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T Higenbottam

Publications and source records attributed to T Higenbottam.

At least 37 records · Page 2Linked to original sources
PubMed1997

Nature and site of action of endogenous nitric oxide in vasculature of isolated pig lungs.

The site of action of endogenous and exogenous nitric oxide (NO) in isolated pig lungs was investigated by using arterial, double, and venous occlusions, which allowed precapillary, postcapillary, and venous segments to be partitioned into arterial, precapillary, postcapillary, and venous segments. NG-nitro-L-arginine (L-NNA; 10(-5) M) increased resistance in the arterial (35 +/- 6.6%. P = 0.003), precapillary (39.3 +/- 5.1%, P = 0.001), and venous (18.3 +/- 4.8%, P = 0.01) segments, respectively. Sodium nitroprusside (10(-5) M) NO (80 parts/million) reversed the effects of L-NNA. Total pulmonary vascular resistance fell with increasing flow, due to a fall in precapillary resistance and dynamic resistance, and was significantly lower than mean total resistance. L-NNA increased the resistances but did not alter the pattern of the pressure-flow relationships. It is concluded that, in isolated pig lungs, the effect of endogenous NO seems to be dependent on flow in the arterial segment and independent of flow in the precapillary segment, but variation of its release does not appear to be fundamental to accommodation to changes in steady flow.

Animals↗
PubMed1996

Nitric oxide and exercise in the horse.

1. The effects of exercise on the production rate of nitric oxide (NO) in exhaled air (VNO) and the effects of inhaled NO (80 p.p.m.) on cardiovascular and respiratory parameters were investigated in five Throughbred horses. 2. The concentration of NO ([NO]) in exhaled air collected from within the nasal opening was lower when collected at a high flow rate of 80 l min-1 than at a low flow rate of 20 l min-1: when trotting at 3.7 m s-1 the values were 0.78 +/- 0.15 and 1.23 +/- 9.14 p.p.b., respectively, and when cantering at 9 m s-1 the values were 1.69 +/- 0.31 and 2.25 +/- 0.32 p.p.b., respectively. 3. Nebulized methoxamine (40 mg ml-1 for 60 s), an alpha 1-adrenergic agonist, further reduced [NO] during the 9 m s-1 canter to 1.05 +/- 0.14 and 1.99 +/- 0.41 p.p.b. when collected at 80 and 20 l min-1, respectively, and induced cyclical changes in the breathing pattern. 4. Exercise induced a linear increase in VNO with work intensity to a maximum (428.1 +/- 31.6 pmol min-1 kg-1) which coincided with the maximal oxygen uptake for the horses (138.3 +/- 11.7 ml min-1 kg-1), although a further increase in VNO (779.3 +/- 38.4 pmol min-1 kg-1) occurred immediately after exercise. The changes in VNO correlated well with the tidal volume (r = 0.968; P < 0.01) and the haematocrit (r = 0.855; P < 0.01). 5. In the first 2 min of high intensity exercise, inhaled NO (80 p.p.m.) significantly (P < 0.05) reduced the pulmonary artery pressure: during the first minute, pulmonary artery pressure was 83.1 +/- 7.6 mmHg compared with a control value of 94.4 +/- 6.3 mmHg, and during the second minute, 84.2 +/- 7.1 mmHg compared with a control value of 98.4 +/- 4.7 mmHg. There were no other significant changes in cardiovascular or respiratory indices, including cardiac output, measured during exercise between control and inhaled NO tests. 6. The results show that exhaled NO is released from the airways of the horse and may contribute to the regulation of pulmonary vascular tone during exercise.

Adrenergic alpha-Agonists↗
PubMed1996

Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group.

BACKGROUND: Recently, a cluster of patients was observed in France in whom primary pulmonary hypertension developed in patients exposed to derivatives of fenfluramine in appetite suppressants (anorexic agents), which are used for weight control. We investigated the potential role of anorexic agents and other suspected risk factors for primary pulmonary hypertension. METHODS: In a case-control study, we assessed 95 patients with primary pulmonary hypertension from 35 centers in France, Belgium, the United Kingdom, and the Netherlands and 355 controls recruited from general practices and matched to the patients' sex and age. RESULTS: The use of anorexic drugs (mainly derivatives of fenfluramine) was associated with an increased risk of primary pulmonary hypertension (odds ratio with any anorexic-drug use, 6.3; 95 percent confidence interval, 3.0 to 13.2). For the use of anorexic agents in the preceding year, the odds ratio was 10.1 (95 percent confidence interval, 3.4 to 29.9). When anorexic drugs were used to a total of more than three months, the odds ratio was 23.1 (95 percent confidence interval, 6.9 to 77.7). We also confirmed an association with several previously identified risk factors: a family history of pulmonary hypertension, infection with the human immunodeficiency virus, cirrhosis, and use of cocaine or intravenous drugs. CONCLUSIONS: The use of anorexic drugs was associated with the development of primary pulmonary hypertension. Active surveillance for this disease should be considered, particularly since their use is expected to increase in the near future.

Adolescent↗
PubMed1996

Bronchiolitis obliterans syndrome (BOS) following heart-lung transplantation.

With the increasing number of successfully performed lung transplants and a longer follow up of patients, there is an interest in the analysis of long-term complications and their impact on patient survival. Heart-lung transplantation was performed in 157 patients with 126 patients surviving at least 6 months. Early death was mainly caused by bacterial and viral infection. Long-term patient survival was decisively influenced by obliterative bronchiolitis. With the new international definition of bronchiolitis obliterans syndrome (BOS) based on an irreversible decline of FEV1 from baseline values, it became possible to analyse the incidence of BOS and the impact on patient mortality in long-term survivors. FEV1 reached a peak value of 102% predicted at a median of 219 days. In 106 of 126 patients (84%), FEV1 showed no decline within the first year. A total of 60 patients (47.6%) developed BOS grade 1 with progression to BOS grade 2 in 85% of these patients. The incidence of BOS was 12.6% at 1 year increasing to more than 50% 5 years after transplantation. Patient mortality due to obliterative bronchiolitis increased from 1% at 1 year to 18% more than 5 years after transplantation. Almost all deaths (86%; 32/37) more than 1 year after HLT were associated with bronchiolitis obliterans. In summary, bronchiolitis obliterans decisively contributes to long-term patient morbidity and mortality after heart-lung transplantation. Clinical and research efforts should be directed towards avoiding this important complication.

Bronchiolitis Obliterans↗
PubMed1996

Reduction of pulmonary capillary blood volume in patients with severe unexplained pulmonary hypertension.

BACKGROUND: Unexplained or primary pulmonary hypertension results in an obliteration and obstruction of resistance pulmonary arteries. In these patients gas exchange is impaired and the measurement of gas transfer for carbon monoxide is usually reduced. This has been thought to represent a reduction in pulmonary alveolar capillary blood volume (Vc). A single breath test, measuring simultaneously the uptake of both nitric oxide (NO) and carbon monoxide (CO), provides a simple and practical measurement of membrane diffusion (Dm) and Vc. METHODS: A standard single breath test for the measurement of gas transfer for carbon monoxide (TLCO) was adapted to include NO (40 ppm) in the inhaled gas mixture and a breath-hold time at total lung capacity of 7.5 seconds was used. Twelve patients with primary pulmonary hypertension and 10 similar normal volunteers were studied while seated at rest. RESULTS: The patients had reduced values for TLCO and TLNO. The mean (SD) value of Dm in the patients was 36.7 (32.1) mmol/min.kPa compared with 52.8 (23.9) mmol/min.kPa in the normal subjects. Vc in the patients was 0.03 (0.03) 1 and 0.06 (0.01) 1 in the normal subjects. CONCLUSIONS: The simultaneous measurement of NO and CO uptake is possible in healthy volunteers and patients with primary hypertension. In these patients capillary blood volume is reduced compared with normal subjects.

Adult↗
PubMed1996

The role of thrombosis in severe pulmonary hypertension.

Considering the important surface in pulmonary circulation where blood can interact with the endothelium, the maintenance of blood fluidity through the lung, by antithrombotic pathways and products of the endothelium, is essential. This function appears to be ineffective in primary pulmonary hypertension and in severe secondary pulmonary hypertension. Thrombotic lesions are frequently found in pulmonary arteries in these diseases. Thrombin activity appears to be increased in severe pulmonary hypertension. Antithrombotic pathway disorders may account for this abnormality, particularly in chronic thromboembolic pulmonary hypertension and primary pulmonary hypertension. Injured endothelium, a constant feature in severe pulmonary hypertension, either primary or secondary, enhances thrombus formation in pulmonary vessels. This is probably related to thrombomodulin and tissue factor imbalance, impairment of prostacyclin and nitric oxide release, as well as inefficiency of fibrinolysis. Moreover, platelets appear to be activated in the pulmonary circulation of these patients. They release several mediators acting on vascular tone and as mitogenic agents, and may also contribute to thrombin and clot generation. Long-term oral anticoagulant and continuous infusion of prostacyclin, treatments which impede thrombosis, are known to improve the survival rate in patients with primary pulmonary hypertension. These are the strongest arguments, so far, in favour of the role of thrombosis in severe pulmonary hypertension. However, we do not know whether these abnormalities result from a previous vascular injury or represent the primary disturbance.

Animals↗
PubMed1996

Lung Transplantation in patients with systemic diseases: an eleven-year experience at Papworth Hospital.

BACKGROUND: The presence of a systemic disease has traditionally been considered a contraindication to lung transplantation. METHODS: We present a retrospective review of 19 patients undergoing lung transplantation for end-stage pulmonary disease associated with a systemic illness since 1984. There were 11 male and 8 female patients, aged from 23 to 59 years (median 43 years) with end-stage pulmonary involvement by sarcoidosis (11 patients), Langerhan's cell histiocytosis (three patients), systemic vasculitis (four patients: three with systemic lupus erythrematosis, one with Churg-Strauss), and common variable immunodeficiency (one patient). Ten patients received a heart-lung transplant, and eight patients received a single lung transplant. One patient underwent single lung transplantation after an earlier heart-lung transplant. RESULTS: The 30-day mortality was 5.3%. Nine patients died overall. Two of these had systemic lupus erythrematosis with anticardiolipin antibodies and died from complications of their underlying vasculitis. The mean 1- and 2-year actuarial survivals for all patients were 71% (standard error +/- 10.8%) and 64% (standard error +/- 11.9%), respectively. All patients surviving longer than 3 months achieved an improvement in functional status to New York Heart Association class I or II, and a significant increase occurred in mean forced expiratory volume in 1 second and forced vital capacity. Disease recurrence without clinical significance occurred in two patients with sarcoidosis. Of the nine patients who died, seven had autopsies and none showed evidence of disease recurrence in the lungs. CONCLUSIONS: Patients with systemic diseases can be considered for lung transplantation and each case should be judged on its individual merits. However, patients with systemic lupus erythrematosis (particularly when associated with anticardiolipin antibodies) should probably not be offered lung transplantation because they are likely to develop further complications of their underlying vasculitis.

Actuarial Analysis↗
PubMed1995

Role of prostacyclin in the treatment of primary pulmonary hypertension.

Over the last decade, new medical and surgical treatments have become available for primary pulmonary hypertension that have influenced the natural history of the disease. Vasodilator therapy is aimed at overcoming pulmonary vasoconstriction with consequent decrease in afterload and improved right ventricular output. The endpoint of vasodilator therapy is therefore to reduce pulmonary vascular resistance, without causing significant systemic hypotension. Prostacyclin, a potent vasodilator and antiaggregating agent, has been successfully used by continuous infusion in the treatment of severe pulmonary hypertension. The marked improvement in quality of life observed with the use of prostacyclin in these patients, as well as the increased survival time on the waiting list for transplantation, has influenced us to adopt prostacyclin infusion as a fundamental element of our therapeutic strategy for the management of this rare but fatal condition.

Epoprostenol↗
PubMed1995

Single lung transplantation for end stage emphysema.

BACKGROUND: The first successful single lung transplantation was carried out in 1983 for pulmonary fibrosis. Because of the inherent advantages of single lung transplantation, a transplantation programme has been started for patients with end stage lung disease due to emphysema. METHODS: Between October 1990 and August 1993 25 patients with severe emphysema (15 men, mean age 51 years) received a single lung transplant at our institution. All patients were severely disabled with a mean (SD) 12 minute walking distance of 281 (165) metres. There were five deaths in the series, four in the first 20 days and one on day 503. Two patients suffered graft compression by air trapping in the native lung. Bronchial narrowing requiring insertion of endobronchial stenting occurred in four patients. RESULTS: Mean (SD) FEV1 improved from a preoperative value of 17.8(13%) predicted to a six month value of 53.6(13)%, and FEV1/FVC from 23.8(12)% to 68.6(15)%. After the transplant 12 patients are in New York Heart Association (NYHA) class I and the rest of the survivors are in NYHA II. Actuarial survival was 82% at one year and 74% at three years. CONCLUSIONS: Single lung transplantation is an effective treatment for end stage lung disease due to emphysema and carries an acceptable mortality and morbidity.

Adult↗
PubMed1995

Exhaled nitric oxide in isolated pig lungs.

Endothelium-derived nitric oxide (NO) is an important regulator of vascular resistance. Low concentrations of NO have been recorded in the exhaled breath of spontaneously breathing animals and humans. To determine whether NO synthesis in the lung contributes to the NO measured in the breath, we measured the concentration of NO in the exhaled air of isolated perfused and ventilated porcine lungs by using a chemiluminescence method. With NO-free normoxic ventilation (21% O2-5% CO2-74% N2) of eight porcine lungs perfused with a Krebs-dextran and albumin perfusate, baseline exhaled NO was 5.8 +/- 1.8 parts per billion (ppb) and pulmonary vascular resistance (PVR) was 8.9 +/- 1.8 mmHg.l-1.min. Hypoxic ventilation (5% O2-5% CO2-90% N2) caused a fall in NO to 3.6 +/- 1.8 ppb and a rise in PVR to 13.6 +/- 3.6 mmHg.l-1.min. Vasoconstriction with the thromboxane analogue U-46619 (10(-9) M) raised PVR to 31.7 +/- 6.8 mmHg.l-1.min but did not decrease NO levels from baseline. Subsequent addition of acetylcholine (10(-6)M) lowered PVR to 22.1 +/- 4.5 mmHg.l-1.min and increased exhaled NO to 7.0 +/- 2.0 ppb. Addition of a NO synthase inhibitor, NG-nitro-L-arginine methyl ester (10(-5) M), to four lungs caused a rise in PVR to 43.0 +/- 7.0 mmHg.l-1.min and a decrease in NO to 1.5 +/- 1.0 ppb. Addition of autologous blood to the perfusate of four lungs caused no change in PVR from baseline but decreased exhaled NO to 2.7 +/- 0.5 ppb.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Effect of inhibitors of nitric oxide release and action on vascular tone in isolated lungs of pig, sheep, dog and man.

1. The actions of inhibitors of the release or action of nitric oxide (NO) on pulmonary vascular resistance (PVR) were investigated in lungs isolated from pig, sheep, dog and man. 2. In pig, sheep and human lungs perfused with Krebs-dextran solution, both N omega-nitro-L-arginine methyl ester (L-NAME; 10(-5) M) and Methylene Blue (10(-4) M) increased basal PVR. This increase was reversed by sodium nitroprusside (10(-5) M). In pig lungs N omega-monomethyl-L-arginine (10(-4) M) increased PVR by 154%. This increase was partially reversed by L-arginine (10(-3) M). L-NAME had no effect in dog lungs. 3. Pulmonary artery pressure-flow (PPA/Q) relationships were studied over a wide range of flows. In pigs, sheep and human lungs perfused with Krebs-dextran solution, L-NAME increased the PPA/Q slope. This increase was reversed by sodium nitroprusside. In dog lungs L-NAME had no effect. 4. In blood-perfused lungs, the respective responses to L-NAME were similar to those observed with saline. Acute hypoxia in pig and dog lungs increased intercept pressure. Addition of L-NAME during hypoxia increased the PPA/Q slope in both species. 5. In the human, there was no difference in the absolute increase of PVR or PPA/Q slope elicited by L-NAME between hypertensive and control lungs. 6. We conclude that NO is continuously released in the pulmonary vascular bed of pig, sheep and humans under normoxic conditions. In dog lungs inhibition of NO synthesis increases PVR only under hypoxic conditions. In human lungs with pulmonary hypertension, NO is still released under basal conditions.

Adolescent↗