Functional consequences of coronary microvascular dysfunction in the failing heart

There is a growing body of evidence to support that heart failure is strongly associated with impaired myocardial vasodilator capacity (coronary flow reserve). While prior studies implicate impaired coronary microvascular reactivity in the initiation and/or progression of the heart failure phenotype, understanding of the regulation of coronary blood flow in the setting of heart failure remains poor. The purpose of this study was to investigate interrelationships between coronary blood flow, myocardial oxygen consumption (MVO2), and regional contractile function in the setting of heart failure. Experiments were designed to test the hypothesis that heart failure attenuates coronary vasodilatory and autoregulatory capacity and subsequent deficits in function are directly tied to reductions in the volume of myocardial perfusion on a per-beat basis. Ossabaw swine were assigned to a control group (n = 5) or heart failure (HF) group (n = 5) produced by chronic right ventricular pacing (180 beats/min for ~4 weeks). Coronary and cardiac responses to the adenosine analog regadenoson, to increases in heart rate, and to a wide range of systemic arterial pressures were assessed in anesthetized open-chest swine during continuous esmolol (400 mg/hr, iv) administration. Baseline mean blood pressure, heart rate, stroke volume, cardiac output and ejection fraction were similar between groups. However, left ventricular (LV) end diastolic pressure was markedly elevated from 8 ± 1 mmHg in control swine to 21 ± 2 mmHg in pacing HF swine (P = 0.01) and lung wet:dry ratios increased by ~45% (P = 0.03) following chronic pacing. Pacing HF reduced regadenoson mediated coronary flow from 3.4 ± 0.5 in control swine to 2.3 ± 0.2 (P = 0.07) in pacing HF swine. Reductions in mean arterial pressure from ~140 mmHg to ~40 mmHg elicited a robust ~70% increase in heart rate in control swine, while heart rate was unaffected by these changes in pressure in pacing HF swine. Echocardiographic assessment of global systolic and diastolic function demonstrated an ~65% reduction in the slope of the relationship between stroke volume and LV end diastolic volume (P < 0.01) and a marked parallel upward shift in the relationship between LV end diastolic pressure and end diastolic filling volume (P < 0.0001). Baseline coronary blood flow was ~45% lower in pacing HF vs. control swine (P = 0.02) which corresponded with an ~30% reduction in MVO2 (P = 0.07) and regional systolic wall thickening (P = 0.01). Coronary autoregulatory gain over blood pressures ranging from 60 mmHg to 120 mmHg was significantly decreased from 0.86 ± 0.24 in control swine to 0.34 ± 0.18 (P = 0.05) in pacing HF swine. Diminished regional wall thickening in pacing HF swine was directly associated with reductions in coronary flow below ~6.0 mL/g/beat. Findings from this study suggest that functional and metabolic consequences of coronary microvascular dysfunction in the failing heart are related to limitations in the volume of myocardial perfusion per beat. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.