Acute ischemic cardiac dysfunction is attenuated via gene transfer of a peptide inhibitor of the β-adrenergic receptor kinase (βARK1)
✍ Scribed by Hendrik T. Tevaearai; G. Brant Walton; Janelle R. Keys; Walter J. Koch; Andrea D. Eckhart
- Book ID
- 102339509
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 127 KB
- Volume
- 7
- Category
- Article
- ISSN
- 1099-498X
- DOI
- 10.1002/jgm.770
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✦ Synopsis
Abstract
Acute myocardial ischemia is a critical adverse effect potentially occurring during cardiac procedures. A peptide inhibitor of the β‐adrenergic receptor kinase (βARK1), βARKct, has been successful in rescuing chronic myocardial ischemia. The present study focused on the effects of adenoviral‐mediated βARKct (Adv‐βARKct) delivery on left ventricle (LV) dysfunction induced by acute coronary occlusion. Rabbits received intracoronary delivery of phosphate‐buffered saline (PBS) (n = 9) or 5 × 10^11^ viral particles of βARKct (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 βARKct group as compared to PBS (P < 0.05, two‐way ANOVA). βAR density was higher in the ischemic area of the LV in the βARKct group (βARKct: 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 βAR stimulation. βARK1 activation was less in the βARKct group (P < 0.05). Therefore, inhibition of myocardial βARK1 may represent a new strategy to prevent LV dysfunction induced by acute coronary ischemia. Copyright © 2005 John Wiley & Sons, Ltd.