title: Nitric oxide spares myocardial oxygen consumption through attenuation of contractile response to beta-adrenergic stimulation in patients with idiopathic dilated cardiomyopathy.
abstract: BACKGROUND
  The results of recent studies suggest that NO synthase may increase in the failing myocardium and that NO modulates the myocardial contractile response to beta-adrenergic stimulation. However, there are few data regarding the physiological role of NO in patients with heart failure. The aim of the present study was to address the role of NO in left ventricular (LV) contractile response to beta-adrenergic stimulation and corresponding oxygen expenditure in human heart failure.
  
  
  RESULTS
  We studied 15 patients with heart failure due to idiopathic dilated cardiomyopathy (mean ejection fraction 0.33). We examined LV contractility (E(max), the slope of end-systolic pressure-volume relation), LV external work (EW), myocardial oxygen consumption (MVO(2)), and mechanical efficiency (measured as EW/MVO(2)) with the use of conductance and coronary sinus thermodilution catheters before and during dobutamine (DOB) infusion via a peripheral vein (4. 8+/-0.3 microg. kg(-1). min(-1) IV). Heart rate was kept constant with atrial pacing. We carried out a similar protocol during the intracoronary infusion of the NO synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 200 micromol). DOB increased E(max), EW, and MVO(2) (by 77+/-17%, 39+/-5%, and 21+/-5%, respectively), leading to an increase in mechanical efficiency (25.4+/-3.1% to 29.6+/-4.1%). L-NMMA alone did not significantly change these variables. Although the concurrent infusion of DOB with L-NMMA increased E(max), EW, and MVO(2) (by 140+/-21%, 64+/-9%, and 35+/-5%, respectively) more than DOB alone, mechanical efficiency did not increase further (24.3+/-3.3% to 29.5+/-4.5%) because EW and MVO(2) increased in parallel. Conclusions-These data suggest that in patients with idiopathic dilated cardiomyopathy, endogenous NO spares MVO(2) through attenuation of LV contractile response to beta-adrenergic stimulation while maintaining LV energy-converting efficiency.
authors.affiliation: First Department of Internal Medicine Kobe University School of Medicine, Kobe, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Shinke
authors.forename: H
authors.initials: H
authors.lastname: Takaoka
authors.forename: M
authors.initials: M
authors.lastname: Takeuchi
authors.forename: K
authors.initials: K
authors.lastname: Hata
authors.forename: H
authors.initials: H
authors.lastname: Kawai
authors.forename: H
authors.initials: H
authors.lastname: Okubo
authors.forename: Y
authors.initials: Y
authors.lastname: Kijima
authors.forename: T
authors.initials: T
authors.lastname: Murata
authors.forename: M
authors.initials: M
authors.lastname: Yokoyama
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002306:Cardiac Volume / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000378:metabolism*; D003971:Diastole / Q000187:drug effects; D004280:Dobutamine / Q000008:administration & dosage*; D004734:Energy Metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D013599:Systole / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000008:administration & dosage
chemical_list: D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004280:Dobutamine