Increased extravascular forces limit endothelium-dependent and -independent coronary vasodilation in congestive heart failure

The increase in coronary blood flow (CBF) in response to endothelium-dependent vasodilators is reduced in congestive heart failure (CHF) suggesting endothelial dysfunction. However, increases in extravascular compressive forces secondary to elevated left ventricular diastolic pressure (LVEDP) in CHF might contribute to this abnormality. We measured CBF responses to intracoronary doses of the endothelium-dependent vasodilators acetylcholine (ACH) and bradykinin (BK) and the endothelium-independent vasodilator sodium nitroprusside (SNP) in the same eight dogs before (control) and after CHF was produced by 23+/-3 days of rapid ventricular pacing. In five of the dogs with CHF the zero-flow pressure (P(zf)), which reflects extravascular compressive forces in the maximally vasodilated coronary circulation (adenosine) was measured and found to strongly correlate with LVEDP (r=0.91). Coronary vascular resistance (CVR) at each concentration of vasodilator before and after the development of CHF was corrected for estimated coronary back pressure: CVR=(P(Ao)-LVEDP)/CBF, where P(Ao) is mean aortic pressure. CHF resulted in a significant decrease in CBF and increase in heart rate and LVEDP compared to control (P