Demonstration of a different sensitivity to epinephrine in isolated and in vivo hearts

Studies in isolated preparations dealing with myocardial effects of catecholamines usually employ epinephrine concentrations 10-1000 times higher (10^-7-10^-5 M) than those observed during maximal cardiac adrenoceptor activation in vivo (10^-9-5 × 10^-8 M) to obtain measurable cardiac responses. The reason for this discrepancy is still unclear, but it may reflect a diminished sensitivity to catecholamines in vitro. The main purpose of this study was to evaluate if a different myocardial sensitivity to epinephrine in vivo and in vitro does exist and to investigate which epinephrine concentrations in vitro mimic the effect of cardiac adrenoceptor activation in vivo. We compared concentration-response curves to cumulative increasing concentrations of epinephrine, measured by high pressure liquid chromatography, in chloralose anesthetized or pithed rats (in vivo) and in isolated Langendorff perfused rat hearts (in vitro). We found that the amplitude of response to epinephrine was significantly higher in vivo at all concentrations. For example, an increase of 50 beats/min was observed at an epinephrine concentration of 29±6 nm in chloralose anesthetized, 25±4 nM in isolated hearts (P <0.05 vs. in vivo). Data on contractility closely parallel those in heart rate. These data indicate that, when methodological differences are minimized, there is a marked reduction in the amplitude of the response to epinephrine in vitro. This depressed response, which is not due to the absence of an intact central or peripheral innervation, implies that in vitro concentration of 5 × 10^-7 M are required to mimic the effect of cardiac adrenoceptor activation in vivo. The physiological significance of even higher concentrations remains unclear.