期刊
CIRCULATION RESEARCH
卷 99, 期 11, 页码 1270-1276出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.RES.0000251282.79411.44
关键词
myocardial infarction; sympathetic nervous system; nitric oxide; regional wall motion; coronary artery occlusion
资金
- NHLBI NIH HHS [HL033107, HL069020, HL069752, HL59139] Funding Source: Medline
- NIA NIH HHS [AG028854, AG023137, AG01412] Funding Source: Medline
We tested the hypothesis that cardiac nerves may mediate ischemic preconditioning. Pigs were chronically instrumented to measure aortic, left atrial and left ventricular pressures, and regional myocardial function ( wall thickening). Hemodynamic variables, area at risk, and tissue blood flows (radioactive microspheres) were similar among groups. Myocardial infarct size following 60 minutes coronary artery occlusion and 4 days reperfusion, expressed as a fraction of the area at risk, was 42 +/- 4.0%, in innervated pigs and similar in pigs with regional cardiac denervation (CD, 41 +/- 2.5%). Infarct size in innervated pigs during the first window of preconditioning (first window) was markedly reduced (6 +/- 1.8%, P < 0.01), as it was in the second window of preconditioning ( second window) (16 +/- 3.3%, P < 0.01). Although infarct size was still reduced in pigs with CD and first window preconditioning (9 +/- 1.8%, P < 0.01), the protective effects of second window were abrogated in pigs with CD resulting in an infarct size of 38 +/- 5.6%. In another group of innervated pigs during pharmacological alpha(1)-adrenergic receptor (AR) blockade, infarct size was also not reduced during the second window (48 +/- 3.2%). Additionally, Western blot analysis of inducible nitric oxide synthase and cyclooxygenase-2 proteins demonstrated significant (P < 0.05) upregulation following the second window in innervated pigs, but not in pigs with CD or alpha(1)-AR blockade. Thus, the mechanism of protection during the second window, but not the first window, appears to be dependent on cardiac nerves and alpha(1)-AR stimulation.
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