Antiarrhythmic effect of ischemic preconditioning during low-flow ischemia. The role of bradykinin and sarcolemmal versus mitochondrial ATP-sensitive K(+) channels.
Short episodes of ischemia (ischemic preconditioning) protect the heart against ventricular arrhythmias during zero-flow ischemia and reperfusion. However, in clinics, many episodes of ischemia present a residual flow (low-flow ischemia). Here we examined whether ischemic preconditioning protects against ventricular arrhythmias during and after a low-flow ischemia and, if so, by what mechanism(s). Isolated rat hearts were subjected to 60 min of low-flow ischemia (12% residual coronary flow) followed by 60 min of reperfusion. Ischemic preconditioning was induced by two cycles of 5 min of zero-flow ischemia followed by 5 and 15 min of reperfusion, respectively. Arrhythmias were evaluated as numbers of ventricular premature beats (VPBs) as well as incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF) during low-flow ischemia and reperfusion. Ischemic preconditioning significantly reduced the number of VPBs and the incidence of VT and of VF during low-flow ischemia. This antiarrhythmic effect of preconditioning was abolished by HOE 140 (100 nM), a bradykinin B(2) receptor blocker. Similar to preconditioning, exogenous bradykinin (10 nM) reduced the number of VPBs and the incidence of VT and of VF during low-flow ischemia. Furthermore, the antiarrhythmic effects of both ischemic preconditioning and bradykinin were abolished by glibenclamide (1 microM), a non-specific blocker of ATP-sensitive K(+) (K(ATP)) channels. Finally, the antiarrhythmic effects of both ischemic preconditioning and bradykinin were abolished by HMR 1098 (10 microM), a sarcolemmal K(ATP) channel blocker but not by 5-hydroxydecanoate (100 microM), a mitochondrial K(ATP) channel blocker. In conclusion, ischemic preconditioning protects against ventricular arrhythmias induced by low-flow ischemia, and this protection involves activation of bradykinin B(2) receptors and subsequent opening of sarcolemmal but not of mitochondrial K(ATP) channels.
Driamov
Sergey
S
Department of Research, University Hospital, Hebelstrasse 20, ZLF 319, 4031, Basel, Switzerland.
Bellahcene
Mohamed
M
Ziegler
André
A
Barbosa
Vânia
V
Traub
David
D
Butz
Silvia
S
Buser
Peter T
PT
Zaugg
Christian E
CE
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology*; D001920:Bradykinin / Q000378:metabolism*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2 / Q000187:drug effects; D012508:Sarcolemma / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D043782:Receptor, Bradykinin B2; D001920:Bradykinin