Biomedical subjects
Publications and source records attributed to S R Gundry.
Cardiac transplantation is an effective therapeutic modality in children, with results comparable to those of adults (5-year actuarial survival, 67 +/- 2%). Infection and rejection are the most frequent long-term complications. Cardiac transplantation provides excellent functional results for many children with severe congenital or acquired heart disease.
Transplant surgeons are reluctant to use hearts that have undergone cardiopulmonary resuscitation for cardiac arrest because of the fear of poor early and late cardiac function. A policy of minimizing contraindications to use of donor hearts has led to the unique opportunity of assessing the effects of donor arrest and successful cardiopulmonary resuscitation on early and late cardiac function in pediatric heart transplantation. A number of 140 infants and children undergoing transplantation from birth to 17 years of age were studied retrospectively and divided into two groups on the basis of cardiopulmonary resuscitation status. Group 1 (72 patients) received donor hearts that were not subjected to cardiopulmonary resuscitation; group 2 (68 patients) received donor hearts that had cardiopulmonary resuscitation for a mean of 18.8 +/- 14.6 minutes, the longest period of time being 60 minutes. Mean ischemic times were almost identical in the two groups: 4.43 +/- 2.0 hours (cardiopulmonary resuscitation) versus 4.5 +/- 2.1 hours (no cardiopulmonary resuscitation). Early cardiac function was assessed on the basis of the number of days the recipient was supported by the ventilator, days receiving dopamine, days receiving isoproterenol, and the amount of inotropic agents required after the operation. The groups did not differ. Parameters of systolic function included fractional shortening, posterior wall thickening, and maximum velocity of change in left ventricular posterior wall dimension during systole. Diastolic function was measured on the basis of left ventricular end-diastolic volume, left ventricular mass, and maximum velocity of change in left ventricular posterior wall dimension during diastole. Both systolic and diastolic function were measured and analyzed from M-mode echocardiography at 1 week, 1 month, 6 months, 1 year, and 2 years after the operation. There were no statistically significant differences in graft function between the two groups in any of the echocardiographic parameters studied, even at 2 years. No group differed from ranges of normal. Our results suggest that hearts undergoing cardiopulmonary resuscitation for periods of up to 60 minutes can be used safely without evidence of deterioration of early or late cardiac function.
Serum levels of cardiac myosin light chain 1 after heart transplantation were studied in 24 infants and children who underwent heart transplantation between June 1990 and April 1991. The ages of the patients ranged from 4 days to 6 years 7 months (mean, 9.9 months), and their body weights ranged from 2.2 to 20 kg (mean, 5.6 kg). The ages of the donors ranged from 2 days to 8 years, 7 months (mean, 26.6 months), and their body weights ranged from 2.5 to 26 kg (mean, 11.4 kg). The donor heart ischemic time ranged from 90 minutes to 482 minutes (mean, 279 minutes). Peak myosin levels after heart transplantation showed significant correlation with the duration of graft ischemia (p < 0.01) and with diastolic cardiac function in the first posttransplant week (p < 0.05). Peak myosin levels did not correlate with systolic cardiac function, age of the donor, or age of the recipient. Myosin levels of the 15 patients with graft ischemic times exceeding 4 hours averaged 6.30 +/- 3.50 ng/ml. These levels were significantly higher than those of patients with graft ischemia lasting less than 4 hours (2.60 +/- 1.20 ng/ml; p < 0.01). Both of the values are higher than previously reported values of normal controls but lower than previously reported values of patients with myocardial infarction. Preservation techniques used for this series of transplant operations provided good clinical protection of the donor heart for up to 8 hours, although release of the cardiac myosin light chain fragment correlated with duration of graft ischemia. Cardiac myosin levels appeared to be a good indicator of heart graft damage during ischemic preservation. It remains to be determined at what level of myosin release (and, hence, at what duration of graft ischemia) irreversible myocardial damage, which might result in permanent functional compromise, occurs.
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There is a rapid growth of interest in heart transplantation therapy during early infancy. From 10% to 25% of the infants who are listed for transplantation annually have died while awaiting a donor heart. There has been no significant trend in this variable. Since November 1985, 140 consecutive orthotopic transplantation procedures were performed in 139 infants who were from 3 hours to 12 months of age. Indications for transplantation included hypoplastic left heart syndrome (63%), other complex structural anomalies (29%), myopathy (6.5%), and tumors (1.5%). Most recipients had ductus-dependent circulation and received continuous infusion of prostaglandin E1. Heart donors were usually victims of trauma, sudden infant death, or birth asphyxia. A donor-recipient weight ratio of 4.0 or less was found to be acceptable. The amount of time the graft underwent cold ischemia, ranged from 64 to 576 minutes. The procurement process was facilitated by a single dose of cold crystalloid cardioplegic solution and cold immersion transport. Profound hypothermic circulatory arrest was used for graft implantation. One hundred twenty-four (89%) recipients survived transplantation and were discharged from the hospital. There were 9 late deaths, which resulted in an 83% overall survival. The 5-year actuarial survival is 80%. The survival among newborn recipients (n = 60) at 5 years is 84%. Chronic immunomodulation was cyclosporine-based and steroid-free. Surveillance was noninvasive and relied heavily on echocardiography, electrocardiography, and clinical intuition. There was one documented late lethal infection, tumor was not encountered, and coronary occlusive disease was known to exist in only one long-term survivor. We concluded that transplantation results in excellent life quality and is a highly effective and durable therapy when applied during early infancy.
Early age at cardiac transplantation may favor successful engrafting with minimal chronic immunosuppression. Fifty-two newborns underwent orthotopic heart transplantation; 47 (90%) survived the operation, and 44 (85%) were late survivors. Actuarial survival was 92% at 1 month, 86% at 1 year, and 84% at 5 years. Forty-four infants who survived 12 weeks and the corresponding 100 rejection episodes were analyzed. Mean follow-up was 2.2 years. The mean number of rejections per year of follow-up was 1.2. No episodes of rejection were identified in six patients. Seven patients had a late rejection episode more than 1 year after transplantation, and only one had a late rejection episode after 2 years. Neonatal cardiac transplantation is effective and durable therapy for uncorrectable heart disease. Intermediate-term results are excellent. Severe rejection is uncommon, and few episodes occur after 1 year of follow-up.
The donor pool for heart transplants is severely limited. Unfortunately, many trauma patients who might be donors die of exsanguination before their organs can be used. We tested whether hearts "dead" for one half hour after exsanguination could be used as heart transplants in 8 lambs (mean weight, 8 kg). Four lambs were exsanguinated by severing the subclavian artery while simultaneously infusing intravenous saline solution to mimic resuscitation attempts. All animals died. Thirty minutes after hypotensive arrest and death, simulating the time needed to secure donation permission, the heart was harvested, perfused with 250 mL of cold cardioplegia containing 200,000 units of streptokinase to dissolve intravascular clots, and stored in iced saline solution for a mean of 1.5 hours while 4 recipient lambs were prepared for operation. After bypass and recipient heart excision, the "dead" donor heart was transplanted orthotopically. The heart was reperfused with low flow (25 mL/min), low pressure (30 mm Hg), low hematocrit (hematocrit, 0.08 to 0.12) blood supplemented with prostaglandin E1 and nifedipine for 15 minutes, followed by full flow rewarming for 45 minutes. All hearts resumed normal contractions. All animals were weaned from bypass without inotropes. Pressures a half hour after bypass were (in mm Hg): aorta, 80 +/- 10; pulmonary artery, 20 +/- 5; right atrium, 9 +/- 5; and left atrium, 9 +/- 2. We conclude that hearts "dead" for one half hour after exsanguination are capable of being reanimated and used successfully as donor organs. With further development, this method could potentially greatly expand the donor heart pool.
Since April 1976, 34 infants (25 male and 9 female) less than 1 month of age underwent a Mustard intraatrial baffle procedure for repair of simple transposition of the great arteries. Thirty patients were less than 2 weeks old and 19 patients less than 1 week (mean 7.8 +/- 6 days). The weights ranged from 2.6 to 4.4 kg (mean 3.4 +/- 0.4 kg). Rashkind balloon atrial septostomy was performed in the first hours or days of life in 29 patients. The average interval from balloon atrial septostomy to baffle repair was 3.9 days (range 2 hours to 14 days). Mechanical ventilation was required in eight patients preoperatively and prostaglandin E1 was infused in 17 patients to maintain ductal patency. In all patients, the Mustard procedure was performed with the use of deep hypothermic circulatory arrest, averaging 53 minutes (range 37 to 82 minutes). The duration of postoperative intubation and ventilatory support averaged 1.7 +/- 1.0 days (range 1 to 5 days). Inotropic drugs were used in 24 patients during a period of 1.4 +/- 1.3 days (range 1 to 6 days) postoperatively. There were no hospital deaths. Follow-up evaluation has extended from 1 month to 14 years (mean 3 +/- 3 years). One infant died 2 months postoperatively as a result of milk aspiration; no cardiac defects were found at the autopsy. A second infant died at 1 year with right ventricular and tricuspid valve dysfunction. Baffle complications occurred in 6 of the 32 survivors, including superior vena caval stenosis in 4, inferior vena caval stenosis in 1, and pulmonary venous obstruction in 3. Reoperations for baffle obstructions were performed in three patients (8.8%) and balloon angioplasties in two. One patient required permanent pacemaker implantation. Results with the Mustard procedure before 1 month of age show that it can be performed with negligible mortality and a low incidence of late complications at an age comparable to when arterial switching would be performed. Until long-term studies demonstrate superiority of arterial operations, the low operative mortality favors continued evaluation of the neonatal Mustard repair as a valid alternative to the arterial switch.
To determine the effect of heart donor and recipient size mismatches in infant and pediatric heart transplantation, we studied all 69 patients (age 1 day to 11 years) having 71 orthotopic heart transplants from 1985 to 1989. Patients were divided into three groups based on donor to recipient weight ratios. Group I comprised 13 heart transplants with a donor to recipient weight ratio less than 0.95 (mean 0.81, range 0.48 to 0.94); group II comprised 29 heart transplants with a weight ratio between 0.95 and 1.60 (mean 1.28); and group III had 27 heart transplants with weight ratios greater than 1.60 (mean 2.2, range 1.61 to 3.09). All chests were closed primarily. The cardiothoracic ratio by chest radiography was significantly larger in group III (p = 0.0002); 75% of group III patients had periods of lobar or complete lung collapse by chest radiography compared with 28% of group II and 19% of group I patients (p < 0.05). Despite this, there was no difference in the number of days of ventilator support for any group (p = 0.92). There was no difference in graft ischemic time or inotropic drug use among groups, nor were differences found in the cardiac systolic function parameters of left ventricular preejection time (p = 0.975), left ventricular ejection time (p = 0.975), left ventricular fiber shortening (p = 0.97), and left ventricular fractional shortening (p = 0.596). Thus despite a high incidence of transient lobar or complete lung collapse in high donor to recipient weight ratio transplants, large donor heart size produces very little clinical impairment in recipient lung function. Size mismatches do not influence cardiac systolic function. Overall, large size mismatches appear to be very well tolerated in infant and pediatric heart transplantation.
Increasing experience suggests that retrograde cardioplegia offers several benefits during cardiac reoperations. However, the need for dissection to allow caval snares for open coronary sinus intubation or to palpate the atrioventricular groove for transatrial coronary sinus intubation may disturb diseased vein grafts or require more dissection than necessary. Although antegrade-retrograde techniques can be used, antegrade cardioplegia risks atheromatous embolization from old vein grafts. To optimize delivery of cardioplegic solution, we designed and used "no touch" transatrial intubation of the coronary sinus for retrograde delivery of cardioplegic solution in 63 consecutive patients aged 20 to 87 years (mean 68 years) undergoing 36 redo coronary bypass operations, 7 combined redo coronary bypass/valve replacements, 6 redo aortic valve repairs/replacements, 6 redo mitral valve repairs/replacements, 4 redo double valve repairs/replacements, 2 redo triple valve repairs/replacements, and 2 redo composite aortic valve and arch replacements. "No touch" coronary sinus cannulation was achieved by minimally dissecting the aorta and high right atrium enough for two purse-string sutures. No attempt was made to dissect the junction of the inferior vena cava and atrioventricular groove if old vein grafts were present. The distal pressure line of the Gundry DLP RCSP retrograde cardioplegia cannula (DPL, Inc., Grand Rapids, Mich.) was connected to a transducer, flushed, and then introduced into the right atrium. The pressure tracing thus obtained was observed while the catheter was advanced, using its curved stylet, "blindly" without touching the heart, through the right atrium into the coronary sinus until a coronary sinus waveform was obtained (similar to floating a thermodilution catheter). The catheter's distal balloon was then inflated to occlude the coronary sinus momentarily. A rise in sinus pressure confirmed placement. If pressure did not rise, the cannula was usually in the right ventricle and was repositioned. All coronary sinuses were successfully intubated blindly. Bypass was then instituted, the aorta crossclamped, and the proximal aorta vented. Old vein grafts were cut at the aorta before retrograde cardioplegia was begun; atheromatous material was routinely flushed retrogradely from vein grafts. Only after arrest were hearts dissected as needed. Antegrade cardioplegia was not used. There were two (3%) deaths, both from hospital-acquired pneumonia, no perioperative myocardial infarctions, and no episodes of heart block. Inotropic agents were used in six of 63 patients (10%). We conclude that "no touch" transatrial retrograde cardioplegia offers optimal, simplified myocardial protection for cardiac reoperations, permits arrest of the heart before cardiac manipulations, and expands the use of retrograde cardioplegia by obviating cardiac dissection.
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Between November 1985 and June 1991, there were 118 orthotopic heart transplantations performed on 117 infants less than 1 year old. Indications for transplantation were dominated by complex congenital heart disease (92%). Weight ratio between donor and recipient was 1.75 +/- 0.72 and ischemic time was 255 +/- 121 minutes. Early mortality was 10.2% and 5-year actuarial survival was 79%. Rejection diagnoses have been achieved mainly with noninvasive techniques. The immunosuppression regimen was comprised of daily cyclosporine A and azathioprine. Steroids were used only for rejection treatment. These results are encouraging and comparable to those of adult transplantation. The shortage of organ donors remains a major problem in pediatric transplantation.
One hundred and six infant and pediatric patients received 108 heart transplantations between November 1985 and December 1990. The age of the recipients was from 0 day to 12 years (mean 11.1 months) and the age of the donors were from 2 days to 24 years (mean 18.3 months). The body weight ratio of donor and recipient were from 59% to 315% (mean 163%). Large donor hearts were well tolerated without serious complication even in small infants. The graft ischemic time was from 51 minutes to 505 minutes (mean 244 minutes) and fifty four grafts had ischemic time more than 4 hours. There was no difference of the frequency of primary graft failure between the grafts with longer and shorter ischemic time. Although diastolic function in the first week post-transplant was more depressed in the grafts with longer ischemic time, no difference was observed after the second post-transplant week. There was no difference in the systolic function in accordance with the ischemic time. Eight hours and more ischemic time was well tolerated in our donor grafts.
One hundred and six infant and pediatric recipients underwent 108 heart transplantation from November 1985 to December 1990 in Loma Linda University Medical Center. Forty-seven recipients were under one month of age at the time of transplantation, 46 from one month to 2 years and 15 over two years. Seventy recipients underwent heart transplantation under the diagnosis of hypoplastic left heart syndrome or the diseases equal to hypoplastic left heart syndrome, seventeen for complex congenital heart disease, sixteen for cardiomyopathy, and five for other reasons. Early mortality was 13% and late mortality was 11% for all cases. Early mortality for the infants under one month of age was 13% and late mortality was 8%. Heart transplantation was considered to be the treatment for choice for the patient with otherwise fatal cardiac diseases.