title: Pulmonary hemodynamics and endothelin levels in pacing-induced heart failure: during rest and exercise.
abstract: Elevated plasma levels of endothelin (ET) have been reported to accompany the development of heart failure (HF), and therefore, this potent vasoconstrictive peptide has been postulated to contribute to the altered pulmonary hemodynamics that occur in this disease process. The overall goal of this study was to examine more carefully the relationship between ET levels in the pulmonary system and pulmonary hemodynamics in the normal and HF states, during both rest and exercise. This study used a porcine model of chronic rapid pacing that has been shown in previous studies to produce left ventricular dysfunction and neurohormonal system activation consistent with the syndrome of HF. Pigs (n = 10) were chronically instrumented to measure pulmonary and systemic hemodynamics, parenchymal flow, and ET content and to obtain blood samples from the pulmonary circuit in the conscious state. Measurements were performed in the normal control state and again following the development of pacing-induced HF (240 beats/min per 21 days), both at rest and during treadmill exercise (3 mph, 15 degrees incline, 12 minutes). With HF, under ambient resting conditions, a threefold increase in pulmonary plasma ET occurred and was accompanied by a fivefold increase in pulmonary vascular resistance. During treadmill exercise, pulmonary plasma ET and pulmonary vascular resistance remained elevated in the HF group when compared with the normal state and were associated with a sixfold decrease in pulmonary parenchymal flow. Pulmonary parenchymal ET content was increased with HF when compared with values for normal control subjects (8.5 +/- 0.6 vs 5.6 +/- 0.8 fmol ET/mg protein, P < .05). Thus, the findings of this study suggest that in this model of HF, increased ET within the pulmonary circuit contributed to abnormalities in resistive properties and parenchymal flow.
authors.affiliation: Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Kribbs
authors.forename: M J
authors.initials: MJ
authors.lastname: Clair
authors.forename: R S
authors.initials: RS
authors.lastname: Krombach
authors.forename: J W
authors.initials: JW
authors.lastname: Hendrick
authors.forename: P B
authors.initials: PB
authors.lastname: Thomas
authors.forename: A T
authors.initials: AT
authors.lastname: Keever
authors.forename: W V
authors.initials: WV
authors.lastname: Houch
authors.forename: R
authors.initials: R
authors.lastname: Mukherjee
authors.forename: F G
authors.initials: FG
authors.lastname: Spinale
mesh_terms: D000818:Animals; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D016232:Endothelins / Q000097:blood*; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics; D008168:Lung / Q000503:physiopathology*; D008297:Male; D010805:Physical Conditioning, Animal; D011652:Pulmonary Circulation; D013552:Swine; D014655:Vascular Resistance
chemical_list: D016232:Endothelins