title: Increased extravascular forces limit endothelium-dependent and -independent coronary vasodilation in congestive heart failure.
abstract: OBJECTIVE
  The increase in coronary blood flow (CBF) in response to endothelium-dependent vasodilators is reduced in congestive heart failure (CHF) suggesting endothelial dysfunction. However, increases in extravascular compressive forces secondary to elevated left ventricular diastolic pressure (LVEDP) in CHF might contribute to this abnormality.
  
  
  METHODS
  We measured CBF responses to intracoronary doses of the endothelium-dependent vasodilators acetylcholine (ACH) and bradykinin (BK) and the endothelium-independent vasodilator sodium nitroprusside (SNP) in the same eight dogs before (control) and after CHF was produced by 23+/-3 days of rapid ventricular pacing. In five of the dogs with CHF the zero-flow pressure (P(zf)), which reflects extravascular compressive forces in the maximally vasodilated coronary circulation (adenosine) was measured and found to strongly correlate with LVEDP (r=0.91). Coronary vascular resistance (CVR) at each concentration of vasodilator before and after the development of CHF was corrected for estimated coronary back pressure: CVR=(P(Ao)-LVEDP)/CBF, where P(Ao) is mean aortic pressure.
  
  
  RESULTS
  CHF resulted in a significant decrease in CBF and increase in heart rate and LVEDP compared to control (P<0.05). The CBF responses to ACH, BK and SNP were all significantly reduced in the failing hearts (P<0.01). However, after correction for the elevated LVEDP in CHF, the response of CVR to the endothelium-dependent vasodilators was not different from normal.
  
  
  CONCLUSIONS
  These findings suggest that endothelium mediated vasodilation is preserved in CHF, but that increased extravascular compressive forces act to limit the increase in CBF.
authors.affiliation: Department of Medicine, Division of Cardiology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Traverse
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Crampton
authors.forename: S
authors.initials: S
authors.lastname: Voss
authors.forename: R J
authors.initials: RJ
authors.lastname: Bache
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D023421:Models, Animal; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine; D001920:Bradykinin