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These studies demonstrate that immune monitoring and individualized modulation of recipient immune reactivity using a quality-controlled preparation of rabbit antithymocyte globulin can improve results of cardiac transplantation. The most valuable assay in individualizing drug doses was the serial measurement of T-cell levels using a complete lymphocyte profile technique and monitoring with phytohemagglutinin to rule out false low T-cell levels. Using this system, the incidence and severity of early rejections were markedly reduced and no grafts were lost to rejection in the first month. The recent first-year graft survival has been about 60%, an improvement largely related to a reduction in early rejection and infection. This technique of immunosuppression appears quite promising for improving the results of future cardiac transplantations.

Heart period variability and arterial baroreceptor-cardiac reflex function were studied in cardiac transplant patients to determine if correction of heart failure restores parasympathetic control mechanisms toward normal. Heart period variability (standard deviation [SD] of 120 consecutive RR or PP intervals) was measured at supine rest in 34 patients with congestive heart failure (23 patients receiving diuretics, digoxin or vasodilators and 11 patients weaned from all medications), 30 cardiac transplant patients (both innervated recipient and denervated donor atrial rates) and 16 age-matched healthy control subjects. Arterial baroreflex gain was evaluated with intravenous bolus injections of phenylephrine in 22 transplant patients. Mean heart period variability (+/- SEM) was significantly lower (p less than 0.05) in the heart failure groups (22 +/- 3 ms for medicated and 17 +/- 3 ms for nonmedicated) than in the transplant patients (41 +/- 5 ms) or control subjects (58 +/- 5 ms). Heart period variability of the transplant patients was less than that of the control patients (p less than 0.05). A stepwise regression model revealed that heart period variability was inversely related to systolic arterial pressure and directly related to time after transplantation (R2 = 0.39; p = 0.03) in the transplant patients. Baroreflex gain of normotensive transplant patients was normal (11.7 +/- 1.0 ms/mm Hg) and correlated directly with heart period variability (r = 0.62; p less than 0.001). These data suggest that subnormal levels of cardiac parasympathetic activity at rest associated with congestive heart failure can be restored progressively toward normal by correction of congestive heart failure after cardiac transplantation. Post-transplant hypertension opposes this correction of baseline parasympathetic activity.

Electrophysiological observations during preoperative and intraoperative study of a 46-year-old patient with incessant ventricular tachycardia and QRS alternans demonstrated a potential mechanism for this electrocardiographic finding. During QRS alternans, conduction delay (or block) was recorded from the site of origin of the tachycardia, high on the anterior septum to the His bundle: After procainamide infusion, the tachycardias slowed and, concurrent with the disappearance of QRS alternans, conduction from the site of tachycardia origin to the His bundle could no longer be demonstrated.

Of 57 patients referred to the McGuire Veterans Administration Medical Center, Richmond, Va, for evaluation for cardiac transplantation, 18 received allografts. The overall graft survival rate was 67% from two to 24 months after transplantation. In 15 recipients receiving immunosuppression with rabbit anti-human thymocyte globulin, prednisone, and azathioprine, previous transfusion and HLA-DR matching resulted in improved graft survival. In three patients receiving cyclosporin and prednisone, hypertension, nephrotoxicity, and hepatotoxicity were seen. All surviving recipients were in functional New York Heart Association class 1 or 2. The cost to the Medical Center was $23,275 per transplant. The results achieved at the center suggested that a regionalized cardiac transplant program can be established within the VA health care system with acceptable clinical results and significant financial savings.

A 15 year old boy had an eight month history of recurrent fever, malaise and poor appetite. Chest roentgenogram revealed a foreign object overlying the right ventricle. Multiple blood cultures grew Enterobacter cloacae. The patients condition improved and blood cultures became negative following gentamicin and carbenicillin therapy. E. cloacae was isolated from the foreign body (a finishing nail) at surgery. Antimicrobial therapy was continued for a total of 30 days, and the patient made an uneventful recovery.

Esophageal electrocardiography is a commonly used tool for the differential diagnosis of arrhythmias. A 39-year-old man who underwent orthotopic heart transplantation developed a narrow complex tachycardia. Esophageal electrocardiography showed a junctional tachycardia (recording native atrial activity alone), whereas atrial intracavitary electrograms showed the correct diagnosis of atrial flutter. Esophageal recording in patients who undergo orthotopic heart transplantation is a useful technique for recording native atrial activity. For arrhythmia diagnosis in these patients it is frequently necessary to record donor atrial activity with intracavitary electrograms. The limitations of esophageal electrocardiography should be recognized by physicians who care for these patients.

We report the vascular surgical strategies and results in 13 patients with heparin-associated thrombocytopenia and describe useful in vitro techniques for the evaluation of anticoagulant therapy. Thirteen of 40 patients with heparin-associated thrombocytopenia had 18 cardiovascular procedures done to save life or limb. Greenfield filters were placed in eight patients to prevent pulmonary embolism. Eight patients had 10 arterial procedures, with alternative anticoagulation that used dextran or warfarin in five cases. In three cases iloprost, a derivative of prostacyclin and a potent platelet inhibitor, was infused intraoperatively and heparin was given. Both the use of alternative anticoagulants and platelet suppression by iloprost were clinically effective strategies. The concurrent measurement of plasma levels of beta-thromboglobulin and fibrinopeptide A in two patients confirmed that both approaches can successfully prevent activation of platelets and plasma coagulation during arterial surgery. One operative death occurred; all vascular reconstructions remained patent at 3 to 6 months. In two patients who received heparin alone for arterial surgery, both procedures resulted in thrombosis and limb loss. When major venous thromboembolism is complicated by heparin-associated thrombocytopenia, insertion of a Greenfield vena cava filter should be considered if there is significant risk of pulmonary embolism. When necessary, arterial surgery is feasible in patients with heparin-associated thrombocytopenia if alternative anticoagulation or adequate suppression of platelet reactivity can be achieved.

Fifty-two consecutive patients who underwent orthotopic heart transplantation at our institution were evaluated by two-dimensional (2D) echocardiography at frequent intervals for 12 weeks after transplantation and at three monthly intervals for 1 year. Thirty-eight of 52 patients had adequate 2D echocardiograms and comprised the retrospective study group. Pericardial effusion was documented in 15 of 38 patients (40%). Pericardial effusion was moderate in two (5%) and small in seven patients (18%). Large pericardial effusion was demonstrated in six of 38 patients (16%). Three of 38 patients (8%) developed cardiac tamponade manifested by hypotension in the presence of a large pericardial effusion. The diagnosis of cardiac tamponade was aided by 2D echocardiography leading to prompt pericardiocentesis. The presence of pericardial effusion in patients after their transplantation did not demonstrate independent correlation with chest tube output after operation, cyclosporine therapy, acute rejection, level of blood urea nitrogen (BUN), infection or preoperative diagnosis of idiopathic dilated cardiomyopathy. The presence of cyclosporine therapy, acute rejection, and a preoperative diagnosis of idiopathic dilated cardiomyopathy, however, yielded an 86% probability of having pericardial effusion. Follow-up 2D echocardiograms obtained 301 +/- 106 days after transplantation were available in 25 patients. Fifteen patients (60%) had no pericardial effusion present on either the initial or follow-up 2D echocardiogram. The majority of cases of the pericardial effusion present on initial or follow-up echocardiograms were resolving on the follow-up study.(ABSTRACT TRUNCATED AT 250 WORDS)

The case of a patient with a chronic, posttraumatic descending thoracic aortic aneurysm and a large diaphragmatic hernia is presented. We repaired the diaphragm with Prolene mesh and externally grafted the aneurysm. To our knowledge, simultaneous repair of these two chronic injuries has not been reported. The merits of external grafting of aortic aneurysms are discussed.

Since the introduction of cyclosporine in heart transplantation, the search for the ideal combination of immunosuppressive agents continues. Between January 1983 and February 1985, 32 patients have been randomized prospectively to either one of two immunosuppressive regimens: one includes pretransplant transfusion, prednisone, azathioprine and rabbit anti-thymocyte globulin [Group I, n = 14], the other includes cyclosporine and prednisone [Group II, n = 18]. There were no differences between Group I and II in relation to age distribution, indications for transplantation, preoperative serum creatinine, length of follow-up, mortality or number of rejection episodes per patient. However, there was a statistically significant increase in the incidence of serious infections in Group I compared to Group II patients, and also in Group II of the incidence of systemic hypertension (p less than 0.001), of symptomatic pericardial effusion (p less than 0.05) and impaired renal function (p less than 0.02). Adding cyclosporine to azathioprine immunosuppression is effective in treating ongoing rejection in patients not previously treated with cyclosporine. In conclusion, patients treated with azathioprine and prednisone (Group I) develop a greater number of serious infections, but both groups had a similar incidence of rejection. The development of renal dysfunction and hypertension in patients treated with cyclosporine continues to be of concern and may preclude its use as an effective long-term immunosuppressive agent in heart transplant recipients.

Forty-one heart transplant recipients were monitored serially for the expression of transferrin receptors and T-helper/T-suppressor cytotoxic ratios on circulating lymphocytes during the hospitalization periods after heart transplantations (60.5 +/- 18.9 days). These values were retrospectively correlated with the patients' clinical status with respect to rejection and infection. During clinically stable periods the average values of percentage of transferrin receptor-positive lymphocytes and T-helper/T-suppressor cytotoxic ratios were 5.9 +/- 4.3 and 1.5 +/- 1.0, respectively. The percentage of transferrin receptor-positive lymphocytes increased to a level of 12.0 +/- 5.4 (p less than 0.001) during the early prerejection phase and remained at this level throughout the rejection period. T-helper/T-suppressor cytotoxic ratios increased to 1.96 +/- 0.92 during the early prerejection phase (p less than 0.05), peaked at 2.30 +/- 1.21 during the late prerejection phase (p less than 0.01), but began to decline by the rejection period. After rejection treatment percentage of transferrin receptor-positive lymphocytes decreased to 8.4 +/- 5.3 (p less than 0.05), and T-helper/T-suppressor cytotoxic ratios decreased to normal levels. In contrast, in patients with infectious complications, a remarkably elevated percentage of transferrin receptor-positive lymphocytes (20.7 +/- 11.7) and relatively low T-helper/T-suppressor cytotoxic ratios (1.3 +/- 0.5) were noted. The data show an association between the clinical status, such as rejection and infection, and these immunologic measurements as transferrin receptor-positive lymphocytes and T-helper/T-suppressor cytotoxic ratios in heart transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the necessity for maintenance dosages of prednisone in the management of heart transplant patients, a retrospective study was made of 86 patients undergoing orthotopic heart transplantation and two patients having heart-lung transplantation from June 1985 through October 1986. Group 1 (n = 52) had maintenance immunosuppressive therapy that included cyclosporine, azathioprine, and prednisone. Group 2 (n = 36) received only cyclosporine and azathioprine with no maintenance dosage of steroids. Data were analyzed for frequency of rejections, infections, noninfectious complications, and mortality. The rate of rejection was 1.44 episodes per patient in group 1 and 1.58 episodes per patient in group 2. Twenty of 52 patients (38%) in group 1 had no rejection compared with 12 of 36 patients (33%) in group 2 (p = not significant [NS]). One or more infections occurred in 30 patients (58%) in group 1, whereas only 12 patients (33%) in group 2 had infections (p less than 0.05). Noninfectious complication rates were noted to be similar in both groups (27% versus 25%, p = not significant). There were five deaths in group 1: three from infections, one from rejection, and one from trauma. There were three deaths in group 2: two from infection and one from rejection. Although 14 patients in group 2 eventually were placed on low-dosage steroid maintenance, the remaining 22 patients (61%) never received maintenance dosages of steroids. We conclude that some patients can be successfully managed without maintenance dosages of steroids after heart transplantation. Such patients do not appear to have an increased risk of rejection and may have a reduced rate of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

The prophylactic use of rabbit antithymocyte globulin (RATG) was evaluated in 13 cardiac allograft recipients who received a low-dose of RATG (175 +/- 32 mg) after transplantation (group 1). The patients were retrospectively compared with 13 parallel cases receiving the same treatment except for the initial RATG (group 2). There were no differences in the patient composition and the level of the basic immunosuppression therapy with cyclosporine. The patients treated with RATG (group 1) showed substantially greater suppression of T helper and total T cells up to 10 and 20 days after surgery, respectively. The incidence of rejection episodes during the initial admission seemed lower in patients receiving RATG, with a borderline significance (1.4 versus 2.4, p = 0.06). This accounts for the reduced requirement of methylprednisolone in treating rejection in patients in group 1 (1.3 gm versus 4.0 gm, p less than 0.02). Moreover, the patients without initial doses of RATG (group 2) more frequently experienced recurrent rejection (five of 12 versus nine of 10, p less than 0.05), which necessitated rescue RATG; the initial difference in the RATG usage disappeared by the time of discharge. Serious infection occurring after antirejection therapy was common in the group 2 patients without initial doses of RATG, although the overall incidence of infection was not statistically different. Prophylactic use of RATG at the dosage used appeared to reduce the incidence of rejection and the requirement for intravenous steroids and other immunosuppressants. It seems warranted to test this approach in a prospective randomized manner.