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Primary graft dysfunction (PGD) is a rare complication associated with high mortality after heart transplantation, which may require veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) support. A standardized definition for PGD was developed by the International Society of Heart and Lung Transplantation in 2014. Due to limited reports using this definition, the detailed outcomes after VA-ECMO support remain unclear. Therefore, we retrospectively analyzed our single-center outcomes of PGD following VA-ECMO support. Between September 2014 and August 2018, 160 patients underwent heart transplantation in our single center. Nine PGD patients required VA-ECMO support, with an incidence of 5.6%. Pre-operative recipient/donor demographics, intra-operative variables, timing of VA-ECMO initiation and support duration, graft function recovery during 30 days after heart transplant, VA-ECMO complications, and survival were analyzed. The indication for VA-ECMO support was biventricular failure for all nine patients. Six patients had severe PGD requiring intra-operative VA-ECMO, while two patients had moderate PGD and one patient had mild PGD requiring post-operative VA-ECMO. All cohorts were successfully decannulated in a median of 10 days. Survival to discharge rate was 88.9%. One-year survival rate was 85.7%. Left ventricular ejection fraction recovered to normal within 30 days in all PGD patients. Our study showed VA-ECMO support led to high survival and timely graft function recovery in all cohorts. Further larger research can clarify the detailed effects of VA-ECMO support which may lead to standardized indication of VA-ECMO support for PGD patients.

Background: Fueled by the burgeoning opioid epidemic, valve surgeries for substance use disorder-related infective endocarditis (SUD-IE) are increasing. The impact of substance use disorder on postvalve replacement morbidity needs further investigation., Methods: We queried The Society of Thoracic Surgeons Adult Cardiac Surgery Database for all valve surgeries for infective endocarditis at Tufts Medical Center (2002-2016) and collected demographic and disease-related data, including timing of mortality subclassified as short-term (<6 months including operative), midterm (6 months to 5 years), and extended-term (>5 years). Patients with documentation of illicit drug use before the operation were considered to have SUD-IE. Deaths were confirmed through review of medical record and matching with the Massachusetts Vital Statistics Database. We performed univariate and multivariate proportional hazard regressions examining the impact of substance use disorder mortality in people who received a valve replacement., Results: In the cohort of 228 patients, 80 (35%) had SUD-IE. Eight-six people (38%) died, and overall mortality was higher in people with SUD-IE compared with non-SUD-IE (48% vs 32%, P = .025). SUD-IE was associated with a higher risk of overall mortality (adjusted hazard ratio, 2.41; 95% confidence interval, 1.38-4.20; P = .002). Although the difference between short-term or extended-term mortality was not significant, SUD-IE was associated with increased frequency of midterm mortality (53% vs 31%, P = .003)., Conclusions: Our data reflect high rates of postvalve surgery morbidity and mortality in people with SUD-IE at a tertiary care center. The midterm postoperative period is a vulnerable period for people with SUD-IE worthy of further investigation., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The left ventricular assist device Impella 5.0 (Abiomed Inc, Danvers, MA) has become widely accepted as a temporary mechanical circulatory support for patients in cardiogenic shock. The Impella 5.0 is placed through an anastomosed graft. When removing the device, blood clot formation has been noted in the anastomosed graft. The blood clot has been reported to dislodge and embolize distally, causing acute limb ischemia. Here, we present our simple, inexpensive, and effective "loop and snare" technique for safer device removal, preventing distal embolic complications. In our experience of 6 patients who had Impella 5.0 removal with this technique, the distal embolic complication was 0%., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

In the modern surgical era, postoperative prosthetic valve endocarditis persists as a potentially devastating complication of valve replacement surgery. While generally resulting in valvular destruction and regurgitation, prosthetic valve endocarditis may also result in valvular obstruction. The diagnosis of prosthetic valve endocarditis may be difficult due to technical limitations affecting the diagnostic capability of transthoracic echocardiography in patients with prosthetic valves and the indolent nature of the infectious process. We describe the first reported case of Aspergillus endocarditis leading to obstruction of a prosthetic valve in a patient with recent aortic valve replacement.

Fatty infiltration of the right ventricle is usually an incidental finding at post-mortem, but may have clinical significance at times of physiologic stress. We report a case of fatal right ventricular dysfunction immediately after cardiac transplantation secondary to massive fatty infiltration of the donor right ventricle. Ante-mortem diagnosis of fatty infiltration may be difficult to determine despite non-invasive cardiac evaluation. If the diagnosis of fatty infiltration is suspected at time of donor harvest, the relative risks and benefits of proceeding with transplantation should be carefully assessed.

Background: Cardiopulmonary bypass has often been applied to revive victims of cold water drowning. The success of resuscitative efforts in patients who have sustained severe hypothermia is largely determined by neurologic outcomes. Measurement of Fos, the protein product of the immediate-early gene c-fos, is a marker of cerebral injury., Study Design: Twenty-eight infant lambs were sedated and ventilated. Group 1 lambs were immersed in a cold water bath for 2 hours (17.3 +/- 2.7 degrees C). Group 2 lambs were placed on normothermic cardiopulmonary bypass for 2 hours (37.7 degrees +/- 0.7 degrees C). Group 3 lambs were immersed in a cold water bath for 2 hours (17.6 degrees +/- 2.4 degrees C), and then rewarmed for a period of 2 hours on cardiopulmonary bypass (37.0 degrees +/- 0.6 degrees C). The lambs were euthanized and immunohistochemical analysis for neuronal Fos was performed., Results: There was significant induction of Fos-labeled nuclear profiles (cells/1130 microm(2)) in group 3 in the hippocampal regions and dentate gyrus compared with groups 1 and 2 (p < 0.001)., Conclusion: Isolated exposure to either hypothermia or cardiopulmonary bypass results in minimal expression of neuronal Fos; the significant induction of Fos in the group 3 animals may represent an ischemic-reperfusion phenomenon. Modifications of rewarming techniques that minimize Fos expression may improve neurologic outcomes in victims of cold water drowning.

Background: Insertion of a competent pulmonary valve has been advocated to reduce right ventricular volume overload associated with pulmonary regurgitation (PR) after repair of tetralogy of Fallot. However the indications, proper timing, and long-term benefits of restoring pulmonary valve function remain controversial., Methods: Thirty-six patients (aged 15.2 +/- 9.2 years) underwent pulmonary valve implantation (31 homografts, 5 heterografts) 12.2 +/- 6.9 years after tetralogy repair. Additional surgical procedures included pulmonary artery augmentation (n = 14), closure of septal defects (n = 10), and cryoablation and endocardial resection of ventricular tachycardia (n = 2)., Results: All patients have had clinical improvement in their exercise capacity. Preoperative and postoperative bicycle ergometry tests in 6 patients demonstrated significant improvement in the percent of predicted peak workload (68.5% +/- 19.8% to 80.7% +/- 17.4%, p < 0.015). One midterm death occurred in a 38-year-old patient with a history of ventricular tachycardia who died suddenly 2 years after pulmonary valve insertion. Postoperative echocardiographic measurements were available in 34 patients at a mean follow-up of 5 years. There was a 30% reduction in right ventricular end-diastolic diameter indexed to body surface area after surgery (30.1 +/- 10.2 to 18.6 +/- 6.0 mm/m(2), p < 0.0001). Two patients required conduit replacements at 1 and 9 years postoperatively., Conclusions: Timely insertion of a competent pulmonary valve in children, adolescents, and young adults with significant PR after tetralogy of Fallot repair results in subjective and objective improvement in exercise capacity and is associated with reduction in right ventricle size.

Under conditions of ischemia, the hydrogen ion [H+] accumulates in the myocardial tissue in proportion to the magnitude of the ischemic insult. The accumulation of [H+] is the result of both increased anaerobic production of [H+] secondary to decreased substrate and decreased washout of [H+] secondary to decreased coronary perfusion. The Khuri tissue pH electrode/monitoring system has been developed and validated over the past two decades. Its scientific basis and correlates have been established, and it is the only system that has been approved for use in humans. Myocardial tissue pH has been monitored in the anterior and posterior walls of the left ventricle in more than 700 patients undergoing major cardiac surgery. An understanding of the relationship between pH and temperature and between the pH and [H+] in tissues is important for the proper interpretation of the myocardial pH data generated in the course of an operation. Intraoperative monitoring of myocardial pH is the only modality available to the cardiac surgeon for online assessment and improvement of the adequacy of myocardial protection. By defining myocardial protection in terms of protection from myocardial tissue acidosis, this technology provides a new tool with which the comparative efficacy of the various myocardial protection techniques can be assessed. It also provides an online tool for assessing the adequacy of coronary revascularization, and has the potential of improving procedures and outcomes for off-pump coronary artery bypass grafting.

Background: In the pediatric and infant age groups, it is unclear whether repeated infusions of blood cardioplegia solution during ischemic arrest are beneficial or detrimental when compared with a single-dose regimen., Methods: Twenty lambs (aged 6 to 7 weeks) were placed on cardiopulmonary bypass. A miniature glass-tip electrode measured myocardial pH and hydrogen ion concentration, [H+], in the anterior wall. The aorta was clamped for 2 hours. Group S (n = 10) received a single dose of blood cardioplegia solution. Group M (n = 10) received multiple doses of blood cardioplegia solution at 20-minute intervals., Results: The amount of [H+] generated during the cross-clamp period was greater in group S than in group M (39.2 +/- 10.1 nmol/L versus 0.4 +/- 1.4 nmol/L, p < 0.008). The percent increase in the time constant, tau, an index of diastolic relaxation, was more prolonged after cardiopulmonary bypass in group S when compared with group M (51.4% +/- 2.8% versus 6.4% +/- 3.0%, p < 0.0001). Similarly, the percent decrease in end systolic elastance, a measure of systolic contractility, was greater in group S after cardiopulmonary bypass when compared with group M (29.5% +/- 1.4% versus 7.3% +/- 1.3%, p < 0.0001)., Conclusions: In this infant lamb model, multiple doses of blood cardioplegia solution provided superior metabolic preservation and hemodynamic support after 2 hours of aortic clamping when compared with a single-dose regimen.

Balloon angioplasty (BA) for native coarctation of the aorta (CA) in infants and neonates remains controversial with a high incidence of restenosis. The purpose of this study is to analyze our acute and midterm results for BA of native CA in infants and neonates and try to identify factors that may be predictive of outcome. Between September 1991 and June 1999, 17 patients with CA underwent BA at a median age of 3 months (range 2 weeks--9 months) and median weight of 4.8 kg (range 2.8--7 kg). Fourteen patients had discrete CA and 3 had tubular hypoplasia. All patients were hemodynamically stable prior to BA and no patients had critical coarctation requiring prostaglandin E(1) infusion to maintain ductus arteriosus patency. Seven patients had other associated cardiac defects. All patients had significant initial improvement. The mean peak systolic gradient across the CA improved from 43 +/- 15 mmHg to 10 +/- 8 mmHg (p < 0.001), and the mean minimum diameter of the aortic lumen increased from 2.4 +/- 0.9 mm to 5.2 +/- 1.0 mm (p < 0.001). There was no mortality or major complication. At median follow-up interval of 2.7 years (0.15-7.75 years), 10 (59%) of 17 patients are clinically well and have an upper to lower limb systolic blood pressure difference of <20 mmHg. Seven (41%) of 17 patients developed significant restenosis (5 of these patients underwent repeat BA, which was successful in 3 patients). Four (24%) patients underwent surgical repair at a median age of 4.5 months (3--6.9 months) and a median time interval of 4 months (2--6.5 months) from the initial BA. All 3 patients with tubular hypoplasia type of CA underwent surgical repair. No patients developed aortic aneurysm following initial or repeat BA. All patients who underwent surgical repair were 1 month or less in age at the time of their initial BA. We conclude that BA of native CA in infants and neonates can be performed safely with low mortality and morbidity. It appears to offer the best results in patients who are older than 1 month with discrete CA and a well-developed aortic arch. Further restenosis of the discrete CA can be managed successfully by repeat BA.

Objective: The influence of endoscopic harvesting techniques on the prevalence of leg-wound complications after coronary artery bypass grafting remains to be defined for patients at high risk for the development of wound infections., Methods: Among 1473 patients undergoing coronary artery bypass grafting who had the saphenous vein harvested by either a continuous incision or skip incisions leaving intact skin bridges, we determined the prevalence of wound infections to be 9.6%. The following variables were entered into logistic regression analysis to identify significant risk factors that might be predictive of wound infection: diabetes, peripheral vascular disease, obesity, renal failure, steroid use, age, sex, and type of closure. We then prospectively randomized 132 patients found to be at high risk of wound infection to either endoscopic vein harvesting or a continuous open incision., Results: Univariate analysis showed female sex (P =.04), diabetes (P <.001), and obesity (P <.001) to be predictors of wound infection. In a multivariate model diabetes (P =.02) and obesity (P =.001) were independent predictors. In patients at high risk, the prevalence of wound infection was 4.5% for the endoscopic group versus 20% for the open group (P =.01). Vein procurement time was greater in the endoscopic group (65 minutes vs 32 minutes, P <.001), as was the number of vein repairs required (2.5 vs 0.6, P <.001)., Conclusion: The use of endoscopic vein harvesting decreases the prevalence of postoperative leg-wound infections in high-risk patients with diabetes and obesity. Whether this translates into an economic benefit that justifies the additional cost of that technology requires further analysis.

Background: Previously described techniques for epicardial pacemakers in children have generally included either a left thoracotomy approach or a subxiphoid incision., Methods: We have recently used a single left subcostal incision for placement of both the epicardial electrodes and the pacemaker generator. We report our initial experience with this technique in 8 patients. The mean age was 4 years (range, 4 months to 12 years). The smallest patient weighed 4,100 g., Results: The subcostal approach was successful in 7 patients. One patient with a narrow costal margin operated on early in our experience required conversion to a thoracotomy. The pacing thresholds were uniformly excellent in all patients. There have been no associated complications., Conclusions: Placement of epicardial leads using a left subcostal incision avoids a thoracotomy, is simpler than a subxiphoid approach, and results in acceptable thresholds with minimal morbidity.

Background: Recent surgical reports on coarctation of the aorta have primarily focused on the relative merits of various operative techniques. However, appropriate timing for elective repair remains unclear., Methods: In a retrospective analysis we examined the surgical outcomes in 176 consecutive patients undergoing repair of coarctation of the aorta in our institution over a 25-year period. Ninety-nine percent of the patients had follow-up for a median of 7.5 years., Results: A total of 13 patients have died (7.4% overall mortality). Nine of these patients had associated complex intracardiac anomalies. There was no mortality in the 113 patients with isolated coarctation. Residual or recurrent coarctation occurred in 27 patients (15.3%). The age at operation and the type of surgical repair did not have an effect on the incidence of recurrence. Persistent or late hypertension was identified in 18 of the 107 patients who have been followed up for more than 5 years (16.8%). A total of 48 patients operated on during infancy have been followed up for more than 5 years. Only 2 have developed late hypertension (4.2%). Both of these patients had recurrence. In contrast, 16 of the 59 patients operated on after a year of age had late hypertension (27.1%)., Conclusions: To minimize the risk of persistent hypertension, elective repair of coarctation should be performed within the first year of life.

Background: This study determined the induction profiles of immediate-early genes in the ovine brain after cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA), and the effects of the noncompetitive N-methyl-D-aspartate antagonist, aptiganel, on immediate-early gene expression, neuronal necrosis, and functional outcome., Methods: Cannulas were inserted into isoflurane-anesthetized neonatal lambs undergoing CPB. One group received 2.5 mg/kg intravenous aptiganel. Animals underwent 90 or 120 min of HCA at 16 degrees C, were rewarmed to 38 degrees C, and were weaned from CPB. One hour after CPB was discontinued, brain perfusion was fixed and removed for immunohistochemical analysis in one half of the animals. The other half survived 2 or 3 days before their brains were evaluated for neuronal degeneration. Data were analyzed using analysis of variance; P < 0.05 was considered significant., Results: Cardiopulmonary bypass and HCA differentially induced c-Jun and Fos proteins in the hippocampal formation, with c-Jun expression increasing with the duration of HCA, whereas Fos protein expressions were greatest after 90 min of HCA. The c-Jun protein was expressed in all neurons except the dentate gyrus. The Fos proteins were expressed in all neurons, including the dentate gyrus. Neuronal necrosis was observed in CA1 (73%) and CA3 (29%) neurons but not in the dentate gyrus after 120 min of HCA. Aptiganel completely inhibited c-Jun expression (P < 0.001) but not Fos, improved functional outcome, and attenuated neuronal necrosis (P < 0.05)., Conclusions: The c-Jun and c-Fos proteins are expressed differentially in hippocampal neurons after CPB and HCA. Expression of c-Jun is associated with neuronal necrosis, whereas Fos protein expression is associated with survival. Aptiganel inhibits c-Jun expression, attenuates neuronal necrosis, and improves outcome.

Background: The positions, sizes, and shapes of ventricular septal defects (VSDs) can be difficult to assess by 2-dimensional echocardiography (2DE). Volume-rendered 3-dimensional echocardiography (3DE) can provide unique views of VSDs from the left ventricular (LV) side, allowing complete assessment of their circumference and spatial orientations to other anatomic structures., Methods and Results: Seventeen experimentally created defects of various locations, sizes, and shapes were imaged and reconstructed in 9 explanted porcine hearts. From an en face projection, major and minor axis diameters of the defects were measured, and these data were compared with direct anatomic measurements. Optimal reconstructions of the VSDs were obtained in all heart specimens, accurately depicting their positions and shapes. The correlations between 3DE and anatomy for the VSD major and minor axis diameters were y=1.0x+0.3 (r=0.88, P<0.001) and y=1.0x-1.4 (r =0.89, P<0.001), respectively. Good agreement between the 2 methods was demonstrated for all measurements. Our experience from the in vitro model was then applied to patient studies. Optimal LV en face reconstructions were obtained in 45 of 51 patients, permitting detailed assessment of the positions, sizes, and shapes of the VSDs. In the 25 patients with comparative surgical measurements, the correlations between 3DE and surgery for the VSD major and minor axis diameters were y =0. 81x+2.1 (r=0.92, P<0.001) and y=0.73x+2.0 (r=0.91, P<0.001), respectively. Good agreement was demonstrated between measurements made by 3DE and those obtained at surgery., Conclusions: 3DE provides excellent visualization of various types of VSDs. From an LV en face projection, the positions, sizes, and shapes of VSDs can be accurately determined. Such precise imaging will be beneficial for surgical and catheter-based closure of difficult perimembranous and singular or multiple muscular VSDs.

The purpose of this study was to evaluate the fate of mitral regurgitation (MR) following repair of atrioventricular septal defects (AVSDs). Echocardiograms of all survivors of isolated AVSD surgery between 1986 and 1996, who had had > or =2 postoperative color Doppler studies (39 patients), were reviewed. On each study, MR severity was graded on a 1+ to 4+ scale, based upon the size of the MR jet. Median age at surgery was 9 months (range 3 to 169); median age at postoperative follow-up was 45 months (range 3 to 107). Mild deterioration of mitral valve function was fairly common. MR severity increased by > or =1 grade in 16 patients (41%) during the course of the study. However, the deterioration in mitral valve function occurred primarily during the early postoperative time intervals. After the initial 32 postoperative months, MR worsened on only 4 occasions and in each instance worsened by only 1 grade. Deterioration to 4+ MR occurred in only 3 patients, and was not observed after the initial 30 postoperative months. Survival curve analysis predicted a 90% probability of not having severe (4+) MR after 30 months (lower 95% confidence bound: 80%). Postoperative MR remains fairly stable following AVSD repair. Serious deterioration is rare, especially after the initial 30 postoperative months.

Background: Altered gene expression occurs in the brain after global ischemia. We have developed a model to examine the effects of cardiopulmonary bypass and hypothermic circulatory arrest (HCA) on the induction of the immediate-early gene c-fos in the brains of neonatal lambs. We then tested the effects of the noncompetitive N-methyl-D-aspartate antagonist, aptiganel hydrochloride (Cerestat), on c-fos expression and neuronal injury., Methods: Neonatal lambs (weight, 4 to 6 kg) anesthetized with isoflurane were supported by cardiopulmonary bypass, subjected to 90 or 120 minutes of HCA at 15 degrees C, and rewarmed on bypass to 38 degrees C. One hour after cardiopulmonary bypass was terminated, the brains were perfusion fixed and removed for in situ hybridization and immunohistochemical analysis. Some animals survived 3 days before their brains were removed to examine for neuronal necrosis. One group of lambs (n = 20) received aptiganel (2.5 mg/kg). A second group (n = 25) received saline vehicle only., Results: Increasing duration of HCA induced a corresponding increase in c-fos messenger RNA expression throughout the hippocampal formation and cortex. However, Fos protein synthesis peaked after 90 minutes of HCA and decreased significantly (p < 0.01) after 120 minutes of HCA. Aptiganel administration caused a significant decrease in (p < 0.001) c-fos messenger RNA expression and Fos protein synthesis after 90 minutes of HCA and preserved Fos protein synthesis after 120 minutes of HCA. Neuronal necrosis was observed in the brains of vehicle-treated lambs after 120 minutes of HCA but was significantly decreased (p < 0.05) in the lambs given aptiganel., Conclusions: These experiments indicate that the transcriptional processes of immediate-early genes remain intact, whereas translational processes are impaired after prolonged HCA. The inability to synthesize Fos proteins after 120 minutes of HCA was associated with neuronal degeneration. Aptiganel preserved translational processes and caused a significant improvement in the neurologic outcome.

Background: Previous surgical models of cyanosis have been permanent. Because normal oxygenation was not restored in these models, it is unclear whether the metabolic changes produced by prolonged exposure to hypoxemia are irreversible. We therefore designed an experimental model of cyanosis that is reversible., Methods: The left atrial appendage was anastomosed directly to the main pulmonary artery in 8 piglets, aged 2 to 4 weeks., Results: The oxygen saturation fell from 95.3% +/- 0.8% to 72.4% +/- 3.9% (p < 0.001). A tourniquet was placed around the anastomosis to produce incremental changes in the level of cyanosis. Complete tourniquet occlusion resulted in obliteration of the right to left shunt, with return of systemic oxygen saturation to baseline levels. Systemic, left atrial, and pulmonary pressures did not change during the study., Conclusions: In this acute preparation, stable hemodynamic conditions were maintained despite substantial variations in systemic levels of oxygenation. Most important, this model allows reversal of cyanosis with the return of normal oxygenation. Application of this experimental design in a chronic model may help to determine whether the metabolic effects of prolonged hypoxemia are potentially reversible.

Background: Cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA) are associated with neurological injury. Altered immediate-early gene expression occurs rapidly in the brain in response to ischemia, hypoxia, and severe metabolic stress, which results in long-term changes in the molecular phenotype of neurons. This study determined the effects of CPB and HCA on the expression of the immediate-early gene c-fos., Methods: Neonatal lambs were subjected to 2 h of CPB at 38 degrees C (n = 4) or 60 min (n = 6), 90 min (n = 7), and 120 min (n = 6) of HCA at 15 degrees C. One hour after terminating CPB at 38 degrees C, the brains were analyzed for FOS-encoding mRNA and FOS-like immunoreactivity in the hippocampal formation. Other animals (n = 15), subjected to the same CPB and HCA protocol, were allowed to survive 3-5 days before their brains were examined for dead neurons., Results: Minimal c-fos mRNA and FOS proteins were observed in neurons of animals subjected to normothermic bypass and of those that served as controls. Non-neuronal FOS proteins were observed in the choroid plexus, ependyma, and blood vessels at all times, including normothermic CPB, but not in the control animals without CPB. The magnitude of c-fos mRNA expression in hippocampal neurons increased directly with the duration of HCA. In contrast, expression of FOS proteins peaked after 90 min of HCA and declined significantly thereafter. Dead neurons were seen in surviving animals after 2 h of HCA only., Conclusions: Cardiopulmonary bypass and HCA alter immediate-early gene expression in the brain. Translational processes are impaired after 120 min of HCA and correlate with neuron death in the hippocampus.

A 61-year-old woman with levo-transposition of the great arteries, double-inlet single left ventricle, and valvar and subvalvar pulmonary stenosis presented with a large pulmonary valve vegetation unresponsive to antibiotic therapy. The diagnostic evaluation and the surgical management are discussed. At operation the pulmonary valve was excised and an abscess cavity was obliterated with a pericardial patch. She is currently doing well 3 years after the operation.

Background: Severe pulmonary regurgitation (PR) and associated right ventricular (RV) dilatation are late complications of surgical repair of tetralogy of Fallot (TOF). For the past several years, we have restored pulmonary valve competence with the exclusive use of cryopreserved allografts., Methods and Results: Sixteen patients with symptoms of diminished exercise tolerance and echocardiographic evidence of progressive PR with severe RV dilatation underwent placement of allografts in the RV outflow tract at a median age of 12 years (10 years after TOF repair). Abnormal exercise tolerance tests were documented in 10 patients. Additional surgical procedures included pulmonary artery augmentation (n = 6), closure of residual left to right shunts (n = 3), and subendocardial resection for monomorphic ventricular tachycardia (n = 1). Six patients had either preoperative or postoperative balloon dilations of pulmonary artery stenoses. All patients had symptomatic improvement after allograft insertion. At a mean follow-up of 26.4 +/- 3.4 months, the severity of PR improved in all but one patient. In 12 patients (group 1), conduit regurgitation was either trace (n = 11) or mild (n = 1). Four patients (group 2) had moderate conduit regurgitation. In a retrospective analysis, pulmonary artery diameters and cross-sectional areas were significantly smaller in the group 2 patients compared with the group 1 patients. With the exception of one patient, RV end-diastolic diameter (RVEDD/BSA) fell after allograft insertion in each patient (P < .01). The reduction in RVEDD/BSA was significantly greater in group 1 than in group 2 (31.8 +/- 3.4% versus 21.4 +/- 11.0%, P < .05)., Conclusions: Thus, restoration of the pulmonary valve with cryopreserved allografts improved exercise tolerance and diminished RV volume overload in patients with severe PR after previous repair of TOF. Optimal results were achieved in patients who did not have significant residual pulmonary artery distortion.

To characterize the ultrastructural and metabolic changes occurring in the hypertrophied ventricle during cardiac operations in man, we studied 36 patients with valvular heart disease undergoing valve replacement, during which multiple doses of cold potassium cardioplegic solution were administered (Group I). Each patient had substantial ventricular hypertrophy according to measurements made of left ventricular mass, with a mean of 232.1 +/- 19.8 gm/m2 (normal: 92 +/- 16 gm/m2). Serial biopsy specimens were obtained from the left ventricular apex at the initiation of bypass, during the cross-clamp interval, and during reperfusion. Each specimen was scored from 0 to 4 according to ischemic changes in nuclear chromatin, mitochondrial swelling, myofibrillar edema, glycogen depletion, and overall cell morphology. Myocardial pH and temperature were measured continuously in the left ventricular free wall. During the cross-clamp period, ischemic injury was evidenced by changes in nuclear chromatin (0.38 +/- 0.10 to 1.25 +/- 0.21, p less than 0.0001), intracellular edema (0.43 +/- 0.06 to 0.97 +/- 0.14, p less than 0.002), overall cell morphology (0.37 +/- 0.06 to 0.97 +/- 0.14, p less than 0.001), and mitochondria (0.10 +/- 0.05 to 0.19 +/- 0.07, p less than 0.0001). During reperfusion, mitochondrial swelling increased further (0.19 +/- 0.07 to 0.35 +/- 0.08, p less than 0.0001) and glycogen stores were depleted (0.63 +/- 0.13 to 0.96 +/- 0.17, p less than 0.02), while the other structures remained unchanged. Myocardial pH declined during ischemic arrest from 6.89 +/- 0.04 to 6.40 +/- 0.04 (p less than 0.001). The changes in myocardial pH in Group I were compared to changes in myocardial pH in 10 patients (Group II) with no left ventricular hypertrophy undergoing isolated coronary bypass graft operations with the same protective techniques. In contrast to Group I, myocardial pH did not fall in Group II during ischemic arrest (6.98 +/- 0.06 to 6.94 +/- 0.05, p = not significant). Thus, with the use of current myocardial protective techniques, ultrastructural and metabolic changes indicative of ischemia are produced in the hypertrophied myocardium. The structural alterations consist of changes in nuclear chromatin and intracellular edema during the ischemic phase and by mitochondrial swelling during reperfusion.

Complement activation was examined prospectively in 100 cardiopulmonary bypass (CPB) patients. Plasma C3a desArg (C3a) increased (cannulation: 234 +/- 33 ng/mL; 20 minutes on CPB: 622 +/- 51; 2 hours after CPB: 1143 +/- 109, p less than 0.0001). C3a at 2 hours was higher in the 13 patients requiring mechanical ventilation for longer than 1 day (1023 +/- 274) than in the 67 without respiratory complication (568 +/- 45, p less than 0.004). Five more patients were studied for neutrophil activation to confirm that a biologic effect of complement activation occurs during CPB; in these five patients C3a increased to 317% of baseline after 10 minutes on CPB with a corresponding rise in neutrophil cell surface receptors for the complement opsonin C3b (as measured by indirect immunofluorescence) to 168% (p less than 0.05). Both increases were sustained at 30 minutes. Temperature, dilution, and heparin were studied as variables relevant to CPB. Exposure of normal neutrophils to C5a in vitro caused an increase in C3b receptors which was dependent on temperature (0 specific fluorescence at 0 C, 30 at 25 C, 180 at 30 C, and 275 at 37 C). Generation of C3a and C5a in normal serum by zymosan was also temperature-dependent (ng/mL C5a generated: 0.7 at 25 C, 200 at 30 C, and 897 at 37 C; ng/mL C3a generated: 546 at 25 C, 10,872 at 30 C, and 65,667 at 37 C). Serum dilution to 33% decreased ng/mL C5a generated in the same system from 200 to 76 with no effect on C3a. Addition of heparin to 20 U/mL decreased ng/mL C3a generated from 10,872 to 913 and C5a from 200 to 8. Thus, hypothermia, dilution, and heparin protect CPB patients from complement activation by reducing both generation of C3a/C5a and the subsequent cellular response of neutrophil activation.

The effects of sanguineous and asanguineous cardioplegia on the generation of myocardial acid in the hypertrophied human heart during aortic clamping and reflow were elucidated by continuous intraoperative monitoring of myocardial pH in 42 patients undergoing valve replacement, with or without coronary bypass. The patients were divided into three groups: Group I (n = 14) received intermittent crystalloid cardioplegia; group II (n = 14) received intermittent blood cardioplegia; and group III (n = 14) received continuous blood cardioplegia. The groups were matched according to six previously elucidated determinants of myocardial acidosis. Measurements were made of myocardial pH, hydrogen ion concentration ([H+]), and the difference in pH units between myocardial pH and the pH of neutrality of water at the corresponding temperature (delta pHn). Throughout aortic clamping, myocardial pH in groups I and II fell significantly by 0.46 +/- 0.08 and 0.15 +/- 0.07 units, respectively (p less than 0.001) between the groups). In contrast, myocardial pH remained statistically unchanged throughout aortic clamping in group III (p less than 0.001 compared to groups I and II). Similar relationships were observed in [H+] and delta pHn during aortic clamping. During the early reflow, myocardial acidosis was observed in all three groups and delta pHn in group III increased from -0.26 +/- 0.10 at the end of aortic clamping to -0.57 +/- 0.07 during reperfusion (p less than 0.03). Patients in groups II and III required significantly less inotropic and mechanical cardiac support than patients in group I (p = 0.017). Hence, although continuous blood cardioplegia does not completely prevent acid accumulation during reflow, it provides better metabolic protection of the hypertrophied human heart than either intermittent crystalloid or intermittent blood cardioplegia.

Clinical measures often fail to detect early tissue ischemia in inadequately perfused flaps. This study investigates the application of a new pH electrode system to monitor tissue metabolism continuously in porcine and human musculocutaneous flaps. Bilateral rectus abdominis flaps based on the deep inferior epigastric pedicle were elevated in eight mixed-breed pigs. Tissue pH was measured in the subcutaneous and muscular layers with miniature glass-tip electrodes. The deep inferior epigastric artery and vein were serially and then concomitantly occluded for 20-minute periods. The decrease in tissue pH was greater following either arterial or pedicle occlusion (each 0.21 +/- 0.03 units) when compared with venous occlusion (0.10 +/- 0.02 units; p less than 0.02). Changes in muscle and subcutaneous hydrogen ion concentration were similar during arterial and venous occlusions (probability not significant). Measurement of subcutaneous pH appears to be a reliable experimental and clinical physiological tool for detecting early tissue ischemia in reconstructive flaps.

Regional differences in myocardial acid production have not been characterized during administration of either asanguineous or sanguineous cardioplegia. To investigate this, miniature glass pH electrodes were placed in the right ventricular (RV) myocardium, the left ventricular subendocardial (LV endo) region, and the subepicardial (LV epi) region in a canine model. Multiple doses of either blood cardioplegia (Group 1; N = 11) or crystalloid cardioplegia (Group 2; N = 11) were administered during 4 hours of aortic cross-clamping. The accumulation of hydrogen ions during the cross-clamp period was greater in Group 2 than Group 1 in the LV endo region (629 +/- 79 nm/L versus 66 +/- 31 nm/L; p less than 0.001), the LV epi region (623 +/- 66 nm/L versus 72 +/- 32 nm/L; p less than 0.001), and the RV myocardium (814 +/- 296 nm/L versus 150 +/- 54 nm/L; p less than 0.05). Within each group, the time course of myocardial pH and the accumulation of hydrogen ions did not differ among the LV endo region, LV epi region, and the RV myocardium (p = not significant). These data indicate that transmural and interventricular differences in myocardial pH and hydrogen ion accumulation are not produced in the vented, arrested canine heart. In addition, when compared with asanguineous cardioplegia, blood cardioplegia globally and transmurally reduces acid accumulation during ischemic arrest.

Coronary angiography is generally considered the gold standard in assessing the significance of coronary stenosis. The inadequacy of coronary angiography has frequently been demonstrated by intraoperative findings that differ from those projected by the catheterization report. To better assess the physiologic significance of coronary stenosis, we measured intramyocardial pH intraoperatively in 50 myocardial segments supplied by stenotic coronary arteries before and after revascularization in 42 patients undergoing coronary artery bypass grafting. The hemodynamic, electrocardiographic, and pH responses to atrial pacing were recorded intraoperatively before and after revascularization. The coronary angiograms, performed within 3 months before bypass grafting, were reviewed by a single independent observer. Preoperative and postoperative radionuclide ventriculograms were performed and also reviewed by an independent observer. In response to atrial pacing, a fall exceeding 0.02 pH units was considered to represent ischemia and was observed in 28 segments. Patients exhibiting this response comprised Group I. Twenty-two segments demonstrated a fall of less than 0.02 pH units or a rise in pH in response to atrial pacing. Patients having this response comprised Group II. Segments in Group I responded dramatically to revascularization, with the pH during atrial pacing rising from -0.09 +/- 0.01 to -0.02 +/- 0.01 (p less than 0.001). Nine patients demonstrated ischemic S-T changes during atrial pacing, all in Group I. Pre-pacing hemodynamic parameters were similar in both groups. Group I patients, however, demonstrated a significant fall in mean arterial pressure during atrial pacing, from 92.0 +/- 3.0 to 78.4 +/- 3.3 mm Hg (p less than 0.001) whereas Group II patients did not. Twelve segments that angiograms indicated were supplied by critically stenotic vessels (greater than 75%) failed to demonstrate a significant fall in their pH during atrial pacing. In these segments, intraoperative findings and postoperative results corroborated the metabolic findings. Coronary angiography, therefore, was only 45% specific in assessing physiologically significant obstructions. The degree of segmental wall motion abnormalities likewise correlated poorly with the pH changes. Unlike coronary angiography, the response of intramyocardial pH to pacing is an accurate metabolic tool to assess myocardial ischemia in humans.

The composition of the ideal cardioplegic solution is controversial. Blood cardioplegia is an attractive alternative to standard crystalloid solutions, though its superiority in preserving myocardial metabolism has not been demonstrated. Using a new pH electrode system, this study contrasts the effects of blood and crystalloid solutions upon the generation of myocardial acidosis during global ischemia. Thirty-eight mongrel dogs underwent a 120-min period of aortic cross clamping using systemic hypothermia. To maintain myocardial temperature below 15 degrees C, 19 dogs received multiple doses of a bicarbonate containing crystalloid cardioplegic solution (Group I), while 19 dogs received multiple doses of blood cardioplegia (Group II). Myocardial pH and temperature were continuously monitored in the subendocardial region of the left ventricle. There was no difference in baseline pH between Group I (7.13 +/- 0.05) and Group II (7.17 +/- 0.05, P:NS). With systemic cooling and the initial bolus of cardioplegia, myocardial pH rose to 7.42 +/- 0.04 in Group I and 7.42 +/- 0.06 in Group II (P:NS). After 120 min of global ischemia, myocardial pH decreased to 6.61 +/- 0.05 in Group I and 7.07 +/- 0.05 in Group II (P less than 0.001). Blood cardioplegia was most effective during the first hour of aortic cross clamp when myocardial pH rose by 0.13 +/- 0.04 pH units. In contrast, myocardial pH in Group I during the first hour of global ischemia fell -0.35 +/- 0.08 pH units (P less than 0.001 compared to Group II). During the second hour of cross clamp, myocardial pH declined both in Group I (0.26 +/- 0.03 pH units) and in Group II (0.24 +/- 0.05 pH units, P:NS). However, the accumulation of hydrogen ion during the second hour was significantly greater in Group I (+128.0 +/- 21.4 nm/liter) than in Group II (+36.6 +/- 9.0 nm/liter, P less than 0.001). Thus, myocardial acidosis was reduced during the administration of blood cardioplegia when compared to a bicarbonate-buffered crystalloid solution. The salutary effects of blood cardioplegia on myocardial metabolism stem from blood's significant buffering capacity and its ability to deliver oxygen.

We reviewed the clinical course of 91 men with mild intermittent claudication who had been followed up for at least six months without operation. During 2.5 years' mean follow-up, 60% of the patients had more severe claudication. Actuarial analysis revealed an annual mortality of 4.5% and an annual operation rate of 9%. Historical factors, including age, race, smoking, exercise, diabetes, hypertension, and the ankle-brachial index (ABI), were analyzed to determine if these variables could predict clinical outcome. Only cigarette smoking, exercise, and the ABI were significant in this regard. Patients who had smoked at least 40 pack-years had an operation rate 3.3 times higher than those who smoked less. Major daily exercise was associated with stable claudication. The initial ABI did not correlate with clinical outcome. A subsequent decrease in the ABI of at least 0.15, however, was associated with an operation rate 2.5 times higher and a symptom progression rate 1.8 times higher than patients without this change in the ABI. When regression analysis was used, the preceding variables were only 63% to 79% accurate in predicting the clinical outcome of individual patients. Careful follow-up of patients with intermittent claudication is therefore recommended to allow timely operative intervention when required.

The spectrum of injuries created by a free fall are governed by distinct physical properties, of which the height of the fall and the nature of the impacted surface are the most important factors. Other determinants include the victim's age and weight and the position at landing. Orthopedic injuries frequently are encountered in falls from two stories and less, and are largely determined by the position at landing. Visceral trauma, produced by deceleration forces, frequently involves the liver, spleen, lung, heart and aorta, and must be suspected in falls from three stories and more regardless of the landing position. Mortality from a six-story fall onto a hard surface such as concrete is almost 100% for adults, although considerably less for children. Falls onto softer surfaces, including water, are better tolerated. By appreciating the physical principles that dictate the type and degree of injury, one may correctly diagnose and manage free-fall injuries.

Previous studies have revealed that the regional accumulation of ischemic metabolites including hydrogen ion (H+) and PCO2 diminish after repeated occlusions. We postulated that this diminution reflects a blunted metabolic response that is related to the severity of ischemic injury and, hence, may be most pronounced in subendocardial (ENDO) regions. To investigate this hypothesis, the left anterior descending coronary artery was serially occluded three times in 51 dogs for a period of either 3 minutes (n = 15), 5 minutes (n = 18), or 15 minutes (n = 18). Each occlusion was separated by 45 minutes of reperfusion. Myocardial [H+] was measured in the endomyocardium and in the epimyocardium of the ischemic anterior wall by use of miniature pH glass electrodes. Accumulation of H+ during occlusion (delta [H+]) in the ENDO region was significantly less during the second occlusion when compared with the first occlusion (3-minute occlusions: 28.2 +/- 3.7 nM/l vs. 39.4 +/- 5.4 nM/l, p less than 0.002; 5-minute occlusions: 49.8 +/- 5.0 nM/l vs. 72.1 +/- 6.5 nM/l, p less than 0.0002; 15-minute occlusions: 132.3 +/- 14.6 nM/l vs. 225.6 +/- 27.7 nM/l, p less than 0.0003). A similar trend was noted for delta [H+] in the subepicardial (EPI) regions. During occlusion, the rise in [H+] occurred sooner, and delta [H+] was consistently greater in the ENDO when compared with the EPI regions (p less than 0.05). Regional myocardial blood flow did not change during the three occlusions, indicating that the diminution in H+ accumulation stemmed from a decrease in H+ production and not from an increase in collateral flow. The decrement in H+ accumulation between the first and second occlusions (delta [H+]1-delta [H+]2) 1) was greater in the ENDO than in the EPI regions (p less than 0.05); 2) correlated with the duration of occlusion (ENDO: r = 0.66, p less than 0.001; EPI: r = 0.82, p less than 0.0001); and 3) was related to the impairment of anterior wall systolic shortening after the first reperfusion period. These findings suggest that the diminution in H+ production that follows serial coronary occlusions reflects a blunted metabolic response that is related to both the duration of ischemia and the degree of systolic dysfunction. Moreover, though attenuation of ischemic metabolite production occurs transmurally, it is most pronounced in the deep ENDO regions.

In 12 dogs, we examined the correspondence between esophageal (Pes) and pericardial pressures over the anterior, lateral, and inferior left ventricular (LV) surfaces. Pleural pressure was decreased by spontaneous inspiration, Mueller maneuver, and phrenic stimulation and increased by intermittent positive pressure ventilation (IPPV) and positive end-expiratory pressure (PEEP). To separate effects due to blood flow, we analyzed beating and nonbeating hearts. In beating hearts, there were no significant differences between changes in Pes and pericardial pressures. In arrested hearts, increasing LV pressure by 8 Torr increased pericardial pressures by only 3.6 Torr. With IPPV and PEEP, increases in Pes and pericardial pressures were equal in live hearts and in low-volume arrested hearts (LV pressure = 4 Torr). In high-volume arrested hearts (LV pressure = 12 Torr), the increase in pericardial pressure over the anterior LV surface was less than Pes, whereas that over the lateral and inferior LV surfaces was the same as Pes. At high LV volume, in arrested hearts pericardial pressures decreased less than Pes during negative pressure maneuvers. In another six dogs, external LV configuration and volume were measured. In beating hearts during spontaneous inspiration, Mueller maneuver, and phrenic stimulation (endotracheal tube open), septal-lateral dimension and LV volume decreased by approximately 3% (P less than 0.05). This was also true for PEEP. In arrested hearts, septal-lateral dimension and LV volume decreased only with PEEP. We conclude that 1) the relationship between Pes and pericardial pressures is complex and depends on LV volume, local pericardial compliance, and the means by which Pes is changed, 2) changes in measured pericardial pressures did not completely explain changes in LV configuration, and 3) during different respiratory maneuvers, different forces account for the same observed changes in LV volume and configuration.

Afterload reduction is an accepted therapeutic modality for the treatment of congestive heart failure caused by chronic aortic regurgitation. However, the role of vasodilator therapy in acute aortic incompetence has not been established. To investigate this, left ventricular volume overload was produced in 18 dogs by constructing a valved conduit from the descending thoracic aorta to the left ventricular apex. The time course of aortic, pulmonary and conduit flows was analyzed in eight control studies and established stability of the experimental model. In the remaining 10 dogs, intravenous nitroglycerin, titrated to reduce mean aortic blood pressure by 40%, and placebo (ethanol) were each infused for 20 min periods. Compared with placebo, nitroglycerin significantly reduced aortic flow (3,945 +/- 324 to 3,397 +/- 362 ml/min, p less than 0.01), regurgitant flow (1,304 +/- 131 to 764 +/- 90 ml/min, p less than 0.001), septal-lateral end-diastolic diameter (47.5 +/- 1.8 to 46.5 +/- 1.8 mm, p less than 0.001), left ventricular end-diastolic pressure (6.9 +/- 0.8 to 6.0 +/- 0.6 mm Hg, p less than 0.05), left ventricular stroke work (19.0 +/- 2.6 to 10.8 +/- 1.7 g-m/beat, p less than 0.001) and systemic vascular resistance (2,253 +/- 173 to 1,433 +/- 117 dyne-s/cm5, p less than 0.001). In contrast, pulmonary flow, left anterior descending coronary flow and subendocardial pH did not change during infusion of either nitroglycerin or placebo. These data indicate that by decreasing preload and afterload, and by preserving coronary flow and tissue pH, nitroglycerin effectively reduced ventricular and regurgitant volumes in the setting of acute volume overload.(ABSTRACT TRUNCATED AT 250 WORDS)