Lack of Myocardial K⁺Release in Exercising Swine Fails to Support a Role for K⁺as a Factor that Couples Coronary Resistance Vessel Control to Myocardial O₂consumption

Coronary blood flow is tightly coupled to myocardial oxygen consumption to maintain a consistently high level of myocardial oxygen extraction. The mechanisms underlying this tight control of coronary blood flow remain incompletely understood. However, recent in vitro evidence has suggested that the metabolic regulation of coronary resistance vessel tone may involve the release of K + from cardiomyocytes, resulting in coronary resistance vessel dilation (Zhao et al. PNAS 2020;117:7461). A role for K + release from skeletal muscle during exercise has been previously demonstrated in humans, reflected in an increase in femoral veno-arterial [K + ] gradient (Juel et al. Acta Physiol Scan 1990;140:147). Here we tested the hypothesis that K + release contributes to exercise hyperemia in the heart. For this purpose we exercised 16 chronically instrumented swine on a motor driven treadmill at 5 levels of exercise and studied myocardial oxygen and K + balance. Exercise increased heart rate from 117±4 at rest to 249±5 beats/min during the highest intensity of exercise and resulted in increases in left ventricular systolic pressure from 110±2 mmHg at rest to 130±3 mm Hg during the highest level of exercise (both p<0.05). These hemodynamic changes were accompanied by exercise-induced increases in myocardial oxygen consumption from 189±18 μmol/min at rest to 503±38 μmol/min (p<0.05), which was principally met by an increase in coronary blood flow from 54±5 ml/min to 122±10 ml/min (p<0.05), as myocardial oxygen extraction remained constant (79.5±1.1% at rest and 79.8±0.8% during the highest level of exercise). Exercise produced a small increase in arterial [K + ] from 3.61±0.09 mmol/l at rest to 4.26±0.07 mmol/l during exercise, which was accompanied by a similar increase in coronary venous [K + ] from 3.49±0.13 mmol/l at rest to 4.20±0.12 mmol/l during exercise (both p<0.05 versus rest). The trans-myocardial arterio-venous [K + ] gradient ([K + ] arterial - [K + ] venous ) was 0.10±0.10 mmol/l at rest and 0.08±0.08 mmol/l at the highest level of exercise (both p=NS from zero), indicating that there was no myocardial K + release over a wide range of exercise intensities and myocardial oxygen consumption values. In conclusion, in contrast to observations in the skeletal muscle circulation in vivo, as well as observations in the coronary circulation in vitro, our findings in exercising swine do not support a role for myocardial release of K + as a metabolic link between myocardial oxygen consumption and coronary resistance vessel control. Dutch Heart Foundation grant # 2020B008 This abstract was presented at the American Physiology Summit 2025 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.