title: Nitric oxide does not modulate myocardial contractility acutely in in situ canine hearts.
abstract: The study was designed to assess the influence of nitric oxide (NO) on myocardial contractility in vivo. The left anterior descending coronary artery (LAD) of 28 anesthetized, open-chest dogs was perfused with arterial blood via an extracorporeal circuit. In the LAD bed, segmental shortening (SS), an index of local myocardial contractility, was measured with ultrasonic crystals. Coronary blood flow (CBF) was measured by Doppler flow transducer and used to calculate myocardial oxygen consumption (MVO2). Studies were performed with coronary perfusion pressure (CPP) constant (n = 23) or with CBF constant (n = 5). Measurements were obtained 1) during intracoronary infusions of the NO donors sodium nitroprusside (SNP, 80 ng/min) and nitroglycerin (NTG, 40 micrograms/min) and of a stimulator of endogenous NO release, acetylcholine (ACh, 20 micrograms/min), and 2) after inhibition of basal NO synthase activity with either NG-nitro-L-arginine methyl ester (L-NAME, 300 micrograms/min ic for 15 min) or NG-monomethyl-L-arginine (L-NMMA 2mg/min ic for 15 min). Decreases in SS (-38%) and MVO2 (-42%) during intracoronary isoflurane infusion verified responsiveness of preparation to negative inotropic agents. With CPP constant, SNP, NTG, and ACh caused increases in CBF (177, 28, and 280%, respectively) with no changes in SS or MVO2. Neither L-NAME nor L-NMMA affected SS, MVO2, or CBF. With CBF constant, the SNP- and ACh-induced decreases in CPP were accompanied by no changes in SS. In conclusion, NO had no direct influence on myocardial contractility or oxygen demand under baseline conditions, or when its local concentration was increased acutely with SNP, NTG, or ACh. An augmented SS secondary to increased CBF per se, i.e., Gregg's phenomenon, did not obscure potential negative inotropic effects of SNP and ACh with CPP constant.
authors.affiliation: Department of Anesthesiology, Illinois Masonic Medical Center, Chicago, 60680, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Crystal
authors.forename: J
authors.initials: J
authors.lastname: Gurevicius
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007530:Isoflurane / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology
chemical_list: D009599:Nitroprusside; D009569:Nitric Oxide; D007530:Isoflurane; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester