Inhibition of nitric oxide synthesis improves left ventricular contractility in neonatal pigs late after cardiopulmonary bypass

Abstract

BACKGROUND Following neonatal open heart surgery a nadir occurs in left ventricular function six to 12 hours after cardiopulmonary bypass. Although initiated by intraoperative events, little is known about the mechanisms involved. OBJECTIVE To evaluate the involvement of nitric oxide in this late phase dysfunction in piglets. DESIGN Piglets aged 2 to 3 weeks (4–5 kg) underwent cardiopulmonary bypass (1 h) and cardioplegic arrest (0.5 h) and then remained ventilated with inotropic support. Twelve hours after bypass, while receiving dobutamine (5 μg/kg/min), the left ventricular response to non-selective nitric oxide synthase inhibition (l-N^G-monomethylarginine (l-NMMA)) was evaluated using load dependent and load independent indices (E_es, the slope of the end systolic pressure–volume relation; M_w, the slope of the stroke work–end diastolic volume relation; [dP/dt_max]_edv, the slope of the dP/dt_max–end diastolic volume relation), derived from left ventricular pressure–volume loops generated by conductance and microtip pressure catheters. RESULTS 10 pigs received 7.5 mg l-NMMA intravenously and six of these received two additional doses (37.5 mg and 75 mg). E_es (mean (SD)) increased with all three doses, from 54.9 (40.1) mm Hg/ml (control) to 86.3 (69.5) at 7.5 mg, 117.9 (65.1) at 37.5 mg, and 119 (80.4) at 75 mg (p < 0.05). At the two highest doses, [dP/dt_max]_edv increased from 260.8 (209.3) (control) to 470.5 (22.8) at 37.5 mg and 474.1 (296.6) at 75 mg (p < 0.05); and end diastolic pressure decreased from 16.5 (5.6) mm Hg (control) to 11.3 (5.0) at 37.5 mg and 11.4 (4.9) at 75 mg (p < 0.05). CONCLUSIONS In neonatal pigs 12 hours after cardiopulmonary bypass with ischaemic arrest, low dose l-NMMA improved left ventricular function, implying that there is a net deleterious cardiac action of nitric oxide at this time.