The Effect of Hypoxic Hypoxia on the Systemic and Myocardial Pharmacokinetics and Dynamics of Lidocaine in Sheep

Abstract

It was hypothesized that the increased myocardial blood flow known to occur during some types of hypoxia may alter the kinetics and dynamics of cardio-active drugs such as lidocaine that act directly on the myocardium. In a randomized cross-over design, iv lidocaine (100 mg over 2 min) was administered to conscious instrumented sheep in a control state (C) or when the sheep were rendered hypoxic (H) by the addition of nitrogen to their inspired air (average Pa(O2) = 26 mmHg). Hypoxia caused a significant increase in myocardial blood flow (193% of control, SD = 37%, p < 0.05), a nonsignificant increase in cardiac output, and unchanged heart rate and blood pressure. Peak arterial lidocaine concentrations were unchanged, but peak concentrations in coronary sinus blood (effluent from the myocardium) were increased (maximum 201% of control, SD = 63%, p < or = 0.05), suggesting more rapid uptake of lidocaine into the myocardium in hypoxia. There was a linear relationship between coronary sinus lidocaine concentrations and reductions in myocardial contractility. However, the higher myocardial concentrations associated with H were not associated with overall greater reductions in contractility, as baseline contractility was elevated by H. Thus, hypoxia was not detrimental with respect to this adverse effect of lidocaine on the myocardium.