Functional consequences of diminished myocardial oxygen delivery per beat in experimental heart failure

Abstract This investigation was designed to test the hypothesis that heart failure (HF) attenuates coronary vasodilation and autoregulation and that deficits in contractile function are proportionally related to reductions in the volume of myocardial perfusion and oxygen delivered per beat. Utilizing a pacing-induced model of HF in Ossabaw swine, we determined that chronic pacing at 180 beats/min for ~ 4 weeks significantly reduced baseline coronary flow by ~ 45% ( P = 0.01), lowered myocardial oxygen consumption (MVO₂) ( P = 0.07) and systolic wall thickening by ~ 30% ( P < 0.01), and increased left ventricular end-diastolic pressure ~ 160% ( P < 0.05). Coronary flow responses to Regadenoson (0.4 mg) and cardiac pacing (180 beats/min) were significantly attenuated in swine with pacing HF ( P ≤ 0.01). Control swine displayed relatively strong autoregulatory capability with coronary flow decreasing ~ 10% ( P = 0.26) as blood pressure was pharmacologically reduced from 120 to 60 mmHg. Alternatively, coronary flow decreased ~ 40% ( P = 0.01) over the same pressure range in pacing HF swine. Regional wall thickening and stroke volume declined once myocardial oxygen delivery fell below ~ 1.0 µL O₂/g/beat. These findings indicate that adaptations in the coronary microcirculation in pacing HF attenuate coronary metabolic and autoregulatory capacity and that subsequent functional deficits are related to reductions in the volume of myocardial perfusion and oxygen delivered per beat.