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Effects of low-dose adrenomedullin on cardiac function and systemic haemodynamics in man
R Del Bene1, C Lazzeri, G Barletta
1Sezione di Ecografia Cardiovascolare, Azienda Ospedaliera Careggi, Firenze, Italy.
Insights
Low-dose adrenomedullin (ADM) administration in healthy individuals significantly improved cardiac function and reduced vascular resistance. These findings highlight ADM's vasodilating effects and potential therapeutic role in cardiovascular conditions.
Area of Science:
- Cardiovascular Physiology
- Endocrinology
- Pharmacology
Background:
- Adrenomedullin (ADM) is a peptide hormone with known vasodilatory properties.
- Understanding ADM's cardiovascular effects at physiological levels is crucial for potential therapeutic applications.
Purpose of the Study:
- To evaluate the cardiovascular and systemic hemodynamic effects of low-dose adrenomedullin (ADM) in healthy human subjects.
- To assess ADM's impact on cardiac function, vascular distensibility, and key hemodynamic parameters.
Main Methods:
- A placebo-controlled, cross-over study involving six healthy subjects.
- Echocardiography was used to assess cardiac volumes and function (systolic and diastolic).
- Systemic hemodynamics, carotid artery distension, and plasma cyclic adenyl monophosphate (cAMP) levels were measured.
Main Results:
- ADM administration significantly increased plasma ADM and cAMP levels.
- Key findings include decreased left ventricular (LV) systolic diameter and systemic vascular resistance.
- Improvements observed in LV posterior wall thickening, ejection fraction, cardiac index, atrial emptying fraction, and carotid artery distension.
Conclusions:
- ADM exerts significant cardiovascular effects in humans at physiological plasma concentrations.
- The primary mechanism appears to be vasodilation, leading to reduced afterload and improved cardiac performance.
- ADM demonstrates potential as a therapeutic agent for cardiovascular diseases due to its beneficial hemodynamic profile.
Abstract:
The cardiovascular effects of low-dose adrenomedullin (ADM, 1, 2 and 3 pmol kg-1 min-1 for 30 min each) were evaluated in six healthy subjects in a placebo controlled, cross-over study by determining cardiac volumes, systolic and diastolic function (echocardiography) and systemic haemodynamics before, during and after ADM or placebo. High-resolution ultrasound was used to evaluate changes in carotid artery distension. ADM caused a +85% increment in its plasma levels and significantly increased plasma cyclic adenyl monophosphate (cAMP). Compared with placebo, ADM induced significant decrements in left ventricular (LV) systolic diameter and systemic vascular resistance, and increments in LV posterior wall thickening, ejection fraction and cardiac index. Right and left atrial emptying fraction and carotid artery distention increased. LV diastolic function, heart rate, and plasma renin activity did not change, whereas packed cell volume increased. These results indicate that ADM influences cardiovascular function and systemic haemodynamics at physiological plasma levels in man mainly because of its vasodilating activity, leading to reduced afterload.