Journal of Critical Care, Vol 15, No 4 (December), 2000: pp 137-141 137 Pur pose : An impaired generation of cGMP may ac- count for the pulmonary hypertension seen in acute lung injury (ALI). We investigated the hemodynamic changes and the plasma levels of cGMP during air em- bolism-induced ALI in two different models: venous air infusion (VAI) and massive air embolism (MAE). Mat er ials and Methods : After a baseline hemodynamic evaluation, anesthetized dogs received a VAI (0.2 mL/kg/min, n = 10) or a bolus of air (MAE, 2.5 mL/kg, n = 10) intravenously.A group of control dogs (n = 5) received no further treatment. Hemodynamic evalua- tion was performed 5 to 60 minutes after the VAI was initiated or after the MAE. Blood samples were drawn for plasma cGMP determinations. Results : The VAI increased the pulmonary artery pres- sure (by 181%, P  .05) after 15 minutes of air infu- sion without changing the cardiac index. The MAE in- creased the pulmonary artery pressure (by 252%) and decreased the cardiac index (by 31%) 5 minutes after the air injection (both P  .05). These variables re- turned to baseline 15 to 30 minutes thereafter. The cGMP concentrations remained unaltered during the VAI. In contrast, cGMP levels increased 26% (P  .05) by 15 minutes after the MAE and returned to basal levels thereafter. Conclusion : These findings suggest that a lack of in- crease in the production of the cGMP may account for the pulmonary hypertension seen in air embolism- induced ALI. Additionally, the small increase in cGMP levels after the MAE may reflect the more severe he- modynamic derangement in this setting. Copyright © 2000 by W.B. Saunders Company Plasma cGMP Levels in Air Embolism-Induced Acute Lung Injury Jose Eduardo Tanus-Santos, Wladimir Mignone Gordo, Maira Cittadino, and Heitor Moreno, Jr A CUTE LUNG INJURY (ALI) encompasses a variety of clinical and experimental condi- tions having pulmonary hypertension as a hall- mark. 1 In this regard, increased levels of circulat- ing or local vasoconstrictors may be the cause for the pulmonary hypertension seen in this condition. 2 Although other complex mechanisms also operate in ALI, a shift of net pulmonary vascular smooth muscle tone in favor of vasoconstriction may result from an impairment of vasorelaxant mecha- nisms. 2,3 Previous studies have clearly demonstrated that air embolism damages the vascular endothelium and produces ALI and endothelial dysfunction. 2,4,5 Though little is known of the mechanisms under- lying pulmonary embolism-induced vascular in- jury, disturbances of generation and metabolism of vasoconstrictors are involved in this condition. 3 On the other hand, increased levels of natriuretic pep- tides (NP), which are vasodilator peptides secreted by the heart in increased amounts during right ven- tricular overload, 6,7 were described during ALI, probably reflecting an adaptive mechanism to re- duce pulmonary hypertension. 8,9 Interestingly, the plasma levels of these peptides were correlated pos- itively with the pulmonary artery pressure and with the pulmonary vascular resistance, thus suggesting that they could reduce the afterload and maintain the cardiovascular homeostasis during right ven- tricule overload. 7 Because the second messenger for the physiologic activity of NP is cyclic 3',5'- guanosine monophosphate (cGMP), a crucial me- diator in the regulation of pulmonary vascular re- sistance, 10 increased plasma levels of cGMP were closely associated with increased concentrations of NP, so that cGMP levels reflect the activity of NP. 11 Because previous studies have found that in- creased cGMP levels relate to the severity of the hemodynamic profile in patients with pulmonary hypertension, 12,13 we investigated the hemody- namic changes and the plasma levels of cGMP dur- ing the ALI and pulmonary hypertension in two an- imal models of venous air embolism with distinguished hemodynamic profiles 14,15 : venous air infusion (VAI) and massive air embolism (MAE). Furthermore, because air embolism alters the vasoregulatory function of the pulmonary vas- cular endothelium, 2 we hypothesized that a lack of increase in the production and release of cGMP could account, at least in part, for the pulmonary hypertension in air embolism-induced ALI. From the Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Sao Paulo, Brazil. In this study,J.E. Tanus-Santos and W.M. Gordo were sup- ported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP,SP,Brazil); and H. Moreno Jr. was supported by Conselho Nacional de Pesquisa (CNPq, Brazil). Received April 7, 2000. Accepted May 5, 2000. Address reprint requests to Heitor Moreno, Jr, MD, PhD, De- partment of Pharmacology, Faculty of Medical Sciences, State University of Campinas, PO Box 6111, 13083-970 Campinas, São Paulo, Brazil. Copyright © 2000 by W.B. Saunders Company 0883-9441/00/1504-0003$10.00/0 doi: 10.1053/jcrc.2000.19229