Hypothermia elongates the contraction-relaxation cycle in explanted human failing heart decreasing the time for ventricular filling during diastole.

Targeted temperature management (TTM) is part of the standardized treatment for cardiac arrest patients. Hypothermia decreases cerebral oxygen consumption and induces bradycardia, thus, increasing the heart rate may be considered to maintain cardiac output. We hypothesized that increasing heart rate during hypothermia would impair diastolic function. Human left ventricular trabeculae obtained from explanted hearts of patients with terminal heart failure were stimulated at 0.5 Hz and contraction-relaxation cycles recorded. Maximal developed force (Fmax ), maximal rate of development of force ((dF/dt)max ), time to peak force (TPF), time to 80% relaxation (TR80) and relaxation time (RT=TR80-TPF) were measured at 37-33-31-29°C. At these temperatures, stimulation frequency was increased from 0.5 to 1.0 to 1.5 Hz. At 1.5 Hz, concentration-response curves for the beta-adrenergic receptor (β-AR) agonist isoproterenol were performed. Fmax , TPF and RT increased when temperature was lowered, whereas the (dF/dt)max decreased. At all temperatures, increasing stimulation frequency increased Fmax and (dF/dt)max , whereas TPF and RT decreased. At 31 and 29°C, resting tension increased at 1.5 Hz, which was ameliorated by β-AR stimulation. At all temperatures, maximal β-AR stimulation increased Fmax , (dF/dt)max and maximal systolic force, whereas resting tension decreased progressively with lowering temperature. β-AR stimulation reduced TPF and RT to the same extent at all temperatures, despite the more elongated contraction-relaxation cycle at lower temperatures. Diastolic dysfunction during hypothermia results from an elongation of the contraction-relaxation cycle which decreases the time for ventricular filling. Hypothermic bradycardia protects the heart from diastolic dysfunction and increasing the heart rate during hypothermia should be avoided.