Abstract 3310: Therapeutic Hypothermia Improves Myocardial Function and Stabilizes Hemodynamic Parameters in Patients After Cardiac Arrest
Post-cardiac arrest myocardial dysfunction is a common phenomenon after return of spontaneous circulation (ROSC) and contributes to hemodynamic instability and low survival rates after cardiac arrest. Mild hypothermia for 24 hours after ROSC has been shown to significantly improve neurologic recovery and survival rates. In the present study we investigate the influence of therapeutic hypothermia on hemodynamic parameters in resuscitated patients and on contractility in human failing myocardium. We analyzed the data from 70 patients (age 62.3±1.9 years) during hypothermia period. The initial LVEF was 35.8±2.2% indicating a significantly impaired LV function. The target temperature of 32–34 °C was achieved after 4.1±0.5 h. During this time, the positive inotropic stimulation with epinephrine could be significantly reduced from 10.66±2.74 μg/min (arrival ICU) to 6.22±1.6 μg/min (34 °C) and 2.93±0.9 μg/min (33 °C). The dobutamine and norepinephrine application rates were not changed significantly. The mean arterial blood pressure (MAP) remained stable at 83.1±2.4 mmHg (arrival ICU), 79.89±1.7 mmHg (34 °C) and 78.23±1.6 mmHg (33 °C). The mean heart rate significantly decreased from 92.7±2.8 bpm (arrival ICU) to 74.1±2.4 bpm (34 °C) and 68.5±2.2 bpm (33 °C). In vitro we treated isolated ventricular muscle strips from explanted failing human hearts with hypothermia and analyzed contractility parameters. With decreasing temperature the contractility significantly increased to a maximum of 167.51±22.95 % at 27 °C (n=16, P <0.05). A subgroup analysis showed a particularly enhanced effect on myocardium from patients with dilative cardiomyopathy (208.62±40.14%, n=7, P <0.05). Inhibiting the sarcoplasmic reticulum Ca2+ release by ryanodine did not significantly reduce the positive inotropic effect of hypothermia. Furthermore, hypothermia reduced cardiac relaxation parameters, indicating an increased Ca2+ -sensitivity as mechanism for the positive inotropic effect of hypothermia. In conclusion, therapeutic hypothermia stabilizes hemodynamic function in patients after cardiac arrest. Mechanistically, we demonstrate that hypothermia improves contractility in failing human myocardium by increasing Ca2+-sensitivity.