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Effects of beta-adrenergic agents on systolic and diastolic myocardial function in patients with and without heart
1Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Insights
Beta-adrenergic agonists and antagonists impact heart function. While direct effects are hard to measure in patients, intracoronary infusion and pressure-volume analysis show promise for evaluating these agents in heart failure.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Cyclic AMP is crucial for myocardial systolic and diastolic function.
- The adrenergic nervous system significantly influences left ventricular function via beta-adrenergic receptors.
- Evaluating direct myocardial effects of beta-adrenergic agents in patients presents challenges due to technical and confounding factors.
Purpose of the Study:
- To discuss strategies for evaluating the direct myocardial actions of beta-adrenergic agents in patients.
- To explore the effects of beta-adrenergic agonists and antagonists on myocardial function, particularly in heart failure.
Main Methods:
- Direct intracoronary drug infusion.
- Analysis of left ventricular pressure-volume relationships.
- In vitro studies demonstrating effects of beta-adrenergic agents.
Main Results:
- Beta-adrenergic agonist inotropic action is often attenuated in heart failure due to desensitization, but can still improve pump function.
- Preliminary data suggest dobutamine (agonist) accelerates isovolumic relaxation.
- Preliminary data suggest esmolol (antagonist) slows isovolumic relaxation.
Conclusions:
- Direct intracoronary infusion and pressure-volume analysis are promising methods for studying beta-adrenergic agents' myocardial effects.
- Further research is needed to confirm effects on diastolic performance and potential attenuation in heart failure patients.
Abstract:
Cyclic AMP plays a central role in modulating systolic and diastolic myocardial function. Consequently, the adrenergic nervous system, acting through myocardial beta-adrenergic receptors, very likely plays a significant role in regulating left ventricular systolic and diastolic function. Theoretically, beta-adrenergic agonists and antagonists may further modify myocardial systolic and diastolic function. Although the effects of beta-adrenergic agents are clearly demonstrable in vitro, it has been more difficult to evaluate the direct myocardial effects of beta-adrenergic agents in patients. These difficulties are related both to technical aspects of the measurement of systolic and diastolic parameters and to the potentially confounding effects of secondary nonmyocardial drug actions and reflex-mediated changes in myocardial and/or vascular adrenergic activity. A number of strategies for evaluating the direct myocardial actions of beta-adrenergic agents are discussed. Two promising approaches are the use of direct intracoronary drug infusion and the analysis of left ventricular pressure-volume relationships. The positive inotropic action of beta-adrenergic agonists is substantially attenuated in many patients with left ventricular failure due to end-organ desensitization of the beta-adrenergic pathway. Nevertheless, a beta-adrenergic agonist may still cause a substantial improvement in left ventricular pump function in such patients. There is less information available regarding the effect of beta-adrenergic agonists on myocardial relaxation. Preliminary data from the intracoronary infusion of dobutamine suggest that isovolumic relaxation is accelerated. Conversely, preliminary data suggest that a beta-adrenergic antagonist, esmolol, causes a slowing of isovolumic myocardial relaxation. Further studies will be needed to determine whether these drug effects result in a significant alteration in hemodynamic performance during diastole, and to evaluate the possibility that beta-adrenergic-mediated myocardial relaxation is attenuated in patients with heart failure.