Helium-induced late preconditioning in the rat heart in vivo.
BACKGROUND
A recent study showed that the noble gas helium induces early myocardial preconditioning. Cyclooxygenase-2 (COX-2) has been shown to be an important mediator in the signal transduction of late preconditioning. In the present study, we investigated whether helium induces late preconditioning in a concentration-dependent, time-dependent, or in both manner and whether COX-2 activity, mitochondrial function, or both are involved.


METHODS
The study was performed in male Wistar rats and consisted of two parts. In part 1, late preconditioning was achieved by administration of 70%, 50%, 30%, and 10% helium for 15 min 24 h before ischaemia/reperfusion (I/R). Based on the findings of part 1, in additional experiments 30% helium was administered subsequently three and two days before I/R. Furthermore, additional rats were pretreated with the COX-2 inhibitor NS-398 (5 mg kg(-1)) with and without 30% helium. Additional experiments were performed for mitochondrial analysis.


RESULTS
Helium concentrations of 70%, 50%, and 30% but not 10% reduced infarct size [He-LPC 70: 37(13)%, He-LPC 50: 34(16)%, He-LPC 30: 40(9)%; each P<0.05 vs


METHODS
55(8)%, He-LPC 10: 53(4)%; P>0.05 vs CONTROL]. Repeated administration of helium did not further enhance cardioprotection. NS-398 completely abolished cardioprotection by 30% helium [He-LPC 30+NS-398: 57(9)%; P<0.05 vs He-LPC 30] but had itself no effect on infarct size [NS-398: 55(9)%; P>0.05 vs CONTROL]. There were no differences in mitochondrial function after helium preconditioning.


CONCLUSIONS
Helium induces late preconditioning. Cardioprotection is already maximal with administration of one cycle of 30% helium and is abolished by functional blockade of COX-2 activity.
Huhn
R
R
Department of Anaesthesiology, Laboratory of Experimental Intensive Care and Anaesthesiology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9 1100, DD, Amsterdam, The Netherlands.
Heinen
A
A
Weber
N C
NC
Hieber
S
S
Hollmann
M W
MW
Schlack
W
W
Preckel
B
B
D000818:Animals; D051546:Cyclooxygenase 2 / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006371:Helium / Q000008:administration & dosage / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D009578:Nitrobenzenes / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D006371:Helium; D051546:Cyclooxygenase 2