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Overexpressed Cardiac Gs alpha Protects Against Myocardial Ischemic Injury in Conscious Rabbits
Author(s) -
Chen Li,
Zhao Xin,
Reinhardt Heather,
Gelpi Ricardo,
Robbins Jeffrey,
Vatner Dorothy E,
Vatner Stephen F
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.51
Subject(s) - cardioprotection , contractility , medicine , cardiology , ventricle , ischemic preconditioning , heart rate , myocardial infarction , anesthesia , ischemia , blood pressure
Overexpression of cardiac Gs alpha increases cardiac rate and contractility and responsiveness to catecholamines. All of these factors should have adverse effects on the response to myocardial ischemia. We examined the effects of 30 min coronary artery occlusion (CAO) and 4 days reperfusion in transgenic (Tg) rabbits with 3–5 fold overexpressed cardiac Gs alpha (beta‐MHC promotor), instrumented with a left anterior descending coronary occluder and a pressure gauge in the left ventricle along with ultrasonic segment length crystals. Infarct size (IF) was assessed histologically and with TTC. In conscious Tg rabbits compared with wild type (WT), heart rate was elevated, p<0.05, (247±10 vs. 207±10 bpm) as was left ventricular dP/dt (5600±413 vs. 3933±161 mmHg/sec). CAO was confirmed by absence of blood flow transmurally and systolic segment length shortening. Surprisingly, the Tg rabbits exhibited marked cardioprotection, where IF/area at risk was 3±1% compared to 50±3 % in WT. Proteins known to induce ischemic preconditioning, e.g., the adenosine receptor A2b and Gsk‐3 beta were upregulated in Tg rabbits. Thus, the rabbit with overexpressed cardiac Gs alpha, despite elevated levels of heart rate and myocardial contractility, exhibit powerful ischemic preconditioning.