Gap junction uncoupling protects the heart against ischemia.
BACKGROUND
Many stimuli can successfully protect the heart against ischemia. We investigated whether gap junction uncoupling before ischemia was myoprotective. We also studied the function of the adenosine triphosphate-dependent potassium channel, which has been implicated in the mechanism of pharmacologic preconditioning, with respect to gap junction physiology.


METHODS
Twenty-eight rabbit hearts were placed on a Langendorff perfusion apparatus. Five were given a 5-minute infusion of 1 mmol/L heptanol (a gap junction uncoupler), 5 were given 10 micromol/L 2,3-butanedione monoxime (an electromechanical uncoupler), and 6 were given no drug. The left anterior descending coronary artery was then occluded for 1 hour and reperfused for 2 hours. Six hearts received 10 micromol/L glybenclamide before heptanol to evaluate the role of the adenosine triphosphate-dependent potassium channel. Six hearts underwent ischemic preconditioning with 2 cycles of 5 minutes of global ischemia and reperfusion. Action-potential duration of the ischemic zone, left ventricular developed pressure, and coronary flow were measured continuously. Infarct size was determined at the end of reperfusion.


RESULTS
Heptanol significantly reduced infarct size (from 46% +/- 2% to 22% +/- 5%, P <.01), an effect that was not prevented by glybenclamide. Butanedione monoxime decreased developed pressure but did not significantly reduce infarct size (46% +/- 5% vs 46% +/- 2%, P = not significant). There were no differences among groups with regard to developed pressure or action-potential duration.


CONCLUSIONS
Directly blocking gap junctions preconditions the heart. This protection is not a direct result of a decrease in developed pressure before a prolonged ischemic period nor is it achieved through a mechanism involving the adenosine triphosphate-dependent potassium channel.
Saltman
Adam E
AE
Division of Cardiothoracic Surgery, The Institute for Molecular Cardiology, State University of New York at Stony Brook, Health Sciences Center T19-080, Stony Brook, NY 11794-8191, USA. adam.saltman@sunysb.edu
Aksehirli
Tunc O
TO
Valiunas
Virginijus
V
Gaudette
Glenn R
GR
Matsuyama
Nanristu
N
Brink
Peter
P
Krukenkamp
Irvin B
IB
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects*; D005905:Glyburide / Q000494:pharmacology; D019850:Heptanol / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011817:Rabbits
D000889:Anti-Arrhythmia Agents; D019188:Organ Preservation Solutions; D015221:Potassium Channels; C004717:diacetylmonoxime; D019850:Heptanol; D003931:Diacetyl; D005905:Glyburide