Biomedical subjects
Publications and source records attributed to R S Bonser.
The results of combined heart-lung transplantation have continued to improve following its reintroduction into clinical practice in 1981. En-bloc implantation has an apparent protective effect on subsequent tracheal anastomotic healing. Continuing developments in immunosuppression, rejection surveillance, and organ preservation will allow the procedure to fulfill its early promise in the management of end-stage lung and heart disease.
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Since the successful clinical reintroduction of heart and lung transplantation in 1981, more than 350 of these procedures have been performed worldwide. Although survival following this operation is less than that reported for heart transplantation, the results are improving. It is clear that the increased technical difficulty of the procedure combined with the exquisite susceptibility of the transplanted lung to postoperative injury from infection, rejection or other causes account for these differences. In this report we provide an overview of the experience in heart-lung transplantation and discuss recent advances. The late complication of chronic obliterative bronchiolitis, which may progress inexorably, has cast a shadow over the potential long-term success of this therapeutic procedure. Current research efforts are directed toward the cause, diagnosis, and treatment of this complication.
The time constant (T) of left ventricular pressure fall is widely used as an index of ventricular "relaxation". It is not known whether its rate limiting step is deactivation, an enzymic energy consuming reaction whose rate is therefore sensitive to temperature, or elastic recoil. To distinguish between these possibilities, the time constant was measured by simple logarithmic (Tlog) and exponential (Texp) methods in 12 patients during cooling before coronary artery grafting. Ventricular loading conditions were altered by transfusion from bypass to maintain arterial and left atrial pressures constant in individual patients, though heart rate fell from 86 (8.4) to 68 (10) beats/min. Tlog increased from 49 (10) ms mean (SD), at 37 degrees C to 86 (15) ms at 31 degrees C, and Texp from 63(14) at 37 degrees C to 112 (23) ms at 31 degrees C with intermediate values at 34 degrees C. Texp proved sensitive to "noise" at low temperatures, but the overall change in Tlog with temperature was 9% per degree C--considerably less than that observed experimentally for the rate of tension decline of isolated myocardium, and possibly itself an overestimate because of the concomitant fall in heart rate. The relatively small effect of temperature on Tlog in humans, associated with a considerable load sensitivity appearing under hypothermic conditions, does not favour simple dependence on deactivation as the rate limiting step of left ventricular pressure fall, but suggests that its determinants may be complex.
Pulmonary emphysema results in hyperinflation of the lungs and concomitant changes in the configuration of the thoracic cavity. We describe a patient who underwent bilateral lung transplantation for emphysema due to alpha 1 antitrypsin deficiency. Dramatic changes in chest dimensions and configuration occurred following transplantation, demonstrating the dynamic and reversible nature of the thoracic cavity abnormalities of emphysema.
Successful clinical double-lung transplantation after 5 1/2 hours of pulmonary ischemia is reported. Static hypothermic preservation with a high-volume, high flow rate-modified Collin's solution pulmonary artery flush was used. Excellent early and late pulmonary function demonstrates the efficacy of the technique that is described in detail. Lung transplantation remains limited by the lack of reliable methods of long-term storage of donor organs, but refinement of current techniques may soon allow its wider application.
Heart-lung transplantation has become an effective form of therapy for end-stage cardiopulmonary disease. Early results have steadily improved, and a 1-year survival rate of over 60% is now expected. The fact that lungs can be preserved for an extended period allows organs to be procured almost anywhere and this, in turn, has slightly improved the availability of organs for transplant. A diagnosis of lung rejection remains imprecise and progress still needs to be made in this area. Obliterative bronchiolitis of a variable degree remains the major medium-term complication, probably representing chronic graft rejection. Although long-term progress cannot yet be predicted, heart-lung transplantation remains the only option for a normal life for this special group of patients.
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Colonic fibrosarcoma is extremely rare. This is a report of a patient with fibrosarcoma of the transverse colon, manifesting as an obstructive lesion with local perforation and abscess formation.
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A patient with long-standing ischaemic heart disease and severe low output congestive cardiac failure received numerous diuretics, which gradually became ineffective. Resistant oedema was treated by adding demeclocycline to the current diuretic regime of frusemide and metolazone. Diuresis resulted, oedema disappeared and body weight fell. This drug combination was continued without complication for a further 6 months until his death.
The effects of social class, season, low temperature and sudden falls in temperature are investigated in 286 cases of Sudden Infant Death Syndrome in Cardiff in the years 1955--1974. The association with low temperature was striking: unsuspected hypothermia may be an important feature of these deaths. Sudden infant death incidence was associated with influenza A but not influenza B epidemics.
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Heart failure and left ventricular dysfunction are common and are most often caused by myocardial ischemia/infarction secondary to occlusive coronary artery disease. Although recent refinements in medical therapy have resulted in improved survival, morbidity and mortality remain high in patients with advanced heart failure. Heart transplantation remains an option for selected patients, and implantable left ventricular assist devices may soon provide another treatment strategy for such patients. However, patients with established postischemic heart failure, significant myocardial viability, and coronary artery anatomy amenable to surgical revascularization can derive significant functional and survival benefit after coronary artery surgery, albeit with an increased perioperative risk. We discuss the role of coronary artery surgery in ischemic heart failure and review the evidence for such an approach.
Pentoxifylline (PTX), a methyl xanthine derivative, reduces endothelial permeability. A double blind, prospective, randomized, placebo controlled, parallel study was undertaken to assess the effect of PTX on leukotriene B4, complement fragment C3a, interleukin 6 (IL6), endothelial injury as measured by von Willebrand factor (vWf), and endothelial permeability as measured by urinary albumin excretion (expressed as excreted urinary albumin to creatinine ratio [ACR]) in patients undergoing cardiopulmonary bypass (CPB) for elective coronary artery bypass grafting. Twenty patients were recruited into each treatment arm and given either PTX 400 mg or placebo three times daily for 1 week before surgery. Patients were well matched. All operations were performed using one anesthetic, CPB, and a myocardial protection technique. Blood and urine samples were taken after anesthetic induction (baseline); 20 min after the start of CPB; 5 min after removal of the cross clamp; and 5 min and 2, 6, and 24 hr after the end of CPB. Pentoxifylline did not reduce IL6, C3a, and LTB4 release but reduced Factor VIIIRAg and urinary albumin excretion preoperatively (PTX vs placebo, ACR 1q.0 vs 2.1 mg/mmol, vWf 0.8 vs 1.3 IU/ml, p < 0.05) and peak levels (PTX vs placebo, ACR 8.9 vs 16.2, vWf 1.2 vs 2.2, p < 0.05) after CPB. These results suggest that PTX may attenuate the endothelial injury and permeability seen in CPB.
The effects of hypothermic lung preservation were evaluated in 12 mongrel dogs receiving double lung allografts. Animals underwent transplant procedures after 12 hours of static preservation at 4 degrees C following pulmonary artery flush with 60 to 80 ml/kg cold modified Collins solution. Donors were pretreated with allopurinol and recipients with methylprednisolone and perireperfusion deferoxamine. Six donor animals received a PGE1 infusion (20 to 500 ng/kg/min) for 20 minutes before harvest at doses causing a significant reduction in pulmonary vascular resistance. After implantation, recipients were maintained at ventilator settings identical to those used in donors. A fixed FIO2 (0.4) was maintained, except for 15-minute periods of FIO2 1.0 that were used to measure left-to-right intrapulmonary shunt fraction (Qs/Qt) and alveolar-arterial oxygen gradients (PAO2-PaO2). Cardiopulmonary function was studied for 20 hours. Pretreatment with PGE1 resulted in reduced survival (p less than 0.05) and increased PAO2-PaO2 (p less than 0.05) and Qs/Qt (p less than 0.05) 30 minutes after reperfusion. After 60 minutes of reperfusion, mean arterial pO2 (FIO2 0.4) was 148 mm Hg in controls and 80.5 mm Hg in the PGE1 group (p less than 0.02). There was no significant difference in pulmonary vascular resistance, cardiac output, mixed venous oxygen saturation, airway resistance, compliance and physiologic dead space between groups at any time after implantation. After 20 hours of reperfusion, pO2 (FIO2 0.4) in the control group was well maintained at 140 (+/- 52) mm Hg. The method of lung preservation in control animals resulted in good survival and adequate gas exchange after 12 hours of ischemia and 20 hours of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)