Left Ventricle Function During Therapeutic Hypothermia with Beta1-Adrenergic Receptor Blockade

Abstract

Therapeutic hypothermia is an established treatment in patients resuscitated from cardiac arrest. It is usually well-tolerated circulatory, but hypothermia negatively effects myocardial contraction and relaxation velocities and increases diastolic filling restrictions. A significant proportion of resuscitated patients are treated with long-acting beta-receptor blocking agents' prearrest, but the combined effects of hypothermia and beta-blockade on left ventricle (LV) function are not previously investigated. We hypothesized that beta₁-adrenergic receptor blockade (esmolol infusion) exacerbates the negative effects of hypothermia on active myocardial motions, affecting both systolic and diastolic LV function. A pig (n = 10) study was performed to evaluate the myocardial effects of esmolol during hypothermia (33°C) and during normothermia, at spontaneous and pacing-increased heart rates (HRs). LV function was assessed by a LV pressure transducer, an epicardial ultrasonic transducer (wall thickness, wall thickening/thinning velocity) and an aortic ultrasonic flow-probe (stroke volume, cardiac output). The data were compared using a paired two-tailed Students t-test, and also analyzed using a linear mixed model to handle dependencies introduced by repeated measurements within each subject. The significance level was p ≤ 0.05. The effects of hypothermia and beta blockade were distinct and additive. Hypothermia reduced myocardial motion velocities and increased diastolic filling restrictions, but end-systolic wall thickness increased, and stroke volume and dP/dt_max (pumping function) were maintained. In contrast, esmolol predominantly affected systolic pumping function, by a negative inotropic effect. In combination, hypothermia and esmolol reduced myocardial velocities in systole and diastole by ∼40%, compared with normothermia without esmolol, inducing in combination both systolic and diastolic LV function impairment. The cardiac dysfunction deteriorated at increased HRs during hypothermia. Beta₁-adrenergic receptor blockade (esmolol) exacerbates the negative effects of hypothermia on active myocardial contraction and relaxation. The combination of hypothermia with beta-blockade induces both systolic and diastolic LV function impairment.

Keywords: beta-blocker; beta1-adrenergic receptor blockade; cardiac function; esmolol; left ventricle function; therapeutic hypothermia.