Pulmonary retransplantation: predictors of graft function and survival in 230 patients. Pulmonary Retransplant Registry.

BACKGROUND: Despite improving results in lung transplantation, a significant number of grafts fail early or late postoperatively. The pulmonary retransplant registry was founded in 1991 to determine the predictors of outcome after retransplantation. We hypothesized that ambulatory status of the recipient and center retransplant volume, which had been previously shown to predict survival after retransplantation, would also be associated with improved graft function postoperatively. METHODS: Two hundred thirty patients underwent retransplantation in 47 centers from 1985 to 1996. Logistic regression methods were used to determine variables associated with, and predictive of, survival and lung function after retransplantation. RESULTS: Kaplan-Meier survival was 47% +/- 3%, 40% +/- 3%, and 33% +/- 4% at 1, 2, and 3 years, respectively. On multivariable analysis, the predictors of survival included ambulatory status or lack of ventilator support preoperatively (p = 0.005; odds ratio, 1.62; 95% confidence interval, 1.15 to 2.27), followed by retransplantation after 1991 (p = 0.048; odds ratio, 1.41; 95% confidence interval, 1.003 to 1.99). Ambulatory, nonventilated patients undergoing retransplantation after 1991 had a 1-year survival of 64% +/- 5% versus 33% +/- 4% for nonambulatory, ventilated recipients. Eighty-one percent, 70%, 62%, and 56% of survivors were free of bronchiolitis obliterans syndrome at 1, 2, 3, and 4 years after retransplantation, respectively. Factors associated with freedom from stage 3 (severe) bronchiolitis obliterans syndrome at 2 years after retransplantation included an interval between transplants greater than 2 years (p = 0.01), the lack of ventilatory support before retransplantation (p = 0.03), increasing retransplant experience within each center (fifth and higher retransplant patient, p = 0.04), and total center volume of five or more retransplant operations (p = 0.05). CONCLUSIONS: Nonambulatory, ventilated patients should not be considered for retransplantation with the same priority as other candidates. The best intermediate-term functional results occurred in more experienced centers, in nonventilated patients, and in patients undergoing retransplantation more than 2 years after their first transplant. In view of the scarcity of lung donors, patient selection for retransplantation should remain strict and should be guided by the outcome data reviewed in this article.

Pulmonary retransplantation: does the indication for operation influence postoperative lung function?

OBJECTIVE: An international series of pulmonary retransplantation was updated to determine the factors associated with pulmonary function, bronchiolitis obliterans syndrome stage, and survival after operation. METHODS: One hundred sixty patients underwent retransplantation in 35 centers from 1985 to 1995. Logistic regression methods were used to determine variables associated with 3-month and 2-year survival after retransplantation. Values of forced expiratory volume in 1 second were contrasted between groups by unpaired, two-tailed t tests. RESULTS: The median follow-up in surviving recipients was 780 days. Actuarial survival was 45% +/- 4%, 41% +/- 4%, and 33% +/- 4% at 1, 2, and 3 years, respectively. On multivariable analysis, the only predictor of 3-month survival was preoperative ambulatory status (p = 0.005), whereas center experience with at least five pulmonary retransplantations was the sole predictor of 2-year survival (p = 0.04). The prevalence of stage 3 (severe) bronchiolitis obliterans syndrome was 12% at 1 year, 15% at 2 years, and 33% at 3 years after retransplantation. Retransplant recipients with stage 3 bronchiolitis obliterans syndrome at 1 year had a significantly worse actuarial survival than those with stages 0 to 2 (p < 0.01). By 3 years after retransplantation, the forced expiratory volume in 1 second was significantly lower in patients who underwent reoperation because of obliterative bronchiolitis than in patients who underwent retransplantation because of acute graft failure or an airway complication (p = 0.02). Only 31% of patients who underwent retransplantation because of obliterative bronchiolitis were free of bronchiolitis obliterans syndrome at 3 years versus 83% of patients who underwent retransplantation because of other indications (p = 0.02). CONCLUSIONS: Preoperative ambulatory status predicts early survival and center volume predicts intermediate-term outcome after retransplantation. Improved management strategies are necessary to prevent the development of progressive graft dysfunction after retransplantation for obliterative bronchiolitis.

Early lung allograft function in twin recipients from the same donor: risk factor analysis.

BACKGROUND: Transplantation of lung allografts from the same donor into 2 recipients ("twinning") provides an opportunity to study recipient and donor factors that influence early allograft function. METHODS: Twenty-seven pairs of recipients were identified and evaluated using multivariate logistic regression analysis (p < 0.05). Four measures of early graft function were analyzed: alveolar-arterial gradient in the operating room, first alveolar-arterial gradient in the intensive care unit, alveolar-arterial gradient at 24 hours, and days of mechanical ventilation. RESULTS: Analysis of the pooled data without regard to pairing showed that alveolar-arterial gradient in the operating room was influenced by donor age, length of donor hospitalization, recipient mean pulmonary artery (PA) pressure at unclamping, and transplantation of a left lung. The alveolar-arterial gradient in the intensive care unit was correlated with donor age, donor cause of death, and mean PA pressure on arrival in that unit. Only mean PA pressure remained significant at 24 hours. Days of mechanical ventilation was determined by mean PA pressure on arrival in the intensive care unit, drop in mean PA pressure during operation, and diagnosis of the recipient. In the paired analysis, receiving a left lung, recipient diagnosis (pulmonary hypertension worse than others), and need of cardiopulmonary bypass were significantly associated with immediate graft dysfunction, although these influences did not persist beyond the immediate postoperative period. Donor arterial oxygen tension and time of ischemia were not significant predictors in any analysis. CONCLUSIONS: Immediate allograft function was associated with donor-related characteristics initially, but these lost importance over the ensuing 24 hours. Recipient PA pressure was an immediate and persisting influence. In the analysis of differences in function between the members of each pair, transplantation of the left lung, recipient diagnosis, and cardiopulmonary bypass were identified, but their influence did not persist beyond the first 6 hours.

A prospective trial of tacrolimus (FK 506) in clinical heart transplantation: intermediate-term results.

Between January 1, 1989, and December 31, 1994, we have treated 122 primary heart recipients with FK 506 (group I) and 121 with cyclosporine (group II). Fifty patients in the cyclosporine (CyA) group received no lympholytic induction (CyA alone) and 71 others received lympholytic induction with either rabbit antithymocyte globulin or OKT3 (CyA+LI). The mean follow-up was longer in the FK 506 group than in the CyA groups (3.2 +/- 1.3 vs 2.3 +/- 1.8 years; p< 0.01). Patient survival did not differ on the basis of the type of immunosuppression used. At 3 months after transplantation, the freedom from rejection in the FK 506 group was higher than that of the CyA-alone group (47% vs 22%, p < 0.01) but similar to that of the CyA+LI group (47% vs 53%). The linearized rejection rate (episodes/100 patient-days) of the FK 506 group (0.09 episodes) was lower (p < 0.05) than that of the CyA-alone group (0.26) and the CyA+LI group (0.13). The requirement for pulsed steroids to treat rejection was less in common in the FK 506 group than in either CyA group. Eighteen patients in the CyA group had refractory rejections; all resolved with FK 506 rescue. Two patients in the FK 506 group had refractory rejection that resolved with total lymphoid irradiation (n=1) and methotrexate therapy (n=1). Patients receiving FK 506 had a lower risk of hypertension and required a lower dose of steroids. Although the mean serum creatinine concentration at 1 year was higher in the FK 506 group, this difference disappeared after 2 years. No patients required discontinuation of FK 506 because of its side effects. Our intermediate-term results indicate that FK 506 compares favorably with CyA as a primary immunosuppressant in heart transplantation.

Solid tumors after heart transplantation: lethality of lung cancer.

BACKGROUND: Prolonged nonspecific immunosuppression after solid-organ transplantation is associated with an increased risk of certain cancers. This study examined the development of solid-organ tumors after cardiac transplantation. METHODS: Thirty-eight solid tumors were identified in 36 (5.9%) of 608 cardiac transplant recipients who survived more than 30 days. Two patients had two types of skin tumors (basal cell and squamous cell). The tumors included the following types: skin (15), lung (10), breast (1), bladder (2), larynx (2), liver (1), parotid (1), testicle (1), uterus (2), melanoma (2), and Merkel's cell (1). Four immunosuppression regimens based on cyclosporin A or FK 506 were used during this period. RESULTS: There was no association between the incidence of solid tumors and the use of lympholytic therapy. After the diagnosis of tumor was made, the actuarial 2-year survival rates of recipients with skin, lung, and other solid tumors were 71%, 22%, and 23%, respectively. Eight of 10 patients with lung cancer were in stage IIIA or higher at the time of diagnosis. CONCLUSION: Skin and lung tumors are the most frequent solid tumors in heart transplant recipients. Skin tumors (except Merkel's cell carcinoma and melanoma) usually have a benign course, whereas lung and other tumors developing in cardiac transplant recipients carry a poor prognosis. Advanced disease stage at the time of diagnosis is responsible for the dismal outcome of recipients in whom solid tumors develop. Close postoperative tumor surveillance after cardiac transplantation is warranted.

Recurrence of obliterative bronchiolitis and determinants of outcome in 139 pulmonary retransplant recipients.

An international series of pulmonary retransplantation was updated to identify the predictors of outcome and the prevalence and recurrence rate of obliterative bronchiolitis after operation. The study cohort included 139 patients who underwent retransplantation in 34 institutions in North America and Europe between 1985 and 1994. Eighty patients underwent retransplantation because of obliterative bronchiolitis, 34 because of acute graft failure, 13 because of intractable airway complications, 8 because of acute rejection, and 4 because of other indications. Survivors were followed up for a median of 630 days, with 48 patients alive at 1 year, 30 at 2 years, and 16 at 3 years after retransplantation. Actuarial survival was 65% +/- 4% at 1 month, 54% +/- 4% at 3 months, 45% +/- 4% at 1 year, 38% +/- 5% at 2 years, and 36% +/- 5% at 3 years; nonetheless, of 90-day postoperative survivors, 65% +/- 6% were alive 3 years after retransplantation. Life-table and univariate Cox analysis revealed that more recent year of retransplantation (p = 0.009), identical match of ABO blood group (p = 0.01), absence of a donor-recipient cytomegalovirus mismatch (p = 0.04), and being ambulatory immediately before retransplantation (p = 0.04) were associated with survival. By multivariate Cox analysis, being ambulatory before retransplantation was the most significant predictor of survival (p = 0.008), followed by reoperation in Europe (p = 0.044). Complete pulmonary function tests were done yearly in every survivor of retransplantation and bronchiolitis obliterans syndrome stages were assigned. Eleven percent of patients were in stage 3 at 1 year, 20% at 2 years, and 25% at 3 years after retransplantation. Values of forced expiratory volume in 1 second decreased from 1.89 +/- 0.13 L early after retransplantation to 1.80 +/- 0.15 L at 1 year and 1.54 +/- 0.16 L at 2 years (p = 0.006, year 2 versus baseline postoperative value). Most of this decrease occurred in patients who underwent retransplantation because of obliterative bronchiolitis, whereas the pulmonary function of patients who underwent retransplantation because of other conditions did not significantly change. We conclude that survival after pulmonary retransplantation is improving. Optimal results can be obtained in patients who are ambulatory before retransplantation. Compared with recent data after primary lung transplantation, bronchiolitis obliterans syndrome does not appear to recur in an accelerated manner after retransplantation. As long as early mortality as a result of infection can be minimized, pulmonary retransplantation appears to offer a reasonable option in highly selected patients.

The need for accurate risk-adjusted measures of outcome in surgery. Lessons learned through coronary artery bypass.

OBJECTIVE: The authors review the Pennsylvania Health Care Cost Containment Council reports on coronary artery surgery and compare this reporting structure to others, including the Society for Thoracic Surgeons database, currently used by their own program. The authors review the growing likelihood of a need for outcome measures for all of the surgical subspecialties. SUMMARY AND BACKGROUND DATA: Pressure from consumers and insurers will require surgical specialties to be graded by objective outcome measures. Practitioners must be prepared and become involved in the process. METHODS: The authors reviewed the data, which grades all of Pennsylvania's hospitals at which coronary artery bypass is performed. Apparently, the major risk factors commonly employed in most other risk adjustment schemes for cardiac surgery have been deleted, and the practitioners might be judged unfairly. The Pennsylvania system appears to be insurance driven to reward low-cost providers who operate on patients with the lowest risk. RESULTS: Review of data suggests that the Pennsylvania Health Care Cost Containment Council's annual publication, A Consumer's Guide for Coronary Artery Bypass Surgery, misrepresents fair risk adjustment in favor of lower-risk patients, thereby encouraging better score cards for those institutions with patients who are less ill. Data regarding charges for the procedure have not been risk adjusted or related to a regional economic index. CONCLUSIONS: Surgeons must prepare to better understand relevant models that evaluate outcome. Cardiothoracic surgery is one of the first specialties to feel the pressures of mandated evaluations, and the lessons learned in Pennsylvania should be applicable to other states and their practitioners.

Perioperative donor bone marrow infusion augments chimerism in heart and lung transplant recipients.

BACKGROUND: We and others have demonstrated that a low level of donor cell chimerism was present for years after transplantation in tissues and peripheral blood of heart and lung recipients; it was associated, in the latter, with a lower incidence of chronic rejection. To augment this phenomenon, we initiated a trial combining simultaneous infusion of donor bone marrow with heart or lung allotransplantation. METHODS: Between September 1993 and January 1995, 15 nonconditioned patients received either heart (n = 10) or lung (n = 5) allografts concurrently with an infusion of unmodified donor bone marrow (3.0 x 10(8) cells/kg), and were maintained on immunosuppressive regimen consisting of tacrolimus and steroids. RESULTS: There was no complication associated with the infusion of donor bone marrow. Chimerism was detectable in 73% of bone marrow-augmented patients up to the last sample tested. Of the 5 control recipients who did not receive bone marrow infusion, only 1 had detectable chimerism by flow on postoperative day 15, which dwindled to an undetectable level by postoperative day 36. None of the patients had evidence of donor-specific immune modulation by mixed lymphocyte reaction. CONCLUSIONS: The combined infusion of donor bone marrow and heart or lung transplantation, without preconditioning of the recipient, is safe and is associated with an augmentation of donor cell chimerism.

Clinical trial of tacrolimus versus cyclosporine in lung transplantation.

BACKGROUND: A prospective clinical trial was undertaken to compare the efficacy of tacrolimus (FK 506) versus cyclosporine as the primary immunosuppressive agent after lung transplantation. METHODS: Between October 1991 and May 1994, 133 single-lung and bilateral-lung recipients were randomized to receive either cyclosporine (n = 67) or tacrolimus (n = 66). The two groups were similar in age, sex, and underlying disease. RESULTS: One-year and 2-year survival rates were similar in the two groups, although the trend was toward increased survival with tacrolimus. Acute rejection episodes per 100 patient-days were fewer (p = 0.07) in the tacrolimus group (0.85) than in the cyclosporine group (1.09). Obliterative bronchiolitis developed in significantly fewer patients in the tacrolimus group (21.7%) compared with the cyclosporine group (38%) (p = 0.025), and there was greater freedom from obliterative bronchiolitis over time for patients receiving tacrolimus (p < 0.03). Significantly more cyclosporine-treated patients (n = 13) required crossover to tacrolimus than tacrolimus-treated patients to cyclosporine (n = 2) (p = 0.02). The switch to tacrolimus controlled persistent acute rejection in 6 of 9 patients. The overall incidence of infections was similar in the two groups, although bacterial infections were more common with cyclosporine (p = 0.0375), whereas the risk of fungal infection was higher with tacrolimus (p < 0.05). CONCLUSIONS: This trial demonstrates the advantage of tacrolimus in reducing the risk of obliterative bronchiolitis, the most important cause of long-term morbidity and mortality after lung transplantation.

Seventy-two pulmonary retransplantations for obliterative bronchiolitis: predictors of survival.

BACKGROUND: Obliterative bronchiolitis (OB) occurs in up to 40% of patients in the intermediate term after lung transplantation. In recent years an increasing number of recipients with end-stage OB have been treated with retransplantation. METHODS: Seventy-two patients with OB underwent retransplantation at 26 North American and European centers a median of 590 days after their first transplant operation. The predictors of survival were determined using life table and Cox proportional hazards methods, and the recurrence rate of OB was determined in survivors. RESULTS: The actuarial survival rate was 71% +/- 5% at 1 month, 43% +/- 6% at 1 year, and 35% +/- 6% at 2 years; nonetheless, of the 90-day postoperative survivors, 63% +/- 7% were alive 2 years after retransplantation. Institutional experience with more than three pulmonary retransplantations (p = 0.008), reoperation in Europe (p = 0.013), donor-recipient ABO blood group identity (p = 0.018), and more recent year of retransplantation (p = 0.03) were associated with survival. On multivariate analysis, reoperation after 1989 (p < 0.001), retransplantation performed in Europe (p = 0.017), and being ambulatory immediately before reoperation (p = 0.022) were found to be predictive of a positive outcome. Pulmonary function test analyses confirmed that the forced expiratory volume in 1 second decreased from postoperative baseline values by 11% +/- 9% at 1 year and 27% +/- 10% at 2 years (p = 0.02; year 2 versus baseline). Fourteen percent of patients were in stage 3 of the bronchiolitis obliterans syndrome at 1 year postoperatively, with 33% affected at 2 years. CONCLUSIONS: The results of pulmonary retransplantation for OB are improving. Current evidence indicates that OB does not recur in an accelerated manner after retransplantation, although pulmonary function does worsen again by 2 years. Pulmonary retransplantation is appropriate only in selected patients with OB who are ambulatory and are operated on at experienced centers.

Analysis of time-dependent risks for infection, rejection, and death after pulmonary transplantation.

Infection and rejection remain the greatest threats to the survival of pulmonary allograft recipients. Furthermore, a relationship may exist between these events, because the occurrence of one may predispose to the other. By using multivariate analysis for repeated events, we analyzed the risk factors for bacterial, fungal, and viral infection, grade II or greater acute rejection, and death among 239 lung transplant recipients who received 250 allografts between January 1988 and September 1993. A total of 90 deaths, 491 episodes of acute rejection, and 542 infectious episodes occurred during a follow-up of 6 to 71 months. The hazard or risk patterns of death, infection, and rejection each followed an extremely high risk during the first 100 days after transplantation, a second modest risk period at 800 to 1200 days, and a lower constant risk. Infection and graft failure manifested by diffuse alveolar damage were the major causes of early death (< 100 days), whereas infection and chronic rejection were primary causes of later death after pulmonary transplantation. By multivariate analysis, cytomegalovirus mismatching risk for primary infection was the most significant risk factor for death, rejection, and infection. Absence of cytomegalovirus prophylaxis was also a risk factor for early and late death and late infection. Survival of recipients who received cytomegalovirus prophylaxis was significantly improved. Immunosuppression based on cyclosporine versus FK 506 was a risk factor for late death and late infection. Graft failure manifested by diffuse alveolar damage/adult respiratory distress syndrome was a significant risk for death late after transplantation. These data suggest the following: (1) The hazard for death, infection, and rejection after pulmonary transplantation appears biphasic; (2) lower survival is associated with ischemia-reperfusion lung injury represented by diffuse alveolar damage/adult respiratory distress syndrome; (3) cytomegalovirus mismatch, absence of cytomegalovirus prophylaxis, and development of cytomegalovirus disease are significant threats for death, rejection, and infection after pulmonary transplantation; (4) prevention of cytomegalovirus disease should improve survival by decreasing the prevalence of infection and rejection.

Indications for and results of single, bilateral, and heart-lung transplantation for pulmonary hypertension.

The indications for single, bilateral, and heart-lung transplantation for patients with pulmonary hypertension remain controversial. We retrospectively analyzed the results from 11 single, 22 bilateral, and 24 heart-lung transplant procedures performed between January 1989 and January 1993 on 57 consecutive patients with pulmonary hypertension caused by primary pulmonary hypertension (n = 27) or Eisenmenger's syndrome (n = 30). Candidates with a left ventricular ejection fraction less than 35%, coronary artery disease, or Eisenmenger's syndrome caused by surgically irreparable complex congenital heart disease received heart-lung transplantation. All other candidates received single or bilateral lung transplantation according to donor availability. Although postoperative pulmonary artery pressures decreased in all three allograft groups, those in single lung recipients remained significantly higher than those in bilateral and heart-lung recipients. The cardiac index improved significantly in only the bilateral and heart-lung transplant recipients. A significant ventilation/perfusion mismatch occurred in the single lung recipients as compared with bilateral and heart-lung recipients because of preferential blood flow to the allograft. Graft-related mortality was significantly higher and overall functional recovery as assessed by New York Heart Association functional class was significantly lower at 1 year in the single as compared with bilateral and heart-lung recipients. Thus bilateral lung transplantation may be a more satisfactory option for patients with pulmonary hypertension with simple congenital heart disease, absent coronary arterial disease, and preserved left ventricular function. Other candidates will still require heart-lung transplantation.

Impact of pulmonary hypertension on outcome after single-lung transplantation.

Single lung transplantation for pulmonary hypertension (PH) remains a controversial therapy. We retrospectively studied 48 consecutive recipients of single-lung allografts to determine if preoperative PH was associated with increased mortality or morbidity. Recipients were divided into two groups; those who did have preoperative PH, defined as mean pulmonary arterial pressure less than or equal to 30 mm Hg (n = 29; group 1), and those recipients with PH who had a mean pulmonary arterial pressure greater than 30 mm Hg (n = 19; group II). Mean pulmonary arterial pressure and pulmonary vascular resistance decreased significantly after transplantation in recipients with PH. These values remained significantly higher as compared with those in recipients without pretransplantation PH. Postoperative pulmonary ventilation/perfusion scans demonstrated significant ventilation/perfusion mismatch in lung allografts with pretransplantation PH (p < 0.05). The mean duration of intensive care unit stay was significantly longer in recipients with PH. Although operative mortality was similar between the groups, preoperative PH was associated with significantly lower 1-year survival (53% versus 72%; p < 0.05) and New York Heart Association functional class (p < 0.05). We conclude that preoperative PH in single-lung transplant recipients is associated with significantly increased mortality, prolonged intensive care unit stay, and less symptomatic improvement. Thus, despite a shortage of donor organs, single-lung transplantation may be suboptimal therapy in patients with PH. Further study comparing single versus bilateral lung transplantation for PH is necessary.

Risk stratification using the Society of Thoracic Surgeons Program.

In an era of progressive cost containment and public scrutiny, the wisdom of aggressive surgical therapy for high-risk candidates has been questioned. At our center in the previous 24 months, 728 patients with coronary artery disease were entered into The Society of Thoracic Surgeons national database, and the hospital outcomes plus length of stay were analyzed. Patients were separated according to the predicted mortality based on the groupings in The Society of Thoracic Surgeons database: 0 to 5% (453 patients); 5% to 10% (126 patients); 10% to 20% (96 patients); 20% to 30% (17 patients); and 30% and greater (36 patients). There was a close correlation with the predicted rates of mortality. Importantly, the preoperative risk stratification demonstrated a strong correlation with the significant morbidity and excessive length of stay in the highest-risk groups (predicted risk of 20% to > or = 30%). The incidences of the most common complications in the group with the highest predicted risk (> or = 30%) were 28%, renal failure; 33%, ventilator dependence; and 17%, cardiac arrest. In addition, at short-term follow-up (6 to 8 months), a 24.3% mortality was identified in patients with a predicted mortality that exceeded 20%. These data quantify the risks and morbidities associated with the care of seriously ill patients with coronary artery disease and demonstrate the need for professional and public discussions focusing on the association of a high preoperative risk status and the consumption of resources.

Anastomotic pitfalls in lung transplantation.

Although airway, arterial, and venous connections required for lung transplantation appear simple, in practice we have encountered morbid early stenosis and obstructions, which are now avoided by technical modifications gradually made since 1985 in 134 cases (60 single lung and 74 double lung). Our initial eight double lung transplant procedures were done with tracheal anastomoses and omental wraps, but ischemic disruption, with a 75% (6 of 8) rate of complications, resulted in the subsequent use of bi-bronchial connections. A total of 192 bronchial anastomoses were reviewed (60 single lung, 66 double lung). Although all anastomoses were constructed between the donor trimmed to one to two rings above the upper lobe origin and the host divided at its emergence from the mediastinum, the suture technique has evolved. Nine (32%) of 28 cases with early bronchial anastomoses with end-to-end suture and intercostal muscle wrap had ischemic or stenotic complications, but the telescoping technique without wrap in 164 bronchial anastomoses reduced the problem to 12% (19 of 164). Twelve anastomoses required temporary intraluminal stenting. Vascular anastomotic obstructions occurred in five arterial (excessive length 2, short allograft artery 1, restrictive suture or clot 2) and two venous (excessive length 1, restrictive suture or clot 1) connections. Suspicion of arterial obstruction was prompted by persisting pulmonary hypertension and reduced flow to the allograft measured by postoperative nuclear scan and hypoxia. Venous obstructions were suggested by persisting radiographic and clinical pulmonary edema. Modifications of earlier techniques have improved our early success in lung transplantation and might be considered by others entering this demanding field.

Effect of cardiopulmonary bypass on early graft dysfunction in clinical lung transplantation.

The records of 100 lung transplant recipients (13 heart-lungs, 45 double-lungs, and 42 single-lungs) from September 1990 through April 1992 were reviewed to determine the role of cardiopulmonary bypass (CPB) in early graft dysfunction. Fifty-five patients requiring CPB (CPB group) for 186 +/- 54 minutes were compared with the 45 patients without CPB (no-CPB group). All of the heart-lung and en-bloc double-lung transplantations were performed under CPB, with pulmonary vascular lung disease the principal diagnosis, resulting in a significantly younger age population in the CPB group. All other donor- and recipient-related factors matched well in both groups. Of 38 bilateral single-lung transplantations, CPB was used in 18. In double-lung and heart-lung recipients gas exchange of the allografts was evaluated by the arterial/alveolar oxygen tension ratios at nine intervals during the first 72 hours. The mean arterial/alveolar oxygen tension ratio in the CPB group was 0.48 +/- 0.19, significantly lower than in the no-CPB group with 0.60 +/- 0.22 (p = 0.025). All patients had radiographic interpretation and scoring of pulmonary infiltrates from chest roentgenograms taken within 12 hours after reperfusion. The CPB group had more severe pulmonary infiltrates than the no-CPB group (p = 0.034). Prolonged intubation defined as 7 days or longer occurred significantly more often (29/55) in the CPB group than in the no-CPB group (8/45) (p = 0.003). Actuarial graft and patient survival at 1 month was better in the no-CPB group than in the CPB group (42/45 versus 44/55 [p = 0.05] and 43/45 versus 45/55 [p = 0.033], respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic mechanical circulatory support: rehabilitation, low morbidity, and superior survival.

Because of donor scarcity, 12 (39%) of a series of 31 Novacor left ventricular assist system recipients required mechanical circulatory support for an average of 125 days before transplantation (range, 61 to 303 days). Ten received a heart transplant and all survived to discharge. Two died of infection before transplantation after 93 and 303 days of support. Significant reductions were noted from preimplantation values of right and left cardiac filling pressures. Right ventricular ejection fraction and cardiac index increased. The 4-month actuarial freedom from infection during support was 75%. Three patients benefited from chronic outpatient housing for 5, 18, and 131 days, respectively, with improvements in quality of life measures. Ten chronically supported patients participated in an intensive rehabilitative exercise program resulting in an improvement of New York Heart Association class from IV to I in 9 patients. Mean oxygen consumption, which was 10 mL.kg-1.min-1 30 days after implantation (mean exercise time, 10 minutes) had risen to 15 mL.kg-1.min-1 before transplantation (mean exercise time, 16 minutes). This series suggests that long-term circulatory support is compatible with low morbidity, significant physical and hemodynamic rehabilitation, and an outpatient setting.

A clinical trial comparing University of Wisconsin solution and cold cardioplegic solution with load-independent mechanical parameters.

To evaluate the efficacy of University of Wisconsin solution for clinical heart transplantation, load-independent parameters were used to assess left ventricular function after transplantation. Donor hearts were arrested with and stored in buffered cold cardioplegic solution for control (n = 5) and University of Wisconsin solution for the experimental group (n = 5). Orthotopic transplantations were performed in a routine manner. Mean donor age (cardioplegic solution, 28 +/- 5.2 years; University of Wisconsin solution, 28 +/- 5.1 years) and ischemic times (cardioplegic solution, 181 +/- 27 minutes; University of Wisconsin solution, 224 +/- 23 minutes) were similar. Two hours after reperfusion of the heart, transesophageal echocardiography was used to image the left ventricle at the mid-papillary muscle level, and a high-fidelity catheter-tipped manometer was placed in the left ventricle to record left ventricular pressure simultaneously. These images were digitized during apneic baseline conditions and during an acute reduction in preload from inferior vena caval occlusion. The left ventricular cross-sectional areas were measured and matched with left ventricular pressure from the catheter-tipped manometer to reveal pressure-area relationships. The baseline parameters fractional area change and stroke force were calculated. End-systolic elastance, the slope of end-systolic pressure-area relationship and preload recruitable stroke force, the slope of stroke force versus end-diastolic area were calculated from the inferior vena cava occlusion measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Lung transplantation at the University of Pittsburgh: 1982 to 1994.

Lung transplantation is a growing modality of treatment for patients with end-stage lung disease. In our program, survival has improved significantly in recent experience. Progress in candidate and donor selection, allograft preservation technique, recipient surgery, and postoperative management combine to reduce recipient morbidity and mortality. Although the tailored antibiotic treatment has significantly reduced the risk of bacterial pneumonia within 2 weeks after operation, infection is still a major cause of death for long-term recipients. Extensive studies need to be continued to understand the pathogenesis of OB and to establish the treatment for OB.