Nitric oxide, an important regulator of perfusion-contraction matching in conscious pigs.
We examined whether nitric oxide (NO) inhibition during moderate reduction in coronary blood flow (CBF) would affect perfusion-contraction matching. Coronary stenosis (CS) was induced in conscious pigs, which resulted in a stable 39 +/- 1% reduction in CBF for 1.5 h. Ischemic zone wall thickening (IZWT) decreased by an average of 56 +/- 2% during CS from 2.7 +/- 0.2 mm. After reperfusion, myocardial stunning was observed, but this recovered without evidence of necrosis. After recovery and subsequent administration of systemic NO synthase inhibition (N(omega)-nitro-L-arginine, 25 mg. kg(-1). day(-1) x 3 days), CS for 1.5 h reduced CBF similarly but decreased IZWT significantly more, P < 0.05, by 89 +/- 5%. Myocardial stunning, i.e., the decrease in IZWT at 12 h post-CS, was more severe (-65 +/- 5% vs. -21 +/- 3%), P < 0.05. Furthermore, CS during NO synthase inhibition resulted in multifocal subendocardial areas of necrosis in the area at risk. These data suggest that in the intact, conscious pig, NO inhibition prevents perfusion-contraction matching, resulting in intensification of post-ischemic stunning and development of subendocardial necrosis.
Kudej
R K
RK
Henry Hood Research Program, Weis Center for Research, Pennsylvania State University College of Medicine, Danville PA 17822, USA.
Kim
S J
SJ
Shen
Y T
YT
Jackson
J B
JB
Kudej
A B
AB
Yang
G P
GP
Bishop
S P
SP
Vatner
S F
SF
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003327:Coronary Disease / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000503:physiopathology*; D009336:Necrosis; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology*; D013552:Swine
D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase