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Copyright of Southern Medical Journal is the property of Lippincott Williams & Wilkins and Its content may not be copied or emailed to multiple sites or posted to a listserv without the Copyright holder's express written permission. [Extracted from the article]

Acidic fibroblast growth factor (aFGF) is a potent growth factor for vascular smooth muscle cells and may mediate vasculopathy in cardiac allografts subjected to chronic immunological injury. Therefore, we examined cardiac expression of aFGF, the number of rejection episodes, and other potential risk factors in 32 heart transplant patients who underwent intravascular ultrasound (IVUS) for detection of cardiac allograft vasculopathy (CAV). As defined by IVUS, CAV was present in 21 patients and absent in 11 patients (follow-up time: 52 +/- 21 vs. 51 +/- 12 months, respectively, P = NS). The level of aFGF in myocardial biopsies obtained at the time of IVUS was measured by semiquantitative reverse transcriptase polymerase chain reaction and expressed as the aFGF:GAPDH ratio. Higher level of aFGF were associated with CAV (mean aFGF:GAPDH ratio was 1.45 +/- 0.99 in patients with vs. 0.18 +/- 0.12 in patients without CAV [P < 0.001]). A strong association was found between high levels of cardiac aFGF and CAV, as 18 of 19 patients (95%) with high levels of aFGF (aFGF:GAPDH > 1) but only 3 of 13 patients with low levels of aFGF had CAV (P < 0.001). The relative risk of high level of aFGF for CAV was 4.1. Untreated low grade rejection (ISHLT I), but not treated high grade rejection (ISHLT > 2), was also associated with CAV (average number of untreated low grade rejection episodes was 3.5 +/- 1.8 in patients with vs. 2.1 +/- 1.0 in patients without CAV [P = 0.04]). Among other risk factors examined (age, sex, serum cholesterol, blood pressure, CMV infection, dose of immunosuppressants, and ischemic time), only triglycerides were higher in patients with than those without CAV (P = 0.003). We conclude that increased cardiac production of aFGF is significantly associated with CAV, which suggests that aFGF may serve as an important mediator in CAV. Untreated low grade rejection also poses an increased risk for CAV.

Objective: This study sought to determine the impact of preoperative chemotherapy and radiation therapy (neoadjuvant therapy) followed by resection in patients with adenocarcinoma of the esophagus., Summary Background Data: Long-term survival in patients with carcinoma of the esophagus has been poor. An increase in the incidence of adenocarcinoma of the esophagus has been reported recently., Methods: Fifty-eight patients with biopsy-proven adenocarcinoma of the esophagus treated at this institution from January 1951 through February 1993 were studied. Since 1989, 24 patients were entered prospectively into a multimodality treatment protocol consisting of preoperative cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without etoposide, and concomitant mediastinal radiation (30 Gy). Patients were re-evaluated and offered resection., Results: There were no deaths related to neoadjuvant therapy and toxicity was minimal. Before multimodality therapy was used, the operative mortality rate was 19% (3 of 16 patients). With multimodality therapy, there have been no operative deaths (0 of 23 patients). The median survival time in patients treated before multimodality therapy was 8 months and has yet to be reached for those treated with the neoadjuvant regimen (> 26 months, p < 0.0001). The actuarial survival rate at 24 months was 15% before multimodality therapy and 76% with multimodality therapy. No difference in survival was noted in neoadjuvant protocols with or without etoposide (p = 0.827)., Conclusions: Multimodality therapy with preoperative chemotherapy and radiation therapy followed by resection appears to offer a survival advantage to patients with adenocarcinoma of the esophagus.

Background: Atrial natriuretic factor (ANF) is produced by myocardial tissue, and the plasma ANF concentration is known to be elevated in congestive heart failure (CHF). Data from animal models indicate that myocardial concentrations of ANF are depleted in CHF, and this has given rise to the hypothesis that CHF is characterized by depletion of stored ANF. To date, the molecular forms of ANF and their concentrations in atrial and ventricular myocardium remain poorly characterized in the normal and the failing human heart., Methods and Results: We measured ANF concentrations in fresh tissue from failing human hearts explanted at the time of cardiac transplantation and from organ donors whose normal hearts could not be used for transplantation. We determined total ANF and alpha, beta, and gamma ANF concentrations in the right and left atrial appendages, atrial free walls, and ventricles. In normal hearts, ANF concentration in the atrial appendages was 40-fold higher than ANF in the rest of the atrial free wall and in the ventricles. In the failing hearts, atrial appendage ANF concentrations increased 5- to 10-fold, and atrial free wall ANF concentrations increased 200-fold. Analysis of molecular forms of ANF demonstrated significant increases in the gamma and beta forms in the left atrial appendage of failing hearts. alpha, beta, and gamma ANF forms were also significantly increased in right and left atrial free wall tissue from failing hearts. In addition, failing hearts were characterized by absolute and relative increases in the precursor form gamma ANF., Conclusions: These data from fresh tissues suggest that cardiac ANF stores are not decreased in severe CHF in humans; rather, chronic CHF is characterized by marked increases in atrial ANF tissue concentrations, particularly the beta and gamma ANF forms. These findings are consistent with intracellular accumulation of precursor ANF forms in severe chronic human CHF.

Orthotopic cardiac transplantation has been performed in 15 consecutive neonates and children since 1987. Diagnoses include hypoplastic left heart syndrome (5 patients), critical aortic stenosis with small left ventricle (1 patient), complex cyanotic heart disease (6 patients), and cardiomyopathy (3 patients). Twelve patients survived operation and have been followed from 1 to 45 months. Patients less than 6 years of age are managed with cyclosporine +/- azathioprine; in older patients steroid weaning is attempted. Monitoring for rejection is performed with serial echocardiography in patients under 6 years of age; older patients undergo serial biopsies. Actuarial freedom from rejection was 26% 3 months after operation; 47% were free of infection 6 months after operation. There have been no late deaths. Actuarial survival at 3 years is 79%. Nine patients have undergone postoperative catheterization. Resting hemodynamics were normal in every patient. All long-term survivors are asymptomatic and fully active. It is concluded that cardiac transplantation in neonates and children is an effective treatment option for end-stage cardiomyopathy or otherwise incurable congenital heart disease. Long-term survivors have excellent potential for full rehabilitation.

Between February 1978 and August 1989, forty patients aged 80 years or older underwent cardiac surgery at this institution. Patient age varied from 80 to 87 years (mean, 82.4 years). Operative indications were angina pectoris or congestive heart failure. Twenty-eight patients underwent coronary artery bypass (CAB) alone and 12 underwent valve replacement(s) with or without CAB. The operative mortality rate was 10%. Postoperative hospitalization averaged 14 days. There were three late cardiac deaths at 13, 36, and 48 months after operation and one late noncardiac death. Thirty-two survivors have been followed from 1 to 86 months (mean, 20 months). All experienced sustained improvement in functional status and minimal late morbidity. All survivors remained in NYHA class 1 or 2. Cardiac surgical procedures in patients older than 80 years can be performed with increased but acceptable mortality and morbidity rates. Most patients achieve sustained symptomatic improvement and excellent long-term survival.

Fifty-one adult patients were referred for surgical treatment during the time period from July 1980 to November 1985. The average age was 59 +/- 6 years (19-70 years). All patients had symptomatic ventricular tachycardia that was refractory to standard or experimental drug therapy. On the basis of patient condition, site of arrhythmia, ventricular function, and extent of coronary disease, 21 patients were classed as good risk (GR) while 30 patients were thought to represent a poor surgical risk (PR). Thirty-two patients (15 GR, 17 PR) underwent electrophysiologic guided endocardial resection of arrhythmic foci. The hospital mortality was 12% (4/32), and two additional patients died late. All deaths were in poor risk patients. Recurrent arrhythmia was the primary cause of death in only one patient. Nineteen patients have required automatic internal cardioverter defibrillation (AICD) or chronic burst pacing (BP) with an implantable radiofrequency stimulator, with no operative mortality. AICD implantation was chosen for 13 drug refractory patients who were either poor surgical risk and/or had a tachycardia rate above 130 beats/minute with multiple scars or a multifocal tachycardia. Six additional patients who had tachycardia less than 130 beats/minute and whose arrhythmia could be safely terminated with BP had radiofrequency stimulator implantation. The one late death in this group was in a medically noncompliant patient. On the basis of this experience, we feel that map-guided endocardial resection should be offered to all good risk patients with a single scar and unifocal tachycardia who are refractory to medical treatment. This operation should be considered in all patients who have frequent, life-threatening attacks of tachycardia of any sort on maximum drug therapy. The remainder can be well managed with an AICD if their tachycardia rate is greater than 130 beats/minute or with BP using a radiofrequency stimulator.

The surgical experience with 18 consecutive neonates with critical pulmonary stenosis (PS) and intact ventricular septum was reviewed. All patients had cardiac catheterization with calculation of right ventricular volume. Group A patients (N = 8) had a small right ventricular end-diastolic volume (RVEDV less than 72% of predicted). Group B patients (N = 10) had a normal or enlarged RVEDV. All patients had a closed pulmonary valvotomy. Five Group A patients required a systemic-pulmonary shunt or prostaglandin (PGE1) after operation; one patient died. Nine Group B patients did well after valvotomy; one moribund patient died after valvotomy and shunt. Six of 16 survivors required reoperation: valvectomy in four patients and shunt takedown in two patients. Four of the six patients who had reoperation also had a transannular patch. There was one unrelated late death. All long-term survivors are asymptomatic. Recatheterization in four patients with a small right ventricle (RV) documented significant RV growth. In conclusion, most neonates with critical PS can be managed with closed valvotomy. Patients with a small RV may require PGE1 or a shunt after operation for persistent hypoxemia. Some patients with a small RV will have significant RV growth after valvotomy.

Acute traumatic tear of the thoracic aorta is a severe injury with a high mortality rate. This condition requires expeditious evaluation and prompt surgical intervention in order to improve patient survival. The experience at the authors' institution from 1971 to 1987 includes 41 patients who sustained acute traumatic tear of the thoracic aorta and reached the hospital alive. The purpose of the study was to evaluate the surgical management of this injury with regards to mortality rate and the incidence of spinal cord injury. Five patients died from exsanguination before definitive repair could be undertaken. Thirty-six patients had repair of traumatic aortic tear in the area of the isthmus. Nine patients were operated upon with the clamp and sew technique, 20 patients had a heparin-bonded shunt placed, and seven patients were treated by repair with cardiopulmonary bypass. There were five operative deaths that were not related to the technique employed. Two patients without preoperative evidence of spinal cord injury developed paraparesis. No patient had postoperative paraplegia. Despite rapid transport, expeditious evaluation, and emergency thoracotomy, some patients die from exsanguination prior to definitive repair. Even with the provision of distal aortic perfusion during clamping, the risk of spinal cord injury is not eliminated.

Long-term results of operation for IHSS were reviewed in 124 patients operated upon between 1960 and 1975. Most patients improved symptomatically and manifested marked reduction in LV outflow gradient at rest postoperatively. However, ten (8%) patients died of causes related to operation, 14 (12%) had persistent or recurrent severe functional limitation, and 11 (9%) died up to 13 years postoperatively due to hypertrophic cardiomyopathy. Overall annual mortality rate was 3.5% and was 1.8% for late deaths alone. Of 11 late postoperative deaths, six were sudden and five were due to chronic heart failure. Atrial fibrillation was significantly more common in patients who died late postoperatively than in survivors. Nine of the 11 late deaths had associated medical problems that may have contributed to their outcome. In conclusion, long-lasting clinical improvement occurred in most patients who survived operation for IHSS. However, 12% of patients deteriorated clinically over the 5.2 year average follow-up, and there is continued, small annual mortality.

Experience was reviewed with 471 consecutive patients who had coronary artery bypass (CAB) operation alone. The hospital mortality rate was 2% in 341 patients operated on for treatment of stable angina pectoris. There were ten deaths (7.7%) in the 130 patients who underwent CAB for treatment of unstable angina. In this series, age greater than 70 years, poor left ventricular function, distal coronary arteries unfavorable for grafting and the presence of main left coronary artery disease were factors associated with increased operative mortality. In 78 patients with unstable angina who had none of these increased risk factors, the mortality rate was 1.3%. Hospital mortality was 33% in patients older than 70 years and 29% in patients with poor left ventricular function and/or distal vessels unfavorable for grafting. In 23 of the 130 patients, the only increased risk factor present was severe stenosis of the main left coronary artery and one of them (4.3%) died. Thus, when elderly patients and patients with poor left ventricular function or poor distal vessels were excluded, the hospital mortality rate associated with CAB in patients with unstable angina was low (2.0%, 2/101 patients) and equal to that for operation in patients with stable angina pectoris.

We evaluated the plasma elimination of recombinant human superoxide dismutase (rHSOD) when given before reperfusion in an experimental canine model of global hypothermic myocardial ischemia. Adult mongrel dogs were placed on cardiopulmonary bypass, and core temperature was reduced to 25 degrees C. Hypothermic global myocardial ischemia was maintained for 90 minutes with intermittent crystalloid cardioplegic solution. Five minutes before reperfusion, rHSOD was administered via the pump oxygenator as a bolus injection. Plasma rHSOD levels were measured at 0, 3, 5, 10, 20, 30, 60, and 120 minutes after injection. Animals were rewarmed and weaned from bypass. Three experimental groups received either 4, 8, or 16 mg/kg rHSOD. Based on previously reported dose-response data, we conclude that desirable peak serum concentrations are achieved with 16 mg/kg rHSOD. In the setting of hypothermic cardiopulmonary bypass and global myocardial ischemia, single bolus administration of rHSOD before reperfusion is an effective method due to the prolonged serum half-life.

Heart-lung transplant recipients represent a unique population who experience episodic lung injury caused by infection or rejection. We hypothesized that the proteins in the respiratory lining fluids of these patients might reflect and provide insights into the in vivo immunologic and inflammatory events that occur in the transplanted lung. Structural, inflammatory, and immune proteins were quantitated in 57 samples of BAL fluid recovered from 17 heart-lung recipients when infections, rejection, or neither was present. Protein levels were compared with those of normal subjects and between the clinical transplant groups. When neither infection nor rejection was present, levels of albumin, fibronectin, and immunoglobulins G, M, and A were all higher in the transplanted lungs as compared with the normal lungs. These findings suggest that a new steady state of these proteins is established in the transplanted lungs. When infection or rejection was present, there was a further significant increase in albumin, fibronectin, IgG, and especially C5a in the transplanted lungs. These findings suggest that at least some elements of host defense remain intact in the posttransplantation period despite the use of immunosuppressive drugs and a HLA-incompatible microenvironment. The profiles of recovered alveolar proteins did not, however, help to differentiate infection from rejection. This is disappointing because distinguishing between infection and rejection without examination of lung tissue remains an unresolved and important clinical problem. Nevertheless these data provide new insights into organ tolerance and defense of the newly transplanted lung from infection or rejection.