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Anesthetic Preconditioning in Normal and Hypertrophic Porcine Myocardium

Jens Kjærgaard Rolighed Larsen

Abstract

The effect of volatile anesthetics on cardiomyocyte injury during ischemia and reperfusion is not yet fully understood. Though the efficacy of sevoflurane upon reducing myocardial infarction during the ischemia-reperfusion process is well-validated in some animal models, clinical studies are partially inconsistent with this, and the cardioprotective effect is yet to be translated into an equivocal improvement in patient outcome. We, therefore, used an intact porcine closed-chest animal model with unparalleled anatomic and physiological similarities to man to investigate sevoflurane volatile anesthetic cardioprotection during ischemia and reperfusion. In order to form a comparative base, we initially studied the efficacy of classical ischemic preconditioning upon histologic myocardial infarct size and simultaneously investigated the effects of sevoflurane administered pre-ischemically, which showed only a tendency towards infarct size reduction compared with the effectiveness of ischemic preconditioning. Global cardiac function was estimated with tissue-Doppler echocardiography and was unrelated to sevoflurane administration or size of irreversible ischemic injury.
Thus, unable to prove the existence of a ‗trigger‘ mechanism for sevoflurane preconditioning, we proceeded to evaluate infarct size mitigation by continuous pre-, per- and post-ischemic sevoflurane administration (=cardioprotection). Sevoflurane inhalation diminished myocardial infarct size by more than 60%. The role of pentobarbital anesthetic infusion was also assessed, both as concomitant and sole sedative during ischemia and reperfusion, showing only an insignificant role on myocardial injury salvage from sevoflurane cardioprotection in the current model.
Finally, the pathologic heart condition known as left ventricular hypertrophy (LVH), not uncommonly encountered in cardiac surgery patients, was investigated for its ability to influence sevoflurane cardioprotection in the porcine model. A model of LVH established within our department was used. It comprised a cohort of aortic banded animals which subsequently developed supravalvular aortic stenosis and LV pressure overload with ensuing development of LV hypertrophy. Animals were since allocated to ischemia-reperfusion protocols and this study showed that LVH diminished sevoflurane cardioprotection, in addition to LVH paradoxical improved tolerance to ischemia in young animals.
In conclusion, this dissertation supports previous experimental results from volatile anesthetic cardioprotection and specifies timing and dosages related to sevoflurane administration in an intact large animal model recognized for its comparability to normal human ischemia pathophysiology. Moreover, a reduced sevoflurane cardioprotective efficacy was found in a model of cardiac (LVH) pathology, offering a possible explanation for diminished clinical capacity for cardioprotection in a typical cardiac surgery cohort.