title: Restoration of normal reflex responses to orthostatic stress during felodipine therapy in congestive heart failure.
abstract: The mechanisms underlying the abnormal responses to orthostatic stress in congestive heart failure are ill defined and little is known about the effects of specific therapy. In the present study intravascular pressures and plasma noradrenaline levels were measured in nine patients with heart failure subjected to 45 degrees and 90 degrees upright tilt. Studies were repeated during 4 weeks of vasodilator therapy with felodipine and again after felodipine withdrawal. Before the introduction of vasodilator therapy, tilt did not activate orthostatic reflexes despite significant reductions in left ventricular filling pressure and cardiac output. Thus, plasma noradrenaline, heart rate and systemic vascular resistance were unaffected and blood pressure fell. Felodipine resulted in a rapid and sustained improvement in left ventricular function but restoration of orthostatic reflexes was delayed and could be detected only after 48 h therapy. At this time, and during the subsequent 4 weeks, tilt-induced reductions in ventricular filling and cardiac output produced a normal rise in plasma noradrenaline and heart rate. A postural drop in blood pressure, however, was not averted because the direct action of felodipine on vascular smooth muscle prevented adrenergically-mediated increments in systemic vascular resistance. Felodipine withdrawal led to a prompt deterioration in left ventricular function. Orthostatic reflexes, however, were still intact 48 h later when tilt elicited a completely normal pattern of responses. These observations confirm that the abnormal responses to orthostatic stress in congestive heart failure are due principally to impairment of autonomic control mechanisms and are not related to the absence of venous pooling. Importantly the autonomic dysfunction is reversible with felodipine therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000328:Adult; D000368:Aged; D015736:Felodipine; D005260:Female; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009638:Norepinephrine / Q000097:blood; D011187:Posture; D012021:Reflex, Abnormal / Q000188:drug therapy / Q000209:etiology*
chemical_list: D009543:Nifedipine; D015736:Felodipine; D009638:Norepinephrine