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CLINICAL STUDIES

Pulmonary blood flow alters nitric oxide production in patients undergoing device closure of atrial septal defects

^a Department of Pediatrics, University of California, San Francisco, San Francisco, California, USA

Manuscript received June 2, 1999; revised manuscript received September 21, 1999, accepted October 27, 1999.

Reprint requests and correspondence: Dr. Jeffrey R. Fineman, University of California, San Francisco, 505 Parnassus Avenue, Box 0106, M-680, San Francisco, California 94143-0106
jfineman{at}pedcard.ucsf.edu

OBJECTIVE

To determine the effect of pulmonary blood flow (Qp) on nitric oxide (NO) production in patients with increased Qp due to an atrial septal defect (ASD).

BACKGROUND

Alterations in pulmonary vascular NO production have been implicated in the development of pulmonary hypertension secondary to increased Qp. In vitro, acute changes in flow or shear stress alter NO production. However, the effect of Qp on lung NO production in vivo is unclear.

METHODS

Nineteen patients (2.4–61 years of age, median 17) with secundum ASD undergoing device closure were studied. Before, and 30 min after ASD closure, exhaled NO and plasma nitrate concentration were measured by chemiluminescence (NOA 280, Sievers, Boulder, Colorado).

RESULTS

Before ASD closure, all patients had increased Qp (Qp: systemic blood flow [Qs] of 2.0 ± 0.7) and normal mean pulmonary arterial pressure (13.4 ± 3.1 mm Hg). Atrial septal defect device closure decreased Qp from 6.0 ± 2.5 to 3.6 ± 1.3 L/min/m² (p < 0.05). Mean pulmonary arterial pressure was unchanged. Associated with the decrease in Qp, both exhaled NO (–22.1%, p < 0.05) and plasma nitrate concentrations (–17.9%, p < 0.05) decreased.

CONCLUSIONS

These data represent the first demonstration that acute changes in Qp alter pulmonary NO production in vivo in humans. Exhaled NO determinations may provide a noninvasive assessment of pulmonary vascular NO production in patients with congenital heart disease. Potential correlations between exhaled NO, pulmonary vascular reactivity and pulmonary hypertension warrant further study.

Abbreviations and Acronyms   ASD = atrial septal defect   cGMP = guanisone 3',5'-cyclic monophosphate   eNOS = endothelial NO synthase   NO = nitric oxide   NOx = nitrate   Qp = pulmonary blood flow   Qs = systemic blood flow   SD = standard deviation

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