Response of non-failing hypertrophic rat hearts to prostaglandin F2α

Anna Maria Krstic; Sarbjot Kaur; Marie-Louise Ward

doi:10.1016/j.crphys.2019.12.002

Response of non-failing hypertrophic rat hearts to prostaglandin F2α

Curr Res Physiol. 2019 Dec 27:2:1-11. doi: 10.1016/j.crphys.2019.12.002. eCollection 2020 Jun.

Authors

Anna Maria Krstic¹, Sarbjot Kaur¹, Marie-Louise Ward¹

Affiliation

¹ Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.

Abstract

Background: Prostaglandin F2α (PGF2α) has a positively inotropic effect on right ventricular (RV) trabeculae from healthy adult rat hearts, and may therefore be therapeutically useful as a non-catecholaminergic inotrope. These provide additional contractile support for the heart without the added energetic demand of increased heart rate, and are also suitable for patients with reduced β adrenergic receptor (β-AR) responsiveness, or impaired mitochondrial energy supply. However, the response of hypertrophied rat hearts to PGF2α has not previously been examined. Our aim was therefore to determine the effect of PGF2α on isolated perfused rat hearts with RV hypertrophy following induction of pulmonary artery hypertension.

Methods: Male Wistar rats (300 g) were injected with either 60 mg kg^-1 of monocrotaline (MCT, n = 10) or sterile saline as control (CON, n = 11). Four weeks post injection; hearts were isolated and Langendorff-perfused in sinus rhythm. Measurement of left ventricular (LV) pressure and the electrocardiogram were made and the response to 0.3 μM PGF2α was determined.

Results: PGF2α increased LV developed pressure in CON and in 60% MCT hearts, with no change in heart rate. However, 40% of MCT hearts developed arrhythmias during the peak inotropic response. For comparison, the response to 0.03 μM isoproterenol (ISO) was also investigated. Peak LV pressure developed sooner in response to ISO compared to PGF2α in both rat groups, although the inotropic response to ISO was reduced in MCT hearts. Analysis of fixed ventricular tissue confirmed that only RV myocytes were hypertrophied in MCT hearts. Our study showed that PGF2α was positively inotropic for healthy hearts, but found it generated arrhythmias in 40% of MCT hearts at the dose investigated. However, a more physiological dose of PGF2α may be a useful alternative without the added energetic cost of catecholaminergic inotropes.

Keywords: Langendorff-perfused hearts; Monocrotaline (MCT); Positive inotrope; Prostaglandin F2α (PGF2α); RV hypertrophy; β-adrenergic response.