Prostaglandin E2 does not attenuate adrenergic-induced cardiac contractile response

Area of Science:

• Cardiovascular Physiology
• Inflammation Research
• Pharmacology

Background:

• Systemic inflammation is implicated in heart failure development.
• Prostaglandin E2 (PGE2) was hypothesized to impair cardiac function by desensitizing the heart to isoprenaline.
• Previous studies suggested PGE2 mediates inflammation-induced cardiac dysfunction in mice.

Purpose of the Study:

• To investigate the role of PGE2 in regulating cardiac function in human heart tissue.
• To determine if PGE2 desensitizes the human heart to catecholamine stimulation.
• To compare the effects of PGE2 on cardiac function in human and murine models.

Main Methods:

• Human atrial and ventricular trabeculae were isolated from surgical and explanted failing hearts.
• Muscle strips were electrically stimulated to measure isometric force development.
• The effects of PGE2 on contractility and beta-adrenoceptor-mediated responses to norepinephrine, epinephrine, and isoprenaline were assessed in human and murine tissues.

Main Results:

• PGE2 exposure did not alter basal contractility in human atrial or ventricular trabeculae.
• PGE2 did not affect the sensitivity or efficacy of beta-adrenoceptor stimulation by catecholamines in human cardiac tissues.
• Contrary to expectations, PGE2 also failed to alter catecholamine inotropy in murine ventricular strips, despite confirming its vasoconstrictive activity in murine aortic rings.

Conclusions:

• The findings do not support a role for PGE2 in modulating catecholamine inotropic responses in the human heart.
• The previously suggested mechanism of PGE2-induced desensitization to isoprenaline was not replicated in human or murine cardiac preparations.
• This study suggests PGE2 is unlikely to be a key mediator of inflammation-induced cardiac dysfunction via catecholamine desensitization.