16. Lung Function and Nitric Oxide Production After Deep Hypothermic Circulatory Arrest in Chronic Cyanotic Neonatal Lambs

Mitsugi Nagashima*, Ulrich Stock*, Georg Nollert*, Jason Sperling*, Dominique Shum-Tim*, Shinichi Hatsuoka*, and John E. Mayer, Jr., Boston, MA

Objectives: The purpose of this study was to assess lung function and nitric oxide (NO) production after deep hypothermic circulatory arrest in a chronic cyanotic neonatal lamb model.

Methods: A chronic cyanosis model was surgically created in 7 lambs (4.7± 0.8 days old) by anastomosing the pulmonary artery (PA) to the left atrium (LA). Another 7 lambs underwent a sham operation (control). One week later, the animals underwent shunt takedown and cardiopulmonary bypass with 90 min of deep hypothermic circulatory arrest at 18° C. Cardiac index (CI), pulmonary vascular resistance index (PVRI), lung dynamic compliance (C_dyn), alveolar-arterial oxygen difference (AaDO₂), left atrial plasma nitrate/nitrite (NO metabolites) levels and pulmonary cyclic GMP production (concentration difference from LA to PA, D cGMP) were measured before bypass and at 1 hr and 2 hrs after reperfusion.

Results: The cyanosis model consistently produced significantly lower arterial oxygen tension (34.8± 2.3 vs 93.1± 8.8 torr in control, p<.01) and Qp/Qs (0.6± 0.1 vs 1.0± 0.0 in control, p<.01) than the control model. Lung function, plasma NO metabolites and D cGMP are shown in the Table. Postoperative PVR was significantly lower in the cyanosis group than in controls, although cardiopulmonary bypass with deep hypothermic circulatory arrest significantly elevated PVR in both cyanotic and control animals. Repeated measured ANOVA revealed a tendency to higher NO metabolite levels in the cyanotic animals (p=0.08).

Conclusion: Chronic cyanosis does not result in reduced pul-monary function after deep hypothermic arrest in neonatal lambs and is associated with lower PVR. The mechanism may involve the NO-cGMP pathway.

 

	Cyanosis Baseline	Cyanosis 1 hr rep	Cyanosis 2 hr rep	Control Baseline	Control 1 hr rep	Control 2 hr rep
Cdyn (ml/H2O)	7.7± 0.5	4.5± 0.5*	4.2± 0.2*	7.6± 0.8	6.2± 0.9*	4.8± 0.4*
AaDO2 (mmHg)	-	315± 54	415± 53	178± 27	258± 54	346± 28*
CI (L/min/m2)	2.9± 0.2	2.8± 0.1	2.3± 0.1	2.5± 0.5	2.5± 0.2	2.3± 0.2
PVRI (Wood.Units)	4.9± 1.0	5.6± 1.2+	6.8± 0.8*+	4.3± 0.5	8.7± 1.0*	9.5± 0.6*
NO (m mol/ml)	6.0± 0.7	7.1± 0.9*	5.5± 0.6	4.4± 0.9	4.7± 0.6	4.4± 0.6
D cGMP(pmol/ml)	-2.2± 1.5	-2.2± 1.4	7.2± 2.9*	-2.7± 1.7	-4.9± 2.3	2.0± 1.9

 

C_dyn = lung dynamic compliance; AaDO₂= alveolar-arterial oxygen difference; CI = cardiac index; PVRI = pulmonary vascular resistance index; NO= nitric oxide; D cGMP = pulmonary cyclic GMP production. Data are mean ± SE; *p<.05 vs baseline within the group; +p<.05 vs Control