Xenon does not alter cardiac function or major cation currents in isolatedguinea pig hearts or myocytes

Background: The noble gas xenon (Xe) has been used as an inhalational anest hetic agent in clinical trials with little or no physiologic side effects. Like nitrous oxide, lie is believed to exert minimal unwanted cardiovascula r effects, and like nitrous oxide, the vapor concentration to achieve 1 min imum alveolar concentration (MAC) for Xe in humans is high. i.e. 70-80%. In the current study, concentrations of up to 80% Xe were examined for possib le myocardial effects in isolated, erythrocyte-perfused guinea pig hearts a nd for possible effects on altering major cation currents in isolated guine a pig cardiomyocytes. Methods: Isolated guinea pigs hearts were perfused at 70 mmHg via,in the La ngendorff technique initially with a salt solution at 37 degrees C. Hearts were then perfused with fresh filtered (40.mu m pore) and washed canine ery throcytes diluted in the salt solution equilibrated with 20% O-2 in nitroge n (control), with 20% O-2, 40% Xe, and 40% N-2, (0.5 MAC), or with 20% O-2 and 80% Xe (1 MAC), respectively. Hearts were perfused with 80% Xe for 15 m in, and bradykinin was injected into the blood perfusate to test endotheliu m-dependent vasodilatory responses. Using the whole-cell patch-clamp techni que, 80% Xe was tested for effects on the cardiac ion currents, the Na+, th e L-type Ca2+ and the Inward-rectifier K+ channel, in guinea pig myocytes s uffused with a salt solution equilibrated with the same combinations of Xe, oxygen, and nitrogen as above. Results: in isolated hearts, heart rate, atrioventricular conduction time, left ventricular pressure, coronary flow, oxygen extraction, oxygen consump tion, cardiac efficiency, and flow responses to bradykinin were not signifi cantly (repeated measures analysis of variance, P > 0.05) altered by 40% or 80% Xe compared with controls. In Isolated cardiomyocytes, the amplitudes of the Na+, the L-type Ca2+, and the inward-rectifier K+ channel over a ran ge of voltages also were not altered by 80% Xe compared with controls. Conclusions: Unlike hydrocarbon-based gaseous anesthetics, Xe does not sign ificantly alter any measured electrical, mechanical. or metabolic factors, or the nitric oxide-dependent flow response in, isolated hearts, at least p artly because lie does not alter the major cation currents as shown here fo r cardiac myocytes. The authors' results indicate that Xe, at approximately 1 MAC for humans, has no physiologically important effects on the guinea p ig heart.