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Background: Recombinant and plasma-derived factor products, such as activated factor seven (rFVIIa) and four-factor prothrombin complex concentrate (4-factor PCC), have been used off-label for bleeding after cardiac surgery, but little evidence has been published regarding their efficacy and safety. Objective: To determine whether there is a difference in chest tube output in patients who have received 4-factor PCC or rFVIIa for critical postoperative bleeding associated with cardiovascular surgery. Methods: A retrospective chart review was conducted utilizing the electronic medical record system at a 657-bed community, tertiary care hospital in Nashville, Tennessee. Nonpregnant patients ≥18 years of age experiencing significant bleeding during cardiac surgery who received either PCC or rFVIIa perioperatively or postoperatively between April 2015 through December 2016 were eligible for inclusion. Patients were excluded if they received 4-factor PCC or rFVIIa for any indication other than bleeding during cardiac surgery or if they received both agents. Results: Data conclude that there is no significant difference in chest tube output 24 hours postoperatively between patients treated with 4-factor PCC or rFVIIa. There was no difference in bleeding, thromboembolic events, or re-exploration between the rFVIIa and 4-factor PCC groups, but there was a difference in units of fresh frozen plasma administered and hospital length of stay. Conclusion: 4-Factor PCC may be an equally efficacious alternative to rFVIIa for patients experiencing significant bleeding during cardiac surgery. There is no difference in chest tube output; therefore, there is no difference in bleeding—either at 24 hours postoperatively or total.

Objective Pulmonary hypertension may complicate surgical correction of congenital heart defects, resulting in increased morbidity and mortality. We have previously shown that plasma levels of the nitric oxide precursors citrulline and arginine drop precipitously after congenital cardiac surgery and that oral citrulline supplementation may be protective against the development of pulmonary hypertension. In this study, we assessed the safety and pharmacokinetic profile of intravenous citrulline as a potential therapy for postoperative pulmonary hypertension. Methods The initial phase of this investigation was a dose-escalation study of intravenously administered citrulline in infants and children undergoing one of five congenital cardiac surgical procedures (phase 1). The primary safety outcome was a 20% drop in mean arterial blood pressure from the baseline pressure recorded after admission to the intensive care unit. Based on our previous work, the target circulating plasma citrulline trough was 80 to 100 μmol/L. Each patient was given two separate doses of citrulline: the first in the operating room immediately after initiation of cardiopulmonary bypass and the second 4 hours later in the pediatric intensive care unit. Stepwise dose escalations included 50 mg/kg, 100 mg/kg, and 150 mg/kg. After model-dependent pharmacokinetic analysis, we enrolled an additional 9 patients (phase 2) in an optimized dosing protocol that replaced the postoperative dose with a continuous infusion of citrulline at 9 mg/(kg·h) for 48 hours postoperatively. Results The initial stepwise escalation protocol (phase 1) revealed that an intravenous citrulline dose of 150 mg/kg given after initiation of cardiopulmonary bypass yielded a trough level of in the target range of approximately 80 to 100 μmol/L 4 hours later. The postoperative dose revealed that the clearance of intravenously administered citrulline was 0.6 L/(h·kg), with a volume of distribution of 0.9 L/kg and estimated half-life of 60 minutes. Because of the short half-life, we altered the protocol to replace the postoperative dose with a continuous infusion of 9 mg/(kg·h). An additional 9 patients were studied with this continuous infusion protocol (phase 2). Mean plasma citrulline levels were maintained at approximately 125 μmol/L, with a calculated clearance of 0.52 L/(h·kg). None of the 17 patients studied had a 20% drop in mean arterial blood pressure from baseline. Conclusions In this first report of the use of intravenous citrulline in humans, we found citrulline to be both safe and well tolerated in infants and young children undergoing congenital cardiac surgery. Because of the rapid clearance, the optimal dosing regimen was identified as an initial bolus of 150 mg/kg given at the initiation of cardiopulmonary bypass, followed 4 hours later by a postoperative infusion of 9 mg/(kg·h) continued up to 48 hours. Using this regimen, plasma arginine, citrulline, and nitric oxide metabolite levels were well maintained. Intravenous citrulline needs to be studied further as a potential therapy for postoperative pulmonary hypertension.

Severe bleeding is a major complication in the postoperative pediatric cardiac surgery patients. We evaluated the efficacy and safety of recombinant factor seven (rFVIIa) therapy in this patient population.A retrospective unmatched case-control study for the previous five years in a single institution was undertaken. Patients with severe bleeding treated with rFVIIa therapy (study group) were compared with patients treated with blood products only (control group) using analysis of variance. Mediastinal bleeding, blood products transfusion, and coagulation studies before and six hours after the first dose of rFVIIa therapy were analyzed using the Student paired t test. The dose, frequency, and side-effects of rFVIIa therapy were studied.Forty-six patients with severe bleeding were studied. Twenty-three of 24 patients in the study group, including 12 patients placed on extracorporeal membrane oxygenation (ECMO), responded to rFVIIa therapy (mean dose 43 +/- 22.9 microg/kg/dose). There was significant reduction in chest tube drainage (from 52.3 +/- 36.1 mL/kg/hour to 18.8 +/- 20.9 mL/kg/hour, p = 0.0003) along with significant reduction of blood products transfusion (p0.001) in the study group patients as compared with control group patients. One patient who failed to respond had surgical bleeding. Two patients developed major thrombotic complications that included clots in the ECMO circuit and thrombosis at bleeding arterial line site resulting in limb ischemia. Four additional patients in the study group developed mediastinal clots. Overall, 25% of patients developed thrombosis after rFVIIa therapy.The rFVIIa therapy seems to be an effective treatment for severe bleeding in postoperative pediatric cardiac surgery patients in the absence of surgical bleeding. It must be judiciously used in patients bleeding from multiple sites or having preexistent clots in the ECMO circuit to prevent major thrombotic complications.

Children frequently undergo bidirectional Glenn anastomosis in the staged surgical management of single ventricle physiology. The purpose of our study was to investigate the role of inhaled nitric oxide therapy in children with marked elevations in Glenn pressures after this surgery.A retrospective study over a 30-month period was performed. The effect of inhaled nitric oxide therapy was analyzed in children with marked elevations of Glenn pressures resulting in decreased systemic perfusion. Effects on Glenn pressures, respiratory indices, and systemic perfusion were evaluated after initiation of nitric oxide therapy and compared with baseline parameters.Sixteen patients were placed on nitric oxide therapy for marked elevations of Glenn pressures (22.4 +/- 3.9 mm Hg). In the 11 responsive patients, there were significant reductions in Glenn pressures (from 22.4 mm Hg to 17.1 mm Hg, p0.001) and significant improvement in partial pressure of oxygen to fraction of inspired oxygen ratio (from 49 to 74.3, p = 0.001) and oxygenation index (from 17 to 12, p = 0.005). There was simultaneous significant reduction in inotrope score (from 14.9 to 11.4, p0.001) and fluid volume support (from 11.4 mL/kg to 2.3 mL/kg, p0.001) in the responsive patients. Five patients that failed to show any response were found, subsequently, to have an anatomic lesion.Inhaled nitric oxide produces significant reduction in Glenn pressures and improvement in systemic perfusion and pulmonary gas exchange in patients with marked elevations of Glenn pressures after bidirectional Glenn anastomosis. Patients who fail to respond should be investigated for an anatomic lesion.

Voltage-gated potassium (K(V)) channels are modulated by at least three distinct classes of proteins including the KCNE family of single transmembrane accessory subunits. In the human genome, KCNE proteins are encoded by five genes designated KCNE1 through KCNE5. KCNE1 associates with KCNQ1 in vitro to generate a potassium current closely resembling the slowly activating delayed rectifier (I(Ks)). Other KCNE proteins also affect the activity of heterologously expressed KCNQ1. To investigate the potential physiological relevance of this gene family in human heart, we examined the relative expression of KCNQ1 and all five KCNE genes in samples derived from normal tissues representing major regions of human heart by real-time, quantitative RT-PCR. KCNE genes are expressed in human heart with a relative abundance ranking of KCNE1 > KCNE4 > KCNE5 approximately KCNE3 >> KCNE2. In situ hybridization revealed prominent expression of KCNE1 and KCNE3-5 in human atrial myocytes. In cardiomyopathic hearts, expression of KCNE1, KCNE3, KCNE4, and KCNQ1 was significantly increased, while KCNE2 and KCNE5 exhibited reduced expression. In a cell line stably expressing KCNQ1 and KCNE1, transient expression of KCNE3, KCNE4, or KCNE5 significantly altered I(Ks) current profiles. Even in the presence of additional KCNE1, KCNE4 and KCNE5 exert dominant effects on I(Ks). Although KCNE1 is the predominant KCNE family member expressed in human heart, the abundance of other KCNE transcripts including potential KCNQ1 suppressors (KCNE4 and KCNE5) and their altered expression patterns in disease lead us to speculate that a balance of KCNE accessory subunits may be important for cardiac K(V) channel function.

Objectives: Mitogen-activated protein kinases (MAPK) are important intermediates in the signal transduction pathways involved in neuronal dysfunction following cerebral ischemia-reperfusion injury. One subfamily, extracellular regulated kinase 1/2, has been heavily implicated in the pathogenesis of post-ischemic neuronal damage. However, the contribution of extracellular regulated kinase 1/2 to neuronal damage following deep hypothermic circulatory arrest and low flow cardiopulmonary bypass is unknown. We attempted to correlate the extent of neuronal damage present following deep hypothermic circulatory arrest and low flow cardiopulmonary bypass with phosphorylated extracellular regulated kinase 1/2 expression in the cerebral vascular endothelium. Methods: Piglets underwent normal flow cardiopulmonary bypass ðn ¼ 4Þ; deep hypothermic circulatory arrest ðn ¼ 6Þ and low flow cardiopulmonary bypass ðn ¼ 5Þ: Brains were harvested following 24 h of post-cardiopulmonary bypass recovery. Cerebral cortical watershed zones, hippocampus, basal ganglia, thalamus, cerebellum, mesencephalon, pons and medulla were evaluated using hematoxylin and eosin staining. A section of ischemic cortex was evaluated by immunohistochemistry with rabbit polyclonal antibodies against phosphorylated extracellular regulated kinase 1/2. Results: Compared to cardiopulmonary bypass controls, the deep hypothermic circulatory arrest and low flow cardiopulmonary bypass piglets exhibited diffuse ischemic changes with overlapping severity and distribution. Significant neuronal damage occurred in the frontal watershed zones and basal ganglia of the deep hypothermic circulatory arrest group ðP , 0:05Þ: No detectable phosphorylated extracellular regulated kinase 1/2 immunoreactivity was found in the cardiopulmonary bypass controls; however, ERK 1/2 immunoreactivity was present in the cerebral vascular endothelium of the deep hypothermic circulatory arrest and low flow cardiopulmonary bypass groups. Conclusions: Our results indicate that phosphorylated extracellular regulated kinase 1/2 may play a prominent role in early cerebral ischemia-reperfusion injury and endothelial dysfunction. The pharmacologic inhibition of extracellular regulated kinase 1/2 represents a new and exciting opportunity for the modulation of cerebral tolerance to low flow cardiopulmonary bypass and deep hypothermic circulatory arrest. q 2004 Elsevier B.V. All rights reserved.

There are an increasing number of adults with congenital heart disease due to greater success with palliative and corrective operations, along with improvements in the medical management of operated and unoperated patients. There are approximately 1 million adult corrected, palliated or uncorrected congenital heart patients; which is estimated to increase by 5% per year w1x The growing importance of this area of cardiology and cardiac surgery is reflected by subspecialty training and education, such as the recent 32nd Bethesda Conference on ‘The Care of Adults with Congenital Heart Disease’ w2x. Surgery on adult congenital heart patients is unique in that the surgical and perioperative care team (cardiology and critical care in particular) should have a thorough understanding of the particular anatomy and physiology involved. In our own experience 260 patients over the age of 18 years have undergone an operation to correct a congenital heart defect over the past 5 years (Table 1). Table 1 represents roughly 15% of our overall operated congenital heart population. These lesions range widely in complexity and include aortic valve disease that has close similarity with acquired heart disease and management to the more complex single ventricle physiology that requires a dedicated congenital heart team. The types of cardiac lesions encountered in adult patients, such as those listed in Table 1 can be divided into lesions by increasing complexity and likelihood of reaching adult age and requiring surgery. Previously operated individuals who require further surgery represent the largest group by far. Need for further intervention is based on a number of factors that include electrophysiologic, valvular (native), prosthetic materials (valves, patches and conduits), myocardial, vascular and neurologic w3x.

Background— The outcome of cardiac surgery is influenced by several factors, but the impact of specific genetic variants has not been systematically explored. Because blood conservation is a pressing issue in cardiac surgery, we tested the hypothesis that factor V Leiden (FVL), a common coagulation factor polymorphism, may protect against blood loss and transfusion in patients undergoing cardiac surgery. Methods and Results— We enrolled 517 patients undergoing cardiac surgery, including 26 heterozygous FVL carriers, and evaluated the impact of FVL on chest tube output and transfusion by using univariate and multivariate techniques. For patients with FVL, blood loss at 6 (238±131 mL) and 24 hours (522±302 mL) was significantly lower than that for noncarriers (358±259 mL and 730±452 mL; P P =0.001, respectively). In a multivariate regression analysis, controlling for ethnicity and factors known to affect blood loss, FVL was a significant independent contributor at both time points. Using a similar regression approach, FVL did not have a significant effect on the number of units transfused. However, logistic regression of the risk of receiving any transfusion during hospitalization demonstrated a significant independent protective effect of FVL on overall transfusion risk. Conclusions— FVL represents a common genetic trait that may protect against blood loss and transfusion in this population. This study demonstrates that genetic variability can affect the outcome of cardiac surgery.

Background . The use of radial arteries for coronary revascularization is increasing. There remain concerns regarding alteration of upper extremity function after radial artery procurement. This study evaluates the functional morbidity in higher risk patients. Methods . Between April 1997 and September 1999, 374 patients underwent unilateral or bilateral radial artery procurement. A questionnaire was used to evaluate symptoms related to motor and sensory function and changes in appearance after radial artery harvest. Results . Two hundred eighty-nine patients were successfully interviewed. The average age was 63 years. Median follow-up was 9.5 months (range, 2 to 23 months). No patient suffered limb loss. Altered gross and fine motor function, residual pain, paresthesias, numbness, pallor, swelling, and altered temperature sensation were compared among diabetic patients, patients older than 70 years, and patients without these characteristics. Conclusions . Radial artery procurement for elective coronary revascularization can be done with minimal serious morbidity in higher risk patients. The most common symptoms were numbness and paresthesia. Despite the finding of greater residual pain in diabetic patients, we do not believe the use of radial artery conduits is contraindicated in these patients.

Renal transplantation remains a mainstay of therapy for end-stage renal disease. Cardiac disease has a high prevalence in this patient population. This study reviews the factors and outcomes associated with cardiac surgery in renal transplant recipients. We performed a retrospective review of all patients at our institution with a functioning renal allograft at the time of their cardiac surgical procedure. Between June 1971 and April 2000, 2343 patients underwent renal transplantation at Vanderbilt University Medical Center. Twenty-six patients with a functioning renal allograft subsequently underwent a cardiac procedure requiring cardiopulmonary bypass. There were 11 women and 15 men. Twenty-four patients underwent coronary bypass, one had a double valve replacement, and one had a combined coronary bypass/valve replacement. The interval from renal transplant to heart surgery ranged between 0.6 and 227 months (mean 79.1). Operative mortality was zero but there were two hospital deaths: one due to multisystem organ failure and one due to pulmonary embolism. Six additional patients died late with only one due to heart disease. Four patients required perioperative dialysis, and one of these went on to require permanent dialysis. Two additional patients returned to dialysis late postoperatively. The requirement for acute perioperative dialysis was predicted by preoperative creatinine, hematocrit, and intraoperative urine output. The overall survival is 69 per cent (18 of 26) with a median follow-up of 38 months. The majority of long-term survivors have minimal cardiac symptoms. Standard cardiac surgery procedures can be performed with relative safety in patients with functioning renal allografts. The incidence of perioperative and late development of renal failure requiring dialysis is low. The long-term survival and symptomatic improvement achieved are favorable and warrant continued performance of cardiac surgery in patients with functioning renal allografts.

Background . The intermediate and long-term results of cardiac transplantation continue to improve. Subsequent cardiac procedures may be required to extend patient survival and protect graft function. Methods . The medical records of all adult and pediatric cardiac transplant recipients who underwent a subsequent cardiac procedure at our institution were reviewed. Results . Three hundred sixty patients have undergone primary orthotopic transplantation in our institution. Seventeen patients (12 adults, 5 children) underwent a subsequent procedure requiring cardiopulmonary bypass including cardiac retransplantation (10), coronary artery bypass grafting (3), ascending aortic replacement (2), tricuspid valve repair (1), and myotomy and myomectomy (1 patient). Mean interval from time of transplantation to second procedure was 8.3 years. There was one perioperative death. Two patients, both retransplants, died late postoperatively at 22 and 84 months, respectively. Overall mean follow-up in the late survivors is 26.6 months. All survivors are currently asymptomatic and doing well. Conclusions . A variety of subsequent cardiac procedures, in addition to retransplantation, can be performed safely in carefully selected cardiac transplant recipients. The intermediate term results are gratifying in terms of survival and freedom from symptoms.

Background: Transplant coronary atherosclerosis is a major limiting factor to successful long-term cardiac transplantation. The depletion of tissue plasminogen activator (tPA) in the arteriolar smooth muscle cells has been associated with a higher incidence of accelerated graft atherosclerosis. In vivo overexpression of tPA may inhibit accelerated graft atherosclerosis and improve the long-term results of heart transplantation. We evaluated the feasibility, distribution, and effects of intracoronary transfer of the human tPA (htPA) gene in a rabbit heterotopic cardiac transplant model, using a novel cationic liposome compound designed for improved delivery to vascular endothelium. Methods Human tPA cDNA under the control of the SV40 promoter (100 μg) was complexed with the novel cationic liposome (±)-N-(3-aminopropyl)-N,N-dimethyl-2,3- bis (dodecyloxy)-1-propanaminium bromide (GAP: DLRIE) (50 μg), and delivered ex vivo to the donor heart by slow intracoronary infusion. Control hearts received an “empty” liposome preparation. Grafts were then implanted into recipient rabbits in the heterotopic cervical position. For the analysis of gene expression, beating donor hearts were collected at 4 days. To examine the effects of htPA expression on graft atherosclerosis, animals received a 0.5% cholesterol diet for 30 days posttransplant, as well as 10 mg/kg cyclosporine A daily. Beating hearts were collected at 30 days posttransplant and analyzed for the development of transplant atherosclerosis by image analysis. Results Northern blot analysis for the htPA messenger RNA (mRNA) transcripts showed significantly higher counts in hearts receiving the htPA gene as compared to controls. The distribution of these transcripts favored the left ventricle (LV) and septal regions over the right ventricle (RV). Scintillation analysis of specimens stained by immunoflourescence showed expression of htPA throughout the perivascular myocardium that was significantly higher in grafts transduced with the htPA gene than in control or native hearts. Expression in the vascular wall was also significantly enhanced. Scintillation counts per × 200 field were 262 ± 145 in htPA-transduced hearts and 20 ± 27 in controls ( p = 0.001), and mean luminescence was 83.7 ± 12.5 in htPA-transduced hearts and 62.9 ± 12.8 in controls ( p = 0.01). Intimal hyperplasia was assessed by mean percent luminal stenosis in small- and medium-sized arteries and was 31.12 ± 23.5% in htPA-transduced hearts and 86.59 ± 17.5% in control hearts ( p Conclusions These results demonstrate that expression of the htPA gene can be induced by ex vivo intracoronary gene transfer at the time of allograft preservation. Liposome-mediated delivery of the htPA gene at the time of transplantation results in significant early transgene expression, and significantly inhibits the development of graft coronary atherosclerosis.

The percutaneous use of stents for the treatment of superior vena cava (SVC) syndrome is well described in the adult population. We report the successful use of intravascular stents to treat an infant with severe SVC syndrome.

Objective: Although activation of protein kinase C (PKC) modulates the function of normal cardiac myocytes and likely plays a role in the pathogenesis of cardiomyopathic disease states, the molecular basis of PKC expression in human ventricle has not been examined in detail. Methods: We have performed Western analysis and immunohistochemistry on explanted human cardiac tissue from nondiseased and diseased specimens using isoform-specific antibodies directed against all known PKC isozymes. Results: In homogenates from left and right ventricle, all isoforms except PKC-γ and θ were detected by immunoblotting, with confirmation using a second antibody directed against a different epitope when possible. For PKC-βII, δ, and e, data indicated that these isoforms were variably phosphorylated in vivo, resulting in multiple bands during immunoblotting. Because of potential antibody cross-reactivity, reverse transcriptase polymerase chain reaction (RT-PCR) was performed which confirmed expression of PKC-α, βI, and ζ. Immunohistochemistry demonstrated that all isoforms detected in ventricular homogenate by Western analysis could be localized to cardiac myocytes. From a methodologic standpoint, significant degradation of PKC isoforms could be demonstrated when samples were either frozen or allowed to remain at room temperature, compared to immediate subcellular fractionation. Conclusions: These findings indicate that the PKC expression in human ventricular myocytes is remarkably diverse, with multiple conventional, novel, and atypical isoforms present, and highlight the importance of sample preparation in comparative studies of PKC isoform expression.

Objectives: Respiratory failure is the major mode of death after general thoracic operations. However, respiratory failure may develop from two very different mechanisms: aspiration, often caused by ileus, and pneumonia, which often results from poor pain control. Epidural catheters help control pain and prevent pneumonia but contribute to ileus and may increase aspiration. We report a decrease in the incidence of aspiration after changing postoperative care to include gastrointestinal tract management. Methods: All patients undergoing elective thoracotomy by a single surgeon were evaluated for hospital mortality and morbidity. For the first 21 months, patients did not receive an intraoperative nasogastric tube and were prescribed an "advance as tolerated" diet after the operation (n = 125). For the second period, nasogastric tubes were placed intraoperatively and patients received nothing by mouth the day of operation, clear liquids the first day, and a regular diet the second day (n = 153). Pneumonia was considered to have developed if infiltrates developed in a single lobe or two adjoining lobes and culture of the sputa grew a dominant organism. Patients were considered to have aspirated if diffuse infiltrates developed or cultures grew multiple organisms. Significance of results was determined by χ 2 testing. Results: A total of 278 patients underwent elective lung resection over a 3½-year period, 125 with ad libitum dietary management and 153 with intensive management of the gastrointestinal tract. Six patients (4.84%) aspirated before the institution of gastrointestinal tract management, whereas none (0.0%) aspirated after the change. This difference was significant ( P = .01). Respiratory mortality was eliminated in the group with gastrointestinal tract management ( P = .04). Conclusions: Aspiration and its subsequent respiratory failure and mortality can be decreased with preemptive gastrointestinal tract management. (J Thorac Cardiovasc Surg 2000;119:449-52)

Background . More accurate staging at the time of initial presentation could improve design of clinical trials and avoid inappropriate surgical decisions in individual patients. Preresection staging of patients with non-small cell lung cancer (NSCLC) is not straightforward, especially in patients with negative mediastinal nodes. The purpose of this study was to compare the results of radiologic, thoracoscopic, and pathologic staging in patients with NSCLC and negative mediastinoscopy. Methods . All patients with NSCLC underwent computed tomographic (CT) scanning before surgical staging with mediastinoscopy. Patients with negative mediastinoscopy then underwent thoracoscopic staging with examination of pleural surfaces, and identification of T (visceral and parietal pleural invasion, sampling of pleural fluid, and pleural lavage) and N (intraparenchymal and inferior mediastinal nodal sampling, if possible) stage descriptors before resection. Results . Thoracoscopy was more accurate than CT scanning in the staging of 50 patients with early lung cancer (stages IA, IB, IIA, and IIB), especially as regards T stage. Further, thoracoscopic examination ruled out malignant pleural effusions in 7 (14%) patients with radiologically obvious effusions, and identified radiologically silent malignant pleural effusions in 3 (6%) patients. Chest wall invasion was accurately identified at thoracoscopy in most patients. Finally, 3 patients with T1 lower lobe lesions and negative mediastinoscopy were found to have involvement of inferior mediastinal nodes (level 8 or 9) at thoracoscopy. However, thoracoscopy did not allow sampling of aortopulmonary window nodes in some patients with bulky left upper lobe lesions. Conclusions . Errors in thoracoscopic staging resulted in no inappropriate operations. However, errors in CT staging would have resulted in operations unlikely to help the patients, or would have inappropriately excluded patients from surgery. Thoracoscopic staging was more accurate than CT staging in this cohort of patients with NSCLC and negative mediastinoscopy.

Background. The criteria for cardiac transplantation recipient selection, including the appropriate recipient upper age limit, continue to expand with an increasing number of recipients greater than 60 years of age. While others have reported their transplant experience in older recipients in terms of quality of life assessment, we have examined the role of exercise cardiopulmonary testing post-transplantation in older cardiac transplant recipients. Methods. We reviewed inpatient and outpatient charts of 28 patients 60 years of age or older who underwent orthotopic heart transplantation at Vanderbilt University Medical Center. Results. In this population, perioperative mortality of 7.1% and Kaplan-Meier survival at 1 and 5 years of 89 and 77%, respectively, were similar to the institutional 1-year (89%) and 5-year (75%) survival among younger adult transplant recipients. Exercise cardiopulmonary testing results were available in 22/25 patients surviving greater than 1 year. Both peak oxygen consumption and percentage of maximum V O 2 were significantly greater among patients reporting NYHA Class 1 or 2 functional status, in comparison with those NYHA Class 3 or greater. Conclusion. Following cardiac transplantation, survival of patients greater than 60 years of age is equivalent to that of younger patients at our institution. Exercise testing provides an objective measure of performance and correlates with subjective status following heart transplantation. Most patients demonstrate good functional status, with minimal symptoms and good exercise capacity. These results, although retrospective, suggest that cardiac transplantation remains a reasonable therapeutic option for patients greater than 60 years of age with end-stage cardiomyopathy.

Although it has gained much interest in other surgical specialties, the application of near-infrared spectroscopy to assess cerebral perfusion during cardiac surgery is relatively new. Regional cerebral oxygen saturation (rSO2) is a function of cerebral oxygen supply and demand. Continuous monitoring of the rSO2 permits early detection of cerebral ischemia allowing for prompt intervention. The following is a description of a repair of truncus arteriosus with type A interrupted aortic arch during which continuous cerebral oximetry assisted with the positioning of the arterial cannula avoiding a prolonged episode of cerebral ischemia.

Plastic bronchitis is an unusual clinical scenario of unknown cause and occurs in multiple clinical settings. The disease is characterized by the development of arborizing, thick, tenacious casts of the tracheobronchial tree that results in airway obstruction. Patients with congenital heart disease who have undergone a Fontan operation are at high risk for having this problem develop. Management of this distressing situation is difficult with only palliative options being available, such as repeated bronchoscopies, inhaled heparin, tissue plasminogen activator, inhaled bronchodilators, or azithromycin. The patients with Fontan circuits have a myriad of unique complications develop, such as atrial arrhythmias, recurrent pleural effusions, chylothoraces, protein-losing enteropathy, and plastic bronchitis. High intrathoracic lymphatic pressures with nondemonstrable lympho-bronchial fistulas were believed to be the cause for the development of these recurrent bronchial casts in plastic bronchitis. Faced with recurrent plastic bronchitis resistant to medical management in 2 Fontan patients with normal Fontan pressures on cardiac catheterization, we decided to explore a surgical solution by performing a thoracic duct ligation. This resulted in complete resolution of the formation of casts in both patients, who were discharged home and remain asymptomatic on continued follow-up. Thoracic duct ligation provides a surgical cure for plastic bronchitis by decreasing intrathoracic lymphatic pressure and flow.

Patients with infective endocarditis who require surgical intervention can be divided into four separate groups, in order of incidence: (1) patients with underlying acquired or congenital cardiac lesions or valvar abnormalities, (2) patients with preexisting prosthetic valves, (3) patients with nosocomial infections who are immunosuppressed, and (4) older patients with infection risk or patients with indwelling deep venous catheters. The surgical management for these individual groups and for specific valve lesions is discussed, along with illustrative case studies.

University of Wisconsin solution has provided excellent myocardial preservation. However, the high potassium content of the currently available University of Wisconsin solution has been implicated in coronary artery endothelial damage. We placed 16 neonatal (age 1 to 3 days) Duroc piglet hearts on an isolated nonworking perfusion circuit. Endothelium-dependent and endothelium-independent vasodilation were tested by measuring coronary blood flow after intracoronary infusion of bradykinin (10-6 mol/L) and nitroprusside (10–6 mol/L), respectively. In addition, nitric oxide levels were measured after bradykinin infusion. The hearts were then arrested blindly with either a modified University of Wisconsin solution (group 1; n = 8, K+ = 25 mEq/L) or standard University of Wisconsin solution (group 2; n = 8, K+ = 129 mEq/L) by infusion of cardioplegic solution every 20 minutes for a total of 2 hours. After bradykinin infusion, the mean coronary blood flow increased by 237.1% ± 14.0% of baseline valves before arrest and by 232.8% ± 16.0% after arrest in group 1 ( p = not significant). As in the first group, the mean coronary blood flow in group 2 increased by 231.1% ± 13.7% before arrest; however, the increase in mean coronary blood flow after arrest was significantly attenuated (163.3% ± 12.8%, p < 0.01). The loss of endothelium-dependent coronary blood flow response in group 2 correlated with a decreased capacity to release nitric oxide after arrest (prearrest 8.25 ± 2.30 nmol/min per gram versus postarrest –2.46 ± 2.29 nmol/min per gram, p < 0.01). Endothelium-independent vasodilatory response revealed no significant difference between groups before and after arrest. These results suggest that the low-potassium University of Wisconsin solution provides superior protection of the endothelium by preserving the endothelium-dependent vasodilatory response to nitric oxide release. (J Thorac Cardiovasc Surg 1996;112:103-10)

This study addresses the effects of early banding of the pulmonary trunk and subsequent management of sub-aortic obstruction on the attainment of acceptable pre Fontan hemodynamics in patients with a single left ventricle and aorta arising from an outflow chamber. We report our experience with 26 patients seen at our institution between January 1984 and December 1994 with a diagnosis of double-inlet left ventricle or tricuspid atresia and transposed great arteries, who were initially managed with pulmonary artery banding in the first 6 months of life. Pulmonary artery band placement was performed at an age of 2.1 ± 1.8 months (mean ± SD). Associated aortic arch abnormalities were present in 8 patients (31%). There were 19 patients (73%) who underwent treatment with a Damus-Kaye-Stansel procedure or ventricular septal defect (VSD) enlargement for a significant subaortic gradient or morphologically small VSD, alone or in conjunction with a Glenn or Fontan procedure. Eighteen of 26 patients (69%) underwent cardiac catheterization to assess their candidacy for the Fontan operation. Of this group, 16 were classified as low to moderate risk and 2 as high-risk Fontan candidates, based on hemodynamic criteria. The cumulative mortality for the entire cohort was 19%. Our results suggest that this high-risk group of patients can undergo effective pulmonary artery banding as an initial palliative step, with subsequent intervention for subaortic obstruction when it is documented or highly suspected, and that acceptable pre-Fontan hemodynamic parameters can be achieved.

The complete and uniform distribution of cardioplegia to the microvasculature of the heart is considered critical for myocardial protection. This study explores the hypothesis that enhanced microvascular perfusion can be achieved by using both antegrade and retrograde cardioplegia.Infant piglet hearts (n = 15) were arrested with antegrade blood cardioplegia, excised, and fixed with 2.5% glutaraldehyde by retrograde perfusion. Hearts were then perfused retrograde with an inert intracapillary marker (NTB-2). Six of these hearts served as controls (group 1) to anatomically demonstrate the degree of capillary perfusion achieved by the retrograde delivery route. Nine experimental hearts (group 2) underwent a subsequent infusion of antegrade blood cardioplegia to wash out NTB-2 capillaries coperfused by both the antegrade and retrograde delivery techniques. Sections of the left ventricular free wall and anterior-mid interventricular septum were taken and examined by light microscopy at four separate sites (average, 126 capillaries per section).In control hearts, 91.9% +/- 0.9% of ventricular capillaries and 91.4% +/- 5.8% of septal capillaries were perfused by retrograde cardioplegia. After antegrade blood cardioplegia washed out group 2 hearts, 14.0% +/- 4.1% of capillaries in the ventricle still contained NTB-2, as did 12.5% +/- 5.4% of capillaries in the septum.In this experimental model, antegrade blood cardioplegia did not coperfuse (and therefore washout) 12.5% to 14% (p0.05) of capillaries perfused by retrograde cardioplegia. This suggests that an additional 12.5% to 14% of capillaries within the myocardium may receive cardioplegia if retrograde cardioplegia is used in addition to antegrade cardioplegia. We conclude that by combining both antegrade and retrograde cardioplegia, there is a potential for enhanced overall microvascular perfusion.

Hypercholesterolemia is common after cardiac transplantation and may contribute to the development of coronary vasculopathy. Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been shown to be effective and safe in lowering cholesterol levels after cardiac transplantation. Cell-culture studies using inhibitors of HMG-CoA reductase have suggested an immunosuppressive effect.Early after transplantation, we randomly assigned consecutive patients to receive either pravastatin (47 patients) or no HMG-CoA reductase inhibitor (50 patients).Twelve months after transplantation, the pravastatin group had lower mean (+/- SD) cholesterol levels than the control group (193 +/- 36 vs. 248 +/- 49 mg per deciliter, P0.001), less frequent cardiac rejection accompanied by hemodynamic compromise (3 vs. 14 patients, P = 0.005), better survival (94 percent vs. 78 percent, P = 0.025), and a lower incidence of coronary vasculopathy in the transplant as determined by angiography and at autopsy (3 vs. 10 patients, P = 0.049). There was no difference between the two groups in the incidence of mild or moderate episodes of cardiac rejection. In a subgroup of study patients, intracoronary ultrasound measurements at base line and one year after transplantation showed less progression in the pravastatin group in maximal intimal thickness (0.11 +/- 0.09 mm, vs. 0.23 +/- 0.16 mm in the control group; P = 0.002) and in the intimal index (0.05 +/- 0.03 vs. 0.10 +/- 0.10, P = 0.031). In a subgroup of patients, the cytotoxicity of natural killer cells was lower in the pravastatin group than in the control group (9.8 percent vs. 22.2 percent specific lysis, P = 0.014).After cardiac transplantation, pravastatin had beneficial effects on cholesterol levels, the incidence of rejection causing hemodynamic compromise, one-year survival, and the incidence of coronary vasculopathy.

Background Cardiac allograft vasculopathy (CAV) is the major cause of late death among heart transplant recipients. The pathogenesis of CAV is poorly understood. Methods and Results To better characterize CAV, we performed immunohistochemical analysis of vascular lesions in a previously described murine model of CAV. The B10.A strain hearts were transplanted heterotopically into B10.BR strain recipients. The cardiac allografts were harvested from 1 to 2 months after implantation. The majority of epicardial and intramyocardial coronary arteries in explanted hearts had developed intimal thickening. The cellular infiltrate of the intimal thickening, major histocompatibility (MHC) antigens, intracellular adhesion molecule–1 (ICAM-1), and vascular cell adhesion molecule–1 (VCAM-1) expression were studied with the use of immunohistochemistry. In experimental CAV in mice, the cellular infiltrate of expanded intima consisted of macrophages, T lymphocytes, and smooth muscle cells. A substantial number of macrophages and T lymphocytes within the expanded intima expressed MHC class II antigen, a marker of cellular activation. The vessel wall cells also appeared to be activated due to their expression of endothelium-leukocyte adhesion molecules. The vascular endothelium of cardiac allografts displayed ICAM-1, VCAM-1, and unmatched MHC antigen (MHC class I in this model) upregulation. The medial smooth muscle cells also expressed VCAM-1 and unmatched MHC antigen. Conclusions These findings suggest that (1) the cellular infiltrate of the expanded intima in experimental CAV is similar to that of human CAV, (2) experimental CAV is a local immune-mediated process requiring active participation of donor vessel wall cells and recipient mononuclear cells, and (3) coexpression of adhesion molecules and unmatched MHC antigen identifies endothelial cells as immune targets for activated host mononuclear cells. Furthermore, the presence of both VCAM-1 and unmatched MHC antigen supports a central role for medial smooth muscle cells as allogeneic immune stimulator.

This study documents the gross flow characteristics and capillary distribution of cardioplegic solution delivered retrogradely with the coronary sinus open versus closed. Methods : Five explanted human hearts from transplant recipients were used as experimental models. Hearts served as their own controls and received two doses of warm blood cardioplegic solution, each containing colored microspheres. The first dose was delivered through a retroperfusion catheter with the coronary sinus open and the second dose was delivered with the sinus occluded. Capillary flow was measured at twelve ventricular sites and gross flow was measured by examining coronary sinus regurgitation, thebesian vein drainage, and aortic effluent (nutrient flow). Results : Coronary sinus ostial occlusion allowed for a significant decrease in total cardioplegic flow (1.74 ± 0.40 ml/gm versus 1.06 ± 0.32 ml/gm; p < 0.05) to occur while maintaining an identical intracoronary sinus pressure. Ostial occlusion also resulted in an increase in the ratio of nutrient flow/total cardioplegic flow from 32.3% ± 15.1% to 61.3% ± 7.9% (p < 0.05). A statistically significant improvement in capillary flow was found at the midventricular level in the posterior intraventricular septum and posterolateral right ventricular free wall. This improvement was also documented for the intraventricular septum and right ventricle at the level of the apex. Conclusion : Coronary sinus occlusion during retrograde cardioplegia significantly improves cardioplegic delivery to the right ventricle and posterior intraventricular septum. Furthermore, the technique affords a significant improvement in nutrient cardioplegic flow while reducing the overall volume of cardioplegic solution administered. ( J T HORAC C ARDIOVASC S URG 1995; 109: 941-7)

In children, subaortic stenosis can be discrete or diffuse and often occurs with other significant cardiovascular lesions. Surgical management of this condition is associated with varying complexities and risks according to the types of associated defects. This review presents general and specific principles of surgical management of subaortic stenosis.

Amino acid enrichment of cardioplegic solutions has been shown to improve both the metabolic and functional recovery of ischemic myocardium. However, because of the marked systemic vasodilatation involved, use of amino acid enrichment is limited to the periods of induction and reperfusion. Fumarate is a Krebs' cycle intermediate whose conversion to succinate is responsible for the generation of adenosone triphosphate and the oxidation of the reduced form of nicotinamide-adenine nucleotide which is the pathway by which aspartate exerts its effect. Fumarate may also function as a free-radical scavenger and is involved in calcium transport. To determine if fumarate-enriched blood cardioplegia would improve the functional recovery of the neonatal heart, 14 neonatal piglet hearts were isolated and placed on a blood-perfused working heart circuit. After the baseline functional and metabolic assessment was done, cold ischemic arrest was initiated with either standard blood cardioplegic solution (group I; N = 7) or fumarate-enriched (13 mmol/L) blood cardioplegic solution (group II; N = 7). Cardioplegic solution was given at a pressure of 40 mm Hg every 20 minutes for 2 hours, and topical hypothermia was used. Sixty minutes after warm whole blood reperfusion, the functional recovery at left atrial pressures of 3, 6, 9, and 12 mm Hg was 70%, 66%, 66%, and 65%, respectively, in group I, versus 102%, 106%, 105%, and 109%, respectively, in group II (p0.05). The tissue creatinine phosphate levels after reperfusion were significantly higher in group II hearts (15.0 +/- 1.2 mumol/g dry heart tissue) than in group I hearts (9.2 +/- 1.9 mumol/g dry heart tissue), although the adenosine triphosphate levels were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Mitral valve repair in children has the advantage of avoiding mitral valve replacement with its attendant need for anticoagulation and reoperation. Seventy-nine children between the ages of 2 months and 17 years (mean 4.9 years) underwent mitral valve repair between May 1982 and April 1993. There were five patients with mitral stenosis and 74 patients with mitral regurgitation, and 19 children were less than 2 years of age. Patients were divided into anatomic subgroups on the basis of the primary cardiac pathologic condition. Forty-three had severe mitral regurgitation, 21 had moderate mitral regurgitation, and 12 patients with primum atrial-septal defect and 2 patients with univentricular hearts had minimal to moderate mitral regurgitation. Associated cardiac anomalies were present in 68 patients and 85 % of the patients required concomitant intracardiac procedures. The methods of mitral valve repair included Annuloplasty in 68 (86%), repair of cleft leaflet in 41(52%), chordal shortening in 9 (11%), triangular leaflet resection in 8 (10%), splitting of papillary muscles with resection of subvalvular apparatus in 7 (9 %), and chordal substitution in 1(1 %). The technique of annuloplasty was modified to allow for annular growth. Follow-up was available from 1 to 10 years (mean 4 ± 2.5 `years). There were three early deaths (4%), all occurring as a result of low output cardiac failure in patients with minimal postoperative mitral regurgitation. Three late deaths (4%) occurred in patients with persistent moderate to severe mitral regurgitation and progressive cardiac failure and eight patients (10%) required either rerepair or replacement of the mitral valve. Actuarial survival was 94% at 1 year, 84 % at 2 years, and 82 % at 5 years, and actuarial freedom from reoperation was 89 % at 8 years. All patients received postoperative echocardiography with 82% having minimal to no mitral regurgitation and 98% of long-term surviving patients being free of symptoms. We conclude that mitral valve repair can be done with low early and late mortality. The need for reoperation is relatively low and valve growth has occurred with the use of a modified annuloplasty.

University of Wisconsin solution has proved to be a superior form of cardioplegia for cardiac transplantation, demonstrating better functional recovery than that provided by extracellular crystalloid solutions. Furthermore, experimental data have suggested a role for University of Wisconsin solution in protection of the neonatal heart during operations for congenital heart defects. However, significant concerns have been raised regarding potential endothelial injury from the high potassium concentration contained in University of Wisconsin solution that could affect its safety and thus its clinical application. Fourteen neonatal (aged 1 to 3 days) piglet hearts were harvested and supported on an isolated, blood-perfused circuit. Endothelium-dependent vasodilatation was measured by bradykinin (10 -6 mol/L) infusion and nitric oxide release was determined. Endothelium-independent vasodilatation was then induced by sodium nitroprusside (10 -6 mol/L) infusion. A 2-hour period of cold cardioplegic arrest was instituted with multidose University of Wisconsin solution (group 1, n=7) or blood cardioplegia (group 2, n=7). After reperfusion and stabilization, another stimulation with bradykinin and nitroprusside was carried out and nitric oxide was again measured. After 2 hours of arrest with University of Wisconsin solution, there was a near-complete loss of vasodilatation in response to bradykinin infusion; coronary blood flow reached 245% of baseline before arrest versus only 117% of baseline after arrest ( p=0.0011). This correlated with an inability of the endothelium to release nitric oxide (96 ± 30 nmol/min before arrest versus -32 ± 9 nmol/min after arrest, p=0.0039. In group 2, the vasodilatory response to bradykinin was preserved after arrest and reperfusion; 265% of baseline before arrest versus 222% of baseline after arrest. These results demonstrate a loss of endothelium-dependent vasodilatation after multidose University of Wisconsin cardioplegia caused by the inability of the endothelium to release nitric oxide. In contrast, blood cardioplegia does not result in impaired endothelial function. (J T HORAC C ARDIOVASC S URG 1994;107:257-64)

In this report, explanled hearts from transplant recipients with the diagnosis of idiopathic cardiomyopathy underwent a blood cardioplegia arrest and extended subatrial resection to preserve their coronary sinus venous system. The coronary sinus and left and right coronary arteries were then cannulated and warm blood cardioplegia retrograde infused at a pressure of 30 to 40 mm Hg. Effluent from the coronary arteries and thebesian veins was then collected. Hearts were subsequently fixed with retrograde glutaraldehyde perfusion and perfused retrograde with NTB-2 (an inert intracapillary marker). Histologic sections were examined from 12 separate sites. There was no significant difference in the percentage of capillaries perfused by retrogradedelivered cardioplegia between corresponding regions of the left and right ventricles. However, effluent analysis indicated that 67.2% ± 6.4% of retrograde-delivered blood cardioplegia was shunted through thebesian veins, thereby bypassing the microvasculature, whereas 29.3% ± 6.3% and 3.5% ± 3.1% traversed the myocardium supplied by the left and right coronary arteries, respectively. The results indicate that all regions of both ventricles are perfused by retrograde blood cardioplegia. However, they also suggest that nutrient flow to the microvasculature of the right ventricle is minimal during retrograde cardioplegia.

Between October 1983 and August 1991, 29 consecutive Damus-Stansel-Kaye procedures were performed. Indications for operation included restrictive bulboventricular foramen or subaortic stenosis associated with complex univentricular congenital heart disease (25) and Taussig-Bing heart, subaortic stenosis, or both associated with complex biventricular congenital heart disease (4). Twelve patients underwent concurrent Fontan procedures. Average age at operation was 39.8 months (range, 1 to 132 months). Average outflow tract gradient was 28 mm Hg (range, dynamic to 80 mm Hg). Of the 29 patients, 23 were male and 6 were female. There were three early deaths (10%), two in patients who had a concurrent Fontan procedure. Although there was a trend toward lower age and higher outflow tract gradients in nonsurvivors, these and other factors were not statistically significant predictors of death. Actuarial freedom from cardiac-related death was 88% at 5 years (n = 7). In a mean follow-up of 3.5 years (range, 0.1 to 7.7 years), 3 patients have required reoperation (10%), 2 for aortic valve insufficiency (5 days and 2.75 years) and 1 for a gradient across the anastomosis (5.75 years). Actuarial freedom from reoperation related to a failed Damus-Stansel-Kaye procedure was 90% at 4 years and 75% at 6 years (n = 7).

The uniform distribution of cardioplegic solution to all areas of the microvasculature is considered critical for myocardial protection. Despite this, little information exists regarding the ability of retrogradely infused cardioplegic solution to perfuse the microvasculature of the heart. In this report, the microvascular distribution of retrogradely delivered cardioplegic solution was studied by means of a technique to quantitatively demonstrate capillary perfusion. Duroc piglet hearts were subjected to either antegrade (n = 4) or retrograde (n = 8) perfusion fixation with 2.5% glutaraldehyde and subsequently perfused with NTB-2 (an intracapillary marker). The results indicate that retrogradely delivered NTB-2 consistently perfused the anterior half of the intraventricular septum and the anterior and lateral free walls of the left ventricle but inconsistently perfused the posterior half of the intraventricular septum, the posterior wall of the left ventricle, and a small paraseptal region of the right ventricle. The remainder of the right ventricle was not perfused. In contradistinction, all regions of the heart were consistently perfused by the antegrade technique. In regions of the heart in which retrograde microvascular perfusion occurred, no statistical difference was found in the quantitative degree of capillary perfusion achieved by either the antegrade or retrograde technique. These results have important implications for planning strategies of myocardial protection and suggest that further investigation concerning the microvascular distribution of retrogradely delivered cardioplegic solution in human beings is merited.

Reperfusion injury remains a limiting factor in extending ischemic storage time for human heart transplantation. In this study, initial myocardial reperfusion with an oxygenated perfluorochemical (Fluosol) was investigated as a means of limiting such injury. Neonatal piglet hearts were arrested with crystalloid cardioplegia, excised, and stored for 12 hours in saline solution at 0 degrees C. Initial reperfusion (10 minutes) was either with whole blood (n = 6), unmodified perfluorochemical (n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (n = 6), and was followed by an additional 40 minutes of whole blood perfusion. Functional evaluation was then completed, and left ventricular biopsy specimens were taken. A control group (n = 7) was evaluated without an intervening period of ischemia. At a left ventricular end-diastolic pressure of 9 mm Hg, hearts stored in whole blood cardioplegia developed a left-ventricular stroke work index of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under the same conditions, perfluorochemical-reperfused hearts achieved a stroke work index of 14.6 +/- 1.3 x 10(3) erg/g, significantly greater than that of the whole blood group (p0.001). Stroke work index for hearts reperfused with aspartate/glutamate-enriched perfluorochemical cardioplegia was 19.8 +/- 1.6 x 10(3) erg/g, significantly increased over that of the nonenriched perfluorochemical group (p0.01) and not different from values obtained in controls (19.2 +/- 0.8 x 10(3) erg/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Addition of leumedin, N-[9H-(2,7-dimethylfluorenyl-9-methoxy) carbon]-L-leucine at 30-60 microM together with LDL almost completely prevented the induction of monocyte chemotactic protein mRNA, reduced monocyte chemotactic protein 1 levels by 84%, and inhibited monocyte migration into the subendothelial space of cocultures of human aortic wall cells by < or = 98%. LDL incubated with leumedin formed a stable complex that remained intact even after refloating in an ultracentrifuge. Leumedin at 50 microM did not change conjugated diene formation during coculture modification of LDL or Cu++ catalyzed oxidation of LDL. Unlike LDL from control rabbits, LDL isolated from rabbits that were injected with 20 mg/kg leumedin was remarkably resistant to modification by the coculture and did not induce monocyte migration to a significant degree. Moreover, HDL isolated from rabbits injected with leumedin was far more effective in protecting against LDL modification by the artery wall cocultures than HDL from control rabbits. We conclude that leumedins can associate with lipoproteins in vivo, rendering LDL resistant to biological modification and markedly amplifying the protective capacity of HDL against in vitro LDL oxidation by artery wall cells.

Although standard blood cardioplegia provides good myocardial protection for cardiac operations in adults, protection of the cyanotic, immature myocardium remains suboptimal. Calcium, which has been implicated in reperfusion injury and in the development of “stone heart” in mature myocardium, is routinely lowered in standard cardioplegic solutions. Immature, neonatal myocardium has lower intracellular calcium stores and is more reliant on extracellular calcium for contraction. To determine if normocalcemic cardioplegia would result in improved cardiac function in the neonatal heart, we conducted a series of experiments using an isolated, blood-perfused working heart model. Thirty-two neonatal piglet hearts (24 to 48 hours) were excised without intervening ischemia and were placed directly on a blood-perfused circuit. Baseline stroke work index was assessed. Hearts were then arrested with cold cardioplegic solution delivered at 45 mm Hg for 2 minutes: group I, low-calcium blood cardioplegic solution (Ca = 0.6 mmol/L); group II, normal-calcium blood cardioplegic solution (Ca = 1.1 mmol/L); group III, University of Wisconsin solution; and group IV, University of Wisconsin solution with added calcium (Ca = 1.0 mmol/L). Cardioplegic solution was administered every 20 minutes for 2 hours and topical hypothermia was used. Hearts were then reperfused with warm whole blood. Functional recovery, expressed as a percentage of control stroke work index, was determined minutes after reperfusion. Hearts preserved with normocalcemic cardioplegic solution (groups II and IV) had complete functional recovery at 60 minutes, whereas hearts preserved with low-calcium cardioplegic solution (groups I and III) achieved functional recoveries of only 80 % and 65 %, respectively, at a left atrial pressure of 9 mm Hg. Electron micrographs taken 1 hour after reperfusion showed minimal edema and only mild myofibrillar changes. They were identical in both the low-calcium and normocalcemic groups. Complete functional recovery is possible in immature myocardium when calcium is added to either blood or an intracellular crystalloid cardioplegic solution. The addition of calcium does not result in ultrastructural damage and does result in good functional recovery.

The partial Fontan procedure has become an accepted alternative for the high-risk candidate. Creation of a small right-to-left shunt will lower the systemic venous pressure and improve systemic cardiac output while maintaining an acceptable systemic arterial saturation. However, because of variations in patient size and postoperative transpulmonary gradient, proper sizing of the residual defect is difficult. We have therefore conducted a series of experiments on a model that simulates the blood flow across interatrial defects of varying sizes at several pressure gradients. We used porcine blood to develop guidelines for the sizing of the residual defect. Our results demonstrate a linear relationship between flow and pressure gradient across all hole sizes tested. In addition, there was a linear relationship between atrial septal defect size and flow at each pressure gradient. Our data show that the Gorlin formula predictions overestimated flow by 10 % to 40%. It is evident from these data that relatively small changes in the size of the atrial septal defect or in the pressure gradient result in significant changes in flow. Therefore we advocate the use of an adjustable interatrial communication such as the snare-controlled adjustable atrial septal defect for patients undergoing partial Fontan procedures.

Blood cardioplegia is considered by many to be the preferred solution for myocardial protection. Proposed benefits include the ability to deliver oxygen and the ability to maintain metabolic substrate stores. However, the decreased capacity of blood to release oxygen at hypothermic conditions as well as the presence of deleterious leukocytes, platelets, and complement may limit complete functional recovery. Fluosol is an asanguineous solution with the ability to bind and release oxygen linearly at low temperatures. Neonatal piglet hearts (24 to 48 hours old) were excised and supported on an isolated, blood-perfused working heart model. After baseline stroke-work index was determined, hearts were arrested with either normocalcemic blood cardioplegia (group 1, n=8) or normocalcemic Fluosol Cardioplegia (group 2, n=8). Cold Cardioplegia was administered at 45 mm Hg every 20 minutes for 2 hours. Hearts were then reperfused with whole blood. Functional recovery, expressed as percent of control stroke-work index, was determined 60 minutes after reperfusion at left atrial pressures of 3, 6, 9, and 12 mm Hg. Functional recovery at 60 minutes was similar between group 1 (95%, 93%, 93%, 88%) and group 2 (100%, 94%, 94%, 95%) at left atrial pressures of 3, 6, 9, and 12 mm Hg, respectively. Mean lactate consumption 5 minutes after reperfusion was significantly greater ( p = 0.0001) in group 1 (31.8 ± 6.3 μg · min −1 · g −1 ) than in group 2 (−0.59 ± 0.1 μg · min −1 · g − ), indicating superior metabolic recovery in the blood cardioplegia hearts. Edema formation, as determined both by water content (group 1, 81.10%; group 2, 81.63%) and by electron microscopy, was not significantly different between groups. Tissue adenosine triphosphate levels 1 hour after reperfusion were also not significantly different. In conclusion, similar to blood cardioplegia, Fluosol results in complete functional recovery after cold ischemic arrest, despite inferior metabolic recovery. Because of the absence of injurious blood elements, Fluosol with added substrate may have a role as a cardioplegic agent when preoperative ischemia or hypoxia exists.

The benefits of combined antegrade-retrograde infusion of blood cardioplegic solution are becoming well known in adult coronary and valvular heart operations. Many of these advantages relate directly to the pediatric patient. They include prompt arrest and even distribution, particularly with aortic insufficiency or open aortic root, avoiding or limiting ostial cannulation, allowing uninterrupted surgical procedures, and flushing air/debris from the coronary arteries. We therefore report on the first 123 pediatric patients at the University of California, Los Angeles, to receive myocardial protection with antegrade (aortic) infusion in conjunction with retrograde (coronary sinus) infusion of blood cardioplegic solution. We employed a retroplegia catheter with a self-inflating and deflating occlusion balloon on the tip of a pressure-monitored infusion cannula that remains in the coronary sinus during the operation. Induction blood cardioplegic solution, 30 ml/kg in equally divided doses, is administered in the coronary sinus first antegrade at an aortic pressure less than 80 mm Hg, followed by retrograde infusion at less than 40 mm Hg. Maintenance cardioplegic solution (15 ml/kg) is administered every 20 minutes through one or both of the infusion cannulas, depending on the surgical procedure. Patients' ages ranged from 1 week to 16 years with a mean of 4.6 years. The following procedures were included in descending order: Fontan 20, atrioventricular valve repair/replacement (and complete atrioventricular canal) 16, aortic root/Konno/Ross 16, Rastelli 13, aortic valve repair/replacement 13, ventricular septal defect (and double-outlet right ventricle) 13, tetralogy of Fallot 10, coronary artery reimplantation/fistula repair 6, truncus arteriosus 4, arterial switch 3, bidirectional Glenn 2, sinus venosus 2, and aortopulmonary window, Senning, Stansel, interrupted aortic arch, and Ebstein's, 1 each. Aortic crossclamp times ranged from 6 to 219 minutes with a mean of 87 minutes. Myocardial oxygen consumption data for a series of six patients indicated the supplemental benefit for retrograde infusion of cardioplegic solution along with antegrade infusion, particularly in hypertrophied myocardium. Three deaths occurred (2.4% 30-day mortality), in the following patients: the first with truncus arteriosus and interrupted aortic arch, the second with complete atrioventricular canal and pulmonary hypertension, and the third with truncal valve regurgitation and replacement. There were no complications related to the retroplegia catheter. From this initial positive experience, we conclude that (1) combined antegrade-retrograde infusion of blood cardioplegic solution can be safely used in an expanding number of pediatric heart operations in all age groups, and (2) combined antegrade-retrograde infusion of blood cardioplegic solution may provide additional myocardial protection, with excellent surgical outcome, in complex congenital heart repairs.

To determine whether coronary anatomy influences the outcome of the neonatal arterial switch operation, we examined the results in all newborn infants (n = 70) with D-transposition of the great arteries who had a corrective operation at our institution between March 1987 and April 1991. The origin and distribution of coronary arteries were identified preoperatively by echocardiography, aortic root angiography, or selective coronary arteriography and intraoperatively by direct inspection. However, the arterial switch operation was performed independent of the coronary anatomy in all but two candidates for the operation. Four early deaths occurred and five surviving patients had symptoms of impaired cardiac function. No late deaths have occurred in patients followed up for 2 to 50 months. Evidence of myocardial ischemia was present in three of the four deaths and in four of the five patients with cardiovascular symptoms. Patients with commissural or intramural coronary origins between the great arteries had significantly greater cardiovascular morbidity and mortality because of coronary ischemia than patients with the most common coronary pattern. Thus coronary anatomy may influence surgical management and the postoperative course of newborn infants with transposition.

Current methods of myocardial preservation for transplantation are suboptimal. A newly developed intracellular cardioplegic and storage solution (modified University of Wisconsin solution, group 1) was compared in a randomized, blinded fashion with our present clinical protocol, Stanford cardioplegic solution and saline storage (group 2) in an isolated neonatal pig model. After arrest and storage for 12 hours at 4 degrees C, biopsy specimens were taken from six group 1 hearts and five group 2 hearts for examination under an electron microscope and assessment of high-energy phosphate levels and water content. The remainder (group 1, n = 7; group 2, n = 6) were reperfused with blood for 50 minutes, after which function curves were obtained at left ventricular end-diastolic pressures of 3 to 12 mm Hg and biopsy tissue was taken. Eight control hearts (group 3) were cannulated in situ and perfused on the circuit without arrest or intervening ischemia. Stroke and minute work index curves were approximately threefold and fivefold higher for group 1 (modified University of Wisconsin solution) than for group 2 (Stanford), respectively (p less than 0.01). The hearts preserved with University of Wisconsin solution did not differ in function from unpreserved control hearts (group 3). High-energy phosphate levels were better maintained in group 1 than group 2 (p less than 0.05), and water content was lower (p less than 0.01). Semiquantitative grading of electron micrographs paralleled the functional and biochemical results.Modified University of Wisconsin intracellular solution provides markedly better heart preservation than conventionally used cardioplegic and storage solutions.

Left atrioventricular valve regurgitation in atrioventricular canal defects is usually due to malalignment of the edges of the cleft or to annular dilatation. Intraoperative assessment and correction of left atrioventricular valve incompetence is critical for successful outcome in the surgical management of complete atrioventricular canal defects. Although some have elected not to suture the cleft in the setting of minimal incompetence, we have found that this often results in significant left atrioventricular valve insufficiency, necessitating reoperation. From January 1982 through December 1990, 105 patients with complete atrioventricular canal underwent definitive repair. Repair was performed with a single pericardial patch technique in 86 patients (82 %). Intraoperative assessment of left atrioventricular valve competence was performed in all cases. Ninety-six patients (91%) required suturing of the cleft and 63 (60%) required annuloplasty to establish satisfactory competence of the left atrioventricular valve. The overall early mortality rate was 10.5% (11/105 patients). From 1986 to 1990, the early mortality rate decreased to 7.7% (6/78 patients). In a mean follow-up of 39 months (range 1 to 106 months), late survival was 96% (90/94 operative or early survivors). Reoperation was performed on eleven (11.5%) patients; six (6.3%) for failure of the atrioventricular valve repair, three for patch dehiscence, and two for residual ventricular septal defects. These data demonstrate that routine approximation of the cleft and aggressive use of left atrioventricular valve annuloplasty is safe and results in an excellent outcome with a low incidence of reoperation for failure of left atrioventricular valve repair. (J T horac C ardiovasc S urg 1992;104:196–203)

A case of heart transplantation with concomitant coronary artery bypass graft is reported. The patient was an alternate transplant list candidate with a history of bilateral below-knee amputation and 2 previous myocardial revascularization procedures. The previously used and patent left internal mammary artery graft was successfully removed and retransplanted from the recipient to the donor heart.

Incubation of cocultures of human aortic endothelial (HAEC) and smooth muscle cells (HASMC) with LDL in the presence of 5-10% human serum resulted in a 7.2-fold induction of mRNA for monocyte chemotactic protein 1 (MCP-1), a 2.5-fold increase in the levels of MCP-1 protein in the coculture supernatants, and a 7.1-fold increase in the transmigration of monocytes into the subendothelial space of the cocultures. Monocyte migration was inhibited by 91% by antibody to MCP-1. Media collected from the cocultures that had been incubated with LDL induced target endothelial cells (EC) to bind monocyte but not neutrophil-like cells. Media collected from cocultures that had been incubated with LDL-induced monocyte migration into the subendothelial space of other cocultures that had not been exposed to LDL. In contrast, media from separate cultures of EC or smooth muscle cells (SMC) containing equal number of EC or SMC compared to coculture and incubated with the same LDL did not induce monocyte migration when incubated with the target cocultures. High density lipoprotein HDL, when presented to cocultures together with LDL, reduced the increased monocyte transmigration by 91%. Virtually all of the HDL-mediated inhibition was accounted for by the HDL2 subfraction. HDL3 was essentially without effect. Apolipoprotein AI was also ineffective in preventing monocyte transmigration while phosphatidylcholine liposomes were as effective as HDL2 suggesting that lipid components of HDL2 may have been responsible for its action. Preincubating LDL with beta-carotene or with alpha-tocopherol did not reduce monocyte migration. However, pretreatment of LDL with probucol or pretreatment of the cocultures with probucol, beta-carotene, or alpha-tocopherol before the addition of LDL prevented the LDL-induced monocyte transmigration. Addition of HDL or probucol to LDL after the exposure to cocultures did not prevent the modified LDL from inducing monocyte transmigration in fresh cocultures. We conclude that cocultures of human aortic cells can modify LDL even in the presence of serum, resulting in the induction of MCP-1, and that HDL and antioxidants prevent the LDL induced monocyte transmigration.