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Biomedical subjects

A Y Butt

Publications and source records attributed to A Y Butt.

8 recordsLinked to original sources
PubMed1998

Treatment of pulmonary hypertension with the continuous infusion of a prostacyclin analogue, iloprost.

OBJECTIVE: To compare prostacyclin with an analogue, iloprost, in treatment of severe pulmonary hypertension. PATIENTS: Eight patients with severe pulmonary hypertension: primary in five, thromboembolic pulmonary hypertension in three. METHODS: All patients underwent right heart catheterisation. Mean (SEM) right atrial pressure was 9.9 (2.2) mm Hg, mean pulmonary artery pressure 67.4 (3.0) mm Hg, cardiac index 1.75 (0.13) l/min/m2 and mixed venous oxygen saturation 59.1(3.1)%. Continuous intravenous epoprostenol (prostacyclin, PGI2) or iloprost was given for phase I (three to six weeks); the patients were then crossed over to receive the alternate drug in an equivalent phase II. MAIN OUTCOME MEASURES: Exercise tolerance was measured at baseline and at the end of phase I and II with a 12 minute walk; distance covered, rest period, percentage drop in arterial oxygen saturation (delta Sao2%) and percentage rise in heart rate (delta HR%). RESULTS: Walking distance covered rose from (mean (SEM)) 407.5 (73) to 591 (46) m with PGI2 (p = 0.004) and to 602.5 (60) m while on iloprost (p = 0.008). Rest period decreased from 192 (73) seconds at baseline to 16 (16) seconds with PGI2 (p = 0.01) and to 58 (34) seconds with iloprost (p = 0.008). Delta HR% was 37.5(6)% at baseline, 35(3)% on PGI2, and 24(6)% on iloprost (p = 0.04). CONCLUSIONS: Both intravenous PGI2 and iloprost caused significant improvement in exercise tolerance. Iloprost offers an alternative to PGI2 treatment of severe pulmonary hypertension.

Adult↗
PubMed1998

Long-term intravenous prostaglandin (epoprostenol or iloprost) for treatment of severe pulmonary hypertension.

OBJECTIVE: To investigate the relation between the severity of pulmonary hypertension and the outcome of medical treatment. METHODS: 98 patients with primary pulmonary hypertension--nine (6%) with systemic disease and pulmonary hypertension and 39 (27%) with thromboembolic pulmonary hypertension--received medical treatment and were followed between 1982 and 1995. They were given long term intravenous prostaglandin treatment (either epoprostenol (n = 61) or iloprost (n = 13)) or conventional treatment with oral anticoagulants (n = 24) with or without calcium channel blockers. Event-free survival was measured to death or transplant surgery, or pulmonary thromboendarterectomy. RESULTS: Prognosis (hazard ratio) was affected by: New York Heart Association grade, 1.52 (95% confidence interval 1.11 to 2.09); mixed venous oxygen saturation (SvO2%), 0.97 (0.95 to 0.98); cardiac index, 0.72 (0.49 to 1.06); mean right atrial pressure, 1.04 (1.01 to 1.07); and pulmonary vascular resistance, 1.02 (1.00 to 1.04). The median event-free survival time of patients with SvO2 < 60% was 239 days (0 to 502) on conventional treatment (n = 22) and 585 days (300 to 870) on prostaglandin treatment (n = 42). No difference was seen in patients with SvO2 > or = 60% between conventional treatment and prostaglandin treatment, survival being 1275 days (732 to 1818; (n = 48)) and 986 days (541 to 1431; n = 30)), respectively. Capacity for pulmonary vasodilatation did not predict outcome of treatment. CONCLUSIONS: Continuous intravenous prostaglandins were more effective than anticoagulants, with or without calcium channel blockers, in prolonging survival in patients with right heart failure. In these patients a capacity to vasodilate did not predict outcome from medical treatment.

Adult↗
PubMed1995

Appetite suppressants and primary pulmonary hypertension in the United Kingdom.

OBJECTIVE: Amphetamine-like appetite suppressants, particularly fenfluramines, have been implicated in the aetiology of primary pulmonary hypertension. At one specialist centre in France 20% of patients with primary pulmonary hypertension had been exposed to fenfluramine. The prevalence of primary pulmonary hypertension associated with fenfluramines and other appetite suppressants in the United Kingdom is unknown. This study was performed to measure prior exposure to appetite suppressants in patients with primary pulmonary hypertension. SETTING: Heart lung transplantation centres in England. PATIENTS: United Kingdom residents with proven primary pulmonary hypertension referred for consideration of heart lung transplantation. METHODS: Case surveillance study, obtaining data from the hospital and general practitioner's notes and directly from the patients or their relatives. RESULTS: 55 patients were identified. Drug histories were available from hospital records in all patients, from the general practitioner's notes in 51, and from the patients or relatives in 44. Of these, 3 female patients had been exposed to appetite suppressants (2 fenfluramine, 1 diethylpropion): 2 have since died. In each case exposure was brief and apparently predated the development of symptoms by several years. CONCLUSIONS: Exposure of patients with severe primary pulmonary hypertension to fenfluramine and other appetite suppressants is uncommon in the United Kingdom unlike in France, where most of the cases associating primary pulmonary hypertension with fenfluramine use have originated. This may reflect more conservative prescribing of these agents in the United Kingdom.

Adult↗
PubMed1993

Impairment of pulmonary-artery endothelium-dependent relaxation in chronic obstructive lung disease is not due to dysfunction of endothelial cell membrane receptors nor to L-arginine deficiency.

1. Endothelium-dependent relaxation mediated by endothelium-derived relaxing factor (EDRF) or nitric oxide (NO), is impaired in pulmonary arteries (PA) of hypoxic patients with chronic obstructive lung disease (COLD). To determine the mechanisms responsible for this impairment, we compared the response of rings of isolated PA from 12 COLD patients and 8 controls to the endothelium-dependent vasodilators acetylcholine (ACh), adenosine diphosphate (ADP), and the calcium ionophore, A23187. The response of PA rings to the endothelium-independent nitro-vasodilator sodium nitroprusside (SNP) was also studied in both groups. The PA rings had been pre-contracted by the alpha-adrenoceptor agonist phenylephrine (PE). 2. Endothelium-dependent relaxation was significantly reduced in PA rings from COLD patients as compared with controls when tested with ACh (37.8 +/- 8.8% vs 73.4 +/- 7.9%), ADP (38.4 +/- 6.7% vs 80 +/- 5.6%), and the calcium ionophore, A23187 (35.8 +/- 6.1% vs 87 +/- 6.6%). Relaxation with SNP was, however, significantly greater in PA rings from COLD patients (99.4 +/- 0.6% vs 90.3 +/- 3.1%), as was the contractile response to PE (1.91 +/- 0.21 g vs 1.33 +/- 0.15 g). Pretreatment with the specific inhibitor of NO formation, NG-monomethyl-L-arginine (L-NMMA; 10(-4) M) significantly reduced the relaxation to ACh in all PA rings. This inhibition could be reversed by L-arginine (10(-3) M), the substrate for NO synthesis. Pretreatment with L-arginine alone, however, did not restore the impaired endothelium-dependent relaxation of PA rings from COLD patients. 3. We conclude that EDRF (NO) production is impaired in PA rings from COLD patients and that this impairment is neither due to endothelial receptors dysfunction nor a defect of L-arginine availability and/or transport. Our hypothesis is that the abnormality must lie within the biosynthesis pathway of NO from L-arginine, possibly involving the endothelial enzyme cell, NO synthase, the normal function of which might be altered by chronic hypoxia.

Acetylcholine↗
PubMed1993

In vitro pulmonary vasorelaxant effect of the phosphodiesterase inhibitor enoximone.

Enoximone is a phosphodiesterase inhibitor that has both positive inotropic and systemic vasorelaxant activities. The latter are mediated by an increase in vascular smooth muscle concentration of cyclic 3'5' guanosine monophosphate. However, the effect of enoximone on pulmonary vasoreactivity is not established. The authors, therefore, have studied its effect on endothelium-dependent relaxation mediated by the endothelium-derived relaxing factor nitric oxide (NO), as well as endothelium-independent relaxation of isolated porcine pulmonary arteries. Enoximone (10(-7) to 10(-4) M) caused a dose-dependent relaxation in all pulmonary arterial rings. This relaxation neither required the presence of the endothelium nor was affected by the addition of the inhibitor of NO synthase omega-nitro-L-arginine methyl ester (10(-4) M). Also, the vasorelaxant response of the rings to the endothelium-dependent vasodilator adenosine diphosphate (10(-10) to 10(-5) M) was not affected by pretreatment with enoximone. The authors conclude that enoximone is a potent vasodilator that relaxes pulmonary vascular rings through mechanisms independent of the endothelium. This endothelium-independent vasodilatory effect of enoximone makes it a potentially valuable drug for the treatment of pulmonary hypertension. This particularly applies to diseases in man where NO production by the endothelial cells is impaired.

Animals↗
PubMed1991

Impairment of endothelium-dependent pulmonary-artery relaxation in chronic obstructive lung disease.

BACKGROUND: Endothelial cells release endothelium-derived relaxing factor (EDRF) in a variety of vascular beds, including the pulmonary circulation. However, the role of EDRF-mediated pulmonary-artery relaxation in chronic hypoxic lung disease is unknown. METHODS: We studied endothelium-dependent relaxation mediated by EDRF in vitro in pulmonary arteries that had been obtained from 22 patients undergoing heart-lung transplantation for end-stage chronic obstructive lung disease. Control pulmonary arteries were obtained from 15 patients undergoing lobectomy for lung carcinoma who did not have evidence of other chronic lung disease. The responses of all vascular rings (external diameter, 1.2 to 3.4 mm) to the endothelium-dependent vasodilators acetylcholine and adenosine diphosphate were studied immediately after lung excision. RESULTS: Pulmonary arterial rings from the patients with chronic lung disease developed a greater tension (2.19 +/- 0.16 g) in response to phenylephrine (10(-6) M) than the rings from control patients (1.28 +/- 0.18 g, P less than 0.05). Inhibition of EDRF synthesis by treatment with NG-monomethyl-L-arginine (10(-4) M) eliminated this difference, increasing the tension in the rings from the controls (P less than 0.01) but not in those from the patients with chronic lung disease. Rings from control patients relaxed in response to cumulative doses (10(-10) to 10(-5) M) of acetylcholine (maximal relaxation, 81.3 +/- 3.9 percent) and adenosine diphosphate (maximal relaxation, 85.3 +/- 2.6 percent). By contrast, rings from patients with chronic obstructive lung disease achieved only 41.3 +/- 4.8 percent of maximal relaxation in response to acetylcholine (n = 32) and 49.4 +/- 5.5 percent in response to adenosine diphosphate (n = 24) (P less than 0.001, as compared with control rings). Rings from both the controls and the patients with chronic lung disease relaxed similarly in response to the endothelium-independent vasodilator sodium nitroprusside (10(-4) M). There was an inverse correlation between the degree of intimal thickening and the level of maximal relaxation of the rings from the patients with chronic lung disease (r = -0.60, P less than 0.001). Maximal relaxation was also related directly to the partial pressure of arterial oxygen before transplantation (r = 0.68, P less than 0.01) and inversely to the partial pressure of arterial carbon dioxide before transplantation (r = -0.55, P less than 0.01), but not to the forced expiratory volume in one second (r = 0.19, P not significant). CONCLUSIONS: Endothelium-dependent pulmonary-artery relaxation in vitro is impaired in arteries from patients with end-stage chronic obstructive lung disease. Such impairment may contribute to the development of pulmonary hypertension in chronic hypoxic lung disease.

Acetylcholine↗