ATP-sensitive potassium channels do not have a main role in mediating late preconditioning protection against arrhythmias and stunning in conscious sheep.

Abstract

OBJECTIVE:

Although late preconditioning protects against stunning following several short periods of ischemia-reperfusion, it is not clear if it confers protection against stunning and malignant arrhythmias after a sustained reversible ischemia, and whether KATP channels are involved as triggers and/or end effectors of the protective mechanism. The purpose of this work was thus to test these issues in conscious sheep.

METHODS:

Five groups were considered: CONT (control): the animals were submitted to 12 min ischemia followed by 2 h reperfusion; SWOP (late preconditioning): on the first day, the animals were preconditioned with 6 periods of 5 min ischemia 5 min reperfusion and 24 h later they were submitted to 12 min ischemia followed by 2 h reperfusion; GLIB: same as CONT with the KATP channel inhibitor glibenclamide (0.4 mg/kg) infused 30 min prior to the 12 min ischemia; SWOPG2: same as SWOP with glibenclamide before the 12 min ischemia; SWOPG1: same as SWOP with glibenclamide prior to the preconditioning stimulus.

RESULTS:

Percent reperfusion recovery of wall thickening fraction (% WTh) showed late preconditioning protection against stunning throughout reperfusion (SWOP vs CONT, p < 0.01). Arrhythmia severity index (ASI) also demonstrated that late preconditioning protects against malignant arrhythmias at the onset of reperfusion (CONT: 4.87 +/- 1.62 vs SWOP: 1.39 +/- 0.93, p < 0.01). Glibenclamide was unable to prevent preconditioning, both against stunning and arrhythmia incidence, when administered either before the preconditioning stimulus (SWOPG1 vs CONT, p < 0.01) or before the sustained ischemia (SWOPG2 vs GLI, p < 0.01).

CONCLUSIONS:

Results indicate that late preconditioning protects against stunning and arrhythmias following a reversible, sustained ischemia in conscious sheep and that KATP channel participation is negligible as triggers and end effectors of both types of protection.

• Authors: Jorge A Negroni, Elena C Lascano, Héctor F del Valle, Alberto J Crottogini
• Journal: Basic research in cardiology (Basic Res Cardiol) Vol. 97 Issue 1 Pg. 55-64 (Jan 2002) ISSN: 0300-8428 [Print] Germany
• PMID: 11998978 (Publication Type: Journal Article)

Chemical References

• Anti-Arrhythmia Agents
• Potassium Channel Blockers
• Potassium Channels
• Adenosine Triphosphate
• Glyburide

Topics

• Action Potentials (drug effects)
• Adenosine Triphosphate (metabolism)
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Arrhythmias, Cardiac (metabolism)
• Consciousness
• Glyburide (pharmacology)
• Hemodynamics (drug effects)
• Ischemic Preconditioning, Myocardial
• Male
• Myocardial Reperfusion Injury (metabolism)
• Myocardial Stunning (metabolism)
• Potassium Channel Blockers
• Potassium Channels (metabolism)
• Sheep