Mechanoenergetics characterizing oxygen wasting effect of caffeine in canine left ventricle

Caffeine causes a considerable Ca waste for positive inotropism in myocardi um by complex pharmacological mechanisms. However, no quantitative study ha s yet characterized the mechanoenergetics of caffeine, particularly its O-2 cost Of contractility in the E-max-PVA-VO2 framework. Here, E-max is an in dex of ventricular contractility, PVA is a measure of total mechanical ener gy generated by ventricular contraction, and VO2 is O-2 consumption of vent ricular contraction. The E-max-PVA-VO2 framework proved to be powerful in c ardiac mechanoenergetics. We therefore studied the effects of intracoronary caffeine at concentrations lower than 1 mmol/l on left ventricular (LV) E- max and VO2 for excitation-contraction (E-C) coupling in the excised cross- circulated canine heart. We enhanced LV E-max by intracoronary infusion of caffeine after beta-blockade with propranolol and compared this effect with that of calcium. We obtained the relation between LV VO2 and PVA with E-ma x as a parameter. We then calculated the VO2 for the E-C coupling by subtra cting VO2 under KCI arrest from the PVA-independent (or zero-PVA) VO2 and t he O-2 cost of E-max as the slope of the E-C coupling VO2-E-max relation. W e found that this cost was 40% greater on average for caffeine than for cal cium. This result, for the first time, characterized integratively cardiac mechanoenergetics of the O-2 wasting effect of the complex inotropic mechan isms of intracoronary caffeine at concentrations lower than 1 mmol/l in a b eating whole heart.