The α-MSH analogue AP214 attenuates rise in pulmonary pressure and fall in ejection fraction in lipopolysaccharide-induced systemic inflammatory response syndrome in pigs

Summary Background: The effect of an α‐melanocyte stimulating hormone (α‐MSH) analogue (AP214) on experimentally endotoxin‐induced systemic inflammatory response syndrome (SIRS) was studied, because α‐MSH in rodent models has shown promise in attenuating inflammatory response markers and associated organ damage in SIRS. SIRS is associated with considerable morbidity and mortality. Consequently, new treatment modalities are still warranted to address the different aspects of the pathophysiological process. Methods: SIRS was induced by lipopolysaccharide (LPS) (Escherichia coli endotoxin) infusion in anaesthetized Danish Landrace pigs (20–25 kg). The pigs received an α‐MSH analogue (AP214) or saline as a bolus at the initiation of the LPS infusion. The hemodynamic response was registered as well as echocardiographic indices of left ventricular function. Results: The cardiovascular response was recorded together with echocardiographic indices of left ventricular function in control and in intervention animals. AP214 reduced the early peak in pulmonary pressure and pulmonary vascular resistance by approximately 33%. Furthermore, AP214 prevented the decline in left ventricular fractional shortening as observed in the control group. Mean change and standard deviation in fractional shortening (ΔFS) in control group: ‐ 7·3 (4·7), AP214 (low dose): 0·9 (8·2) and AP214 (high dose) 4·1 (6·0), P