Histological findings in heart grafts after orthotopic pig to baboon cardiac transplantation.
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Animals↗
Biomedical subjects
S R Gundry
Publications and source records attributed to S R Gundry.
The use of larger size pulmonary homografts for the Ross operation in children.
Nine pediatric patients received an adult size cryopreserved pulmonary homograft for right ventricular outflow tract reconstruction as part of the Ross procedure. The early postoperative results are excellent. It is suggested that a full, adult size pulmonary homograft should be used in the future in pediatric patients undergoing the Ross procedure.
Adolescent↗
Ventricular remodeling following infant-pediatric cardiac transplantation. Does age at transplantation or size disparity matter?
Early left ventricular (LV) remodeling following pediatric cardiac transplantation has not been described. To identify patterns and determinants of change in left ventricular mass and volume posttransplant, we studied 125 consecutive children who underwent cardiac transplantation between January 1, 1989 and July 31, 1993. Two-dimensional imaging-directed M-mode echocardiograms were studied weekly until 26 weeks post-transplant. LV mass and volume (indexed to BSA1.5) were measured. LV mass index increased until 3 weeks post-transplant, and then decreased. The mean decrement in LV mass index after 8 weeks post-transplant (relative to baseline) was significantly larger in patients with donor-recipient weight ratio > 1.5 compared with patients with donor-recipient weight ratio < or = 1.5 (-2.2 g/m3 compared with 33.4 g/m3, respectively, P < 0.01). Multiple linear regression was performed employing donor-recipient weight ratio, time since transplantation, ischemic time, and age at transplant as prognostic variables. Donor-recipient weight ratio (P < 0.0001), time since transplant (P < 0.01), and age at transplant (P = 0.02) were identified as independent predictors of change in LV mass index. Donor-recipient weight ratio (P = 0.001) and time since transplantation (P = 0.02) were independent predictors of change in LV volume index. There was an interaction between donor-recipient weight ratio and time since transplantation, suggesting that donor-recipient weight ratio has an independent effect as well as a time-dependent effect on change in LV mass and volume indices. LV mass and volume indices increased early posttransplant and then decreased; this pattern was temporally predictable, and dependent on donor-recipient weight ratio and age at transplant.
Child, Preschool↗
Growth of oversized grafts in neonatal heart transplantation.
BACKGROUND: Because of the severe shortage of neonatal organ donors, oversized cardiac allografts are frequently transplanted. This study examined body and graft growth of neonates who receive an oversized heart. METHODS: We studied 51 neonates, who received transplants between November 1986 and August 1992, for changes in body weight, left ventricular mass, and end-diastolic volume measured at 1 week, 1, 3, and 6 months, and yearly after cardiac transplantation. Patients were divided into two groups according to donor/recipient weight ratios: the normal group, where the donor/recipient weight ratio was 1.5 or less (1.06 +/- 0.05; n = 24), and the oversized group, where the donor/recipient weight ratio was more than 1.5 (2.22 +/- 0.10; n = 27). RESULTS: After cardiac transplantation, body weight increased continuously in both groups with no difference between groups. In the oversized group, left ventricular end-diastolic volume at 1 week and left ventricular mass at 1 week and 1 month were significantly higher than those in the normal group (p < 0.01). In the normal group, end-diastolic volume and left ventricular mass increased continuously. In the oversized group, however, left ventricular mass significantly decreased until 3 months after cardiac transplantation and then increased continuously, whereas end-diastolic volume increased continuously throughout the posttransplantation period. CONCLUSIONS: These data suggest that oversized cardiac allografts shrink at first and then grow as the recipient grows. There appears to be a size adaptation of the large cardiac allograft to accommodate to the reduced requirements of the neonate.
Body Surface Area↗
Percutaneous transluminal coronary angioplasty failures in patients with multivessel disease. Is there an increased risk?
In recent years, there has been a nationwide trend toward performing percutaneous transluminal coronary angioplasty in patients with multivessel coronary artery disease. The clinical course of 57 consecutive patients who required emergency first-time coronary artery bypass grafting operations were reviewed to assess for difference in outcome between the 28 patients (49%) with single-vessel disease and the 29 patients (51%) with multivessel disease. The two groups were similar in preoperative characteristics except for a higher proportion of chronic obstructive pulmonary disease in the patients with multivessel disease (p = 0.03). Twice as many patients with multivessel disease were in shock (single-vessel disease = 4 [14%], multivessel disease = 8 [28%], p = not significant) en route to the operating room and significantly more patients with multivessel disease required on-going cardiopulmonary resuscitation (single-vessel disease = 0 [0%], multivessel disease = 5 [17%], p = 0.03). Significantly more coronary artery bypass grafts were placed in the patients with multivessel disease (single-vessel disease = 1.5 +/- 0.6, multivessel disease = 2.9 +/- 0.7, p < 0.01), which required longer aortic clamping time (p = 0.02) and cardiopulmonary bypass time (p < 0.01). There were seven postoperative deaths; all but one occurred in patients with multivessel disease (single-vessel disease = 1 [4%], multivessel disease = 6 [21%], p = 0.05). According to multivariate analysis, incremental risk factors of mortality were preoperative shock (p < 0.01), urgent or emergency percutaneous transluminal coronary angioplasty (p = 0.06), and multivessel disease (p = 0.12). Despite a similar incidence of myocardial infarction (single-vessel disease = 8 [29%], multivessel disease = 12 [41%], p = not significant), patients with multivessel disease had a higher incidence of cardiac morbidity (single-vessel disease = 4 [14%], multivessel disease = 11 [38%], p = 0.04) and noncardiac morbidity (single-vessel disease = 4 [14%], multivessel disease = 12 [41%], p = 0.02). By multivariate analysis, incremental risk factors of morbidity were preoperative shock (p < 0.01), multivessel disease (p = 0.02), and ejection fraction < 50% (p = 0.07). In the subset of patients with multivessel disease, preoperative shock, ejection fraction < 50, and an age of 60 years or greater were associated with higher morbidity and mortality. In conclusion, the risk of percutaneous transluminal coronary angioplasty failure is considerably higher in patients with multivessel disease. In certain subsets of patients with multivessel disease, coronary artery bypass grafting would be a safer procedure when compared with percutaneous transluminal coronary angioplasty for initial myocardial revascularization.
Age Factors↗
Successful survival of primates receiving transplantation with "dead," nonbeating donor hearts.
A paucity of donor organs is the principal limitation in human heart transplantation. Prompted by our short-term studies of reanimating "dead" donor hearts in sheep, we applied the same reperfusion modifications in juvenile baboons to determine human applications in an anoxic arrest model (as occurs when non-brain-dead patients are extubated and allowed to die). Ten juvenile baboons (mean weight 3.6 kg) were studied. Five baboons were used as donors. After being anesthetized, donors were pretreated with methylprednisolone (Solu-Medrol), 50% dextrose, nifedipine, and prostaglandin E1 and then paralyzed and extubated. Donors became pulseless at 7 +/- 1 minutes and had electric arrest 9 to 18 minutes after paralysis. The five donors were left undisturbed and warm for 15, 22, 30, 30, and 31 minutes, respectively, after asystole. They were then given 250 ml of 4 degrees C Roe's crystalloid cardioplegic solution via the aortic root and the hearts were explanted into iced Euro-Collins solution. Five baboons served as recipients. After donor harvest, recipients were placed on cardiopulmonary bypass, given prostaglandin E1, and cooled to 18 degrees C; circulatory arrest was instituted and the recipient's heart excised. The donor heart was transplanted in an orthotopic position. Before reinstitution of bypass, 250 ml of terminal leukocyte-depleted blood cardioplegic solution was given, then bypass was restarted and the hearts were reperfused for 60 minutes. All animals were weaned from bypass without the use of inotropic agents. All animals were extubated within 2 to 4 hours after bypass and received standard immunosuppression. Peak creatine kinase MB/total creatine kinase ratio was 0.2% +/- 0.2%. Postoperative ejection fractions by echocardiography were 75% to 80% (mean 76%). Animals survived 1, 9, 13, 16, and 34 days, with three deaths caused by acute rejection and one each by stroke and diarrhea/dehydration. Pathologic findings showed no areas of fibrosis or ischemic damage. We conclude that successful reanimation and engraftment can be achieved with the use of the asystolic primate heart; this work suggests that human application is realistic and could greatly expand the donor pool.
Animals↗
One-stage primary repair of distal esophageal perforation using fundic wrap.
Esophageal leak following primary repair of esophageal perforation is a serious complication that can lead to severe mediastinitis and sepsis. Complete diversion with esophageal exclusion or resection is designed to minimize further mediastinal contamination. However, this approach is not necessarily associated with less morbidity or mortality. Furthermore, a second stage operation is required to restore esophageal continuity. From 1986 to 1994, we performed a one-stage primary repair of the distal esophagus in seven patients with either iatrogenic (n = 5) or spontaneous (n = 2) perforations and reinforced the repair by a fundic wrap. One patient underwent an additional modified Heller myotomy for achalasia. Delay between perforation and operation was less than 6 hours in 3 patients, 6 to 24 hours in 2 patients, and greater than 24 hours in 2 patients. Only one patient (14%) developed a small esophageal leak that spontaneously resolved with adequate mediastinal drainage, intravenous antibiotics, and aggressive nutritional support. One patient (14%), whose repair was delayed by 12 hours, died postoperatively of profound sepsis. This patient was moribund from sepsis preoperatively, and postmortem examination of the esophagus revealed no evidence of esophageal leak. Esophageal continuity was maintained in all patients. The median length of stay was 21 days (range, 15-58 days). We conclude that primary reinforced repair of esophageal perforation using a fundic wrap is an effective method of treatment for distal esophageal perforation, even when the repair is delayed by more than 24 hours.
Adult↗
Graft vasculopathy among recipients of heart transplantation during the first 12 years of life. The Pediatric Heart Transplant Group.
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Age Factors↗
The role of anti-pig antibody in pig-to-baboon cardiac xenotransplant rejection.
The role of naturally produced antibody in discordant xenograft rejection is still uncertain. Twelve orthotopic pig-to-baboon heart transplants (HTx) were performed. In 2 baboons, no antibody adsorption (AbA) was performed. In 5 baboons, AbA with a pig lung was performed during circulatory arrest. In 5 baboons, AbA and blood exsanguination at the beginning of cardiopulmonary bypass (CPB) were performed. Baboons were divided into 2 groups; group 1 (n = 4) died within 24 hr of HTx and group 2 (n = 8) survived more than 24 hr. Mean survival period was 9.8 +/- 3.0 hr in group 1 and 151 +/- 33 hr in group 2. Baboon anti-pig antibody (Ab) was measured before CPB, before circulatory arrest, during AbA, at the end of CPB, and daily after HTx. Anti-RBC Ab was measured by the titration method at temperatures of 4 degrees C and 37 degrees C (RAb-4 and RAb-37). Anti-endothelial cell Ab (EAb) and anti-white blood cell Ab (WAb) titers were measured with ELISA. RAb titration > or = 1/4 and EAB and WAb > or = 1/256 were determined to be seropositive (S(+)). S(+) rate of RAb-37 at the end of CPB (endCPB) in group 2 was significantly higher than that in group 1 (8/8 vs. 1/4; P < 0.05). The seronegative (S(-)) rates of RBC-4 and EAb (endCPB) in group 2 were higher than those in group 1 (7/8 vs. 1/4 and 6/8 vs. 1/4, respectively), but not significantly. There was no difference in S(-) rate of WAb (endCPB) between group 1 and group 2. More than 4-fold decrease in RAb-4 and RAb-37 by AbA with a pig lung was observed in 5 and 7 of 8 baboons, while EAb and WAb did not change by AbA. In all of group 2, RAb-4 reverted to S(+) within 3 days after HTx. One baboon had no rejection episode and died of infection 16 days after HTx (baboon 16); however, it also became S(+) for RAb-4 a day after HTx until death. In 4 of group 2, RAb-37 became S(+) 1 or 2 days before death by rejection. Baboon 16, however, became S(+) for RAb-37 7 days after HTx and S(-) again 9 days after HTx until death. EAb became S(+) in all of group 2, but 5 of them survived more than 5 days after seroconversion.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Simple approach for extrapericardial placement of defibrillator patches via median sternotomy.
The intrapericardial placement of implantable cardioverter defibrillator patches has been associated with a variety of complications due to the patch-epicardial interface. Extrapericardial placement of defibrillator patches minimizes these problems. We describe a simple and reproducible technique to achieve this goal whenever a median sternotomy approach is used.
Defibrillators, Implantable↗
Risk factors for graft failure associated with pulmonary hypertension after pediatric heart transplantation.
Postoperative pulmonary hypertension can be a major cause of early death after heart transplantation in children. To identify predictive risk factors of pulmonary hypertension after heart transplantation, we performed a retrospective analysis of our 194 infant and pediatric recipients who underwent heart transplantation between 1987 and 1992. Because the response of pulmonary vasculature may change during growth, the patients were divided into two groups: age less than 1 year in group I (n = 152) and 1 year or older in group C (n = 43). The following risk factors were evaluated: cardiomyopathy, congenital heart disease and hypoplastic left heart syndrome, pretransplant pulmonary hypertension, history of operation, oversized donor (donor/recipient weight ratio greater than 2), donor's history of cardiopulmonary resuscitation, and prolonged graft ischemic time (graft ischemic time 360 minutes or longer). Though there was no significant difference between group I and group C in overall early mortality including early graft loss (19 of 152 versus 5 of 42), the mortality rate from pulmonary hypertension in group I was significantly lower than that in group C (2 of 152 versus 4 of 42; p < 0.05). The mortality rate from pulmonary hypertension in patients with congenital heart disease in group I was significantly lower than that in group C (0 of 44 versus 4 of 24; p < 0.05). In group I, there was no significant difference in the early mortality rate or the mortality rate from pulmonary hypertension from any factors studied. The mortality rate from pulmonary hypertension in association with prolonged graft ischemic time in group C was significantly higher than when no prolonged graft ischemic time was present in group C and with either prolonged graft ischemic time or no prolonged graft ischemic time in group I (4 of 16 versus 0 of 26, 0 of 37, and 2 of 115). In conclusion, older patients had a higher mortality rate from pulmonary hypertension after heart transplantation, especially in patients with congenital heart disease who received a graft preserved more than 6 hours. This study demonstrates another benefit of early heart transplantation in infancy, that is, prevention of death from pulmonary hypertension.
California↗
Lymphocyte subset monitoring can detect xenoheart rejection in primates.
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Animals↗
Graft atherosclerosis in concordant cardiac transplantation.
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Animals↗
Fate of the pericardial monocusp pulmonary valve for right ventricular outflow tract reconstruction. Early function, late failure without obstruction.
Sudden change from a pressure-loaded to a volume-loaded right ventricle as a result of transannular patch reconstruction of the right ventricular outflow tract may result in early hemodynamic compromise. Tri-leaflet porcine valves in conduits function well early but typically create late obstruction. We studied the fate of a pericardial monocusp valve constructed during transannular patch reconstruction for right ventricular outflow tract obstruction in 19 patients, 2 weeks to 27 years of age (mean age 61 months). Patients had the monocusp constructed of autologous (n = 16) or bovine pericardium (n = 3) when the former was not available during transannular patch reconstruction associated with repair of tetralogy of Fallot (n = 12), pulmonary stenosis/atresia (n = 4), and truncus arteriosus (n = 3). Function of the monocusp was assessed by presence of a split-second heart sound, echocardiographic assessment of right ventricular dilatation, monocusp competence, and fluoroscopic evaluation of monocusp motion. Functional assessments were accomplished immediately after the operation and at 2, 6, 12, and 24 months after the operation. There were no operative deaths, but there was one late hospital death. Sixteen of nineteen patients (84%) had competent pulmonary monocusp valves immediately after the operation, but, by 24 months, only one of seven patients (14%) had a competent valve. No patient had monocusp stenosis. We conclude that a pericardial monocusp valve for right ventricular outflow tract reconstruction provides excellent early hemodynamic function but that these effects are limited in duration. Because late stenosis has not been seen, this inexpensive and easily constructed valve can be used as an excellent short-term adjunct to right ventricular outflow tract reconstruction.
Bioprosthesis↗
Transplantation and reanimation of hearts removed from donors 30 minutes after warm, asystolic 'death'.
OBJECTIVE: To test whether hearts from "dead," pulseless, asystolic donors could be transplanted and reanimated successfully using reperfusion manipulations. DESIGN AND INTERVENTIONS: Ten infant lambs (mean [+/- SD] weight, 4 +/- 1 kg) were anesthetized and pretreated with 50% dextrose, methylprednisolone, prostaglandin E1, and sublingual nifedipine. Five of these lambs were paralyzed; hypoxic asystolic arrest occurred 10 +/- 2 minutes later. Thirty minutes following asystole (mean, 40 +/- 2 minutes after paralysis) sternotomy was performed and the hearts were excised. Aortic blood gases were as follows: pH, 6.6 +/- 0.1; PCO2, 180 +/- 20 mm Hg; and PO2, 8 +/- 2 mm Hg. Donor hearts were given 30 mL/kg of Cardiosol (Water's Instrument Co, Danburg, Conn), a new cardioplegic agent, at 4 degrees C, and explanted into iced saline. The remaining five lambs then underwent cardiopulmonary bypass, were cooled to 20 degrees C, and hypothermic arrest was instituted. After excision of the recipient's heart, the donor heart was implanted in an orthotopic position. Total cold ischemic time was 1 hour 40 minutes +/- 10 minutes. The donor heart was retroperfused for 10 minutes with low-hematocrit, low-calcium blood via a coronary sinus catheter, then normal aortic inflow reperfusion was continued for 50 minutes. MAIN OUTCOME MEASURES: Removal of the cardiopulmonary bypass and measurement of hemodynamic parameters. RESULTS: One half hour after the bypass, mean systolic aortic pressure was 71 +/- 6 mm Hg; mean right atrial pressure was 6 +/- 2 mm Hg; mean left atrial pressure was 7 +/- 2 mm Hg; and mean pulmonary arterial pressure was 20 +/- 8 mm Hg. No inotropic drugs were given for postbypass blood pressure support. CONCLUSION: It is possible to transplant and reanimate hearts that have been dead for 30 minutes. When further developed, the use of donors who were not brain dead but allowed to die naturally could greatly increase the donor pool.
Animals↗
Male donor into female recipient increases the risk of pediatric heart allograft rejection.
Sixty-one infants and children, 12 years old or younger, who received an orthotopic cardiac allograft between November 1985 and December 1989 were analyzed for the incidence of rejection. Rejection was diagnosed non-invasively within the first 3 months and during the first year. Rejection episodes were diagnosed by signs and symptoms according to previously reported criteria. Multiple regression analysis with recipient age, donor age, donor-recipient weight ratio, number of HLA mismatches, sex of the recipient, sex-encoded minor tissue antigen incompatibility (H-Y: female recipients receiving male donor organ), graft ischemic time, lowest cyclosporine level during the first 2 postoperative weeks, and prophylactic use of OKT3 showed that H-Y was the only significant contributing factor for rejection at 3 months and 1 year (r = 0.308, p < 0.02; r = 0.308, p < 0.02; respectively). Patients were divided into two groups: group 1, 45 patients who were H-Y compatible (male and female recipients receiving female donor hearts); and group 2, 16 patients who were H-Y incompatible (female recipients with male hearts). Patients in group 2 had significantly more episodes of graft rejection than did patients in group 1 by 3 months and by 12 months after heart transplantation (3 months: 2.75 +/- 1.48 versus 1.67 +/- 1.41, p < 0.05; 1 year: 4.80 +/- 1.87 versus 2.59 +/- 1.93, p < 0.01; respectively). There were six grafts lost due to rejection in group 2 (6/15, 37.5%) and 7 grafts lost (7/45, 15.5%) in Group 1 (not significant). Heart transplantation with H-Y incompatibility resulted in a significantly greater incidence of rejection episodes.
Child↗
Retrograde continuous warm blood cardioplegia: maintenance of myocardial homeostasis in humans.
Recent clinical reports have suggested that continuous delivery of oxygenated warm blood cardioplegia through the coronary veins (retrograde cardioplegia) produces good myocardial preservation during aortic cross-clamping. No data exist, however, about actual myocardial metabolism/homeostasis during retrograde warm blood cardioplegia. We studied 100 consecutive patients undergoing coronary artery bypass grafting, aortic valve replacement, or both who received retrograde continuous warm blood cardioplegia (4:1 dilution) during aortic cross-clamping for 54 to 174 minutes. We measured pH, oxygen tension, carbon dioxide tension, HCO3, base excess, and oxygen content of the inflow cardioplegia and the blood egressing from coronary arteries during each arteriotomy for bypass grafting (arteries act as postcapillary veins with retrograde cardioplegia) or the left and right coronary orifices during aortic valve replacement. We also measured these variables from the coronary sinus effluent 1 minute after release of the aortic cross-clamp. Retrograde cardioplegia flow ranged from 50 to 250 mL/min (mean flow, 150 mL/min). All patients were maintained at normothermia during bypass. A total of 460 samples were analyzed (4.6 per patient). Neither the duration of aortic cross-clamping nor the artery sampled affected myocardial blood gases. The pH dropped from 7.41 +/- 0.05 for the inflow cardioplegia to 7.32 +/- 0.1 when sampled from coronary arteries, and the oxygen tension fell from 181 +/- 25 to 28 +/- 5 mm Hg, respectively. Carbon dioxide tension rose from 31.0 +/- 4.1 to 41.4 +/- 9.8 mm Hg. Coronary sinus blood gases 1 minute after cross-clamp removal showed no acidosis or oxygen debt.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood↗
Prolonged survival of orthotopically transplanted heart xenograft in infant baboons.
Orthotopic concordant xenotransplantation in a juvenile primate model was examined. Eighteen donor rhesus monkeys weighing 2.4 to 3.8 kg (mean 2.9 kg) were matched with juvenile baboons, aged 9 to 19 months (mean 12.7 months) and weighing 3.2 to 4.8 kg (mean 3.9 kg), using ABH blood type and mixed lymphocyte culture. Rhesus monkey hearts were orthotopically transplanted without immunosuppression into six control baboons (group I). In five baboons (group II), 4 mg/kg per day of antilymphocyte globulin was administered for 3 days before the operation and 5 days after the operation. Splenectomy was also performed, and 18 mg/kg per day of FK 506 was administered orally. Intravenous methotrexate, methylprednisolone, or both were used as rescue therapy. Seven baboons (group III) received the same immunosuppression as those in group II, but an intravenous dose of methotrexate (0.1 to 5 mg) was given twice weekly to suppress the proliferative response as monitored by in vitro immunologic assays. Baboons in group I had a mean survival of 8 days; all died as a result of classic cellular rejection. Baboons in group II had a mean survival of 48.4 days (p < 0.05 versus group I). Two died during rescue therapy for rejection, and three died of cytomegalovirus infection. Two group II baboons showed mild rejection at autopsy. Baboons in group III had a mean survival of 127 days, and one baboon was still alive after 286 days. Two died of cytomegalovirus infection, one of toxoplasmosis, one of Klebsiella pneumoniae, one of massive micropulmonary embolism, one of renal failure aggravated by ganciclovir. Only two of the baboons that died showed rejection (estimated as mild) at autopsy. The baboon still alive at 286 days had no rejection on myocardial biopsy on the two hundred forty-fourth postoperative day. FK 506 coupled with low-dose maintenance methotrexate and splenectomy has produced prolonged host survival in this xenotransplantation model. Results suggest that concordant xenotransplantation would be a suitable biologic bridge to allotransplantation.
Animals↗