In vivo studies of myocardial beta-adrenergic receptor pharmacology in patients with congestive heart failure.
The functional importance of abnormalities in the myocardial beta-adrenergic receptor (BAR) pathway of patients with congestive heart failure (CHF) is not known. To address this issue, the inotropic, chronotropic, and lusitropic responses to BAR stimulation were studied in patients with CHF and in patients without cardiac disease. To evaluate inotropic responsiveness, dobutamine was infused directly into the left main coronary artery. The maximum inotropic response, as assessed by measurement of left ventricular +dP/dt, was markedly reduced in patients with CHF; however, the concentration-response curve for the effect of dobutamine was not shifted relative to that of normal subjects. The magnitude of the impairment in the inotropic response to intracoronary dobutamine was inversely related to resting plasma norepinephrine. Although there was no relation between resting plasma norepinephrine and any measure of hemodynamic function, the improvement in pump function that occurred with intracoronary dobutamine resulted in a rapid decrease in plasma norepinephrine. Preinfusion of the phosphodiesterase inhibitor, milrinone, into the coronary artery resulted in a significant increase in the response to intracoronary dobutamine. To evaluate chronotropic responsiveness, the heart rate responses to a graded infusion of isoproterenol and during maximal exercise on a cycle ergometer were determined. The isoproterenol dose causing a 25 beat/min increase in heart rate (ISO25) was significantly higher in patients with CHF than in normal subjects. Likewise, the heart rate at peak exercise was significantly reduced in patients with CHF, despite similar levels of plasma norepinephrine at peak exercise.(ABSTRACT TRUNCATED AT 250 WORDS)
Colucci
W S
WS
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
D003971:Diastole; D015444:Exercise; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D009411:Nerve Endings / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013268:Stimulation, Chemical
D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol