We studied the effects of inhibition of nitric oxide (NO) (endothelium-derived relaxation factor) synthase in combination with alpha and beta adrenergic receptor blockade on pulmonary vascular tone during exercise. In paired studies, we exercised sheep on a treadmill at a speed of 4 mph, and measured blood flow and pressures across the pulmonary circulation with and without inhibition of NO synthase (Nw-nitro-L-arginine 20 mg/kg intravenous Ii.v.I), alpha receptor blockade (phentolamine 5 mg i.v.), beta receptor blockade (propranolol 1 mg i.v.), and combined alpha and beta receptor blockade. Activation of both types of adrenergic receptors occurs with exercise, and because increased release in NO is hypothesized to occur during exercise, these studies were designed to determine the magnitude of effect and interactions of these competing dilator and constrictor influences. We found that inhibition of NO synthase raised pulmonary vascular resistance (PVR) at rest and that, although a reduction in PVR occurred with exercise from this new baseline, vasoconstriction persisted. Combined beta blockade and NO synthase inhibition unmasked unopposed alpha vasoconstriction; PVR rose at rest and continued to rise with exercise; and mean pulmonary arterial pressures approached very high levels, 43.8±4.4 cmH20. Using a distal wedged pulmonary artery catheter technique, most of the vasoconstriction was found to be in vessels upstream from small pulmonary veins. During exercise in sheep there appears to be a high degree of alpha and beta adrenergic-mediated tone in the pulmonary circulation. Endogenous production of NO actively dilates pulmonary vessels at rest and opposes potent alpha-mediated pulmonary vasoconstriction during exercise. (J. Clin.

In paired experiments, we exercised sheep at a constant rate of 4 mph on a treadmill and measured the hemodynamic effects of alpha receptor blockade (phentolamine 5 mg intravenously), beta receptor blockade (propranolol 1 mg intravenously), and combined alpha and beta receptor blockade. Beta blockade increased pulmonary vascular resistance (PVR) at rest and during steady-state exercise compared with control runs. PVR decreased slightly at rest with alpha blockade, but it was not different during exercise from that of control runs. Combined alpha and beta blockade restored PVR to that of control runs, showing that the vasoconstrictor effect of beta blockade was due to unopposed alpha receptor activation. In all sheep an early rapid decrease in PVR within the first 20 s of the onset of exercise was followed by a smaller, slower change over the next 40 to 240 s. The early decrease in PVR was unaffected by either alpha or beta receptor blockade, suggesting that it was due to recruitment of nonmuscular microvessels. We conclude that alpha and beta receptor activation occurs during exercise but that the net vasoactive effect is neutral. The changes in PVR during normal exercise are a combination of rapid recruitment of microvessels followed by slower vasodilation of resistance vessels.

Between October 1991 and October 1993, 17 AIDS patients (14 intravenous drug users, 3 sexually acquired) were commenced on percutaneous endoscopic gastrostomy (PEG) feeding in St James's Hospital. Indications were progressive weight loss related to severe anorexia, persistent oesophageal candidiasis (5) and absence of gag reflex (1). Two patients requested PEG tube removal after one week because of crampy abdominal pain without peritonitis. Five patients died from AIDS related infections within 6 weeks of PEG insertion. Ten patients were followed up for > 2 months (mean 5.2 months, range 2.5-15.5 months). In these 10 patients, 1 patient developed a PEG site infection which responded to topical antibiotics. There were no other complications. There was a significant (P < 0.001) increase in energy and protein intake at 2 months. Variant degrees of weight gain occurred in all patients (mean 2.6 kg) (P < 0.01). Small but significant increases in other anthropometric variables occurred. Patients who died within 6 weeks of PEG insertion were older, and had a lower serum albumin than the group who survived > 2 months (P < 0.01). A self-administered questionnaire demonstrated that the majority of patients found PEG feeding acceptable and preferable to nasogastric (NG) feeding.

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