Perfusion-induced changes in cardiac O2 consumption and contractility are based on different mechanisms

Abstract

Increased cardiac perfusion results in increased oxygen consumption (VO2) and increased contractility (Gregg phenomenon) in the isolated heart. We investigated whether these two aspects of the Gregg phenomenon are related to coronary flow or arterial pressure. Coronary flow and, thus, arterial pressure were changed in the reference state and during vasoconstriction (3 nM vasopressin) in the Langendorff-perfused rat heart contracting isovolumically (ventricular balloon) at 27 degrees C (n = 5). All hearts showed an increase in developed isovolumic left ventricular pressure (measure of contractility) and in VO2 with increased perfusion. Developed left ventricular pressure depended primarily on arterial pressure, so its relationship with coronary flow was shifted by vasoconstriction. Conversely, VO2 primarily depended on coronary flow, so its relationship with arterial pressure was shifted with vasoconstriction. By use of vasoconstriction (decreased vascular radii), the effects of arterial pressure and wall shear stress (proportional to arterial pressure x radius) should be separable, but the results did not reach significance. Thus contractility is related to arterial pressure or shear stress, whereas VO2 is related to coronary flow. We conclude that the two aspects of the Gregg phenomenon are based on different mechanisms.

Increased coronary perfusion augments cardiac contractility in the rat through stretch-activated ion channels

“…Perfusion-induced changes. In our isolated perfused papillary muscles, where autoregulation is restricted due to adenosine addition, an increase in coronary perfusion pressure results in an increase in F dev , the Gregg effect, and is in line with earlier findings (13,16,36). From the literature it is known that in perfused papillary muscles an increase in oxygen delivery is not responsible (17,36).…”

“…The membrane deformation changes ion fluxes through SACs, resulting in increased cardiac contractility. This hypothesis is supported by the findings that the Gregg response was related to capillary perfusion (13,15) and changes in coronary vascular volume (3), but was not related to arterial endothelium or its released inotropic substances (12,14,32,33). The identity of the coronary perfusion-induced increased cation influx is not yet clear and needs further experiments.…”

Coronary perfusion and muscle lengthening increase cardiac contraction: different stretch-triggered mechanisms

“…From the literature, it is known that SACs could be located on the sarcolemma or t-tubular system of the cardiomyocytes (45); however, SACs have also been found on the vascular (33) or endocardial (24,27) endothelium. Dijkman et al (16)(17)(18) showed that perfusion-induced changes in contractility were related to Fig. 2.…”

Changes to both cardiac metabolism and performance accompany acute reductions in functional capillary supply

“…Indeed, inhibition of fatty acid -oxidation with trimetazidine led to increased glucose oxidation, coupled with increases in cardiac mechanical work despite no changes in oxygen consumption for both rat [2] and human hearts [3], suggesting more efficient ATP production. Given the relationship between oxygen consumption and coronary flow [4], substrate selection by the working heart may be dictated by the availability of oxygen and/or coronary flow. Hence, conditions such as compensated cardiac hypertrophy that are characterised by regions of tissue ischaemia within the myocardium [5] exhibit increased glucose oxidation and decreased fatty acid -oxidation [6].…”