Nitric oxide attenuates neutrophil-mediated myocardial contractile dysfunction after ischemia and reperfusion.
With the knowledge of NO as an antiadhesion molecule, we performed studies to investigate the effects of NO on postischemic polymorphonuclear leukocyte (PMN)-medicated myocardial contractile dysfunction. Studies were performed with isolated perfused rat hearts subjected to 20 minutes of global ischemia and 45 minutes of reperfusion. Human PMNs (50 million) were infused over the first 5 minutes of reperfusion, and the recovery of left ventricular function was compared with baseline values. Infusion of PMNs alone (n = 10) led to a 61% reduction in left ventricular developed pressure (LVDP) and a 57% reduction in the pressure-rate product (PRP) at 45 minutes of reperfusion. Infusion of an NO donor, CAS-754 (n = 9), resulted in 80.2 +/- 6.7% recovery of LVDP and 77.0 +/- 8.6% recovery of PRP. Treatment with L-arginine (2.5 mmol/L, n = 10) resulted in a similar improvement in the postischemic contractile state of the heart. In contrast, NG-nitro-L-arginine methyl ester (L-NAME) treatment (250 mumol/L, n = 10) resulted in an exacerbation of contractile dysfunction, as evidence by a 93% reduction in LVDP at 45 minutes of reperfusion and a 91% reduction in PRP. The deleterious effects of L-NAME were prevented by L-arginine coperfusion. We failed to observe any cardioprotective effects when NO or L-arginine was administered to hearts subjected to 25 minutes of ischemia and 45 minutes of reperfusion in the absence of PMNs. In conclusion, PMN-mediated myocardial contractile dysfunction is attenuated by NO and exacerbated by blockade of NO synthesis.
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Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Buda
A J
AJ
Flynn
D M
DM
Blessé
S A
SA
Shin
A M
AM
Curtis
M J
MJ
Lefer
D J
DJ
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004730:Endothelium, Vascular / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D009504:Neutrophils / Q000473:pathology* / Q000637:transplantation; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013558:Sydnones / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects
D013558:Sydnones; D014665:Vasodilator Agents; C072857:3-(cis-2,6-dimethylpiperidino)sydnonimine; D009569:Nitric Oxide