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We present the case of a 4 year old child who developed cardiogenic shock due to permanent junctional reciprocating tachycardia, requiring left ventricular assist device (LVAD) support. Despite the initial critical clinical presentation, successful myocardial recovery was achieved over 5 months, allowing for successful LVAD explantation. The patient's young age and behavioral issues were constraining factors for a prolonged LVAD wean trial. A modified wean protocol over a 3 day period with parameters for assessment of cardiac recovery before LVAD explantation is described., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2024.)

Objectives: Currently, surgical repair of tetralogy of Fallot (TOF) is associated with an 1.1% 30-day mortality rate. Those with junctional ectopic tachycardia (JET) and restrictive right ventricular physiology have poorer outcomes. Routine postoperative adrenergic or inodilator therapy has been reported, while beta-blockade following cardiopulmonary bypass has not. This study evaluated routine perioperative treatment with esmolol in infants undergoing TOF repair., Design: Retrospective chart review of the perioperative course following TOF repair., Setting: Single-center case series describing perioperative management of TOF in a cardiac ICU., Patients: This study reviewed all patients less than 18 months old who underwent TOF repair, excluding cases of TOF with absent pulmonary valve or atrioventricular septal defect, at our institution from June 2018 to April 2021., Interventions: This review investigates the hemodynamic effects of esmolol following cardiopulmonary bypass for TOF repair., Measurements and Main Results: Preoperative clinical characteristics and perioperative course were extracted from the medical record. Descriptive statistics were used. Twenty-six patients receiving perioperative esmolol after TOF repair were identified and included. Postoperative hemodynamic parameters were within a narrow range with minimal vasoactive support in most patients. Three of 26 patients experienced JET, and one of 26 of whom had a brief cardiac arrest. Median and interquartile range (IQR) for hospital and postoperative length of stay was 7 days (IQR, 6-9 d) and 6 days (IQR, 5-8 d), respectively. There were no 30-day or 1-year mortalities., Conclusions: In this infant cohort, our experience is that the routine use of postoperative esmolol is associated with good cardiac output with minimal requirement for vasoactive support in most patients. We believe optimal postoperative management of infant TOF repair requires a meticulous multidisciplinary approach, which in our experience is enhanced with routine postoperative esmolol treatment., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Background: Intraseptal anomalous aortic origin of a coronary artery is considered a benign condition. However, there have been case reports of patients with myocardial ischemia, arrhythmia, and sudden cardiac death. The purpose of this study was to determine the clinical presentation, myocardial perfusion on provocative stress testing, and management of children with anomalous aortic origin of a coronary artery with an intraseptal course in a prospective cohort., Methods: Patients with anomalous aortic origin of a coronary artery and intraseptal course were prospectively enrolled from December 2012 to May 2019, evaluated, and managed following a standardized algorithm. Myocardial perfusion was assessed using stress imaging. Fractional flow reserve was performed in patients with myocardial hypoperfusion on noninvasive testing. Exercise restriction, β-blockers, and surgical intervention were discussed with the families., Results: Eighteen patients (female 6, 33.3%), who presented with no symptoms (10, 55.6%), nonexertional (4, 22.2%), and exertional symptoms (4, 22.2%), were enrolled at a median age of 12.4 years (0.3-15.9). Perfusion imaging was performed in 14/18 (77.8%) and was abnormal in 7/14 (50%); fractional flow reserve was positive in 5/8 (62.5%). All 4 patients with exertional symptoms and 3/10 (30%) with no or nonexertional symptoms had myocardial hypoperfusion. Coronary artery bypass grafting was performed in a 4-year-old patient; β-blocker and exercise restriction were recommended in 4 patients not suitable for surgery. One patient had nonexertional chest pain and 17 were symptom-free at median follow-up of 2.5 years (0.2-7.1)., Conclusions: Up to 50% of patients with intraseptal anomalous aortic origin of a coronary artery had inducible myocardial hypoperfusion during noninvasive provocative testing. Long-term follow-up is necessary to understand the natural history of this rare anomaly.

Background: Anomalous aortic origin of a coronary artery (CA) is the second leading cause of sudden cardiac death in young athletes. Management is controversial and longitudinal follow-up data are sparse. We aim to evaluate outcomes in a prospective study of anomalous aortic origin of CA patients following a standardized algorithm., Methods: Patients with anomalous aortic origin of a CA were followed prospectively from December 2012 to April 2017. All patients were evaluated following a standardized algorithm, and data were reviewed by a dedicated multidisciplinary team. Assessment of myocardial perfusion was performed using stress imaging. High-risk patients (high-risk anatomy-anomalous left CA from the opposite sinus, presence of intramurality, abnormal ostium-and symptoms or evidence of myocardial ischemia) were offered surgery or exercise restriction (if deemed high risk for surgical intervention). Univariate and multivariable analyses were used to determine predictors of high risk., Results: Of 201 patients evaluated, 163 met inclusion criteria: 116 anomalous right CA (71%), 25 anomalous left CA (15%), 17 single CA (10%), and 5 anomalous circumflex CA (3%). Patients presented as an incidental finding (n=80, 49%), with exertional (n=31, 21%) and nonexertional (n=32, 20%) symptoms and following sudden cardiac arrest/shock (n=5, 3%). Eighty-two patients (50.3%) were considered high risk. Predictors of high risk were older age at diagnosis, black race, intramural course, and exertional syncope. Most patients (82%) are allowed unrestrictive sports activities. Forty-seven patients had surgery (11 anomalous left CA and 36 anomalous right CA), 3 (6.4%) remained restricted from sports activities. All patients are alive at a median follow-up of 1.6 (interquartile range, 0.7-2.8) years., Conclusions: In this prospective cohort of patients with anomalous aortic origin of a CA, most have remained free of exercise restrictions. Development of a multidisciplinary team has allowed a consistent approach and may have implications in risk stratification and long-term prognosis.

The Berlin Heart EXCOR Pediatric Ventricular Assist Device (BH) was approved for use in the United States in December 2011, based on a prospective investigational device exemption (IDE) trial. Strict exclusion criteria for the trial selected a low-risk "ideal" cohort. We sought to determine whether postapproval usage of the BH in a "real world" cohort of recipients would result in similar outcomes. Preimplant diagnostic information was collected for all patients. Efficacy was evaluated by comparison of all children (efficacy group, n = 247) implanted between FDA approval and April 2015 to those in the IDE trial (IDE, n = 48), with regard to achievement of one of four end-states: transplanted, successful weaning, death/unsuccessful weaning, or still-on-device. Safety outcomes were compared between IDE patients and a subset of postapproval patients (safety group, n = 39) for whom adjudicated adverse events were tracked in a regulator-mandated dataset. Diagnostic categories were similar between groups: IDE (congenital 19%, dilated cardiomyopathy/myocarditis/other 81%) versus Efficacy Group (congenital 24%, dilated cardiomyopathy/myocarditis/other 75%). Patients in the IDE cohort were larger (median 14.8 kg, range 3.6-58.1 kg vs. 10.7 kg, 2.9-112.0 kg, p = 0.02). More IDE patients were successfully supported than in the efficacy group cohort (90% vs. 77%, p = 0.05). Proportions with bleeding and stroke were similar between the IDE and safety group cohorts (46% vs. 41%, p = 0.65; 29% vs. 33%, p = 0.68, respectively). With usage of the BH in a less-ideal population, rates of bridge to transplant and weaning have declined slightly, but remain encouragingly high. Bleeding and neurologic event rates have not increased.

We sought to determine whether ventricular assist device (VAD) support is an effective therapy in children with cardiac graft dysfunction. We conducted a retrospective review of VAD usage in this scenario at our institution. Although short-term VAD support was highly successful (89% [eight out of nine] were bridged to recovery), only 29% (2 out of 7) with long-term VAD survived to retransplant. Of note, three out of five mortalities with long-term VAD were related to sepsis (two fungal and one Gram-negative bacterial). Infectious risk imposed by ongoing immunosuppressive therapy limits the role of long-term VAD in this population.

The field of pediatric mechanical circulatory support with ventricular assist devices has lagged significantly behind that of adult patients. However, there is increasing attention on the emerging field of pediatric ventricular assist device support. In this review, part of the Pediatric Cardiac Intensive Care Society/Extracorporeal Life Support Organization Joint Consensus Statement on Mechanical Circulatory Support, we discuss several important aspects of pediatric ventricular assist device, focusing on biomechanics and selection of the most appropriate device.

Background: Postoperative electroencephalographic (EEG) seizures are reported to occur in 14% to 20% of neonates after cardiac surgery with cardiopulmonary bypass (CPB). EEG seizures are associated with prolonged deep hypothermic circulatory arrest and with adverse long-term neurodevelopmental outcomes. We performed video/EEG monitoring before and for 72 hours after neonatal cardiac surgery, using a high-flow CPB protocol and cerebral oxygenation monitoring, to ascertain incidence, severity, and factors associated with EEG seizures., Methods: The CPB protocol included 150 mL/kg/min flows, pH stat management, hematocrit >30%, and high-flow antegrade cerebral perfusion. Regional cerebral oxygen saturation (rSo(2)) was monitored, with a treatment protocol for rSo(2) <50%. EEG was assessed for seizures., Results: Sixty-eight patients (36 single ventricle [SV] and 32 2-ventricle [2V]) were monitored for a total of 4824 hours. The total midazolam dose was 2.4 mg/kg (1.5-7.3 mg/kg) (median, 25th-75th percentile) for the SV group and 1.3 mg/kg (1.0-2.7 mg/kg) for the 2V group (P = 0.009). One SV patient experienced 2 brief EEG seizures postoperatively (1.5% incidence; 95% confidence interval: 0.3%-7.9%). The SV patients experienced a significant incidence of cerebral desaturation (rSo(2) <45% for >240 minutes total) perioperatively (18 of 36 SV vs 0 of 32 2V patients, P < 0.001). This difference did not affect electrographic seizure occurrence or other EEG characteristics., Conclusions: EEG seizures are infrequent in neonates undergoing surgery with high-flow CPB. Cerebral desaturation did not affect EEG seizure occurrence; however, benzodiazepines may play a role in suppressing postoperative seizures caused by cerebral hypoxemia in this patient population. Using this anesthetic and surgical protocol, EEG seizures are a poor surrogate marker for acute neurological injury in this population.

Objective: The natural history of standard (large, transmural right ventriculotomy) repair of tetralogy of Fallot (TOF) is associated with a concerning incidence of right ventricular (RV) failure and reoperation. We believe preserving the infundibulum using a TOF repair method with a mini-(<5 mm) or no ventricular incision optimizes RV function and confers long-term benefit. Over the past 13 years, we have uniformly applied this RV infundibulum sparing (RVIS) strategy., Methods: Using a retrospective cohort study design, 304 TOF patients who underwent the RVIS strategy (July 1995-June 2008) were reviewed. Median weight and age at repair: 8 kg (3-62 kg) and 9 months (2 days-23 years). Seventeen percent (51) of patients required a systemic-to-pulmonary artery shunt., Results: Ninety-nine percent of patients had a mini- 73% (222) or no 26% (79) ventricular incision. Postoperative morbidity included arrhythmias 3% (10), postoperative bleeding 2% (7), temporary renal failure 1% (3), and neurologic injury <1% (2). Thirty-day survival was 99.7%. Overall 1 and 7-year Kaplan-Meier survivals were 97% and 96%. In nonsyndromic children, only 1 patient has died in the RVIS strategy. A total of 3.2% (10) of patients had reoperations. Twenty-one percent (65/304) of patients have been followed for >7 years (median: 8.5 years). None of them have severe dilation, > mild RV outflow obstruction, an arrhythmia, or a pacemaker/AICD. Ninety-five percent of these patients have normal RV function; 3 (4.6%) had mild dysfunction. This cohort has excellent exercise tolerance (MaxVO2 (mean): 41 ± 12 mL/kg/min)., Conclusion: The RVIS strategy has allowed morbidity, mortality, and reoperation rates to be minimized. Midterm results suggest that RVIS does appear to preserve RV function. Longer term follow-up will be essential in establishing if the RVIS strategy can change the natural history of repaired TOF.

Patients suffering from acute cardiac graft rejection can die because of hemodynamic collapse while being treated with vigorous immunosuppressive therapies. There is little pediatric data on the use of mechanical circulatory support (MCS) in patients with acute cardiac graft rejection accompanied by hemodynamic instability. This report reviews our experience using MCS in patients with severe acute allograft rejection and cardiogenic shock. Between July 1995 and December 2006, 7 of 117 heart transplant recipients (6%) had MCS placed in 8 cases of acute graft rejection with hemodynamic instability. Devices used were BioMedicus (five), Thoratec (two), and extracorporeal membrane oxygenation machine (one). Mean age was 12 +/- 6.6 years. Median duration of support was 7.5 days (range, 3-28 days). Medical therapy applied included pulse steroids (eight), antithymocyte globulin (five), intravenous immunoglobulins (five), and plasmapheresis (five). Eighty-eight percent (seven of eight cases) weaned from MCS. Five patients weaned to recovery and two were bridged to retransplant. Five of the seven patients weaned (71%) were discharged home, all with normal left ventricular function. Median follow-up was 3.0 years (4.5 months to 3.5 years). One-year survival is 50% and 3 year survival is 38%. Mechanical circulatory support can be applied in patients with acute cardiac graft rejection causing hemodynamic instability with acceptable weaning and discharge rates. Unfortunately, late survival for this cohort remains poor.

Background: Combined transplantation of the lungs and liver is indicated for patients who would not be expected to survive transplantation of either organ alone. No single center has accumulated a significant experience, and as a result the expectations for this operation in the current era are unknown., Methods: Patients that have undergone combined lung-liver transplantation in the United States were enrolled through the United Network for Organ Sharing Organ Procurement and Transplantation Network database. In addition, the English-language literature was searched for additional cases of combined lung-liver transplantation., Results: Eleven patients have undergone combined lung and liver transplantation in the United States at different centers. The 1- and 5-year patient survival rates are of 79% and 63%, respectively, and no patient has required retransplantation. These patient survival rates are equivalent to similar a combined lung-liver case series from the United Kingdom (P=0.37, log-rank test) and isolated orthotopic liver transplantation in the United States (P=0.59, log-rank test), and are comparable to patient survival rates following isolated lung transplantation in the United States., Conclusions: Patient survival of combined lung-liver transplantation is comparable to that of isolated liver and isolated bilateral lung transplantation. This option should be considered for patients with end-stage lung disease and liver disease when transplantation of a single organ transplantation is precluded by severe disease in the other organ system.

Background: The arterial switch operation (ASO) represents a remarkable success story in the surgical treatment of cyanotic congenital heart disease. This study is designed to assess recent outcomes after the ASO in babies presenting with transposition of the great arteries (TGA) and Taussig-Bing anomaly (TBA)., Methods: One hundred twenty-five consecutive neonatal and infant ASOs were performed by 2 surgeons at Texas Children's Hospital between July 1, 1995 and October 1, 2003. Patients with TGA and TBA were offered ASO irrespective of patient size and associated cardiac malformations. Primary cardiac diagnoses included TGA with intact ventricular septum (TGA/IVS, n = 79, 63%), TGA with ventricular septal defect (TGA/VSD, n = 37, 30%), and Taussig Bing Anomaly (TBA, n = 9, 7%)., Results: With complete follow-up, we observed a 30-day mortality rate of 1.6% (n = 2) with 2 late deaths (1.6%), for an overall actuarial survival rate of 96.3% at 7 years. Although there was a significant incidence of complex coronary ostial origin and branching including single coronary (n = 8, 6.4%) and intramural coronary artery (n = 8, 6.4%), this was not associated with increased operative risk. All patients are fully saturated and NYHA functional class I at latest clinic visit (0.3 to 88.4 months postoperatively). There have been no late coronary events. Of 121 survivors, 7 patients (5.8%) have required cardiovascular reoperation at an average of 15.3 +/-11.7 months postoperatively (range, 3.6 to 30.6 months) for an actuarial freedom from reoperation of 90% at 7 years., Conclusions: Using current methodologies, the ASO can be performed safely and with a low incidence of need for reoperation on intermediate follow-up. Recent experience indicates operative survival rates approaching 100%.

Unlabelled: In this study, we measured cerebral oxygenation in both cerebral hemispheres by using near-infrared spectroscopy before, during, and after regional low-flow cerebral perfusion (RLFP) to determine whether bilateral monitoring was necessary. Neonates undergoing aortic arch reconstruction with RLFP were studied. The bilateral regional cerebral oxygenation index was measured and recorded at 1-min intervals during the following periods: 1) before bypass, 2) during bypass before RLFP, 3) during RLFP, 4) on bypass after RLFP, and 5) post-bypass. Before bypass and on bypass before RLFP, the correlation (r = 0.979 and 0.852) and agreement (mean bias, right versus left, 0 and +2) between hemispheres were excellent. During RLFP, however, correlation (r = 0.35) and agreement (mean bias of the right versus left side, +6.3) worsened and only partially returned to baseline values after RLFP. Nine of 19 patients had sustained differences in cerebral oxygen saturation of >10%, always with the left side values less than the right. Bilateral monitoring detects desaturation in the left cerebral hemisphere during RLFP. The long-term consequences of lower saturations on the left side of the brain are unclear., Implications: Left-sided cerebral hemisphere oxygen saturation, measured with near-infrared spectroscopy, was less than right-sided cerebral oxygen saturation during regional low-flow cerebral perfusion used for neonatal aortic arch reconstruction.

Pediatric myocardial related morbidity and mortality after cardiopulmonary bypass (CPB) are well documented, but the effects of pulsatile perfusion (PP) versus nonpulsatile perfusion (NPP) on myocardial blood flow during and after hypothermic CPB are unclear. After investigating the effects of PP versus NPP on myocardial flow during and after hypothermic CPB, we quantified PP and NPP pressure and flow waveforms in terms of the energy equivalent pressure (EEP) for direct comparison. Ten piglets underwent PP (n = 5) or NPP (n = 5). After initiation of CPB, all animals underwent 15 minutes of core cooling (25 degrees C), 60 minutes of hypothermic CPB with aortic cross-clamping, 10 minutes of cold reperfusion, and 30 minutes of rewarming. During CPB, the mean arterial pressure (MAP) and pump flow rates were 40 mm Hg and 150 ml/kg per min, respectively. Regional flows were measured with radiolabeled microspheres. During normothermic CPB, left ventricular flow was higher in the PP than the NPP group (202+/-25 vs. 122+/-20 ml/l 00 g per min). During hypothermic CPB, no significant intragroup differences were observed. After 60 minutes of ischemia and after rewarming (276+/-48 vs. 140+/-12 ml/100 g per min; p < 0.05) and after CPB (271+/-10 vs. 130+/-14 ml/100 g per min; p < 0.05), left ventricular flow was higher in the PP group. Right ventricular flow resembled left ventricular flow. The pressure increase (from MAP to EEP) was 10+/-2% with PP and 1% with NPP (p < 0.0001). The increase in extracorporeal circuit pressure (ECCP) (from ECCP to EEP) was 33+/-10% with PP and 3% with NPP (p < 0.0001). Pulsatile flow generates significantly higher energy, enhancing myocardial flow during and after hypothermic CPB and after 60 minutes of ischemia in this model.

Impairment of cerebral oxygenation in neonates and infants after hypothermic nonpulsatile cardiopulmonary bypass (CPB) support is well documented. The objectives of this study were: 1) using a neonatal piglet model to continuously monitor the regional cerebral oxygen saturation (rSO2) by near-infrared spectroscopy during pulsatile hypothermic CPB; and 2) to quantify the pulsatile flow in terms of energy equivalent pressure (EEP). After initiation of CPB, all piglets (n = 5) were subjected to 15 minutes of core cooling, reducing the rectal temperature to 25 degrees C, followed by 60 minutes of hypothermic CPB, then 10 minutes of cold reperfusion, and 30 minutes of rewarming. During CPB, mean arterial pressures (MAPs) and pump flow rates were maintained at 40-45 mm Hg and 150 ml/kg/min, respectively. During normothermic CPB, the rSO2 was significantly increased, compared with the pre-CPB level (56.8 +/- 5.2% vs. 41.8 +/- 5.5%, p < 0.01). At the end of cooling, the rSO2 level was 76.8 +/- 8.6% (p < 0.001 vs. pre-CPB). After 60 minutes of hypothermic CPB and 30 minutes of rewarming, the rSO2 level was decreased to 38.6 +/- 4.2%, which was not significantly different compared with the pre-CPB level. The average increase in pressure (from MAP to EEP) was 5 +/- 1%, and the average increase in extracorporeal circuit pressure (from ECCP to EEP) was 13 +/- 2%. This extra pressure may help to provide better regional cerebral oxygen saturation. During pulsatile CPB, there was no rSO2 deficiency in this high flow model. Near-infrared spectroscopy responded well to changes in rSO2 during different stages of these experiments and might be a helpful tool for intraoperative monitoring.

The purpose of this study was to quantify and compare pulsatile and nonpulsatile pressure and flow waveforms in terms of energy equivalent pressure (EEP) during cardiopulmonary bypass in a neonatal piglet model. EEP is the ratio of the area under the hemodynamic power curve and the flow curve. Piglets, mean weight of 3 kg, were used in physiologic pulsatile pump (n = 7), pulsatile roller pump (n = 6), and nonpulsatile roller pump (n = 7) groups. Data (waveforms of the femoral artery pressure, pump flow, and preaortic cannula extracorporeal circuit pressure) were collected during normothermic cardiopulmonary bypass at 35 degrees C (15 minutes on-pump), before deep hypothermic circulatory arrest (pre-DHCA) at 18 degrees C, and after cold reperfusion and rewarming (post-DHCA) at 36 degrees C. The pump flow rate was 150 ml/kg/min in all three groups. During pulsatile perfusion, the pump rate was 150 bpm in both pulsatile groups. Although there was no difference in mean pressures in all groups, EEP and the percentage increase of pressure (from mean pressure to EEP) of mean arterial pressure and preaortic cannula extracorporeal circuit pressure were higher with pulsatile perfusion compared with nonpulsatile perfusion (p < 0.001). In particular, the physiologic pulsatile pump group produced significantly higher hemodynamic energy compared with the other groups (p < 0.001). These results suggest that pulsatile and nonpulsatile flows can be quantified in terms of EEP for direct comparisons, and pulsatile flow generates higher energy, which may be beneficial for vital organ perfusion during cardiopulmonary bypass.

An alternate physiologic pulsatile pump (PPP) system was designed and evaluated to produce sufficient pulsatility during neonate-infant open heart surgery. This hydraulically driven pump system has a unique "dual" pumping chamber mechanism. The first chamber is placed between the venous reservoir and oxygenator and the second chamber between the oxygenator and patient. Each chamber has two unidirectional tricuspid valves. Stroke volume (0.2-10 ml), upstroke rise time (10-350 msec), and pump rate (2-250 beats per minute [bpm]) can be adjusted independently to produce adequate pulsatility. This system has been tested in 3-kg piglets (n = 6), with a pump flow of 150 ml/kg/min, a pump rate of 150 bpm, and a pump ejection time of 110 msec. After initiation of cardiopulmonary bypass (CPB), all animals were subjected to 25 minutes of hypothermia to reduce the rectal temperatures to 18 degrees C, 60 minutes of deep hypothermic circulatory arrest (DHCA), then 10 minutes of cold perfusion with a full pump flow, and 40 minutes of rewarming. During CPB, mean arterial pressures were kept at less than 50 mm Hg. Mean extracorporeal circuit pressure (ECCP), the pressure drop of a 10 French aortic cannula, and the pulse pressure were 67+/-9, 21+/-6, and 16+/-2 mm Hg, respectively. All values are represented as mean+/-SD. No regurgitation or abnormal hemolysis has been detected during these experiments. The oxygenator had no damping effect on the quality of the pulsatility because of the dual chamber pumping mechanism. The ECCP was also significantly lower than any other known pulsatile system. We conclude that this system, with a 10 French aortic cannula and arterial filter, produces adequate pulsatility in 3 kg piglets.

Neurological side effects associated with cyclosporine immunosuppressive therapy are generally believed to occur with CsA blood concentrations above the therapeutic range. The effects of high blood CsA levels on cerebral hemodynamics, metabolism, and electrophysiologic activity were studied in acute (no CsA prior treatment) and chronic (with CsA prior treatment) dogs. In acute animals, when parenteral CsA (10 mg/kg or 25 mg/kg) was administered intravenously (CsA blood level 2000-22,000 ng/ml), slight but significant time-dependent decreases in cerebral blood flow (CBF), prolongation of absolute latencies of somatosensory-evoked potential (SSEP), and brainstem auditory-evoked responses (BAER) were noted. In the CsA chronically administered animals (oral CsA 25 mg/kg/24 hr for 14 days, CsA blood level 1077 ng/ml), baseline cerebral physiologic parameters were normal, and the cerebral responses to further administration of CsA (25 mg/kg, CSA blood level 56,000 ng/ml) intravenously were similar to those of the acute animals. Animals given Cremophor EL, the solvent for parenteral CsA preparation, showed similar cerebral responses to those observed in animals given CsA. Thus this study showed that CsA, regardless of the dose given, whether chronically or acutely administered, or the solvent for CsA all induced similar cerebral physiologic responses. We suggest that the cerebral physiologic and functional changes associated with parenteral CsA administration were small and were likely caused by its solvent, Cremophor EL, rather than CsA itself. Furthermore on the basis of our results, it is unlikely that high blood CsA per se can account for neurological side effects that occur in immunosuppressed patients.

Numerous techniques have been devised for the harvesting of individual organs during a multiorgan procurement operation. Cardiopulmonary bypass with profound hypothermia (PH) has been employed in successful harvesting of heart-lung, kidney, pancreas, and liver grafts. This report summarizes our experience using CPB-PH for the harvesting of multiple organs from 10 brain-dead donors during the period from July 1983 to January 1988. Organs harvested included 10 heart-lungs, 17 kidneys (3 kidneys were not harvested due to anatomy and elevated creatinine), 1 liver, and 1 pancreas. Mean ischemic time for the distantly procured heart-lung grafts was 281 +/- 10 min. Adequate pulmonary function, as assessed by arterial blood gases, was observed in each heart-lung recipient (mean PO2 was 119 +/- 46 mmHg, 164 +/- 47 mmHg, 130 +/- 30 mmHg, 114 +/- 26 mmHg at immediate post-CPB, 6 hr postop, 24 hr postop, and postextubation, respectively). Mean length of intubation was 34 +/- 8 hr. Mean creatinines of kidney recipients at days 2, 7, and current creatinine were 7.4 +/- 3.6 mg%, 3.6 +/- 2.4 mg%, and 1.6 +/- 0.66 mg%, respectively. Eight kidney recipients (47%) required dialysis, (2 patients required only a single dialysis). Ninety-four percent of the kidney transplant patients are alive, and 88% (15/17) have functioning kidneys. One liver and 1 pancreas were harvested during this time period. Preservation was satisfactory in both the pancreas (Johns Hopkins Hospital) and liver (Dr. Thomas Starzl, personal communication). The technique of CPB-PH has resulted in excellent function of heart-lung grafts. Follow-up of the transplanted kidneys, liver, and pancreas utilizing this technique shows equal or better function compared with standard techniques. This technique offers other advantages in addition to satisfactory multiorgan preservation. Placement of an unstable patient on CPB ensures adequate organ perfusion and allows for a gradual yet uniform cooling of all organ systems. Cooling to a core temperature of 10-15 degrees C requires 30 min, during which time preliminary intraabdominal and mediastinal dissection can be carried out. Following cessation of CPB and subsequent exsanguination, organs can be more easily dissected in a near-bloodless field. This technique does not preclude additional crystalloid organ flushing. Since multiorgan procurement occurs with virtually every donor, this technique may be the optimal method providing excellent preservation, ease of dissection, and better control of hemodynamics during the operation.

Eight beagles receiving heterotopic (cervical) cardiac allografts from outbred donors were evaluated by serial 31P NMR, septal endocardial biopsy, and left ventricular pressure measurements for signs of rejection. Early postoperative myocardial energy levels, as assessed by ratios of phosphocreatine to inorganic phosphate (PCr/Pi) and phosphocreatine to beta-ATP (PCr/B-ATP), were acceptable in all recipients. In these nonimmunosuppressed animals, the mean ratios of PCr/Pi and PCr/B-ATP progressively decreased, with a greater than 25% reduction noted by postoperative day two and greater than 50% reduction by day three. In sharp contrast, left ventricular end-diastolic pressures remained stable and at baseline levels for the first three postoperative days, and only then markedly increased. Likewise, histologic evidence of rejection did not become prominent until postoperative day four. These results suggest that metabolic abnormalities significantly precede either functional or histologic changes in rejecting allografts. The early detection of these metabolic changes by 31P NMR appears to have important potential for the noninvasive diagnosis of cardiac allograft rejection.