CARDIOVASCULAR AND METABOLIC RESPONSES TO ANESTHETIC-INDUCED MALIGNANT HYPERTHERMIA IN SWINE

Background: Several cardiovascular disturbances, such as tachycardia a nd hypotension, are observed during human and porcine malignant hypert hermic (MH) crises. However, the pathophysiologic mechanisms responsib le for the deterioration of cardiovascular function during MH are not completely known. The purpose of this study was to elucidate the chang es in left ventricular (LV) function and metabolism and the systemic a nd regional hemodynamics during anesthetic-induced MH in swine. Method s: The study was carried out in 12 open-chest MH-susceptible pigs and in 8 healthy control (non-MH-susceptible) pigs under the same conditio ns, The cardiovascular and metabolic responses to halothane (1% inspir ed) and succinylcholine (3 mg . kg(-1) intravenously 15 min after the start of halothane administration) were studied, Global hemodynamic an d LV variables (expressed as means +/- SEM) were determined over a per iod of 90 min after the beginning of halothane exposure. Simultaneous investigations were performed on hindleg and cardiac muscle to compare the regional functional and metabolic changes in these tissues. Resul ts: MH was triggered in all MH-susceptible pigs. Early (10-30 min) car diovascular changes during the development of MH consisted of a rapid increase in heart rate (from 86 +/- 4 to 204 +/- 8 beats . min(-1)), c ardiac index (+84%), and peak rate of change in LV pressure (+150%); s troke volume index (-24%) and mean aortic pressure (-13%) decreased pr ogressively even in the early stage of MH. These alterations were acco mpanied by an early and persistent reduction in systemic vascular resi stance (maximally -57%) with an increase in aortic pressure amplitude, Early changes in coronary and peripheral hemodynamics during the deve lopment of MH consisted of a threefold increase in coronary blood now in conjunction with a marked decrease (-77%) in coronary vascular resi stance. The early circulatory changes were associated with a fourfold increase in myocardial and a 2.5-fold increase in peripheral O-2 consu mption. The ratio of the LY stroke work index (LVWI) to myocardial O-2 consumption (MV(O2)) was significantly decreased, by a factor of 5. I ncreased catecholamine concentrations and myocardial lactate and H+ pr oduction could be demonstrated throughout the MH crisis, In the late s tage of MH (>30 min), pronounced hypotension and a subsequent decrease in cardiac index were noted. These changes were associated with a sig nificant reduction in LV end-diastolic pressure, from 9 +/- 1 to 6 +/- 1 mmHg (P < 0.05), and in the rate of change in LV pressure, by a max imum of -25%. Coronary vascular resistance remained reduced while coro nary blood now decreased. Peripheral (hind-leg) blood now initially in creased by 48% while peripheral vascular resistance decreased by 42%, followed by a fivefold increase in peripheral vascular resistance with a marked decrease in peripheral blood flow (-88%) in the late phase o f MH. Conclusions: The current findings indicate that metabolic status during MH is characterized by a demand ischemia of the heart and of t he skeletal muscle. Insufficient coronary blood flow and increased met abolism as a result of tachycardia and increased concentrations of cat echolamines are the dominant factors contributing to the dramatic alte ration in cardiac performance during porcine MH. Acidosis, hypovolemia , and hyperkalemia, especially in the late phase of MH, are additional essential factors responsible for the progressive cardiovascular dete rioration and cardiac death.