No abstract

Patients with portal hypertension of varying etiology may develop pulmonary artery hypertension. In the present autopsy study, pulmonary and hepatic tissue was studied in 12 patients in whom pulmonary and portal hypertension coexisted. Plexogenic pulmonary arteriopathy was present in 10 patients, 7 of whom had coexistent thromboembolic lesions. One patient had isolated medial hypertrophy, which may be an early stage in the plexogenic category, whereas isolated thromboembolic pulmonary vascular disease was observed in one subject. Hepatic disease was consistent with alcoholic cirrhosis in seven patients, cryptogenic cirrhosis in four and extrahepatic portal hypertension without cirrhosis in one. Thrombocytopenia was present in all 10 patients whose platelet count was determined. This study suggests that pulmonary hypertension associated with portal hypertension commonly has a plexogenic appearance on histologic examination. However, thrombosis (whether embolic or in situ) may also contribute to vascular obstruction.

oseph priestley, one of the three scientists credited with the discovery of oxygen, described the death of mice that were deprived of oxygen. However, he was also well aware of the toxicity of too much oxygen, stating, "For as a candle burns much faster in dephlogisticated [oxygen-enriched] than in common air, so we might live out too fast, and the animal powers be too soon exhausted in this pure kind of air. A moralist, at least, may say, that the air which nature has provided for us is as good as we deserve." 1In this review we examine the remarkable mechanisms by which different organs detect and respond to acute changes in oxygen tension. Specialized tissues that sense the local oxygen tension include glomus cells of the carotid body, neuroepithelial bodies in the lungs, chromaffin cells of the fetal adrenal medulla, and smooth-muscle cells of the resistance pulmonary arteries, fetoplacental arteries, systemic arteries, and the ductus arteriosus. Together, they constitute a specialized homeostatic oxygen-sensing system. Although all tissues are sensitive to severe hypoxia, these specialized tissues respond rapidly to moderate changes in oxygen tension within the physiologic range (roughly 40 to 100 mm Hg in an adult and 20 to 40 mm Hg in a fetus) (Fig. 1).In fetal life, the pulmonary vascular bed has a high resistance to blood flow. Consequently, oxygenated blood returning from the placenta is diverted from the unventilated lungs and across the foramen ovale and ductus arteriosus. At birth, when air breathing begins, the lungs expand and oxygen levels rise. With reversal of fetal hypoxic pulmonary vasoconstriction, the pulmonary vessels dilate and the ductus arteriosus constricts, thereby establishing the transition from the fetal to the neonatal circulation.After birth, hypoxic pulmonary vasoconstriction remains important, because it reduces perfusion of poorly ventilated areas of lung, and in so doing it decreases the shunting of desaturated, mixed venous blood to the systemic circulation. Inhibition of hypoxic pulmonary vasoconstriction reduces the systemic arterial oxygen tension, particularly in small-airway disease. 2 Moreover, as was first demonstrated in humans in 1947, 3 the intensity of hypoxic pulmonary vasoconstriction depends on the severity and duration of alveolar hypoxia. 4,5 The endothelium produces vasodilators, such as nitric oxide and prostacyclin, and vasoconstrictors, such as endothelin and thromboxane A 2 ; these molecules from endothelial cells modulate hypoxic pulmonary vasoconstriction, but the ability of small pulmonary vessels to contract in response to hypoxia resides in their smooth-muscle cells. 6 Three sites in these cells are involved in the mechanism of hypoxic pulmonary vasoconstriction: the membrane, the sarcoplasmic reticulum, and the contractile apparatus.

Prostaglandins are naturally occurring substances with powerful vasoactive effects that are released from tissues during hypoxia or ischemia. Several workers have suggested that a prostaglandin may help to mediate the pulmonary vascular pressor response to alveolar hypoxia. To investigate this possibility, we have measured the pressor responses to hypoxia before and after prostaglandin synthesis antagonism with meclofenamate in eight anesthetized dogs, two groups of awake calves (n=10 and =5), and nine isolated, perfused rat lungs. In addition, synthesis was inhibited by the use of indomethacin in nine additional dogs. The stability of the pulmonary vascular response to repeated hypoxic challenges was demonstrated in nine other dogs. In each species and with both prostaglandin antagonists, the pulmonary pressor responses to hypoxia were significantly increased rather than reduced. We conclude that prostaglandins do not mediate the pulmonary vasoconstriction caused by hypoxia. The consistent increase observed suggests that hypoxic vasoconstriction stimulates prostaglandin synthesis, the net effect of which is pulmonary vasodilatation which opposes the constriction.

This study was conducted to identify and clarify the actions of pulmonary and systemic H1- and H2-receptors by utilizing specific histamine receptor antagonists. Histamine was infused in anesthetized dogs during control conditions, after H2-receptor blockade with metiamide, after H1-receptor blockade with chlorpheniramine, and after combined H1- and H2-receptor blockade. Histamine infusion, alone, induced marked systemic vasodilatation, pulmonary vasoconstriction, and transient increases in cardiac output and heart rate. H2-receptor blockade prevented the systemic vasocilatation and potentiated the pulmonary vasoconstriction induced by histamine. H1-receptor blockade augmented the systemic vasodilatation, prevented the pulmonary vasoconstriction, and increased the cardiac output and heart rate responses induced by histamine. Thus, H2-receptors appear to mediate the vasocilatation, tachycardia, and increased cardiac output induced by histamine, whereas H1-receptors appear to mediate the vasoconstrictor and the minimal cardiac depressent actions of histamine. Histamine stimulates only H1- and H2-receptors, since combined H1- and H2-receptor antagonism prevented almost all of the cardiovascular actions of histamine.