Evaluation of cardiac beta 1-adrenergic sensitivity with dobutamine in healthy volunteers.
1. Evaluation of cardiac beta 1-adrenergic sensitivity in heart failure should provide instructive therapeutic as well as prognostic information. We set up a non-invasive test in healthy volunteers to evaluate beta 1-adrenergic reactivity using dobutamine as a preferential agonist. 2. The range of i.v. bolus doses was 3.2 to 12.2 micrograms kg-1. The test was well tolerated. The parameters that were most sensitive and best correlated to dobutamine doses were systolic blood pressure and the rate-corrected electromechanical systole (QS2i). The reproducibility of the test over 48 h and over 1 month was satisfactory for most parameters, with a mean variation coefficient ranging from 9 to 26%, and was better for QS2i than for heart rate. 3. Slope of log dose-response for heart rate and QS2i was similar with dobutamine and with isoprenaline, corresponding to stimulation of the same type of beta-adrenergic receptors (beta 1-subtype). This result was obtained despite a higher vagal stimulation with dobutamine. We conclude that the left ventricular contractile response assessed by QS2i provided the best parameter for evaluation of beta 1-adrenergic cardiac effects either with dobutamine or with isoprenaline. 4. In heart failure patients such a dobutamine test should allow separation of altered contractility and beta-adrenergic desensitization, since alteration of inotropic response to dobutamine should depend on both altered contractile function and adrenergic desensitization but heart rate response should only depend on the latter phenomenon.
Pousset
F
F
Pharmacology Department, Hôpital Pitié-Salpétrière, Paris, France.
Chalon
S
S
Thomaré
P
P
Diquet
B
B
Lechat
P
P
D000328:Adult; D000704:Analysis of Variance; D002303:Cardiac Output, Low / Q000378:metabolism; D004280:Dobutamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects* / Q000378:metabolism; D015203:Reproducibility of Results
D018342:Receptors, Adrenergic, beta-1; D004280:Dobutamine; D007545:Isoproterenol