent vasodilators were evaluated. In addition, coronary pressure-flow relations and vascular reserve after inhibition of nitric oxide and prostaglandin release were evaluated. Under resting conditions, myocardial oxygen consumption increased in dogs with ARF compared with no renal failure (NRF; 11.8 +/- 9.2 versus 5.0 +/- 1.5 ml O(2)/min per 100 g; P = 0.01), and the autoregulatory break point of the coronary pressure-flow relation was shifted to higher diastolic coronary pressures (60 +/- 17 versus 52 +/- 8 mmHg in NRF; P = 0.003); the latter was shifted further rightward after inhibition of both nitric oxide and prostaglandin release. The endocardial/epicardial blood flow ratio was comparable for both groups, suggesting preserved ventricular distribution of blood flow. In dogs with ARF, coronary vascular conductance also was reduced (P = 0.001 versus NRF), but coronary zero-flow pressure was unchanged. Vessel reactivity to each endothelium-dependent/independent compound also was blunted significantly. In conclusion, under resting conditions, coronary vascular tone, reserve, and vessel reactivity are markedly diminished with ARF, suggesting impaired vascular function. Consequently, during ARF, small increases in myocardial oxygen demand would induce subendocardial ischemia as a result of a limited capacity to increase oxygen supply and thereby contribute to higher risk for adverse coronary events and mortality.