Effect of ischaemia and reperfusion on the intracellular concentration of taurine and glutamine in the hearts of patients undergoing coronary artery surgery.

Taurine and glutamine are the most abundant intracellular free amino acids in mammalian hearts where changes in their intracellular concentrations are likely to influence a number of cellular activities. In this study we investigated the effects of ischaemia and reperfusion on the intracellular concentrations of taurine and glutamine in the hearts of patients undergoing coronary artery bypass surgery using cold crystalloid or cold blood cardioplegic solutions. Ischaemic arrest (30 min), using cold crystalloid cardioplegic solution (n = 19), decreased the intracellular concentrations (micromol/g wet weight) of taurine (from 9.8 +/- 0.8 to 7.7 +/- 0.7, P < 0.05) and glutamine (8.7 +/- 0.5 to 7.2 +/- 0.6). After 20 min of normothermic reperfusion the fall in taurine and glutamine was maintained (7.5 +/- 0.5 and 7.4 +/- 0.7 for taurine and glutamine respectively). Myocardial ischaemic arrest with cold blood cardioplegic solution (n = 16) did not cause a significant fall in tissue taurine or glutamine. However, on reperfusion there was a marked fall in the intracellular concentrations of taurine (9.4 +/- 0.5 to 6.5 +/- 0.7) and glutamine (8.0 +/- 0.7 to 5.8 +/- 0.4). The fall in amino acids was associated with a fall in ATP and a rise in tissue lactate. This work demonstrates that irrespective of the cardioplegic solution used to arrest the heart, there is a marked fall in tissue taurine and glutamine which may influence the extent of recovery following surgery. The fall in taurine is largely due to efflux whereas changes in glutamine are due to both transport and metabolism. Ischaemia, hypothermia and changes in the transmembrane concentration gradients are the likely factors responsible for the changes in tissue amino acids.

Antiinflammatory C-glucosyl chromone from Aloe barbadensis.

A new antiinflammatory agent identified as 8-[C-beta-D-[2-O-(E)-cinnamoyl]glucopyranosyl]-2- [(R)-2-hydroxypropyl]-7-methoxy-5-methylchromone (1) has been isolated from Aloe barbadensis Miller. At a dose of 200 microg/mouse ear, 1 exhibited topical antiinflammatory activity equivalent to 200 microg/ear of hydrocortisone. There was no reduction in thymus weight caused by treatment with 1 for any of the doses tested, while 200 microg/ear of hydrocortisone resulted in a 50% decrease in thymus weight.

Aprotinin use with hypothermic circulatory arrest for aortic valve and thoracic aortic surgery: renal function and early survival.

BACKGROUND AND AIM OF STUDY: Aprotinin is widely used during high risk cardiac surgery to reduce blood loss. Concern has been expressed about the safety of aprotinin in association with hypothermic circulatory arrest for surgery of the thoracic aorta and aortic valve. METHODS: A consecutive series of 19 patients undergoing surgery of the ascending aorta and/or the aortic arch using hypothermic circulatory arrest (15 - 20 degrees C) in conjunction with the use of aprotinin were studied prospectively from January 1993 to October 1994. The indications for operation were aortic dissection (n = 15) (11 acute) or annuloaortic ectasia (n = 4); 11 were emergency procedures. Ten patients underwent aortic valve replacement as part of a composite aortic root replacement and in seven patients aortic valve resuspension was possible. RESULTS: Mean total chest tube drainage was 878 +/- 548 ml (range 300 - 2,000 ml) with a mean usage of homologous blood of 2,328 +/- 1,600 ml. All but one patient survived (mortality 5.3%). None of the survivors experienced any adverse cardiac or neurological events. Serum creatinine rose significantly from a mean of 102 +/- 17 micromol/L preoperatively, to a mean of 172 +/- 100 micromol/L postoperatively (p<0.05), however, none of the patients became anuric or required dialysis and all values returned to preoperative levels by six weeks after surgery. Median intensive care stay was two days (range 1 - 20 days) and the median postoperative hospital stay was 11 days (range 6 - 50 days). CONCLUSION: These data suggest that aprotinin in conjunction with hypothermic circulatory arrest for surgery of the thoracic aorta and aortic valve has no adverse effect on early survival. However, significant though transient postoperative renal dysfunction was commonly observed in our experience.

Posterior pericardiotomy reduces the incidence of supra-ventricular arrhythmias following coronary artery bypass surgery.

A prospective study of 100 patients undergoing coronary artery bypass surgery was performed to demonstrate the effectiveness of a posterior pericardiotomy in reducing the incidence of pericardial effusions and, consequently, reducing the incidence of supraventricular arrhythmias in the post-operative period. Pericardial effusion occurred in 4 of 50 patients following a posterior pericardiotomy, whereas effusion occurred in 20 of 50 patients in whom a pericardiotomy was not created (P < 0.0005). Supra-ventricular arrhythmias occurred in 4 patients in the pericardiotomy group and 18 in the group treated without pericardiotomy (P < 0.005). No complications resulted from this procedure. We conclude that pericardiotomy is a simple, safe and effective method for reducing the incidence or pericardial effusion and thereby post-operative supra-ventricular arrhythmias.

Early experience with the Jyros bileaflet valve. Is leaflet rotation clinically important?

The design of the Jyros bileaflet prosthesis provides for a continuous, circumferential rotation of the hinge. Previous in vitro testing has confirmed the uninterrupted gyration of the leaflets, which reduces the risk of stasis within the hinge area, and as a consequence, possibly reduces the risk of thromboembolism. Twenty Jyros bileaflet valves were implanted in 19 patients between July 1991 and September 1992. There was one hospital death not related to the prosthesis. One valve had to be removed from the mitral position immediately after implantation because preservation of the posterior mitral leaflet led to malfunction of the prosthesis. Clinical and radiological follow up demonstrated that all surviving patients were clinically well, but nine of the remaining 18 valves (50%) showed no rotation of the leaflets.

Medium-term clinical results after the Senning procedure with haemodynamic and angiographic evaluation of the venous pathways.

OBJECTIVE: To assess the clinical condition of patients and the adequacy of their newly constructed venous pathways after the Senning operation for simple transposition of the great arteries. PATIENTS AND DESIGN: All 34 patients who had the Senning operation between March 1983 and December 1986 were reviewed. Survivors had detailed cardiac catheterisation studies one to two years later and clinical evaluation two to six years after surgery. RESULTS: There were two operative deaths (6%), one sudden late death (after two years), and 31 survivors (91%). No clinical evidence of obstructed venous pathways was found and there was no need for reoperation for any reason. The average mean (SD) pressure gradient at the junction of the superior vena cava and systemic venous atrium was 2.0 (1.7) mm Hg, although two patients had gradients of 7 mm Hg. The average gradient was 0.7 (1) mm Hg in the inferior vena caval pathway, and 1.4 (1.1) mm Hg between the mean pulmonary arterial wedge and pulmonary venous atrial pressures. Only the two patients with gradients of 7 mm Hg at the junction of the superior vena cava and the systemic venous atrium had considerable narrowing of the pathway and retrograde flow in the azygos vein to below the diaphragm. CONCLUSION: A small series of patients were comprehensively studied after the Senning operation for simple transposition of the great arteries. Scrupulous technique in the construction of the venous pathways has had excellent results with no need for reoperation for obstruction in either the systemic or pulmonary pathways. Clinical observation alone may fail to identify patients with venous pathway obstruction, therefore careful assessment is required, even in patients who are physically normal.

A loss of taurine and other amino acids from ventricles of patients undergoing bypass surgery.

OBJECTIVE: To study the changes in amino acid content of left ventricles of patients during cardiac surgery that involves cardiopulmonary bypass and cold cardioplegia. DESIGN: Biopsy specimens (up to 10 mg wet weight) from the left ventricle of 30 patients undergoing coronary artery bypass graft and valve replacement surgery on cardiopulmonary bypass (protected by cold cardioplegia with St Thomas' solution) were taken immediately before the infusion of the cardioplegic solution and just before the removal of the cross clamp, and were analysed for their amino acid content. RESULTS: Of the most abundant cellular amino acids in the left ventricle taurine, glutamine, glutamate, and aspartate, but not alanine, showed a significant fall during the period of cross clamping. A rise in intracellular sodium (Na) is known to occur during cold cardioplegic arrest so that an activation of an amino acid/Na efflux, similar to that seen in animal experiments, seems a likely mechanism. The anomalous behaviour of alanine suggests some recovery of metabolism. CONCLUSIONS: The loss of alpha amino acids (by contrast with the loss of taurine) will depress protein synthesis and reduce energy reserves after cardiac surgery. Attempts to preserve the concentrations of intracellular alpha amino acids must be balanced against the need to regulate intracellular Na concentration and hence intracellular pH and calcium ions. The presence of alpha amino acids in the cardioplegic solution (or in a resuscitation solution) should maintain the intracellular concentrations and favour activation of the taurine/Na symport to oppose the rise in intracellular Na concentration. Because the reservoir of tissue taurine is limited, the potential benefits of increasing the concentration of taurine in the heart by diet before surgery and addition of alpha amino acids to the cardioplegic solution merits further assessment.

Effects of the immunosuppressant cyclosporine on the circulation of heart transplant recipients.

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.

Some prognostic factors for the development of transplant-related coronary artery disease in human cardiac allografts.

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.

Management of rejection in heart transplant recipients: does moderate rejection always require treatment?

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.

The management of empyema thoracis by thoracoscopy and irrigation.

A technique of irrigation for the management of empyema thoracis is described. Initial thoracoscopy using a laparoscope under general anaesthesia enabled adequate debridement and breakdown of loculi within the empyema cavity under direct vision. Following this procedure irrigation of the cavity with two tubes was started and continued until three consecutive cultures of drained irrigation fluid became sterile. The procedure was then discontinued. The results in 14 patients are presented using this method, irrigation was required for an average of 14 days. Patients remained in hospital for an average of 4.8 weeks. Tuberculous empyema was not found to be a contra-indication to the irrigation technique.

The management of cardiac surgical patients in a general surgical recovery ward.

A suitable combination of anaesthetic and surgical techniques has allowed the safe management of post-operative cardiac surgical patients to be conducted in a surgical recovery area rather than in the intensive care ward. The results of the first 103 patients so managed (aged 49 +/- 10.7 years) are presented. Coronary artery bypass grafts were performed on 98 patients, 4 patients underwent repair of atrial septal defect and on 1 patient a pulmonary valvotomy was performed. The complications and their management are described.

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.