Mechanoenergetics Characterizing Oxygen Wasting Effect of Caffeine in Canine Left Ventricle

Caffeine causes a considerable O2 waste for positive inotropism in myocardium by complex pharmacological mechanisms. However, no quantitative study has yet characterized the mechanoenergetics of caffeine, particularly its O2 cost of contractility in the Emax-PVA-VO2 framework. Here, Emax is an index of ventricular contractility, PVA is a measure of total mechanical energy generated by ventricular contraction, and VO2 is O2 consumption of ventricular contraction. The Emax-PVA-VO2 framework proved to be powerful in cardiac mechanoenergetics. We therefore studied the effects of intracoronary caffeine at concentrations lower than 1 mmol/l on left ventricular (LV) Emax and VO2 for excitation-contraction (E-C) coupling in the excised cross-circulated canine heart. We enhanced LV Emax by intracoronary infusion of caffeine after β-blockade with propranolol and compared this effect with that of calcium. We obtained the relation between LV VO2 and PVA with Emax as a parameter. We then calculated the VO2 for the E-C coupling by subtracting VO2 under KCl arrest from the PVA-independent (or zero-PVA) VO2 and the O2 cost of Emax as the slope of the E-C coupling VO2-Emax relation. We found that this cost was 40% greater on average for caffeine than for calcium. This result, for the first time, characterized integratively cardiac mechanoenergetics of the O2 wasting effect of the complex inotropic mechanisms of intracoronary caffeine at concentrations lower than 1 mmol/l in a beating whole heart.