Effect of hypothermia on cellular membrane function during low-flow extracorporeal circulation.

The use of systemic hypothermia is known to allow recovery from potentially lethal states of profound hypoperfusion or total circulatory arrest. While the cellular alterations accompanying states of decreased perfusion in skeletal muscle are well defined, little is known regarding the impact of coexistent hypothermia. To investigate this issue, nine dogs were placed on total cardiopulmonary bypass (CPB) and perfused in nonpulsatile fashion. The following flow and temperature parameters were used in three different perfusion models: 3.5 L/min/m2 at 23 degrees C (group A, n = 3), 1.6 L/min/m2 at 37 degrees C (group B, n = 3), and 1.6 L/min/m2 at 23 degrees C (group C, n = 3). Assessment of cellular function in a hind limb adductor muscle by measurement of resting transmembrane potential difference (Em) and determination of tissue electrolyte distribution in a biopsy specimen was performed in the control state and again after 60 minutes of total CPB. Low-flow/hypothermic CPB (group C) was associated with depolarization of resting Em to -63.3 +/- 3.2 mV from a control value of -87.0 +/- 1.3 mV (p less than 0.05), an increase in the calculated intracellular Na ([Na]i) to 16.4 +/- 4.0 mEq/L from a control value of 7.6 +/- 1.4 mEq/L (p less than 0.05), and an increase in the ratio of the selective membrane permeabilities of Na+ to K+ (pNa/pK), to 0.067 +/- 0.013 from a control value of 0.013 +/- 0.002 (p less than 0.05). In contrast, resting Em was maintained at -86.4 +/- 6.1 mv during normal-flow/hypothermic CPB (group A), while low-flow/normothermic CPB (group B) produced an intermediate depolarization to -75.2 +/- 3.0 mV (p less than 0.05). Neither [Na]i or pNa/pK was altered significantly in group A or group B dogs. These data characterize a physiologic alteration in the cellular membrane function of skeletal muscle during low-flow/hypothermic CPB, which is similar in many respects to that accompanying hemorrhagic shock. This suggests that during periods of profound hypothermia certain flow-related derangements in skeletal muscle are not obviated and may be exacerbated.