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Biomedical subjects

T Higenbottam

Publications and source records attributed to T Higenbottam.

At least 91 records · Page 5Linked to original sources
PubMed1989

Ventilatory compensation for changes in posture after human heart-lung transplantation.

We have studied the contribution of vagal pulmonary receptors to the stability of breathing during postural changes in humans. Quiet breathing was quantified in the seated and the supine postures in 10 patients with chronic pulmonary denervation due to heart-lung transplantation and 10 age and sex matched normal controls. In the vast majority of patients and normal subjects frequency histograms for tidal volume and mean inspiratory flow rate were virtually superimposed seated and supine. There were no significant differences in the mean levels of respiratory variables between postures in either group (except for mean inspiratory flow rate in the patients which was slightly greater seated than supine). Experiments performed on a tilt table in two additional patients showed that the ventilatory response to postural changes was immediate. In addition, the response was maintained after blockade of intact tracheal stretch receptors with aerosolized lidocaine. These results indicate that adequate ventilatory compensation during postural changes does not depend on vagal afferent information arising in intrapulmonary or tracheal airway stretch receptors. The appropriate receptors may be diaphragmatic Golgi tendon organs.

Adolescent↗
PubMed1989

Heart-lung transplantation at Papworth Hospital.

Combined heart-lung transplantation has been performed in 51 patients since 1984. A pulmonary preservation fluid preceded by prostacyclin infusion has allowed distant procurement. Early organ function has been good in all cases. Maintenance immunosuppression is cyclosporine and azathioprine. Steroids are given to treat rejection episodes. Transbronchial biopsy has allowed the accurate, early and safe diagnosis of rejection. Acute cardiac rejection has not occurred in these patients. Thirty-seven patients are alive between 1 and 54 months following transplantation. The actuarial survival at 1 year is 76% and 68% at 2 years. Four patients died in the early postoperative period as a result of primary Cytomegalovirus (CMV). Other causes of early death were bacterial infection (4), cerebrovascular event (1), tracheal dehiscence (1) and small bowel infarction following retransplantation for obliterative bronchiolitis. Three other patients have died as a result of obliterative bronchiolitis. Patients and donors have been carefully selected to ensure that this scarce resource is utilised most effectively.

Adolescent↗
PubMed1989

Cough associated with angiotensin converting enzyme inhibition.

The therapeutic inhibition of angiotensin converting enzyme (ACE) is associated with the production of a dry cough, which occurs more commonly in women than men and appears to be unrelated to concurrent illness. At present the exact incidence of ACE inhibitor cough and the substrate of ACE responsible for this effect is unknown. Cough challenge by inhalation of aerosols of tussive agents such as citric acid and capsaicin may be used to study the effect of drug administration on the cough reflex. In normal subjects, an oral dose of captopril (25 mg) causes a significant shift in the dose-response curve to capsaicin inhalation, but not that to distilled water or citric acid. The exacerbation of artificially induced cough by ACE inhibition may be the result of a local increase in perineuronal substance P or bradykinin concentrations within the lung.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Lung lipids and disease.

Pulmonary surfactant is a complex mixture of proteins and phospholipids which possesses unique physical properties. It is no longer viewed just as a system for lowering surface tension but may play a protective role particularly with reference to inhalation of noxious substances. Derangement of the surfactant system may proceed to the development of disease by opening the way to toxic injury of the delicate epithelial lining of the lungs. Currently, it is believed that surfactant, which is synthetised, stored and secreted by type II alveolar pneumocytes, spreads rapidly on release to form a monomolecular layer covering the squamous surface lining of the alveoli. Furthermore, physiological and histological studies show that this monolayer extends into the bronchioli and possibly bronchi also. Effectively, the inspired air encounters an extensive and continuous 'oily' surface. It has been known for some time that cigarette smokers appear to sequester pulmonary surfactant into alveolar macrophages, leaving less free surfactant on the alveolar and bronchiolar surfaces. This process may be initiated by physical inactivation of surfactant by tobacco smoke. The tar of tobacco smoke alters the surface properties of surfactant as well as the compliance of the lung in vitro. This process may not only lead to the associated increase in the number of alveolar macrophages found in smokers, but could, by lessening the effective protective role of surfactant, lead to direct toxic injury of the lung and the development of chronic obstructive lung disease.

Animals↗
PubMed1989

Lung rejection and bronchial hyperresponsiveness to methacholine and ultrasonically nebulized distilled water in heart-lung transplantation patients.

Acute denervation of the lungs occurs after heart-lung transplantation (HLT), affecting both afferent and efferent nerves below the tracheal anastomosis. After surgery, the carina and main bronchi are perfused by mediastinal collaterals derived from the coronary arteries, and the intrapulmonary airways by retrograde blood flow from pulmonary artery collaterals. During acute rejection, the lungs are subjected to inflammation, particularly perivascular lymphocytic infiltrates. Rejection can be diagnosed by transbronchial biopsy (TBB). We report the bronchial responses to inhaled methacholine and ultrasonically nebulized distilled water (USNDW) in 16 HLT patients 2 wk to 43 months after surgery, relating them to the lung histopathology from concurrent TBB. Methacholine bronchial hyperresponsiveness was common, but it was not associated with airway epithelial or submucosal inflammation or perivascular lymphocytic infiltration. Six patients had a modest response to USNDW (fall in FEV1 greater than 10%). The responsiveness to USNDW was not associated with enhanced methacholine responsiveness or epithelial and mucosal inflammation. However, it was more commonly seen in patients with lung rejection and perivascular infiltrates. Methacholine hyperresponsiveness in HLT patients could therefore reflect denervation hypersensitivity of airway smooth muscle muscarinic receptors. The modest response to USNDW in some patients cannot be a result of a vagal reflex but could reflect a pathologic vascular response associated with lung rejection. These observations offer insight into the possible mechanisms of bronchial hyperresponsiveness in disease.

Adult↗
PubMed1989

The cough response to ultrasonically nebulized distilled water in heart-lung transplantation patients.

As a result of clinical heart-lung transplantation, the lungs are denervated below the level of the tracheal anastomosis. It has been questioned whether afferent vagal reinnervation occurs after surgery. Here we report the cough frequency, during inhalation of ultrasonically nebulized distilled water, of 15 heart-lung transplant patients studied 6 wk to 36 months after surgery. They were compared with 15 normal subjects of a similar age and sex. The distribution of the aerosol was studied in five normal subjects using 99mtechnetium diethylene triamine pentaacetate (99mTc-DTPA) in saline. In seven patients, the sensitivity of the laryngeal mucosa to instilled distilled water (0.2 ml) was tested at the time of fiberoptic bronchoscopy by recording the cough response. Ten percent of the aerosol was deposited onto the larynx and trachea, 56% on the central airways, and 34% in the periphery of the lung. The cough response to the aerosol was strikingly diminished in the patients compared with normal subjects (p less than 0.001), but all seven patients coughed when distilled water was instilled onto the larynx. As expected, the laryngeal mucosa of heart-lung transplant patients remains sensitive to distilled water. However, the diminished coughing when the distilled water is distributed by aerosol to the central airways supports the view that vagal afferent nerves do not reinnervate the lungs after heart-lung transplantation, up to 36 months after surgery.

Adult↗
PubMed1989

Airway mucosal bioelectric potential difference in cystic fibrosis after lung transplantation.

Bioelectrical potential difference (PD) across the respiratory mucosa is raised in cystic fibrosis (CF). We have recorded airway potentials from seven patients with CF who had undergone heart-lung transplantation and from eight patients without CF who had had transplants for cardiovascular disease; comparison of these populations controls for the effects of denervation and immunosuppressive treatment. Six patients without CF who had not had transplants formed an additional control. PD was recorded during routine fiberoptic bronchoscopy, using a Ringer's-perfused exploring bridge connected across a high impedance amplifier to an intravenous reference bridge. Bronchial lavage and sputum culture revealed no evidence of infection. Bronchial PD was similar in all three groups of patients at equivalent sites. However, nasal PD was raised in the CF group (mean value, 44 mV +/- 3.9 SE) compared with the patients who had transplants for cardiovascular disease (mean, 18 mV +/- 1.1 SE), and the control patients (mean, 15 mV +/- 1.2 SE). We conclude that the epithelial defects that result in raised airway potentials in CF do not recur in the transplanted lung.

Adolescent↗
PubMed1989

The importance of cytomegalovirus in heart-lung transplant recipients.

The first 33 heart-lung transplant recipients in our series were studied for evidence of CMV infection. CMV infection was diagnosed by a change in the serologic status, viral culture, or histology of lung tissue. Of 18 patients who were preoperatively negative for CMV antibody, eight received organs from CMV antibody-positive donors. Five developed pneumonitis (fatal in three)l; one survived primary CMV of the GI tract. Those who recovered from CMV pneumonitis received IV ganciclovir with CMV hyperimmune globulin given prophylactically from the time of transplantation. Only three of ten antibody-negative patients receiving organs from antibody-negative donors developed primary CMV, characterized by only fever in two but associated with rejection, and repeated infection was fatal in a third. CMV reactivation/reinfection occurred in seven of 15 (47 percent) without clinical disease in all but one case. Following heart-lung transplantation, CMV is the cause of considerable mortality and morbidity. We recommend that CMV antibody-negative recipients should receive organs only from antibody-negative donors. If a donor/recipient mismatch occurs, hyperimmune globulin and ganciclovir may improve survival.

Adult↗
PubMed1989

Pulmonary vasodilation with prostacyclin in primary and secondary pulmonary hypertension.

Twenty-three patients with pulmonary hypertension underwent right cardiac catheterization and measurement of their response to a short-term infusion of prostacyclin. Pulmonary vasodilation with a greater than 20 percent fall in PVR occurred in all five patients with primary pulmonary hypertension where the predominant lesions were plexogenic; in three out of five patients where the predominant lesions were thrombotic; in three out of five patients with pulmonary hypertension and obstruction of proximal vessels; in three out of five patients with COPD; in both patients with pulmonary fibrosis due to sarcoidosis; and in the one patient with pulmonary veno-occlusive disease, where the pulmonary vasodilation was offset by a fall in arterial oxygen content. Prostacyclin is a safe and effective drug to use for testing the response of the pulmonary circulation to a vasodilator in pulmonary hypertension due to different causes. Short-term testing for a vasodilator response, with a view to instituting long-term therapy, should not be restricted to those patients with primary pulmonary hypertension due to plexogenic pulmonary arteriopathy.

Adult↗
PubMed1989

[Clinical applications of the heart-lung transplant. Clinical results 5 years after the start of the program at Papworth].

In this study is reviewed the experience at Papworth Hospital, Cambridgeshire, and Great Ormond Street Hospital, London, with combined heart-lung transplantation. Between April 1984 and June 1989, 73 patients have undergone heart-lung transplantation. Donors and recipients were carefully matched with regards to serology, morphology and cytomegalovirus compatibility. Heart preservation was based on use of cold St. Thomas' cardioplegic solution; a pulmonary preservation fluid has been developed that allows distant organ procurement with a single pulmonary artery flush technique (Papworth solution). The recipients were: 21 pts with Eisenmenger's syndrome, 15 pts with pulmonary hypertension, 37 pts with pulmonary disease (including 22 cystic fibrosis). The results are: no surgical mortality; no acute cardiac rejection episodes. Twenty-three patients died (16 with infections, 3 with obliterative bronchiolitis, 2 with cerebral embolism and 2 others). The actuarial survival rate at one year is 73.2%; 63% at two years and 47.4% at four years. The use of transbronchial biopsy of the lung has provided accurate early and safe diagnosis of pulmonary rejection. Development in organ preservation and patient management, as well as careful selection of recipients and donors, have led to the effective use of resources and thereby to these good results.

Adolescent↗
PubMed1989

The effect of recipient lung size on lung physiology after heart-lung transplantation.

We studied the postoperative course of lung volumes in 32 heart-lung transplant recipients relative to the predicted total lung capacity of the individual donors, to assess the degree of inaccuracy likely to result from the radiological method of matching of donor and recipient lung sizes. There was a tendency for recipients with large preoperative lung volumes--from, for example, emphysema--to receive smaller lungs, while those with smaller volumes from pulmonary vascular disease received bigger donor lungs, but no immediate problems were incurred. After an initial fall in total lung capacity, the postoperative value of the total lung capacity approached the recipients' pretransplant value about one year after the operation irrespective of the size of the donor lungs. This suggests that chest wall compliance is the major determinant of postoperative lung volume and not the donor lung size or compliance. Exact matching of donors' and recipients' lung sizes may not be necessary, and if required can be simply achieved by comparing the measured total lung capacity in the recipient with the predicted value of the donor based on sex, age, and height.

Anthropometry↗
PubMed1988

Heart-lung transplantation for cystic fibrosis.

13 patients with severe lung disease and cor pulmonale from cystic fibrosis were accepted for heart-lung transplantation (HLT). 6 have had the operation, of whom 5 are well, with normal lung function, 3-29 months after operation. 1 patient died from adult respiratory distress syndrome after reoperation to control persistent chest-wall bleeding: at necropsy, this patient proved to have cirrhosis. Respiratory tract infections and acute lung rejection after HLT for cystic fibrosis were no more common than in other HLT patients. Of the 7 patients for whom suitable donor organs were not found, 3 died within 3 months of assessment. Initial severity of disease had been similar to that in the transplant group. The cost of assessment, operation, and 1 year's treatment after HLT is similar to that of medical treatment for such patients.

Adult↗
PubMed1988

Heart-lung transplantation: better use of resources.

PURPOSE: Our goal was to review the experience at Papworth Hospital, Cambridgeshire, England, with combined heart-lung transplantation. PATIENTS AND METHODS: Since April 1984, 31 patients have undergone heart-lung transplantation. Donors and recipients are carefully matched with regards to serology, morphology, and cytomegalovirus compatibility. A pulmonary preservation fluid has been developed that allows distant organ procurement with a single pulmonary artery flush technique. RESULTS: Acute cardiac rejection has not occurred in these patients. Twenty-three patients are alive between two months and over three years following transplantation. The actuarial survival rate at one year is 78 percent, and 70 percent at two years. Three patients died as a result of cytomegalovirus pneumonitis; in two patients, obliterative bronchiolitis developed, and both died, one after an opportunistic infection developed. Three patients died from other causes. The use of transbronchial biopsy of the lung has provided accurate, early, and safe diagnosis of pulmonary rejection. CONCLUSION: Developments in organ preservation and patient management, as well as careful selection of recipients and donors, have led to the effective use of resources and thereby to these good results. In particular, the incidence of obliterative bronchiolitis has been low, which is attributed to the early treatment of pulmonary rejection following diagnosis by transbronchial biopsy.

Adolescent↗
PubMed1988

Low dose infusion of atrial natriuretic peptide causes salt and water excretion in normal man.

1. The effects of low dose infusion of atrial natriuretic peptide (ANP) were observed in double-blind, placebo-controlled study in six fluid-loaded volunteers. After baseline observations, hourly increments of 0.4, 2 and 10 pmol min-1 kg-1 were infused with continuous observation of heart rate, blood pressure and cardiac output. Plasma ANP, aldosterone, and catecholamines, and urinary volume and sodium excretion, were estimated at half-hourly intervals. 2. ANP infusion resulted in an increase of 35, 98 and 207% in urinary sodium excretion and of 10, 20 and 71% in urinary volume when compared with placebo. Plasma ANP was markedly elevated above placebo levels only during infusion of 10 pmol of ANP min-1 kg-1. 3. No change in heart rate of blood pressure was noted during the study, but a significant fall in stroke volume index was observed during active treatment. Plasma levels of aldosterone and catecholamines were not significantly different on the 2 treatment days. 4. The potent natriuretic and diuretic effects of this peptide at plasma concentrations not significantly elevated from physiological suggest a hormonal role for ANP in the homoeostasis of salt and water balance.

Adult↗
PubMed1988

Transbronchial lung biopsy for the diagnosis of rejection in heart-lung transplant patients.

Long-term success of human lung transplantation has been hindered by the lack of an effective and repeatable method of obtained tissue from the transplanted lung for histology. Management of patients is complicated by the difficulty in distinguishing clinically between opportunistic infection of the lung and rejection. As a result, a large number of patients in recent reports develop chronic disabling obliterative bronchiolitis, believed to be the consequence of "chronic" rejection. Twenty-one patients have undergone heart-lung transplantation in our institute since 1984. During fiberoptic bronchoscopy, 43 transbronchial lung biopsies were performed in 15 patients. Twenty episodes of rejection occurred in 11 patients, from whom 16 sets of biopsies showed the typical changes of perivascular infiltrate and mucosal inflammation. Three biopsies were falsely negative; six routine biopsies performed when patients were well were all normal. Overall sensitivity was 84% and specificity 100%. By contrast, the sensitivity of the chest radiograph was only 40%. Opportunistic lung infection in 8 patients was diagnosed by transbronchial biopsy with a sensitivity of 38% and specificity of 100%. In no patient with opportunistic infection were the histologic features of rejection seen. Transbronchial lung biopsy offers a safe and repeatable method to obtain tissue from heart-lung transplants for histology. It has enabled the management of the lung transplant patient to be equivalent to that of the kidney, liver, and heart transplant patient.

Biopsy↗