An exaggerated hypoxic pulmonary vasoconstriction is essential for development of high-altitude pulmonary edema (HAPE). We hypothesized that susceptibility to HAPE may be related to decreased production of nitric oxide (NO), an endogenous modulator of pulmonary vascular resistance, and that a decrease in exhaled NO could be detected during hypoxic exposure. Therefore, we investigated respiratory tract NO excretion by chemiluminescence and pulmonary artery systolic pressure (Ppa,s) by echocardiography in nine HAPE-susceptible mountaineers and nine HAPE-resistant control subjects during normoxia and acute hypoxia (fraction of inspired oxygen [FI(O2)] = 0.12). The subjects performed oral breathing. Nasally excreted NO was separated from respiratory gas by suction via a nasal mask. In HAPE-susceptible subjects, NO excretion in expired gas significantly decreased (p < 0.05) during hypoxia of 2 h in comparison with normoxia (28 +/- 4 versus 21 +/- 2 nl/min, mean +/- SEM). In contrast, the NO excretion rate of control subjects remained unchanged (31 +/- 6 versus 33 +/- 6 nl/ min, NS). Nasal NO excretion did not differ significantly between groups during normoxia (HAPE-susceptible group, 183 +/- 16 nl/ min; control subjects, 297 +/- 55 nl/min, NS) and was not influenced by hypoxia. The changes in Ppa,s with hypoxia correlated with the percent changes in lower respiratory tract NO excretion (R = -0.49, p = 0.04). Our data provide the first evidence of decreased pulmonary NO production in HAPE-susceptible subjects during acute hypoxia that may contribute among other factors to their enhanced hypoxic pulmonary vascular response.
The phagocytic function and biokinetics of the hepatic reticuloendothelial system (RES) were evaluated using a 25-nm diameter colloid (NanocollTM) and a scintillation camera technique in opossums with obstruction of the pancreatic duct (group I) and additional obstruction of the common bile duct (group II). The liver net uptake curve was analysed using natural log regression. The regression curves proved to fit very well (r > 0.93) and a parameter R was calculated to describe the curves. In group I there was a slight but significant decrease in the RES function and no morphological change in the pancreas. In group II, RES function was significantly more suppressed than in group I. The opossums developed severe haemorrhagic pancreatitis. The results show that the regression parameter R is well suited to describe liver RES function, and suggest that a suppressed liver RES after biliary obstruction could be an important factor in the pathogenesis of biliary pancreatitis.
ObjectiveTo examine the relation between hepatic reticuloendothelial system (RES) dysfunction and the development of acute biliary pancreatitis. In an opossum model, the authors tested the hypothesis that RES blockade can turn the mild pancreatitis seen after pancreatic duct obstruction (PDO) into the severe form. Summary Background DataBiliary obstruction is considered the decisive event in gallstone pancreatitis. Suppression of the RES occurs during biliary obstruction. MethodsEighteen opossums were placed into three groups of six animals each: group A, RES blockade with -carrageenan; group B, PDO; and group C, PDO and RES blockade with carrageenan. The severity of pancreatitis was evaluated by enzyme serum levels and percentage of pancreatic tissue necrosis. RES capacity was measured by dynamic liver scintigraphy, and hepatic blood flow was documented using the hydrogen clearance technique. ResultsNo changes in hepatic blood flow occurred in groups A to C. RES capacity was suppressed in groups A and C; in group B, RES function remained unchanged. In group A, amylase and lipase levels remained normal, 3 Ϯ 1.9% of pancreatic tissue were necrotic. The animals in group B developed mild edematous pancreatitis with an increase in amylase and lipase levels and 15 Ϯ 10% of pancreatic necrosis. In group C, amylase and lipase increased significantly and histology revealed severe necrotizing pancreatitis, with 72 Ϯ 11% of necrotic areas. ConclusionsArtificial RES blockade can promote the progression from mild pancreatitis as observed after PDO to the severe necrotizing form of the disease. Thus, RES dysfunction resulting from biliary obstruction might be an important cofactor in the pathogenesis of bile-induced pancreatitis.Acute biliary pancreatitis is an inflammatory disease that varies in severity and outcome. Mild edematous pancreatitis usually results in morphologic and functional recovery, whereas severe necrotizing pancreatitis is often associated with multisystemic complications and a death rate of 10% to 50%. 1 The reason for this variety in manifestation is not known. The identification of factors determining the severity of acute pancreatitis is essential to improve the understanding of the pathophysiology of bile-induced pancreatitis and its complications.Obstruction of the terminal biliopancreatic ductal system is considered to be the triggering event in human gallstone pancreatitis. Opie, 2 in 1901, postulated that reflux of bile, caused by a gallstone impacted in a common terminal biliopancreatic duct, initiates the process of pancreatic inflammation. Today, most authors disagree with this socalled common channel theory, and not reflux of bile but simultaneous obstruction of the biliary and the pancreatic ducts and their pathophysiologic consequences are considered to be the determining factors in the development of severe pancreatitis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.