Effects of flestolol, an ultra-short acting beta-adrenoceptor antagonist, on hemodynamic changes produced by treadmill exercise or isoprenaline stimulation in conscious dogs.
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| Abstract |
The beta-blocking activity of flestolol was established during increasing isoprenaline infusions and during graded physical exercise in conscious, chronically instrumented dogs. After a control cycle, flestolol was infused at three doses (1, 2.67, and 10 micrograms/kg/min). Flestolol has an extremely short half-life, demonstrated by an 83% loss of effect within 25 min. Thus, flestolol allows easy titration of the effect, which might be a valuable property for its use in the treatment of critically ill patients. Due to the difference between pure beta-adrenergic stimulation and the much more complex regulation of circulation during exercise, the hemodynamic response to flestolol elicited marked differences between both set ups. Flestolol shifted the dose-response curves of isoprenaline-induced changes in heart rate, positive left ventricular dp/dtmax, and diastolic arterial pressure dose dependently to the right, while its main effect during exercise was a decrease in positive left ventricular dP/dtmax. Thus, testing of beta-adrenoceptor blockers using isoprenaline-induced tachycardia leads to an overestimation of potency and therefore is not appropriate to predict the clinical efficacy of these drugs to prevent stress- or exercise-induced increases in heart rate and hence myocardial oxygen-demand.
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| Authors | J G Grohs, G Fischer, G Raberger |
| Journal | Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 15 Issue 2 Pg. 175-81 (Feb 1990) ISSN: 0160-2446 [Print] United States |
| PMID | 1689410 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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