Biomedical subjects
Publications and source records attributed to L A Gray.
Mediastinal masses remain an interesting diagnostic and therapeutic challenge for clinicians because of the low incidence of the tumors, frequent lack of symptoms, and the inaccessibility of the tumors for biopsy. An unusual mediastinal liposarcoma with intracavitary cardiac extension is presented to illustrate the approach to mediastinal tumors in general.
Heterotopic prosthetic ventricles were used to support the circulation in 29 candidates for heart transplantation who were expected to die before procurement of a donor heart. Twenty-one of these patients (average age, 36 years) underwent successful transplantation after 8 hours to 31 days of circulatory support. The other eight patients died because their condition could not be stabilized for transplantation, despite restoration of blood flow. Fourteen patients received biventricular support; 15 received only left ventricular support, with pharmacologic assistance of right heart function. Before transplantation, blood flow from the left prosthetic ventricle averaged 2.8 +/- 0.4 liters per minute per square meter of body-surface area, and from the right prosthesis 2.4 +/- 0.4 liters, as compared with an average flow of 1.6 +/- 0.5 liters per minute per square meter before implantation. Of the 21 patients who received heart transplants, 20 were discharged from the hospital after a median of 31 days. Nineteen patients were alive at 7 to 39 months, and 11 of the first 12 were alive at one year. We conclude that heterotopic placement of prosthetic ventricles as a bridge to transplantation provides an effective method of temporarily supporting cardiac function in critically ill patients without removing the natural heart. The early survival rate after transplantation is similar to that with elective cardiac transplantation.
Two hundred nine Duncan-Harley guinea pigs had intrathoracic inoculation with 10(8) Staphylococcus aureus, accompanied by blood and umbilical tape. One hundred fifty-two animals were excluded because of clinical recovery, early death, or complications related to intrathoracic polymethylmethacrylate (PMMA) bead placement. The remaining 57 animals had clinical signs of empyema thoracis and were the subjects of this study. Group I animals (N = 24) served as the controls and had no therapy. Group II animals (N = 14) were treated by intrathoracic placement of placebo PMMA beads. Group III animals (N = 19) were treated by intrathoracic placement of tobramycin sulfate-impregnated PMMA beads. There were no differences between the groups in pleural reaction or pneumonia scores. These findings demonstrate a similar host response to the established infection. Group III, however, had a higher sterilization rate than Groups I and II (p less than 0.05), a finding underlining the therapeutic effect of tobramycin-treated PMMA beads. We conclude that intrathoracic local antimicrobial therapy with slow-release tobramycin-impregnated PMMA beads may enhance empyema treatment by increasing the rate of local sterilization. More experiments are necessary to assess the efficacy of this potentially important therapeutic arm for the treatment of thoracic empyema.
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OKT3 is a murine monoclonal antibody that recognizes the T3 surface antigen present on mature T cells, and it has been used to successfully treat renal allograft rejection. We report our experience with OKT3 in the treatment of cardiac allograft rejection. Eight patients with endomyocardial biopsy evidence of moderate or severe rejection were given fourteen daily intravenous treatments of OKT3. Six of the eight patients had complete recovery following OKT3 therapy; one required additional steroid therapy for recurrence and one patient failed to respond. Five of the six patients with a complete response have experienced no further rejection (mean follow-up 437 days). Adverse reactions to OKT3 were common early in the treatment course, but were well tolerated. We concluded that OKT3 is a safe and effective treatment of cardiac allograft rejection and that a majority of patients experience long-term rejection-free periods.
Infant orthotopic cardiac transplantation has been recently applied to various forms of congenital heart disease with encouraging short-term results. Between June 1986 and September 1987 we evaluated 16 infants for orthotopic cardiac transplantation. Fourteen had hypoplastic left heart syndrome, one had endocardial fibroelastosis with aortic atresia, and one had anomalous pulmonary arterial origin of the left main coronary. Eight families accepted the treatment program and eight families refused (two because of associated anomalies and six on philosophical grounds). Of the eight patients who were candidates for orthotopic cardiac transplantation, one died 6 hours after diagnosis, one was allowed to die after 60 days because of acquired neurologic complications, and another had congenital cytomegalic virus infection. The remaining five patients (four with hypoplastic left heart syndrome, one with anomalous pulmonary arterial origin of the left main coronary) had orthotopic cardiac transplantation. The operation was performed with absorbable polydioxanone suture with deep hypothermia and circulatory arrest in four neonates for hypoplastic left heart syndrome (average time 47 minutes) and bicaval cannulation and continuous bypass in one 11-month-old infant for anomalous origin of the left main coronary. In-house retrieval was used in all. One neonate died of complications as a result of pretransplant donor heart dysfunction and size discrepancy, whereas the remaining three neonates and one infant survived and are home 23 months, 12 months, and 8 months (the patients with hypoplastic left heart syndrome) and 17 months (the patient with anomalous origin of the left main coronary) postoperatively. Triple-drug immunosuppression included cyclosporine, azathioprine, and prednisone. Rejection was diagnosed by clinical evaluation of child activity and monocyte cell cycle analysis from peripheral blood samples without myocardial biopsies. Routine echocardiograms, electrocardiograms, and chest x-ray films were not helpful. Six episodes of rejection were successfully treated in four patients. Twelve-month postoperative catherization in one patient (hypoplastic left heart syndrome) showed appropriate graft growth, no aortic or pulmonary anastomotic strictures, normal right and left ventricular function, and no coronary artery disease. We conclude that infant orthotopic cardiac transplantation is an acceptable procedure for severe forms of untreatable congenital heart disease. The excellent short-term results warrant continued application of orthotopic cardiac transplantation.
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The results of orthotopic cardiac transplantation have improved dramatically since the early experiences in the late 1960s. After almost 20 years of research and experience and the introduction of cyclosporine, 1 and 5 year survival rates are now 80 percent and 60 percent, respectively. The number of potential recipients far exceeds that of available donors, which is the limiting factor in cardiac transplantation. Complications related to immunosuppressive therapy remain significant, and despite decreased length of hospitalization, costs remain high. The majority of patients have good functional rehabilitation and are free of cardiac symptoms. Moreover, orthotopic cardiac transplantation has finally become a therapeutic treatment of end-stage heart disease.
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From August 1984 to August 1986, 75 patients with end-stage heart disease and cardiac failure were evaluated. Twenty-five patients received orthotopic cardiac transplants from donors as far away as 1300 miles with an ischemic time of less than 4 hours. Seventeen of 25 patients are alive 3-24 months after transplantation. Evidence of rejection was seen in each patient. Twelve patients had mild, easily controlled rejection; 13 patients had severe rejection averaging 3.1 episodes per patient. The initial immunosuppressive regimen included cyclosporine and prednisone. To decrease complications related to high dose steroids, azathioprine has recently been added to our maintenance regimen to lessen steroid requirements. Acute rejection episodes were treated with 500-1000 mg of methylprednisolone for 3 days; antithymocyte globulin or the murine monoclonal antibody, OKT3, was added for severe or resistant rejection episodes. Three patients died of rejection, and two patients died of infection. Seventeen of 18 survivors are New York Heart Association (NYHA) Class I; 15 patients have returned to employment or full activity. Because of new developments in support of transplant candidates and treatment of complications, as well as the introduction of cyclosporine, orthotopic cardiac transplantation has become an effective treatment for end-stage heart disease.
Direct sagittal computed tomographic scanning (DSCT) of the shoulder was performed in 42 symptomatic patients, six healthy volunteers, and two cadaver shoulders. Axial CT scanning and double-contrast arthrography with plain radiographs were performed in 41 patients for comparison. DSCT enabled correct identification of 27 of 29 lesions in 24 patients. Seventeen patients had normal shoulders. Axial CT scanning and DSCT together enabled correct identification of all lesions and were markedly superior to plain-film arthrography. DSCT enabled diagnosis of all cases of complete rotator cuff tear plus three cases of incomplete tear and three of rotator cuff atrophy not identified by the other techniques. Axial CT scanning was better than DSCT for diagnosis of Bankart lesions.
Survival of patients with cardiac injuries requires prompt intervention and cardiography. Approximately 50 years ago, Dr. R. Arnold Griswold instituted a treatment plan for the management of cardiac injuries. Many of the tenets he espoused are still in use today. We have been able to collect data on 266 patients with heart wounds from 1913 to 1982 at Louisville General Hospital. Trends in the evolution of injury patterns and their treatment will be discussed.
Emergency pneumonectomy for penetrating and blunt trauma has an attendant high mortality. Patients with major lung injuries presenting with prolonged shock followed by control of bleeding, resuscitation with or without aortic cross-clamping and pneumonectomy have had uniformly unsatisfactory results. From 1972 to 1982, eight patients at the University of Louisville Hospital underwent emergency pneumonectomy. All patients underwent expeditious evaluation, resuscitation, and thoracotomy with pneumonectomy. Three patients died of exsanguination (2 patients had major associated intra-abdominal injuries). Three other patients died due to pulmonary edema and right ventricular failure 2 to 3 hours after hemorrhage had been controlled and intravascular volume restored. Aortic cross-clamping was employed in four patients due to persistent hypovolemia with 100 per cent mortality. Of the two surviving patients, one presented with stable blood pressure and had pneumonectomy for tracheobronchial disruption, while the other had pneumonectomy for tangential laceration of the lung at the hilum. Pulmonary edema and right ventricular failure were responsible for mortality following emergency pneumonectomy and control of hemorrhage and restoration of blood volume. The addition of aortic cross-clamping did not seem to alter survival and may, indeed, hinder therapy due to increased vascular afterload and increased heart failure and pulmonary edema.
The closer to birth that congenital heart defects are simulated, the more valid the model. Unlike obstructive lesions such as pulmonic and aortic stenosis, which can be constructed in utero or in infancy, left-to-right shunts are more difficult to create due to the extreme friability of fetal and neonatal tissue. A method for creating left-to-right shunts in infant pigs using a pleural-sparing transverse sternotomy and direct side-to-side anastomosis between the redundant pulmonary artery and the ascending aorta has been introduced. The pigs developed palpable thrills, systolic and diastolic flow murmurs, and congestive heart failure. The average pulmonary-to-systemic flow ratio by the microsphere technique was 2.1:1 compared to 2.1:1 by oximetry. Left-to-right shunts can be constructed in infant pigs to simulate congenital heart defects.
Surface cooling, deep hypothermia and circulatory arrest have been used effectively for correction of congenital heart defects in infancy. Which patients are best suited for this technique has not been addressed. The addition of surface cooling to deep hypothermia and circulatory arrest provides homogeneous cooling and avoids swelling due to reperfusion injury after circulatory arrest. However, surface cooling in patients with large left-to-right shunts causes increased peripheral resistance and increased shunting which can result in decreased perfusion of vital organs. The purpose of this study is to measure the effect of a large left-to-right shunt on total organ blood flow distribution in infant piglets during surface cooling, deep hypothermia, and circulatory arrest. Eleven 2-week-old piglets had surface cooling, deep hypothermia, and circulatory arrest for 45 minutes, followed by rewarming and weaning from cardiopulmonary bypass. Microspheres (15 mu) were injected before surface cooling, at 28 degrees C, at 15 degrees C, and after weaning from cardiopulmonary bypass. Group I (five piglets) was the control. Group II (six piglets) had a large (6 mm) left-to-right aortopulmonary shunt established before microsphere injection. Cardiac outputs in both Groups I and II decreased with surface cooling. The distribution of cardiac output in Group I did not change with surface cooling; however, Group II pigs showed marked change in distribution of cardiac output, resulting in decreased renal, visceral, and pulmonary flow (p less than 0.05). Amylase determinations before and after surface cooling, deep hypothermia, and circulatory arrest were unchanged in Group I but elevated in Group II (p less than 0.05). These observations suggest altered cellular metabolism in visceral organs during the period of surface cooling which may be compounded by circulatory arrest and rewarming.
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Delayed diagnosis of tracheobronchial disruption resulting from blunt trauma continues to cause major morbidity and death. At the University of Louisville from 1968 to 1982, 13 patients had tracheobronchial disruption resulting from blunt trauma. All injuries were caused by motor vehicle accidents. Disruptions were located in the trachea in six patients and in the right bronchus in seven patients. Physical findings included: subcutaneous emphysema (11 patients), respiratory distress (10 patients), hemoptysis (six patients), and flail chest (four patients). Four patients (30%) died, three from multiple major associated injuries and the other before therapy could be instituted. Among the nine survivors, six had immediate diagnosis and prompt surgical treatment, which consisted of suture repair in five and pneumonectomy in the other patient. Two patients had delay in diagnosis, and repair was attempted at 4 and 30 days, respectively; bronchial stricture resulted in one and pneumonectomy, empyema, and bronchopleural fistula in the other. Another patient with a bronchial mucosal tear was treated nonoperatively without complication. Tracheobronchial disruption should always be considered with massive blunt chest trauma. Repeated bronchoscopy is indicated for unexplained pleural air leaks, lobar atelectasis, or persistent pneumothorax. Prompt diagnosis and expeditious surgical therapy result in fewer complications and increased survival.