期刊
JOURNAL OF GENE MEDICINE
卷 7, 期 9, 页码 1172-1177出版社
WILEY
DOI: 10.1002/jgm.770
关键词
myocardial ischemia; beta-adrenergic receptor; gene therapy; off-pump coronary artery bypass graft; beta-adrenergic receptor kinase
资金
- NHLBI NIH HHS [R01 HL56 205, HL59 533] Funding Source: Medline
Acute myocardial ischemia is a critical adverse effect potentially occurring during cardiac procedures. A peptide inhibitor of the beta-adrenergic receptor kinase (beta ARK1), beta ARKct, has been successful in rescuing chronic myocardial ischemia. The present study focused on the effects of adenoviral-mediated beta ARKct (Adv-beta ARKct) delivery on left ventricle (LV) dysfunction induced by acute coronary occlusion. Rabbits received intracoronary delivery of phosphate-buffered saline (PBS) (n = 9) or 5 x 10(11) viral particles of beta ARKct (n = 8). A loose prolene 5-0 Potz-loop suture was placed around the circumflex coronary artery (LCx) with both ends buried under the skin. Four days later, the suture was retrieved and pulled to occlude the LCx. Ischemia was confirmed by immediate ECG changes. LV function was continuously recorded for 45 min. Contractility (LVdP/dt(max)), relaxation (LVdP/dt(min)) and end diastolic pressure (EDP) were less impaired in the beta ARKct group as compared to PBS (P < 0.05, two-way ANOVA). beta AR density was higher in the ischemic area of the LV in the beta ARKct group (beta ARct: 71.9 +/- 4.6 fmol/mg protein, PBS: 54.5 +/- 4.0 fmol/mg protein, P < 0.05). Adenylyl cyclase activity was also improved basally and in response to beta AR stimulation. beta ARK1 activation was less in the beta ARKct group (P < 0.05). Therefore, inhibition of myocardial beta ARK1 may represent a new strategy to prevent LV dysfunction induced by acute coronary ischemia. Copyright (c) 2005 John Wiley & Sons, Ltd.
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