Pretreatment with the gap junction uncoupler heptanol does not limit infarct size in rabbit heart.
Previous findings indicate that heptanol, an agent well-recognized to disrupt chemical signaling between myocytes by uncoupling of gap junctions, significantly limited infarct size when administered at the time of reperfusion. Our aim was to assess on the potential role of cell--cell communication via gap junctions during ischemia by investigating whether "loading" the soon-to-be ischemic territory with heptanol would limit myocardial necrosis. Five isolated buffer-perfused rabbit hearts were pretreated with heptanol (0.5 mM) for 10 min, while 12 served as controls. In the final 30 s of treatment, a large marginal branch of the left circumflex coronary artery was occluded for 30 min followed by 2 h of reperfusion, and infarct size was delineated by tetrazolium staining. Heptanol had no significant effect on the extent of infarct: area of necrosis (AN, expressed as a percentage of the myocardium at risk) was 75+/-3% and 72+/-8% in vehicle- and heptanol-treated groups (P=.76). Thus, our results suggest that cell-to-cell communication via gap junctions during coronary artery occlusion does not contribute importantly to the development of necrosis in rabbit heart.
Gysembergh
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A
Heart Institute/Research, Good Samaritan Hospital and Department of Medicine, Section of Cardiology, University of Southern California, 1225 Wilshire Boulevard, Los Angeles, CA 90017-2395, USA.
Kloner
R A
RA
Przyklenk
K
K
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D017629:Gap Junctions / Q000187:drug effects*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D019850:Heptanol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control; D009336:Necrosis; D010477:Perfusion; D011817:Rabbits; D014475:Uncoupling Agents / Q000494:pharmacology*; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
D014475:Uncoupling Agents; D019850:Heptanol