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The study was undertaken to examine the heart rate (HR) and stroke volume (SV) responses to upright exercise in patients after orthotopic cardiac transplantation (Group A). The findings were compared to data obtained from post-coronary artery bypass surgery patients (Group B) and from healthy subjects (Group C). All three groups (n = 12 in each group) were matched for age and gender. The preexercise HR and blood pressure were significantly higher in Group A (p < 0.05), whereas the SV was significantly lower (41 +/- 4mL.beat-1 vs 63 +/- 3 and 65 +/- 2 mL.beat-1 in Group B and C respectively, p < 0.05). In Group A, at submaximal work loads, the SV was consistently lower than in Groups B and C. During the early phases of exercise, the HR was consistently higher in Group A also. Systemic vascular resistance remained significantly higher in Group A throughout exercise (p < 0.05).

The development of transplant-related coronary artery disease (TCAD) is the major determinant of long-term heart transplant survival. To test the hypothesis that TCAD might be related to cellular myocardial rejection, the grades of rejection seen at all biopsies performed in the first 6 months after heart transplantation were analyzed in 108 patients who survived more than 6 months. The development of TCAD was assessed at routine follow-up coronary angiography in 101 patients and at necropsy in seven patients. This data was analyzed with Kaplan-Meier survival curves and Cox proportional hazard regression analysis. No significant association was found between either moderate rejection or any level of rejection and the later development of TCAD, nor did the absence of any rejection protect against its development.

This study demonstrates the importance of analyzing survival by cause of death in order to achieve a better understanding of the prognostic indicators involved. It further emphasizes the need for analysis of risk factors in both univariate and multivariate models, and the danger of making judgements based on premature analysis of data on follow-up after heart transplantation. Survival following transplantation is characterized by the major hazards of early death due to infection and rejection and late graft loss due to coronary occlusive disease (COD). This study summarizes the first-graft survival experience for 323 transplant patients at Papworth Hospital, and assesses a number of potential risk factors for (1) early mortality, (2) late mortality from COD, and (3) development of COD. The potential risk factors considered for all hazards are donor and recipient age, sex, blood group, and matching of these factors; donor cause of death and recipient immunosuppression; inotropic support; waiting time; preoperative diagnosis and previous cardiac surgery; ischemic time; and extubation time. In addition, for development of, and graft loss from, COD, perioperative rejection and cytomegalovirus infection; hypertension at discharge; and cholesterol, triglycerides, and lipids at two years were assessed as risk factors. Advances in immunosuppression were observed to have increased overall survival rates and decreased mortality from infection, rejection, and COD, as well as decreasing morbidity from COD. Fatal rejection was found to be more likely in female recipients, recipients over 40 years, recipients of grafts from donors over 30 years old, patients who were transplanted for valvular heart disease, and patients who waited less than three months for their transplant. Male recipients of female donor organs were more likely to lose their grafts as a result of COD. Patients older than 50 and hearts from donors older than 40 conferred a high risk of development of and loss from COD. Patients transplanted for ischemic heart disease were more likely to develop COD. High cholesterol, low HDL, high LDL, and high triglycerides at two years after transplant showed some evidence of high risk for the subsequent development of COD, although these relationships are not statistically significant at this stage. Contrary to other recent studies, cytomegalovirus infection was not found to be a risk factor for the development of COD.

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.

Successful treatment of severe cardiac failure in a patient with end-stage renal failure by combined renal and cardiac transplantation is described. The possible causes of myocardial disease in the dialysis population are discussed.

Between 1975 and 1979 140 cardiac bioprostheses were implanted in 133 patients (mean age 60 years) at Papworth Hospital, Cambridge, England. Of these 85 remained available for analysis in the mid- and long term. Incidence of thromboembolism, bleeding, and infectious endocarditis were 2.1% +/- 0.6% (Standard error of mean), 0.2% and 0.8% +/- 0.4% per patient-year respectively. Primary valve failure occurred in only 5 patients. Freedom from primary valve failure was 98.3-r +/- 0.3% at 10 years and 82.3 +/- 4.5% at 12 years after replacement. Many patients died of old age before valve failure could occur. Therefore the percentage of tissue failure compared with the original number of patients operated on is even lower. Low incidence of valve failure, lack of need for long-term anticoagulation, and low incidence of thromboembolism make the bioprosthesis a good choice for valve replacement in older patients.

The study of endomyocardial biopsy specimens taken in the first 130 days after transplantation has yielded no histologic features predictive of later development of transplant-related coronary artery disease. This study, however, indicated that a combination of the following factors might be predictive in cyclosporine-treated patients: untreated histologically proven episodes of rejection, infection with cytomegalovirus or reactivation of infection, ischemic heart disease in the recipient as the reason for heart transplantation, and possibly HLA-B5 or -B8 mismatch.

Three hundred-thirteen heart transplant procedures were performed in 303 patients in the 10 years between January 1979 and December 1988. The incidence, histologic type, and site of malignant disease have been analyzed in the 275 patients (91%) who survived more than 1 month after heart transplantation. Four immunosuppressive regimens have been used during this period. Patients 1 through 29 received azathioprine and steroids with 28 days of intravenous antithymocyte globulin. Patients 30 through 89 received cyclosporine and low-dose steroids; the next 61 patients were randomized between cyclosporine and low-dose steroids and cyclosporine and azathioprine; and after patient 150 we have used triple therapy. All cyclosporine-based regimens have included a short course of prophylactic antithymocyte globulin. Eleven malignant tumors have been diagnosed, between 2 months and 6 years after the transplant procedure, and these have been treated by a variety of means. These tumors were two squamous cell carcinomas of the skin; a malignant anal wart that recurred after excision and radiotherapy and necessitated abdominoperineal resection: two small-cell carcinomas of the lung: one squamous cell carcinoma of the esophagus and one of the larynx; two carcinomas of the kidney were found at postmortem examinations; and there were two malignant lymphomas, one of which disseminated rapidly, whereas the other has had prolonged remissions with reduction in immunotherapy with acyclovir. These 11 tumors were responsible for four deaths. No relationship has been demonstrated between type of immunosuppression and tumor development. All patients who are immunosuppressed remain at increased risk for malignant changes. Close surveillance is needed to detect tumors at an early stage.

Twenty-one patients were studied at rest and during exercise after heart transplantation to compare cardiac output measured by thermodilution and impedance cardiography. Exercise was performed on a bicycle ergometer over a limited range of work load (25 and 50 watt) whilst metabolic gas exchange was recorded. One patient was studied at rest whilst his circulation was maintained by a Jarvik-7 artificial heart. The values of cardiac output measured by impedance cardiography corresponded closely with the flow rate from the artificial heart. There was also close agreement between the impedance and thermodilution measurements of cardiac output at rest and during exercise. Both measurements followed the changes in heart rate and oxygen consumption. Both thermodilution and impedance cardiography methods elicited good reproducibility of cardiac output measurements at rest and during exercise. These observations suggest that the noninvasive and continuous record of cardiac output obtained by impedance cardiography can be used for the postoperative monitoring of heart transplant recipients.

Triple-drug immunosuppression with cyclosporine, azathioprine, and steroids was introduced at Papworth Hospital in 1986. The management of rejection episodes in the first 40 patients receiving this regimen was reviewed for a minimal follow-up period of 18 months. Routine endomyocardial biopsy specimens were taken and classified into nil, minimal, mild, moderate, and severe rejection categories. Management was dependent on the biopsy result, in addition to the clinical state of the patient. In the early postoperative period (day 0 to 30) 2% of biopsy results showed severe rejection and 27% showed moderate rejection; all but one of the latter patients received augmentation of immunosuppression. In the intermediate period (days 31 to 90) severe rejection was present in 1% and moderate rejection in 36 (31%) of biopsies. Immunosuppression was augmented in 13 symptomatic patients, but in 23 asymptomatic patients additional therapy was withheld and the biopsy was repeated in 5 to 7 days. If moderate rejection was still present (11 cases), immunosuppression was augmented. Later (3 to 12 months) augmentation of immunosuppression was given on only four occasions. When the histologic criteria for diagnosis of moderate rejection are present during the early period after transplantation, we recommend augmented immunosuppression. In cases of later rejection we suggest that the decision be based on the biopsy result and the clinical condition of the patient; however, a prospective controlled trial will be required to confirm that this policy is correct.

Platelet damage during cardiopulmonary bypass (CPB), although proportional to the duration of bypass, may result in significant dysfunction after the initial contact with an extracorporeal circuit, the so-called 'first pass' phenomenon. The platelet sparing effect of prostacyclin (PGI2) infusion was studied in a double-blind randomized trial on male patients undergoing coronary artery bypass grafts to assess the effect of the 'first pass' through the CPB circuit. Prostacyclin infusion was begun before the onset of CPB or during CPB in two groups which were compared to a placebo control group. A standardized anaesthetic, surgical and perfusion technique were used. Preoperatively and during surgery at pre-set intervals, whole blood platelet aggregation was studied using ADP and collagen agonists. Platelet numbers and function measured by ADP aggregation were conserved in the two PGI2 groups. There was no significant difference between the treated groups. We conclude, therefore, that the initial contact of platelets with the CPB circuit, in the absence of PGI2 did not irreversibly affect platelet function. In addition, the hypotensive action of PGI2 was easier to control once on bypass. It may therefore be preferable to delay PGI2 infusion until CPB has been established.

We report the intensive care management of 23 children (age 3-15 years) following orthotopic heart (HT) and combined heart and lung transplantation (HLT) performed at our 2 institutes between February 1985 and August 1989. Cyclosporin A, azathioprine and steroids were given as routine immunosuppression, whilst anti-thymocyte globulin (ATG) was used for the first 3 post-operative days. Mean ventilation time was 24.6 h (range 4-74 h). Cardiovascular support comprised isoprenaline infusions in all patients (mean period 65.7 h) whilst dopamine and other inotropic agents were used less frequently. Sequential atrioventricular pacing was required more often in the HT patients (n = 9) than in the HLT patients (n = 4). Fluid input was restricted to maintain a plasma osmolality of 290-300 mosm/kg. There were 2 perioperative deaths both due to acute right heart failure. Other post-operative complications included: bleeding (n = 3); acute graft rejection (n = 4); infection (n = 3); systemic hypertension (n = 6); neurological abnormalities (n = 2); renal dysfunction (n = 6) and hyperglycaemia (n = 6).

The electrophysiologic characteristics of the denervated human heart were assessed in 14 cardiac transplant recipients. Conduction intervals and refractory periods were measured at pacing cycle lengths of 500 msec and 400 msec. The faster pacing rate caused lengthening of the AH interval (83 +/- 23 msec to 116 +/- 41 msec, p less than 0.01) and shortening of the QT (338 +/- 27 msec to 313 +/- 22 msec, p less than 0.001) and JT (249 +/- 21 msec to 229 +/- 19 msec, p less than 0.001) intervals. There was no change in the SA, HV, or QRS durations. Wenckebach periodicity occurred at a longer cycle length in the retrograde than in the anterograde direction (409 +/- 96 msec vs 318 +/- 46 msec, p less than 0.01) and anterograde conduction was better than retrograde conduction in 13 of the 14 patients (93%). Increasing pacing cycle length resulted in shortening of the atrial effective (203 +/- 28 msec to 190 +/- 25 msec, p less than 0.001), ventricular effective (224 +/- 18 msec to 211 +/- 17 msec, p less than 0.01), and AV nodal functional (367 +/- 38 msec to 357 +/- 36 msec, NS) refractory periods. The AV nodal effective refractory period lengthened (294 +/- 31 msec to 314 +/- 52 msec, p less than 0.05). There was a close correlation between AV Wenckebach cycle length and the functional refractory period of the AV node (r = 0.853, p less than 0.001). These results are qualitatively and quantitatively similar to those reported in the innervated heart. The autonomic nervous system appears to have little influence on the resting electrophysiologic characteristics of the atrioventricular conduction system in the innervated heart.

Peripheral T-cell subsets were monitored in ten heart and two heart-lung recipients pre- and up to one year post-operatively. Prior to transplantation four patients had T-helper/T-cytotoxic suppressor ratios (TH/TS-C) above the range for normal healthy controls and all required treatment for rejection episodes, as compared with three of eight patients whose pre-transplantation ratios were within the normal range. No patient with high TH/TS-C ratios developed cytomegalovirus infection as compared with all of the eight patients with normal ratios. Post-transplantation cytomegalovirus infection was the major cause of alterations in TH/TS-C ratios. T-cell subset inversion always preceded the diagnostic rise in cytomegalovirus antibody titre in both primary and secondary cytomegalovirus infections. Inversion was also noted with Pneumocystis carinii infection. Reversal of the TH/TS-C ratio was due to a major increase in the absolute numbers of TS-C cells and was usually followed by a rise in the number of cells expressing a natural killer cell phenotypic marker (Leu-7). All patients with primary cytomegalovirus and two of four cases with secondary cytomegalovirus retained inversion throughout follow-up and showed significantly increased numbers of TS-C and Leu-7 bearing cells. However, the absolute numbers of TH fell by 200 days after transplantation in all patients irrespective of their TH/TS-C ratio. Although TH/TS-C ratio inversion was a predictor of cytomegalovirus infection, no association was found between changes in T-cell subsets after transplantation and rejection episodes.

At present there is no satisfactory technique for repeated lung biopsy in recipients of heart-lung transplants. A new technique for lung biopsy, which might be adopted for this purpose, has been developed. A Teflon sheath is inserted through the jugular vein into the pulmonary artery with the aid of a balloon catheter. A flexible biopsy forceps is then introduced through the sheath into the pulmonary arterial tree and advanced into the periphery of the lung, where biopsy samples are taken. The procedure was attempted in 14 pigs. Initially crocodile jaw (two pigs) and fenestrated cups forceps (five pigs), which are currently in use for transbronchial lung biopsy, were used. Subsequently the biopsy forceps was modified and the jaws were replaced by a cutting needle mechanism (six pigs). Out of the 13 animals in which the procedure was technically possible, lung parenchyma was obtained from nine and pulmonary arterial wall from 11. One animal died shortly after the procedure. The cause of death could not be determined with certainty at postmortem examination. There was, however, a small tear on the surface of the lung, which could have produced a tension pneumothorax. The other 12 animals recovered from the procedure. They were killed 24 hours later and postmortem examination was carried out. One animal in which the crocodile jaw forceps had been used had a haematoma in the lower lobe (3 X 3 X 4 cm) and 100 ml of blood in the pleural cavity. In the other 11 animals, in which the fenestrated cups or the cutting needle forceps had been used, the intrapulmonary haematomas were 1-2 cm in diameter and the pleural surface was intact. It is concluded therefore that transvenous lung biopsy is feasible and that this procedure might find an application in monitoring rejection in recipients of heart-lung transplants.

The function of both the denervated donor and innervated recipient sinus nodes of 14 asymptomatic cardiac transplant recipients was assessed. Tests of sinoatrial function were performed in 14 donor and 10 recipient atria. The mean spontaneous cycle length of the recipient atria was significantly longer than that of the donor atria (944 +/- 246 versus 663 +/- 158 ms, p less than 0.01). Donor sinus node recovery time was prolonged in four patients (greater than 2,500 ms in two) and recipient recovery time was prolonged in six patients. In those patients with normal sinus node function tests, the recovery time of the recipient sinus node was longer than that of the donor sinus node (1,170 +/- 207 versus 864 +/- 175 ms, p less than 0.02). The pattern of response of recovery times to increasing pacing rate was predictable and organized in the donor but chaotic in the recipient, and the longest sinus node recovery time occurred at the shortest pacing cycle length used in 12 of the 14 donor atria but in only 1 of the 10 recipient atria (p less than 0.001). Secondary pauses occurred in none of the normal donor atria and in all of the abnormal donor atria (p less than 0.001); however, they occurred in both normal and abnormal recipient atria. The recipient and donor atria were paced alone and synchronously in the same patients. Synchronous pacing had no effect on the recovery times of the donor sinus node but significantly lengthened those of the recipient (sinus node recovery time: 1,266 +/- 218 to 1,547 +/- 332 ms, p less than 0.02; corrected recovery time: 322 +/- 102 to 686 +/- 188 ms, p less than 0.01). In the donor atria, abnormal recovery time was invariably associated with abnormal sinoatrial conduction time. There was a strong correlation between sinoatrial conduction time measured by the methods of Strauss and Narula and their coworkers in the donor atria (r = 0.98, p less than 0.001) but not in the recipient atria (r = 0.72). In the absence of autonomic influences, tests of sinus node function of the donor atria produce predictable and consistent results and, therefore, may be more clinically reliable than in intact human subjects. There is a high incidence of recipient sinus node dysfunction in asymptomatic long-term survivors of cardiac transplantation.

Chronic denervation of the heart leads to depletion of tissue catecholamines, giving rise to metabolic abnormalities, including a reduction in cardiac glucose oxidation. Impaired glucose oxidation could cause an increased oxidation of fat, which in turn could lead to development of coronary artery disease. Cardiac glucose oxidation (using 14C-(U),D-glucose) was studied in female baboons, before, and three to five weeks after, autotransplantation. Systemic arterial and coronary sinus samples were analyzed for total CO2 content, O2 content, 14CO2, glucose, lactate, pH, PCO2, and PO2. Tissue for metabolite assays (adenosine-5'-triphosphate [ADP] and creatine phosphate [CP]; glucose-6-phosphate [G6P] and fructose 6-phosphate [F6P] was obtained from the right ventricle before and after autotransplantation in some animals. There were no significant changes. Tissue was also obtained postmortem for analysis of noradrenaline, soluble tyrosine hydroxylase activity, and contractile and regulatory proteins. There was a large decrease in tissue noradrenaline, suggesting almost total sympathetic denervation. The level of tyrosine hydroxylase activity shows that the denervated heart can synthesize dopamine. There were no detectable changes in the contractile or regulatory proteins. In six of the nine baboons successfully studied, there was a distinct decrease in the oxidation of glucose after autotransplantation (P less than 0.05). This indicates that the removal of the sympathetic and parasympathetic nerve supply to the heart affects the ratio of glucose oxidized to other substrates.

Data for 1977-82 obtained from the Cardiac Surgical Register, established by the Society of Thoracic and Cardiovascular Surgeons of Great Britain and Northern Ireland in 1977, were analysed for trends in incidence and mortality of cardiac surgery and regional workload in the United Kingdom. Operative mortality for most types of cardiac operation showed a general decline. The numbers of operations performed for valvular and congenital heart disease had remained unchanged, but a striking increase had occurred in the number of coronary bypass graft operations: 2297 in 1977 to 6008 in 1982. The figure for 1982, representing an annual rate of 107 operations per million population, was still well below that for other countries such as Australia (410 per million in 1982) and the United States (750 per million in 1981). A wide variation was seen in the regional provision of cardiac surgical services within the United Kingdom. This was particularly appreciable for coronary bypass graft surgery, in which there was a 10-fold difference in numbers of operations performed between the various regions. The UK Cardiac Surgical Register provides an important source of information on trends within the specialty that could well be followed by other surgical specialties.

A system that uses a chemical method of cooling has been developed for the storage and transport of heart and heart-lung donor organs. This provides a precisely controlled environmental temperature without the use of ice, with its attendant problems of availability and potential contamination with pathogens. Storage and preservation solutions are transported to the donor hospital within the temperature-controlled polyurethane container, and the organs are returned in the same container, within an inflatable cushion. We have used this method for the distant procurement of over 260 hearts and for the most recent 30 heart-lung organ blocks. The mean ischemic time for hearts is 2.5 hours (1.5 to 4.2 hours) and for heart-lung blocks 2.2 hours (1.2 to 4.1 hours). Most donors give multiple organs such as kidney, liver, and pancreas. One patient received heart and kidney grafts from the same donor, and another received combined heart-lung and liver grafts. In relation to primary donor organ failure, there have been four deaths of patients who have had heart transplantations and no deaths of patients who received heart-lung organ blocks. We believe that the method offers advantages over the more conventional methods of organ storage with regard to convenience, temperature control, and sterility.

Insertion of a Celestin tube was employed in the treatment of 5 elderly patients who sustained perforations of the thoracic or abdominal esophagus during dilation of benign or malignant strictures. Two perforations treated within 24 hours were closed by direct suture in addition to intubation. There was a delay of 24 to 48 hours between the occurrence of the perforation and treatment in the other 3 cases. Only 1 of the latter patients subsequently developed pleural effusion, and this responded to drainage. One patient died 3 weeks after intubation; there was no evidence to suggest continued leakage through the perforation. The Celestin tube appears to be effective in sealing off esophageal perforations while healing occurs and merits consideration in the management of esophageal perforations associated with stricture in elderly patients when more radical treatment is not envisaged.

Of the first 250 heart and 35 heart and lung transplant recipients at Papworth Hospital, Cambridge, who survived for more than one month after transplantation, 217 heart and 33 heart and lung patients were investigated serologically for evidence of Toxoplasma gondii infection. Six patients acquired primary T gondii infection, most probably from the donor organ. Five patients experienced T gondii recrudescence, two of whom had recovered from primary infection a few years earlier. Two patients died from primary T gondii infection and the severity of symptoms in the other patients with primary infection was related to the amount of immunosuppressive treatment. Prophylaxis with pyrimethamine (25 mg a day for six weeks) was introduced for T gondii antibody negative transplant recipients who received a heart from a T gondii antibody positive donor after the first four cases of primary toxoplasmosis. Of the seven patients not given pyrimethamine, four (57%) acquired primary T gondii infection. This compared with two of the 14 patients (14%) given prophylaxis.

Evaluation of the functional condition of the heart prior to its removal from the donor or after transport to the recipient is difficult. Biopsies of the myocardium allow serial assessments to be made throughout this period, but suffer from the disadvantage that the average analysis of biopsies has only a tenuous connection with physiological function. Quantitative birefringence measurements (QBM), on the other hand, assess the ability of myocardial fibres to respond to ATP and calcium and have been shown to correlate well with measurements of cardiac function (P less than 0.001). A prospective study of myocardial biopsies before excision, after transport and again after transplantation, using quantitative birefringence measurement of biopsies of the heart has recently been completed. These studies have shown evidence of impaired myocardial function in 73 (43%) of 172 donor hearts studied prior to excision, with a further 27% showing significant deterioration during storage and transport to the recipient. Biopsy assessments therefore indicated that at the moment of implantation, only 30% of the donor hearts were normal. Functional assessment of the biopsies by QBM correlated with early clinical outcome of transplantation (P less than 0.001). Longer term follow-up of the recipients (up to 5 years) has shown that the mortality of recipients of hearts with impaired function before transplantation is significantly increased (44% of 120) compared with that of recipients of undamaged hearts (6% of 52, P less than 0.001).

It is usual to record independent activity from both the innervated recipient and the denervated donor atria in cardiac transplant recipients except for occasional, short-lived periods of entrainment that may occur during exercise. In this report a case is described in which, following orthotopic cardiac transplantation, the recipient and donor atria remained synchronized during a variety of physiological and non-physiological situations. Under no circumstances did the two sets of atria beat independently. The mechanisms that might be involved in this unique situation are discussed.

Phosphorus-31 nuclear magnetic resonance has been used to measure changes in tissue adenosine triphosphate and pH that occur during hypothermic preservation of rabbit hearts. Three potential preservation solutions were studied: the St. Thomas' Hospital no. 1 cardioplegic solution, Bretschneider's HTP solution, and a solution originated in our laboratory, CP5, which we have previously studied in the rabbit heart with functional assessment by Langendorff perfusion. After being flushed with one of these solutions, each heart was stored at 0 degrees C for 12 hours, during which time it was subjected to repeated phosphorus-31 nuclear magnetic resonance scans. It was shown that adenosine triphosphate levels decayed more slowly with CP5 than with either of the other solutions or in the control experiments. Adenosine triphosphate decay was also slower with Bretschneider's HTP than with St. Thomas' Hospital solution, but pH was somewhat better maintained with Bretschneider's HTP than with either other solution or in the control hearts, although the pH did not decrease drastically in any group. CP5 was designed to prevent cell swelling and to reduce the uptake of calcium during storage, for which reasons it contains 30 mmol/L glucose and 0.1 mmol/L calcium. The potassium content is somewhat higher and the sodium and magnesium content somewhat lower than in St. Thomas' Hospital solution, with the objective of stabilizing intracellular concentrations of these ions during storage.

Four patients are described with a recently recognized variant of double outlet right ventricle. Clinical examination favoured tetralogy of Fallot, but the chest X-ray suggested corrected transposition. Catheterization and angiocardiography showed that the aorta was to the left of the main pulmonary artery, and both arose from a normally positioned morphological right ventricle. Egress of blood from the left ventricle was through a subaortic ventricular septal defect. In all patients severe pulmonary stenosis was present and the right coronary artery ran an anomalous course anterior to the pulmonary valve ring. Two children had successful total correction, and one a palliative Blalock-Taussing shunt. Necropsy material from the fourth patient allowed confirmation of the ventricular morphology and the conducting tissued was examined. In corrective surgery, blood from the left ventricle was rerouted into the aorta by an intraventricular baffle. Pulmonary stenosis was relived by infundibulectomy and outflow tract patch.

The success of orthotopic heart transplantation depends wholly on satisfactory function of the new heart on completion of the operation. This in turn depends on the quality of the donor heart before its removal, the effectiveness of the methods used to preserve it during transport from the donor to the recipient hospital, and the accuracy of the operative procedure. From January 1979 to December 1983, 62 donor hearts were transplanted into 61 recipients at Papworth Hospital. These hearts were selected from 250 offered for consideration. The most common reasons for not proceeding with an initial inquiry were failure of the donor to meet the medical criteria for selection (77 cases) and lack of intensive care facilities or staff shortages such that a transplant could not be accommodated at the time of inquiry (80). Eight early deaths occurred, of which three were due to primary failure of the donor heart. Actual one and three year survivals for the whole programme were 58% and 50% respectively, the current actual one year survival being 70%. Forty per cent of patients selected for transplantation died while waiting for a heart to become available. Their average survival time was 46 days. The number of donor hearts referred for transplantation depends on public attitudes towards organ transplantation, the willingness of doctors looking after brain dead patients to seek permission from relatives for the heart to be donated, and the cooperation of local kidney transplant surgeons. A larger number of suitable donor hearts to choose from would enable more patients to be treated, as transplant operations could be arranged so that existing facilities were used to their maximum capacity.

Rupture of thoracic aortic aneurysms usually result in death from tamponade. Rarely does fistulous formation between the aorta and pulmonary artery complicate rupture. Such a complication results in the development of an acute left to right shunt. Although many previous reports occur in the literature only 10 include surgical management of an acquired aortic-pulmonary fistula. Two cases are presented with a description of their surgical management and outcome. Both these patients had previously undergone aortic valve replacement in the distant past for aortic regurgitation. These were the only 2 cases found in a review of 890 aortic valve replacements in Papworth Hospital over a 10 year period from 1975. The sicker of the two patients died during the operation and the second made a prompt recovery, succumbing a few years later to a cerebro-vascular accident.

Serial myocardial biopsy specimens, taken up to the time of serological evidence of primary cytomegalovirus (CMV) infection in 22 heart transplant patients, were examined and compared with those taken over similar times after transplantation in 21 patients who did not develop CMV infection. None of these 43 patients had serological evidence of CMV infection before their heart transplantation. There was no evidence of an increased cellular infiltrate in the myocardium at the time of the active CMV infection, even though the donor heart is the likeliest source of infection, nor was there any change in myocyte, interstitial cell, or vascular endothelial cell nuclei to identify active CMV infection.

Rapid uniform cooling of the heart is the most important requirement of any method using local hypothermia for protection of the myocardium during open intracardiac surgery. We report the construction and operation of a recirculation cooling circuit comprising a reservoir, pump, and heat-exchanger for this purpose. It is operated by the perfusionist and can deliver up to 1 litre of fluid per minute at 4 degrees C into the pericardium or interior of the heart. Advantages of the system include rapid cooling of the myocardium, simplicity of operation, and applicability to all routine cardiac surgical procedures.

One thousand two hundred and three open-heart operations were performed at Papworth Hospital between January 1973 and December 1978 with an early (30 day) operative mortality of 5.3%. One hundred patients were treated on an emergency basis. This is defined as an operation necessarily performed within 24 hours of referral to a surgeon. The early mortality in this group was 24 (24 per cent) and accounted for one third of the early deaths during the period under review. The main clinical conditions requiring emergency surgery included ischaemic heart disease (36 patients, early mortality 22.2%); critical valve disease (24 patients, 12.5%); bacterial endocarditis (14 patients, 28.5%); acute aortic dissection (11 patients, 36%) and complications associated with valve substitutes (11 patients, 36%). Almost all the deaths in the ischaemic heart disease group occurred in those undergoing operation for the complications of infarction. Many factors contribute to the higher risk of emergency open-heart surgery. Of these, dysfunction of other organ systems secondary to low cardiac output and the state of the left ventricle are the most important. Earlier referral for operation of patients with critical valve disease should help to reduce mortality.

A raised hemidiaphragm has been reported as an uncommon complication of cardiopulmonary bypass, possibly resulting from cold injury to the phrenic nerve. At Papworth Hospital myocardial protection during cardiac arrest relies in part on irrigation of the pericardial cavity with large volumes of Hartmann's solution at 4 degrees C. Retrospective review of the chest radiographs of 100 consecutive patients undergoing cardiopulmonary bypass showed that 31 had a raised left hemidiaphragm soon after operation. The only significant correlation was with aortic cross clamp time (p less than 0.03). A prospective study of 36 consecutive patients undergoing cardiopulmonary bypass was then undertaken with diaphragmatic screening and chest radiography. Preoperative screening gave normal results in all patients. In the early postoperative period 16 (44%) had left diaphragmatic weakness or paralysis, two (5.5%) right sided weakness, and two (5.5%) bilateral weakness. Repeat screening of these patients showed resolution in all but four cases (80%) at six months and in all but two (90%) at one year. The greater number of left sided lesions than of right (8:1) is probably due to the fact that the cold jet of irrigating fluid is directed towards the left phrenic nerve. These findings have implications with regard to the optimum temperature of the irrigant fluid for myocardial protection during cardiopulmonary bypass.

The first case of disseminated toxoplasmosis following cardiac transplantation in the UK is described, with details of Toxoplasma antibody tests made on other cardiac transplant patients. Sixteen of 40 (39%) of recipients had Toxoplasma antibody before operation. Eleven of 30 (37%) of donors had Toxoplasma antibody. The were four occasions when a negative recipient received a heart from a positive donor. Three survived the immediate postoperative period and two became infected with toxoplasmosis. The implications of this are discussed. Disseminated toxoplasmosis appears much more often when heart muscle from a dye test positive donor is given to a dye test negative recipient. Antibiotic therapy is limited by the fact that the antitoxoplasma drugs available are static in their effect, and need to be given for prolonged periods postoperatively.

This paper describes the behavior of orthotopically allografted hearts in the pig. Rejection between littermate pigs varied from under 7 days to more than 5 mo in unimmunosuppressed animals.

Over a three year period we have used haemodialysis and haemofiltration in parallel with cardiopulmonary bypass in 26 patients. Impaired renal function and excessive fluid retention have been the main indications. Patients on haemodialysis programmes for end stage renal failure did not require further dialysis until at least the third postoperative day, when they could tolerate the haemodynamic disturbance of dialysis. In the other patients these techniques proved valuable in reversing the effects of haemodilution and in controlling the concentration of serum potassium. Our experience has confirmed that haemodialysis and haemofiltration in parallel with cardiopulmonary bypass are useful adjuncts in the perioperative management of patients with impaired renal function undergoing open heart surgery. The techniques are also effective in correcting the fluid retention and biochemical imbalance in patients with congestive cardiac failure, including those with heart transplants.

A case of myxoma of the mitral valve is reported. The clinical features were indistinguishable from left atrial myxoma with prolapse through the mitral valve. Because of the known tendency for these tumours to recur it was treated by wide excision which necessitated replacement of the mitral valve.

The major factors contributing to the recommencement of clinical heart transplantation in the United Kingdom last year were the steadily improving results from Stanford University, the clarification of the diagnosis of brain death, and advances in preserving donor hearts. Twelve men aged 16 to 52 years received heart transplants at Papworth Hospital from January 1979 to July 1980. Six had cardiomyopathies and six ischaemic heart disease. The donors were aged 16 to 35 (mean 21) years. A combination of road and air transport was used to transport the heart to Papworth in seven cases. The total donor heart ischaemic time ranged from 108 to 171 minutes (mean 151), and early graft function was satisfactory in all cases. Postoperative management was directed towards preventing rejection and infection. Equine antihuman thymocyte globulin, prednisolone, and azathioprine were used for immunosuppression. Endomyocardial biopsy was performed every 10 to 14 days during the early postoperative period. There were three deaths: one at 17 days from brain damage and two at 59 and 76 days from rejection. Of the remaining nine patients six left hospital and three returned to work. The number of patients who might benefit from heart transplantation is large, but the cost is high. The cost would fall if an effective non-toxic immunosuppressive agent were developed. Meanwhile, a careful evaluation of the benefits of heart transplantation should continue.

The quality of life for those who survive the first 3 months after transplantation is generally good (10). The duration of hospital stay and the cost of transplantation per patient has been reduced during the last 3 years. Cardiologists are coming to appreciate the therapeutic potential of both heart and heart-lung transplantation. One of the chief logistical problems now being faced is that of increasing the provision of transplant services to match the increasing demand. It was said in an earlier edition of this book that this would be donor organ limited and that pattern already seen in the United States is becoming apparent in the United Kingdom. The broad principles of management of heart and heart-lung recipients have been established. Further improvements in medium and long-term results can be anticipated as a result of refining immunosuppression and defining the cause of chronic donor organ related damage (small vessel coronary occlusive disease in heart transplants and chronic obliterative bronchiolitis in heart-lung transplants). Heart transplantation has become firmly established as a therapeutic option for life threatening heart disease. It is probably too early to attribute this label to heart-lung transplantation which continues through its developmental phase with acceptable short-term results. Improvements in chronic damage characteristic of long-term survival in both heart and heart-lung transplant recipients will be a significant clinical step forward in this field.

A 51-year-old man presented with an abscess in his sternotomy scar 33 months after orthotopic heart transplantation. After surgical drainage he developed a febrile illness which led to renal and pulmonary failure. Twenty-three days after the illness began, blood cultures grew Staphylococcus aureus and he died 11 days later. Post-mortem examination revealed acute bacterial endocarditis with dense colonies of gram-positive cocci on the mitral valve leaflets and microabscesses in the myocardium of the transplanted heart.