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CARDIOVASCULAR ANESTHESIA

Anesthetic Preconditioning Attenuates Mitochondrial Ca²⁺ Overload During Ischemia in Guinea Pig Intact Hearts: Reversal by 5-Hydroxydecanoic Acid

Matthias L. Riess, MD^*, Amadou K. S. Camara, PhD^*, Enis Novalija, MD^*, Qun Chen, MD^*, Samhita S. Rhodes, MS, and David F. Stowe, MD PhD^*&Verbar||¶

Anesthesiology Research Laboratory, Departments of *Anesthesiology and Physiology, and &Verbar||Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Anesthesiology and Intensive Care Medicine, University Hospital Münster, Münster, Germany; Department of Biomedical Engineering, Marquette University, Milwaukee, Wisconsin; and ¶Research Service, Veterans Affairs Medical Center, Milwaukee, Wisconsin

Address correspondence and reprint requests to David F. Stowe, MD, PhD, M4280, 8701 Watertown Plank Rd., Medical College of Wisconsin, Milwaukee, WI 53226. Address e-mail to dfstowe{at}mcw.edu

Cardiac ischemia/reperfusion (IR) injury is associated with mitochondrial (m)Ca²⁺ overload. Anesthetic preconditioning (APC) attenuates IR injury. We hypothesized that mCa²⁺ overload is decreased by APC in association with mitochondrial adenosine triphosphate-sensitive K⁺ (mK_ATP) channel opening. By use of indo-1 fluorescence, m[Ca²⁺] was measured in 40 guinea pig Langendorff-prepared hearts. Control (CON) hearts received no treatment for 50 min before IR; APC hearts were exposed to 1.2 mM (8.8 vol%) sevoflurane for 15 min; APC + 5-hydroxydecanoate (5-HD) hearts received 200 µM 5-HD from 5 min before to 15 min after sevoflurane exposure; and 5-HD hearts received 5-HD for 35 min. Sevoflurane was washed out for 30 min and 5-HD for 15 min before 30 min of global ischemia and 120 min of reperfusion. During ischemia, the peak m[Ca²⁺] accumulation was decreased by APC from 489 ± 37 nM (CON) to 355 ± 28 nM (P < 0.05); this was abolished by 5-HD (475 ± 38 nM m[Ca²⁺]). APC resulted in improved function and reduced infarct size on reperfusion, which also was blocked by 5-HD. 5-HD pretreatment alone did not affect m[Ca²⁺] (470 ± 34 nM) or IR injury. Thus, preservation of function and morphology on reperfusion is associated with attenuated mCa²⁺ accumulation during ischemia. Reversal by 5-HD suggests that APC may be triggered by opening mK_ATP channels.

IMPLICATIONS:Myocardial ischemia/reperfusion injury is associated with mitochondrial Ca²⁺ overload. Mitochondrial [Ca²⁺] and function were measured in guinea pig isolated hearts. Anesthetic preconditioning attenuated mitochondrial Ca²⁺ overload during ischemia, improved function, and reduced infarct size. Reversal by 5-hydroxydecanoate suggests that anesthetic preconditioning may be triggered by mitochondrial adenosine triphosphate-sensitive K channel opening.

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