title: Impaired muscle metaboreflex-induced increases in ventricular function in heart failure.
abstract: We investigated to what extent heart failure alters the ability of the muscle metaboreflex to improve ventricular function. Dogs were chronically instrumented to monitor mean arterial pressure (MAP), cardiac output (CO), heart rate (HR), stroke volume (SV), and central venous pressure (CVP) at rest and during mild treadmill exercise (3.2 km/h) before and during reductions in hindlimb blood flow imposed to activate the muscle metaboreflex. These control experiments were repeated at constant heart rate (ventricular pacing 225 beats/min) and at constant heart rate coupled with a beta-adrenergic blockade (atenolol, 2 mg/kg iv) in normal animals and in the same animals after the induction of heart failure (HF, induced via rapid ventricular pacing). In control experiments in normal animals, metaboreflex activation caused tachycardia with no change in SV, resulting in large increases in CO and MAP. At constant HR, large increases in CO still occurred via significant increases in SV. Inasmuch as CVP did not change in this setting and that beta-adrenergic blockade abolished the reflex increase in SV at constant HR, this increase in SV likely reflects increased ventricular contractility. In contrast, after the induction of HF, much smaller increases in CO occurred with metaboreflex activation because, although increases in HR still occurred, SV decreased thereby limiting any increase in CO. At constant HR, no increase in CO occurred with metaboreflex activation even though CVP increased significantly. After beta-adrenergic blockade, CO and SV decreased with metaboreflex activation. We conclude that in HF, the ability of the muscle metaboreflex to increase ventricular function via both increases in contractility as well as increases in filling pressure are markedly impaired.
authors.affiliation: Dept. of Physiology, Wayne State Univ. School of Medicine, 540 East Canfield Ave., Detroit, MI 48201, USA. doleary@med.wayne.edu
authors.forename: Donal S
authors.initials: DS
authors.lastname: O'Leary
authors.forename: Javier A
authors.initials: JA
authors.lastname: Sala-Mercado
authors.forename: Robert A
authors.initials: RA
authors.lastname: Augustyniak
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hammond
authors.forename: Noreen F
authors.initials: NF
authors.lastname: Rossi
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Ansorge
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004285:Dogs; D005260:Female; D006321:Heart / Q000502:physiology*; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate; D008297:Male; D009200:Myocardial Contraction; D012018:Reflex / Q000502:physiology; D013318:Stroke Volume