Anesthetic preconditioning attenuates mitochondrial Ca2+ overload during ischemia in Guinea pig intact hearts: reversal by 5-hydroxydecanoic acid.

Abstract

UNLABELLED:

Cardiac ischemia/reperfusion (IR) injury is associated with mitochondrial (m)Ca(2+) overload. Anesthetic preconditioning (APC) attenuates IR injury. We hypothesized that mCa(2+) overload is decreased by APC in association with mitochondrial adenosine triphosphate-sensitive K(+) (mK(ATP)) channel opening. By use of indo-1 fluorescence, m[Ca(2+)] 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 micro M 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[Ca(2+)] 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[Ca(2+)]). 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[Ca(2+)] (470 +/- 34 nM) or IR injury. Thus, preservation of function and morphology on reperfusion is associated with attenuated mCa(2+) 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 Ca(2+) overload. Mitochondrial [Ca(2+)] and function were measured in guinea pig isolated hearts. Anesthetic preconditioning attenuated mitochondrial Ca(2+) 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.

• Authors: Matthias L Riess, Amadou K S Camara, Enis Novalija, Qun Chen, Samhita S Rhodes, David F Stowe
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 95 Issue 6 Pg. 1540-6, table of contents (Dec 2002) ISSN: 0003-2999 [Print] United States
• PMID: 12456413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anesthetics
• Decanoic Acids
• Hydroxy Acids
• Methyl Ethers
• Sevoflurane
• 5-hydroxydecanoic acid
• Calcium

Topics

• Anesthetics (pharmacology)
• Animals
• Calcium (metabolism)
• Decanoic Acids (pharmacology)
• Guinea Pigs
• Heart Rate (drug effects)
• Hydroxy Acids (pharmacology)
• Ischemic Preconditioning, Myocardial
• Methyl Ethers (pharmacology)
• Mitochondria, Heart (metabolism)
• Myocardial Ischemia (metabolism)
• Sevoflurane