Influence of mild hypothermia on myocardial contractility and circulatory function

Abstract

Myocardial contractility depends on temperature. We investigated the influence of mild hypothermia (37–31°) on isometric twitch force, sarcoplasmic reticulum (SR) Ca²⁺-content and intracellular Ca²⁺-transients in ventricular muscle strips from human and porcine myocardium, and on in vivo hemodynamic parameters in pigs. In vitro experiments: muscle strips from 5 nonfailing human and 8 pig hearts. Electrical stimulation (1 Hz), simultaneous recording of isometric force and rapid cooling contractures (RCCs) as an indicator of SR Ca²⁺-content, or intracellular Ca²⁺-transients (aequorin method). In vivo experiments: 8 pigs were monitored with Millar-Tip (left ventricular) and Swan-Ganz catheter (pulmonary artery). Hemodynamics parameters were assessed at baseline conditions (37°), and after stepwise cooling on cardiopulmonary bypass to 35, 33, and 31°C. Hypothermia increase isometric twitch force significantly by 91 ± 16% in human and by 50 ± 9% in pig myocardium (31 vs. 37°C; p < 0.05, respectively). RCCs or aequorin light emission did not change significantly. In anesthetized pigs, mild hypothermia resulted in an increase in hemodynamic paramters of myocardial contractility. While heart rate decreased from 111 ± 3 to 73 ± 1 min⁻¹, cardiac output increased from 2.4 ± 0.1 to 3.1 ± 0.3 l/min, and stroke volume increased from 21 ± 1 to 41 ± 3 ml. +dP/dt_max increased by 25 ± 8% (37 vs. 31°C; p < 0.05 for all values). Systemic and pulmonary vascular resistance did not change significantly during cooling. Mild hypothermia exerts significant positive inotropic effects in human and porcine myocardium without increasing intracellular Ca²⁺-transients or SR Ca²⁺-content. These effects translate into improved hemodynamics parameters of left ventricular function.