Left ventricular dysfunction following rewarming from experimental hypothermia

Abstract

This study was aimed at elucidating whether ventricular hypothermia-induced dysfunction persisting after rewarming the unsupported in situ dog heart could be characterized as a systolic, diastolic, or combined disturbance. Core temperature of 8 mongrel dogs was gradually lowered to 25°C and returned to 37°C over a period of 328 min. Systolic function was described by maximum rate of increase in left ventricular (LV) pressure (dP/d tmax), relative segment shortening (SS%), stroke volume (SV), and the load-independent contractility index, preload recruitable stroke work (PRSW). Diastolic function was described by the isovolumic relaxation constant (τ) and the LV wall stiffness constant ( Kp). Compared with prehypothermic control, a significant decrease in LV functional variables was measured at 25°C: dP/d tmax2,180 ± 158 vs. 760 ± 78 mmHg/s, SS% 20.1 ± 1.2 vs. 13.3 ± 1.0%, SV 11.7 ± 0.7 vs. 8.5 ± 0.7 ml, PRSW 90.5 ± 7.7 vs. 29.1 ± 5.9 J/m ⋅ 10−2, Kp0.78 ± 0.10 vs. 0.28 ± 0.03 mm−1, and τ 78.5 ± 3.7 vs. 25.8 ± 1.6 ms. After rewarming, the significant depression of LV systolic variables observed at 25°C persisted: dP/d tmax1,241 ± 108 mmHg/s, SS% 10.2 ± 0.8 J, SV 7.3 ± 0.4 ml, and PRSW 52.1 ± 3.6 m ⋅ 10−2, whereas the diastolic values of Kpand τ returned to control. Thus hypothermia induced a significant depression of both systolic and diastolic LV variables. After rewarming, diastolic LV function was restored, in contrast to the persistently depressed LV systolic function. These observations indicate that cooling induces more long-lasting effects on the excitation-contraction coupling and the actin-myosin interaction than on sarcoplasmic reticulum Ca2+trapping dysfunction or interstitial fluid content, making posthypothermic LV dysfunction a systolic perturbation.