title: Minimal role of nitric oxide in basal coronary flow regulation and cardiac energetics of blood-perfused isolated canine heart.
abstract: 1. The role of nitric oxide (NO) in the regulation of basal coronary perfusion and ventricular chamber energetics was studied in isovolumetrically contracting isolated blood-perfused canine hearts. Hearts were cross-perfused by a donor animal prior to isolation, and chamber volume controlled by a servo-pump. Coronary sinus flow and arterial-coronary sinus oxygen difference were measured to determine energetic efficiency. 2. NO synthase (NOS) was competitively inhibited by NG-monomethyl-L-arginine (L-NMMA; 0.5 mg kg-1, intracoronary), resulting in a reduction of acetylcholine (50 micrograms min-1)-induced flow augmentation from 143 to 62% (P < 0.001). 3. NOS inhibition had no significant effect on basal coronary flow. Coronary pressure-flow relationships were determined at a constant cardiac workload by varying mean perfusion pressure between 20 and 150 mmHg. Neither the shape of the relationship, nor the low-pressure value at which flow regulation was substantially diminished were altered by NOS inhibition. 4. Myocardial efficiency was assessed by the relationship between myocardial oxygen consumption and total pressure-volume area (PVA), with cavity volume altered to generate varying PVAs. This relative load-independent measure of energetic efficiency was minimally altered by NOS inhibition. 5. These results contrast with isolated crystalloid-perfused heart experiments and suggest that in hearts with highly controlled ventricular loading and whole-blood perfusion, effects of basal NO production on coronary perfusion and left ventricular energetics are minimal.
authors.affiliation: Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: A
authors.initials: A
authors.lastname: Saeki
authors.forename: F A
authors.initials: FA
authors.lastname: Recchia
authors.forename: H
authors.initials: H
authors.lastname: Senzaki
authors.forename: D A
authors.initials: DA
authors.lastname: Kass
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D004285:Dogs; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000494:pharmacology*; D010101:Oxygen Consumption; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000109:Acetylcholine