Additive protective effects of late and early ischaemic preconditioning are mediated by the opening of KATP channels in vivo.
We investigated whether a combination of ischaemic late preconditioning (LPC) and ischaemic early preconditioning (EPC) induces additive myocardial protection in vivo, and the role of ATP-sensitive K (KATP) channels in ischaemic LPC and in LPC + EPC. Sixty rabbits were divided into seven groups. Anaesthetized animals were subjected to 30 min of coronary artery occlusion and 120 min of reperfusion (I/R). Controls (CON, n = 9) were not preconditioned. LPC (n = 10) was induced in conscious rabbits by a 5-min period of myocardial ischaemia 24 h before I/R. The KATP channel blocker 5-hydroxydecanoate (5-HD, 5 mg/kg) was given 10 min before I/R with (LPC + 5-HD, n = 9) or without LPC (5-HD, n = 8). EPC (n = 8) was induced by a 5-min period of myocardial ischaemia 10 min before I/R. Animals received LPC and EPC without (LPC + EPC, n = 8) or with 5-HD (LPC + EPC + 5-HD, n = 8). LPC reduced infarct size (IS, triphenyltetrazolium staining) from 57 +/- 11% (MW +/- SD, CON) of the area at risk to 31 +/- 19% (LPC, P = 0.004). 5-HD did not affect IS (5-HD: 60 +/- 12%, P = 0.002 versus LPC), but abolished the cardioprotective effects of LPC (LPC + 5-HD: 62 +/- 18%, P = 0.001 versus LPC). EPC reduced IS to 18 +/- 8%. Additional LPC led to a further reduction to 8 +/- 4% (LPC + EPC, n = 8; P = 0.005 versus EPC; P = 0.004 versus LPC). 5-HD abolished this additional cardioprotective effect of LPC + EPC (LPC + EPC + 5-HD, n = 8; 46 +/- 11%, P < or = 0.001 versus LPC + EPC). We conclude that the combination of ischaemic LPC and EPC induces additive cardioprotection. KATP channel opening mediates the cardioprotective effects of ischaemic LPC and LPC + EPC.
Müllenheim
J
J
Klinik für Anaesthesiologie, Heinrich-Heine-Universität, Postfach 10 10 07, 40001 Düsseldorf, Germany. jost@herzkreis.uni-duesseldorf.de
Schlack
W
W
Frässdorf
J
J
Heinen
A
A
Preckel
B
B
Thämer
V
V
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology; D006439:Hemodynamics; D006880:Hydroxy Acids / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011817:Rabbits; D013997:Time Factors
D003652:Decanoic Acids; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate