Faculty Collaboration Database

Anesthetic preconditioning enhances Ca2+ handling and mechanical and metabolic function elicited by Na+-Ca2+ exchange inhibition in isolated hearts. Anesthesiology 2006 Sep;105(3):541-9

Date

08/26/2006

Pubmed ID

16931987

DOI

10.1097/00000542-200609000-00018

Scopus ID

2-s2.0-33748190403 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

BACKGROUND: Anesthetic preconditioning (APC) is well known to protect against myocardial ischemia-reperfusion injury. Studies also show the benefit of Na+-Ca2+ exchange inhibition on ischemia-reperfusion injury. The authors tested whether APC plus Na+-Ca2+ exchange inhibitors given just on reperfusion affords additive protection in intact hearts.

METHODS: Cytosolic [Ca2+] was measured by fluorescence at the left ventricular wall of guinea pig isolated hearts using indo-1 dye. Sarcoplasmic reticular Ca2+-cycling proteins, i.e., Ca2+ release channel (ryanodine receptor [RyR2]), sarcoplasmic reticular Ca2+-pump adenosine triphosphatase (SERCA2a), and phospholamban were measured by Western blots. Hearts were assigned to seven groups (n = 8 each): (1) time control; (2) ischemia; (3, 4) 10 microM Na+-Ca2+ exchange inhibitor KB-R7943 (KBR) or 1 microM SEA0400 (SEA), given during the first 10 min of reperfusion; (5) APC initiated by sevoflurane (2.2%, 0.41 +/- 0.03 mm) given for 15 min and washed out for 15 min before ischemia-reperfusion; (6, 7) APC plus KBR or SEA.

RESULTS: The authors found that APC reduced the increase in systolic [Ca2+], whereas KBR and SEA both reduced the increase in diastolic [Ca2+] on reperfusion. Each intervention improved recovery of left ventricular function. Moreover, APC plus KBR or SEA afforded better functional recovery than APC, KBR, or SEA alone (P < 0.05). Ischemia-reperfusion-induced degradation of major sarcoplasmic reticular Ca2+-cycling proteins was attenuated by APC, but not by KBR or SEA.

CONCLUSIONS: APC plus Na+-Ca2+ exchange inhibition exerts additive protection in part by reducing systolic and diastolic Ca2+ overload, respectively, during ischemia-reperfusion. Less degradation of sarcoplasmic reticular Ca2+-cycling proteins may also contribute to cardiac protection.

Author List

An J, Rhodes SS, Jiang MT, Bosnjak ZJ, Tian M, Stowe DF

MESH terms used to index this publication - Major topics in bold

Anesthetics
Aniline Compounds
Animals
Calcium
Calcium-Transporting ATPases
Guinea Pigs
Ischemic Preconditioning, Myocardial
Myocardium
Phenyl Ethers
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Sodium-Calcium Exchanger
Thiourea