Hyperacute rejection of rabbit hearts by human blood is mediated by the alternative pathway of complement.
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Biomedical subjects
Publications and source records attributed to J Wallwork.
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The acute effects of inhaled nitric oxide (NO) (40 ppm in air) on pulmonary (PVR) and systemic (SVR) vascular resistance were compared with those of an intravenous infusion of prostacyclin (24 micrograms/h) in 8 patients with severe pulmonary hypertension and 10 cardiac patients with normal values of PVR. 10 healthy volunteers were studied non-invasively. In the patients with pulmonary hypertension, PVR fell significantly after inhaled NO and after prostacyclin. PVR also fell significantly in the cardiac patients after inhaled NO. Although SVR fell substantially after prostacyclin in patients with pulmonary hypertension, inhaled NO had no effect on SVR in any patient or volunteer. Inhaled NO therefore seems to be both a selective and effective pulmonary vasodilator.
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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.
The effect of cyclosporine on the systemic circulation and on heart rate is unknown for heart transplant recipients. Thirty-four heart transplant recipients were studied by right-sided cardiac catheterization after endomyocardial biopsy. A direct linear relation was found between systemic and pulmonary vascular resistance and cyclosporine trough blood levels, which were negatively related to heart rate. The effect of cyclosporine on pulmonary vascular resistance, however, was not statistically significant by multivariate analysis when patient age was considered. In contrast, renal function appeared unrelated to systemic vascular resistance or heart rate. It appears that cyclosporine trough blood levels may have a direct effect on systemic vascular resistance as well as an unexplained negative chronotropic effect on heart rate.
OBJECTIVES: Measurement of changes in patients' perceptions of how differing states of health affect their lives and determination of the ability of preoperative variables to predict outcome after coronary artery bypass grafting. DESIGN: Prospective study with completion of questionnaires before coronary artery bypass grafting and at three months, one year, and five years afterwards. SETTING: Regional cardiothoracic centre. PATIENTS: 100 Male patients all aged below 60 at the time of operation, who were patients of two cardiothoracic surgeons. MAIN OUTCOME MEASURES: Patients' assessment of their health state in terms of functional capacity and aspects of distress, according to the Nottingham health profile and outcome of operation in terms of changes in symptoms, working life, and daily activities determined by self completed study questionnaires before operation and at three and six months afterwards. RESULTS: Intermediate one year results are reported. The differences between the Nottingham health profile scores before operation and at three months afterwards were significantly different (p less than 0.01), indicating an appreciable improvement in general health state, and at one year compared favourably with those from a normal male population. Analysis of responses to the study questionnaire showed that 65 of 89 patients (73%) were working at one year after operation with a further seven (8%) maintaining that they were fit to work but unable to find employment. The proportion of patients complaining of chest pain fell from 90% (88/98) before grafting to 19% (17/89) at one year after coronary artery bypass grafting, when 91% (81/89) patients maintained that their condition was either completely better or definitely improved. The significant positive factors affecting return to work and home activities were working before operation, short wait for operation, absence of breathlessness, and low physical mobility score in the Nottingham health profile (all p less than 0.001). CONCLUSIONS: Improvements were evident in general health state, symptoms, and activity at three months and one year after coronary artery bypass graft surgery. Interventions likely to influence outcomes included reduction in waiting times for operation; rehabilitation initiatives; and more attention to the quality of information given to patients, their relatives, and the community.
OBJECTIVE: By audit from January to June 1989 to quantify, separately for hearts, kidneys, liver, lungs and corneas, the possible increases in transplantable organs from brain stem dead potential donors in intensive care units and to compare them with the increases achieved in October-November 1989, during intense, national publicity about transplantation. DESIGN: Prospective audit of all deaths in intensive care units in England from 1 January to 30 June 1989 and subsequent case study of the impact of publicity on offers and donations during October-November 1989. SETTING: 15 regional and special health authorities in England. PATIENTS: 5803 patients dying in intensive care units, of whom 497 were confirmed as brain stem dead and had no general medical contraindication to organ donation. MAIN OUTCOME MEASURES: Organ specific suitability for transplantation (as reported by intensive care units); consent for donation of specific suitable organs; and procurement of specific organs reported as suitable for transplantation and offered. RESULTS: In the 497 (8.6%) brain stem dead potential donors were estimated the organ specific suitability for heart as 63%, kidneys 95%, liver 70%, lungs 29%, and corneas 91%. Refusal of relatives (30%) accounted for major losses of suitable organs of all types. For kidneys the loss was equivalent to 44% of brain stem dead actual kidney donors. No discussion of organ donation was the second most important reason for missed kidney donors, the loss being equivalent to 10% of brain stem dead actual donors. Non-procurement or difficulties with allocating organs was the second most notable cause of missed suitable liver and lung donors; 29% (55) of the offered total of 189 liver donors and 27% (21) of 78 offered suitable lung donors in six months. Non-procurement of suitable, offered organs was rare for kidneys and modest, of the order of 13% and 10% respectively, for heart and corneas. Corneal donation from brain stem dead potential donors might be improved nearly as much (that is, a 78% increase in brain stem dead actual corneal donors) by specific measures to promote corneal donation when other organs are offered as by reducing the overall refusal rate. Restricted offers, non-procurement, and no discussion of donation accounted for nearly equal numbers of lost donations of hearts (each equivalent to 15% of donated hearts). During October-November 1989 when there was intense, positive publicity about transplantation the rates of refusal and non-discussion fell compared with during January-June (22%, 36/163 v 30%, 138/460; 7%, 33/497 v 2%, 4/167 respectively). Offers of suitable donors increased significantly (p less than 0.02) compared with the first six months of 1989, most notably for heart donors (80 v 60.1 expected) and kidney donors (122 v 102.1 expected) but only for kidneys was there a noticeable 17% increase in actual donors (118 actual audited donors v 100.8 expected donors; p = 0.09). CONCLUSIONS: Four strategies to increase the supply of transplantable organs from brain stem dead potential donors in intensive care units were identified: (a) reducing refusal of relatives (b) avoiding non-procurement of actually suitable organs (by logistical initiatives) and deterioration of initially suitable organs (by donor care initiatives); (c) converting restricted offers to unrestricted offers; and (d) ensuring discussion with families. Early referral to the transplant team or coordinator gives time for discussion about donor care and agreement on medical suitability for donation of specific organs. Solving some of the logistical problems of non-procurement may be a prerequisite for increased offers to be translated into increased donations. The impact of publicity therefore needs to be measured on offers of suitable donors as well as by actual donations.
In the first 11 years of the heart and heart-lung transplantation programme at Papworth Hospital, Cambridge, 356 patients underwent heart transplantation, and 73 patients received both heart and lungs. Out of 429 patients 41 (9.5 per cent) developed abdominal complications within the first 30 days, and 20 of the 41 required surgery. The complications included pancreatitis (10), peptic ulceration (8), and pseudo-obstruction (8), in addition to colonic perforation and small bowel obstruction. When laparotomy was performed it was well tolerated. This paper supports the view that successful management of abdominal complications following transplantation requires prompt diagnosis and treatment. Where doubt exists in the presence of an acute abdomen, laparotomy is the appropriate way to establish a definitive diagnosis.
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Heart-lung transplantation involves denervation of the lungs below the tracheal anastomosis, with associated permanent loss of all pulmonary innervation except post-ganglionic efferent nerves. This is supported by loss of the cough reflex to inhaled USNDW, which also implies that the RARs which mediate this cough mechanism lie in the central airways. Bronchoconstriction following inhalation of USNDW developed only in those HLT recipients with acute lung rejection; this was not related to methacholine responsiveness and may therefore represent a pathologic vascular response. Hyperresponsiveness to methacholine has been reported following HLT, which we found unrelated to inflammation or acute rejection. A similar hyperresponsiveness to histamine was seen, which correlated with the response to methacholine. This also implies that histamine may act directly on smooth muscle receptors, and not solely via a cholinergic reflex. Hyperresponsiveness following HLT may be due to development of a generalized denervation hypersensitivity. Bronchodilation following capsaicin inhalation has been observed in HLT recipients, and may be due to unopposed release of VIP from retained post-ganglionic efferent nerves.
We evaluated the role of percutaneous transluminal coronary angioplasty (PTCA) in a series of orthotopic cardiac transplant recipients with severe epicardial coronary occlusive disease. Ten orthotopic cardiac transplant patients treated by PTCA up to March 1990 were reviewed. All had significant epicardial coronary artery lesions (greater than 70% stenosis compared with the adjacent healthy artery) and exercise electrocardiogram or isotope perfusion evidence of myocardial ischaemia in the relevant region. Primary angiographic PTCA success was achieved in 12 of the 16 lesions attempted (75%). Mean stenosis improvement was from 80% of adjacent healthy artery (range 70-90%) to 12% (range 0-20%). Median angiographic follow-up of 9 months (2-25 months) is available for all patients. The mean recurrence rate is 33% (4 of 12 successfully treated lesions) defined as greater than 50% reduction in the original gain at the PTCA. We have shown that PTCA is technically possible in a series of cardiac transplant recipients. The primary success and recurrence rates are comparable to the use of PTCA in conventional atherosclerotic coronary disease.