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Editor,—I read with interest the leading article on hepatopulmonary syndromes (
) . The author describes explicitly the various associations between the liver and lung disorders. Several clinical studies and autopsy findings have demonstrated a 20% higher prevalence of pulmonary hypertension in patients with advanced liver disease and portal hypertension, the histological findings of which show features similar to those seen in pulmonary hypertension from other causes.1 2 However, the underlying mechanism(s) responsible for pulmonary hypertension in these patients is not known. It has been recently hypothesised that increased circulating levels of noradrenaline (NA) or increased activity of α1 adrenergic receptors in the pulmonary arteries can produce excessive pulmonary vasoconstrictor and proliferative responses leading to pulmonary hypertension.3
It is generally believed that pulmonary hypertension results from defective hepatic elimination of a vasoconstrictive agent produced in the splanchnic territory which reaches the pulmonary arteries through porto-systemic shunts.4 The mesenteric organs produce about 50% of the total NA present in the human body5which is rapidly metabolised by liver parenchymal cells to vanillylmandelic acid before it reaches the systemic circulation.5-7 Following hepatectomy, circulating levels of NA have been shown to be increased by up to 10-fold in experimental animals8 while patients with liver cirrhosis or those undergoing extracorporeal hepatic resection or liver transplantation have levels of circulating NA up to 2.6-fold greater.9 10Increased pulmonary vascular resistance has often been observed during the anhepatic phase of liver transplantation8 while several studies have demonstrated that pulmonary hypertension often resolves completely in patients with liver cirrhosis following liver transplantation.11 Formation of a portocaval shunt without liver cirrhosis has also been shown to produce severe pulmonary hypertension.12 It has been demonstrated recently that hepatectomy produces a sharp increase in pulmonary vascular resistance which correlates positively with pulmonary arterial NA levels.8
Defective hepatic metabolism by diseased liver parenchymal cells could greatly increase circulating levels of NA. The resulting portal hypertension and porto-systemic shunt also transfers large amounts of NA directly from the mesenteric bed to the systemic and pulmonary circulation. High circulating levels of NA could then stimulate α1 adrenergic receptors present in the pulmonary arteries to produce excessive pulmonary vasoconstrictor and proliferative responses leading to pulmonary hypertension. Increased NA levels could also explain the association of increased cardiac output noted in patients with porto-pulmonary hypertension. α1Antagonists or drugs that rapidly metabolise circulating levels of NA could therefore prevent the development of pulmonary hypertension in patients with advanced liver disease and portal hypertension.
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