Cardiovascular and Metabolic Responses to Anesthetic-induced Malignant Hyperthermia in Swine
Authors: Roewer Norbert , Dziadzka Andreas , Greim Clemens A. , Kraas Eberhard , am Esch J. Schulte 
Published: November 2003

Background
Several cardiovascular disturbances, such as tachycardia and hypotension, are observed during human and porcine malignant hyperthermic (MH) crises. However, the pathophysiologic mechanisms responsible for the deterioration of cardiovascular function during MH are not completely known. The purpose of this study was to elucidate the changes in left ventricular (LV) function and metabolism and the systemic and regional hemodynamics during anesthetic-induced MH in swine.

Methods
The study was carried out in 12 open-chest MH-susceptible pigs and in 8 healthy control (non-MH-susceptible) pigs under the same conditions. The cardiovascular and metabolic responses to halothane (1% inspired) and succinylcholine (3 mg.kg-1 intravenously 15 min after the start of halothane administration) were studied. Global hemodynamic and LV variables (expressed as means +/- SEM) were determined over a period 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.

Results
MH was triggered in all MH-susceptible pigs. Early (10-30 min) cardiovascular changes during the development of MH consisted of a rapid increase in heart rate (from 86 +/- 4 to 204 +/- 8 beats.min-1), cardiac index (+84%), and peak rate of change in LV pressure (+150%); stroke volume index (-24%) and mean aortic pressure (-13%) decreased progressively even in the early stage of MH. These alterations were accompanied by an early and persistent reduction in systemic vascular resistance (maximally -57%) with an increase in aortic pressure amplitude. Early changes in coronary and peripheral hemodynamics during the development of MH consisted of a three-fold increase in coronary blood flow in conjunction with a marked decrease (-77%) in coronary vascular resistance. The early circulatory changes were associated with a fourfold increase in myocardial and a 2.5-fold increase in peripheral O2 consumption. The ratio of the LV stroke work index (LVWI) to myocardial O2 consumption (MVO2) was significantly decreased, by a factor of 5. Increased catecholamine concentrations and myocardial lactate and H+ production could be demonstrated throughout the MH crisis. In the late stage of MH (> 30 min), pronounced hypotension and a subsequent decrease in cardiac index were noted. These changes were associated with a significant 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 maximum of -25%. Coronary vascular resistance remained reduced while coronary blood flow decreased. Peripheral (hind-leg) blood flow initially increased 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 of MH.

Conclusions
The current findings indicate that metabolic status during MH is characterized by a demand ischemia of the heart and of the skeletal muscle. Insufficient coronary blood flow and increased metabolism as a result of tachycardia and increased concentrations of catecholamines are the dominant factors contributing to the dramatic alteration 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 deterioration and cardiac death.