Myocardial protection by isoflurane preconditioning preserves Ca2+ cycling proteins independent of sarcolemmal and mitochondrial KATP channels.
BACKGROUND
Anesthetic preconditioning (APC) with volatile anesthetics improves recovery of contractile function and reduces calcium overload after ischemia/reperfusion (I/R). Mitochondrial and sarcolemmal K(ATP) channel openings have been implicated in APC-induced cardioprotection. In this study, we investigated the effect of APC on major calcium cycling proteins and its relation to K(ATP) channels.


METHODS
Isolated perfused rat hearts were divided into seven groups: Time control (n = 10), ischemia control (n = 8), APC (n = 8), Mitochondrial K(ATP) inhibitor 5-hydroxydecanoate (5-HD, 200 microM, n = 8), Sarcolemmal K(ATP) inhibitor HMR1098 (HMR, 20 microM, n = 8), and APC plus 5-HD or APC plus HMR1098 (n = 8 each). APC was initiated by administering 1.5% isoflurane for 15 min, followed by a 15 min washout before 30 min of myocardial ischemia and 60 min of reperfusion. Ca2+-release channels (RyR2), Ca2+-adenosine triphosphatase (SERCA2a), phospholamban, plasma membrane Ca2+ ATPase, and sodium-calcium exchanger in the homogenate were determined by Western blot assay.


RESULTS
APC improved contractile recovery (left ventricular developed pressure, +dP/dt, -dP/dt) after I/R, which was blocked by 5-HD and HMR. I/R depressed the density of RyR2, SERCA2a, and phospholamban, with no changes in the density of plasma membrane Ca2+ ATPase and sodium-calcium exchanger. APC reversed I/R-induced degradation of RyR2 and SERCA2a in the presence or absence of 5HD and HMR.


CONCLUSIONS
I/R-induced depression in cardiac performance is associated with a down-regulation of the major sarcoplasmic reticulum Ca2+-cycling proteins. Anesthesia preconditioning with isoflurane prevents I/R-related degradation of the RyR2 and SERCA2a in the sarcoplasmic reticulum. However, this effect was independent of its activation of K(ATP) channels.
An
Jianzhong
J
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. jzan@mcw.edu
Bosnjak
Zeljko J
ZJ
Jiang
Ming Tao
MT
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D007530:Isoflurane / Q000627:therapeutic use*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000032:analysis / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism*
D015221:Potassium Channels; D019837:Ryanodine Receptor Calcium Release Channel; C117780:mitochondrial K(ATP) channel; D007530:Isoflurane; D002118:Calcium