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

Background-Following neonatal open heart surgery a nadir occurs in left ven tricular function six to 12 hours after cardiopulmonary bypass. Although in itiated by intraoperative events, Little is known about the mechanisms invo lved. Objective-To evaluate the involvement of nitric oxide in this late ph ase 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 ino tropic support. Twelve hours after bypass, while receiving dobutamine (5 mu g/kg/min), the left ventricular response to non-selective nitric oxide syn thase inhibition (I-N-G-monomethylarginine (1-NMMA)) was evaluated using lo ad dependent and load independent indices (E-es, the slope of the end systo lic pressure-volume relation; M-w, the slope of the stroke work-end diastol ic volume relation [dP/dt(max)](edv) the slope of the dP/dt(max)-end diasto lic volume relation), derived from left ventricular pressure-volume loops g enerated by conductance and microtip pressure catheters. Results-10 pigs received 7.5 mg 1-NMMA intravenously and six of these recei ved two additional doses (37.5 mg and 75 mg). E-es (mean (SD)) increased wi th all three doses, from 54.9 (40.1) nun 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) nun 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 isc haemic arrest, low dose 1-NMMA improved left ventricular function, implying that there is a net deleterious cardiac action of nitric oxide at this tim e.