title: Anesthetic preconditioning enhances Ca2+ handling and mechanical and metabolic function elicited by Na+-Ca2+ exchange inhibition in isolated hearts.
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.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Wisconsin 53226, USA.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: An
authors.forename: Samhita S
authors.initials: SS
authors.lastname: Rhodes
authors.forename: Ming Tao
authors.initials: MT
authors.lastname: Jiang
authors.forename: Zeljko J
authors.initials: ZJ
authors.lastname: Bosnjak
authors.forename: Ming
authors.initials: M
authors.lastname: Tian
authors.forename: David F
authors.initials: DF
authors.lastname: Stowe
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D006168:Guinea Pigs; D019157:Ischemic Preconditioning, Myocardial; D009206:Myocardium / Q000378:metabolism*; D010647:Phenyl Ethers / Q000494:pharmacology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000777:Anesthetics; D000814:Aniline Compounds; D010647:Phenyl Ethers; C430918:SEA 0400; D019831:Sodium-Calcium Exchanger; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D013890:Thiourea; D002118:Calcium