Histocompatibility studies in a closely bred colony of dogs. II. Influence of the DL-A system of canine histocompatibility upon the survival of cardiac allografts.

The DL-A system of histocompatibility plays an important role in conditioning the survival of cardiac allografts in the unmodified canine host. The mean survival time of six cardiac allografts performed in DL-A-compatible littermate dogs obtained from a closely bred colony of beagles was 53.2 days, while the MST of transplants performed in seven DL-A-incompatible animals was 7.3 days. The MST of cardiac allografts performed in nine DL-A-compatible nonlittermate beagles was 26.3 days, as compared with 6.3 days in six DL-A-incompatible nonlittermate transplants. The results did not appear to be affected by Swisher erythrocyte-group incompatibilities. The MST of 28 cardiac allografts performed in randomly selected mongrel dogs was 10.0 days. Incompatibilities for DL-A antigens e, f, g, l, and m may constitute major barriers to transplantation, but antigens b, c, d, and k appeared to act as weak histocompatibility antigens. Under controlled conditions of donor-recipient DL-A compatibility, cardiac allografts may be less immunogenic than renal transplants. Heart transplants performed across major donor-recipient DL-A incompatibilities appeared, however, to be more vulnerable to the events of allograft rejection than renal allografts performed under similar conditions. The selection of optimally compatible donor-recipient combinations for organ transplantation may be aided materially by genetic studies of the transmission of DL-A antigens to the animals under consideration.

Challenges in presenting high dimensional data to aid in triage in the DARPA virtual soldier project.

One of the goals of the DARPA Virtual Soldier Project is to aid the field medic in the triage of a casualty. In Phase I, we are currently collecting 12 baseline experimental physiological variables and a cardiac gated Computed Tomography (CT) imagery for use in an prototyping a futuristic electronic medical record, the "Holomer". We are using physiological models and Kalman filtering to aid in diagnosis and predict outcomes in relation to cardiac injury. The physiological modeling introduces another few hundred variables. Reducing the complexity of the above into easy-to-read text to aid in the triage by the field medic is the challenge with multiple display solutions. A description of the possible techniques follows.

The significance of coronary arterial stenosis during cardiopulmonary bypass.

Myocardial infarction may develop during an uneventful open-heart operation. In order to better understand this complication, we undertook an experimental study. The left circumflex coronary artery of 20 dogs was narrowed to 50 per cent of its area by a metal screw clamp to produce a localized coronary stenosis. Regional myocardial perfusion in the distribution of both the stenotic circumflex and normal left anterior descending (LAD) coronary arteries was measured by injection of a radioactive-labeled microsphere (15 +/- 5 mu). Circumflex coronary artery flow was measured with an electromagnetic flow probe. An epicardial electrogram was recorded in the distribution of the left circumflex. Measurements of regional myocardial perfusion, circumflex flow, and the epicardial electrogram were performed in each animal during the control (prebypass) state and during cardiopulmonary bypass with a beating and fibrillating ventricle. Half the animals had cardiopulmonary bypass performed at 50 mm. Hg perfusion pressure and half at 100 mm. Hg. The animals were put to death at the end of the study, and the hearts were sectioned, weighed, and counted. A cast was made of the stenotic circumflex coronary artery, the degree of stenosis is measured, and the per cent area stenosis calculated. The study showed that the effect of a 50 per cent coronary stenosis in reducing distal flow is apparent only during cardiopulmonary bypass at reduced pressure. The mechanism whereby a myocardial infarction develops during cardiopulmonary bypass could evolve from the development of a "critical" stenosis out of a mild-moderate one at a reduced perfusion pressure during cardiopulmonary bypass.

Intrathoracic extramedullary hematopoiesis simulating anterior mediastinal tumor.

Intrathoracic extramedullary hematopoiesis is a rare tumor occurring predominantly in the posterior mediastinum, most commonly in patients with congenital hemolytic anemias. The first reported case of this entity's occurring in the anterior mediastinum is described in a 68-year-old man with an incompletely characterized anemia. Definitive diagnosis was established only after median sternotomy and removal of the tumor.

A prospective study of complications of pulmonary artery catheterizations in 500 consecutive patients.

Five hundred twenty-eight pulmonary artery catheters were inserted in 500 patients at the New York University Medical Center between May and November, 1981. Complications occurred in 126 of 528 catheterizations. Serious complications occurred in only 23 of these 528 catheterizations (4.4 percent). These complications, while serious, did not contribute directly to any of 31 deaths seen in these patients. Pulmonary artery catheters were reported by clinicians to have been of benefit in the management of 80 percent of these patients. We conclude, in view of this experience, that the wide use of these catheters is justified, but only if there is a probability that the catheters will significantly contribute to the management of the individual patient.

The effect of normothermic anoxic arrest and ventricular fibrillation on the coronary blood flow distribution of the pig.

Normothermic anoxic arrest of 15 and 30 minutes, repeated for up to a total of 90 minutes of anoxia was employed in 24 pigs. The purpose was to determine the effect of varying the duration of anoxia on coronary blood flow, coronary vascular resistance, and the distribution of coronary flow to the free wall of the ventricle. Five minutes of reperfusion at pressures of 50 and 100 mm. Hg with the ventricle fibrillating, was employed between each anoxic interval. Results were compared to control studies performed during ventricular fibrillation without anoxic arrest in 12 pigs. Prolonging the anoxic interval to 30 minutes served to create a maldistribution of coronary flow away from the left ventricular endocardium and to reduce the reactive hypermic response to anoxia. Increasing the perfusion pressure to 100mm. Hg accentuated these changes. Both light and electron microscopy of sections demonstrated edema and early myocardial necrosis in the subendocardial layer of the left ventricle subjected to repeated 30 minute intervals of anoxia at a high perfusion pressure. We postulate that repeated anoxic insults with inadequate repayment of oxygen debt results in subendocardial edema, a decrease in perfusion, increasing necrosis, and further edema. A myocardial infarction must result if this vicious cycle cannot be interrupted.

A method of closed-chest cannulation of the left atrium for left atrial-femoral artery bypass.

A large-bore polyvinyl catheter was devised for passage into the left atrium by means of a modified transseptal catheterization technique. This was performed without difficulty using both pulsatile and nonpulsatile bypass in the closed-chest animal as well as in 3 terminally ill patients. Blood was drained from the left atrium and returned to the femoral artery through an extracorporeal circuit. The shock syndrome produced by coronary embolization in dogs was successfully managed in this fashion. The results of the clinical trials were encouraging. Assisted left heart circulation using a closed-chest left atrial-femoral artery bypass seems feasible by this technique.

Esophagogastrostomy. Analysis of 55 cases.

At the New York University Medical Center from January, 1969, through December, 1973, esophagogastrostomies were performed in 56 patients. In 30 (Group A), fundoplications were combined with the esophagogastrostomies; in the other 26 (Group B), esophagogastrostomies only were performed. These two groups have been compared in an effort to determine the effectiveness of fundoplication in preventing gastric reflux following esophagogastrostomy. The operative mortality rate (10 per cent) and the 3 year survival rate (20 per cent) were approximately equal in the two groups. Clinical evidence of reflux was noted in 10 per cent of Group A and 47 per cent of Group B patients, while complications of reflux were noted in 5 per cent of Group A and in 33 per cent of Group B patients. The results of the present study suggest that fundoplication, while not prolonging survival, does prevent the symptoms and complications of gastric reflux and improves the quality of survival in these unfortunate patients. This leads us to recommend the routine use of fundoplication with esophagogastrostomy in patients with carcinoma of the esophagus and gastric cardia.

Infective endocarditis. An analysis of 54 surgically treated patients.

One hundred seventy-seven patients were admitted to the New York University Medical Center from 1970 through 1975 with infective endocarditis. Fifty-four of these patients required surgical treatment. The over-all mortality rate was 28 per cent. Two thirds of the deaths were early (10 patients) and one third late (5 patients). The mortality rate was 90 per cent in 10 patients treated for 4 to 6 weeks in whom the infection was uncontrolled and the clinical condition was deteriorating. However of the 12 patients with uncontrolled infection who were operated upon promptly within 10 days, 83 per cent survived. The fact that fungal and gram-negative infections responded poorly to medical therapy suggests the need for prompt, early surgical intervention. The mortality rate in the 32 patients operated upon in whom the infection was controlled was 12.5 per cent. It is our conclusion that all patients with infective endocarditis who develop progressive congestive failure, recurrent embolization, or progressive sepsis, despite treatment, shold have prompt valve replacement within 7 days of the institution of appropriate antimicrobial therapy.

Surgical treatment of osteoarthritis of the shoulder.

Shoulder dysfunction is unusual in osteoarthritis and usually responds to conservative treatment. The primary indication for surgery is pain unresponsive to medical management. The procedure of choice for degenerative changes in the glenohumeral joint is hemiarthroplasty or total shoulder replacement depending on the condition of the glenoid. Shoulder fusion is rarely necessary for osteoarthritis and is recommended for chronic infection, flail shoulder, and failed total shoulder replacement not amenable to revision. Joint resection is reserved for infected joints with massive bone loss. The results of shoulder arthroplasty are good to excellent in 86 to 94 per cent of all patients. The results of shoulder arthrodesis are less predictable, but are usually satisfactory in approximately 75 per cent of patients with 10-year follow-up. The treatment of AC and SC joint arthritis is conservative with rest, local heat, and medication. Pain unresponsive to this regimen is an indication for resection of the joint. Good results with this procedure directly correlate with pain relief on injection of the joint with local anesthetic.

Chevalier Jackson: the father of American bronchoesophagoscopy.

Chevalier Jackson was involved with bronchoesophagoscopy from the late 1800s until shortly before his death in 1958. A pioneer in the field, he developed numerous instruments used in peroral endoscopy and taught their safe and effective use. Most of the next generation of leaders in the field of bronchoesophagoscopy were trained in his clinics in Pittsburgh and in Philadelphia, where he held academic appointments at the six leading medical institutions of these cities. He was a keen observer, inventor, prolific writer, and humanitarian.

A special rongeur for removal of extensively calcified mitral valves.

A rare complication of advanced mitral valve disease occurs when calcium extends from the valve downward along the wall of the left ventricle into the ventricular cavity. This unusual condition can be recognized on fluoroscopy because the calcium is visible at right angles to the calcium in the valve. The surgeon faces a very difficult technical problem because it is hard to obtain adequate exposure and to remove the calcium without injury to adjacent tissues or loss of calcific fragments, with resulting embolization. Such difficulties were encountered a year ago in a patient undergoing mitral and aortic valve replacement and ultimately resulted in the patient's death. After this event, the special rongeurs described here were designed.

Myocardial injury associated with potassium arrest.

The relative efficacy of potassium-induced ischemic arrest using buffered, isosmotic potassium (25 mEq/liter) was compared with hypothermic arrest in an experimental protocol employing an intact canine heart preparation. Myocardial function (LVSW, dp/dt max), serum creatine phosphokinase levels, myocardial perfusion, and light and electron microscopical examination of the heart were assessed in five groups of 5 dogs each. There was one control group (90 minutes of bypass, no anoxia) and four experimental groups, each subjected to 1 hour of ischemic arrest and 30 minutes of reperfusion, comparing normothermic ischemic arrest (NIA), hypothermic ischemic arrest (myocardial temperature less than 25 degrees C) (HIA), normothermic potassium arrest (NKA), and hypothermic potassium arrest (HKA). Myocardial function decreased significantly following NIA and NKA but remained essentially equal in the control, HIA and HKA groups. Serum creatine phosphokinase analysis documented a significant increase in each group of animals: 2,250 mU after NIA, 1,778 mU after NKA, 1,388 mU after HIA, 1,220 mU after HKA, and 838 mU after control bypass. Left ventricular myocardial perfusion was unmeasurably low after NIA, reduced to 111 m/100 gm of tissue/min after NKA, and increased to 165 to 188 ml/100 gm/min in the control, HIA and HKA groups. Electron microscopical studies showed a range of myocardial changes, from probably irreversible damage after NIA to similar but less diffuse changes after NKA, and to potentially reversible changes after HKA and HIA with the least alteration from control after HIA. The results indicate that potassium arrest alone is not as effective as hypothermia in preventing ischemic injury, and the combination of hypothermia with a single 150 cc administration of potassium (25 mEq/liter) does not appear to provide significant additional protection.

Treatment of AIDS-related bronchopleural fistula by pleurectomy.

Spontaneous pneumothorax in patients with acquired immunodeficiency syndrome (AIDS) may require prolonged therapy for treatment of a persistent bronchopleural fistula, and treatment by standard methods often fails. This pilot study was done to test the effectiveness of aggressive surgical therapy for definitive treatment of persistent bronchopleural fistula in patients with AIDS. Between March 1989 and September 1991, 44 patients with AIDS were treated for spontaneous pneumothorax with closed tube thoracostomy; 14 of these patients had development of persistent bronchopleural fistula for more than 10 days, and 2 patients had subsequent bronchopleural fistula on the opposite side. Operative therapy in 14 patients included 15 thoracotomies and one sternotomy. The bronchopleural fistula was closed directly with suture or staples in 15 procedures and resected by lobectomy in 1 patient. All 14 patients received adjuvant parietal pleurectomy. Operative mortality was 7% (1 of 14 patients). The fistula was closed in all survivors and 13 patients were discharged between 7 and 28 days postoperatively. Pathologic examination confirmed Pneumocystis carinii in 13 patients with a high incidence of diffuse involvement and subpleural necrosis, further demonstrating the need for pleurectomy. These data suggest that in selected patients bronchopleural fistulas associated with AIDS can be effectively controlled by surgical closure combined with pleurectomy.

Immediate reconstruction of full-thickness chest wall defects.

Twenty-one patients had full-thickness chest wall defects reconstructed at the New York University Medical Center in the last ten years. Marlex mesh provided chest wall stability in 5 patients. In 9 patients with radiation ulcers Marlex mesh was not required; a severe fibrotic reaction had obliterated the pleural space and prevented paradoxical motion. Partial sternal resections did not require Marlex stabilization, while a total sternectomy resulted in marked ventilatory insufficiency in a patient who would have benefited from the use of a stabilizing material. Random pattern flaps were used initially; more recently, axial pattern, myocutaneous, and myocutaneous free flaps were employed. Necrosis developed in 4 (36%) of the 11 patients with random pattern flaps, but was not seen with the newer flap techniques. Myocutaneous free flaps provided uncomplicated coverage of and stability to three large, potentially contaminated defects. It seems that with the currently available flap techniques and the methods of chest wall stabilization, immediate repair of all full-thickness chest wall defects is possible.

Fractures adjacent to humeral prostheses.

In a review of records and radiographs from 1974 through 1988, we identified seven patients who had a humeral fracture after either a total shoulder replacement or a shoulder hemiarthroplasty. All seven patients had complications after the fracture, and five fractures did not unite until an operation was done. All of the fractures that were treated operatively healed without sequelae. Four patients who were managed operatively had satisfactory relief of pain and one had fair relief. One patient who had a non-union refused further treatment for medical reasons. The one fracture that united without operative treatment healed with the tip of the prosthesis outside of the humeral shaft, but persistent pain led to a revision total shoulder replacement. The average time to union after the operation was approximately five months (range, four to seven months). There was a permanent decrease in the motion of the shoulder from preinjury levels in five of the six patients who had union of the fracture.

Long-term complications after total knee arthroplasty with or without resurfacing of the patella.

The long-term complications related to the patella were retrospectively evaluated for 891 knees (684 patients) that had had a total arthroplasty, with or without resurfacing of the patella, with use of an unconstrained, condylar, posterior-cruciate-preserving prosthesis. The study population comprised two groups of patients who were similar in size, age, sex distribution, and diagnosis. One group (396 knees [303 patients]) had had a total knee arthroplasty with patellar resurfacing and the other group (495 knees [381 patients]) had had the same procedure without resurfacing. The average duration of follow-up was six and one-half years (range, two to fifteen years). The decision to resurface the patella was based on subjective inspection of the articular surface and on assessment of patellar tracking at the time of the operation. Resurfacing was performed if there was loss of cartilage, exposed bone, gross surface irregularities, or tracking abnormalities. Complications occurred an average of three years (range, immediately postoperatively to nine years) after the operation in the group that had had resurfacing and an average of four years (range, immediately post-operatively to ten years) postoperatively in the group that had not had resurfacing. In the group that had had resurfacing, there was loosening of the patellar component in five knees, patellar subluxation in four knees, fracture of the patella in three knees, rupture of the patellar tendon in three knees, and chronic peripatellar pain in one knee. In the group that had not had resurfacing, the complications included patellar subluxation in five knees, rupture of the patellar tendon in two knees, and chronic peripatellar pain in fifty-one knees.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of deep-vein thrombosis after total hip arthroplasty. Comparison of warfarin and dalteparin.

The effectiveness and safety of warfarin were compared with those of a low-molecular-weight heparin (dalteparin) for the prevention of deep-vein thrombosis after total hip arthroplasty in a prospective, randomized, multi-institutional trial. Patients who were older than eighteen years of age and were scheduled to have an elective primary or revision total hip arthroplasty were eligible; 580 patients were randomized, 550 had the operation and received prophylaxis, and 382 had evaluable venograms. Prophylaxis was provided either with warfarin beginning the night before the operation or with dalteparin beginning two hours before the operation and was continued until venography was performed. Bleeding was assessed on the basis of intraoperative blood loss, transfusion requirements, a decrease in hematocrit, and clinically identified bleeding complications. The prevalence of deep-vein thrombosis was found to be significantly lower in the patients who had received dalteparin than in those who had received warfarin (twenty-eight [15 per cent] of 192 patients compared with forty-nine [26 per cent] of 190 patients; p = 0.006). Deep-vein thrombosis occurred in the calf veins of twenty-one patients (11 per cent) who had received dalteparin and of forty-three patients (23 per cent) who had received warfarin; this difference was significant (p = 0.003). Proximal deep-vein thrombosis occurred in ten patients (5 per cent) who had received dalteparin and in sixteen patients (8 per cent) who had received warfarin; however, with the numbers available, no significant difference could be detected (p = 0.185). We also could not detect a significant difference with regard to the intraoperative and postoperative blood loss, the decrease in hematocrit, and the prevalence of major bleeding complications between the two groups; however, the patients who had received dalteparin had a significantly higher prevalence of bleeding complications involving the operative site (p = 0.03), and a significantly greater percentage required postoperative transfusions (p = 0.001). We concluded that preoperative prophylaxis with dalteparin is significantly more effective than that with warfarin in preventing deep-vein thrombosis after total hip arthroplasty. The greater effectiveness of dalteparin must be considered, however, in light of an increased need for postoperative transfusions and an increase in the prevalence of wound-related bleeding complications.

The influence of diabetes and hypertension on the results of coronary revascularization.

The effects of diabetes and hypertension on the early postoperative course of patients undergoing coronary revascularization were studied by reviewing the records of 177 patients operated upon in 1972. There were 121 nondiabetic, nonhypertensive; 32 hypertensive; ten diabetic; and 14 diabetic-hypertensive patients. The incidence of postoperative low cardiac output, renal insufficiency and arrhythmia was significantly higher in the hypertensive patient. Operative mortality ranged from 0 in diabetic patients, to 0.8 per cent in nondiabetic, nonhypertensives, to 7.1 per cent in diabetic-hypertensives and 12.5 per cent in hypertensive patients, suggesting an increased risk for the hypertensive patient. The one- to two-year follow-up results documented symptomatic improvement in 90.7 per cent of patients with little adverse effect apparent from diabetes or hypertension. Pre- and postoperative coronary angiography was carried out in 103 patients between 1968 and 1973 with a mean elapsed time between operation and postoperative angiogram of 9.3 months. The progression of atherosclerosis was graded on a 0-4 basis in both grafted and ungrafted coronary arteries. While hypertension appeared to contribute to disease progression, the incidence of vein graft and internal mammary artery bypass occlusion was not significantly affected by either diabetes or hypertension. This study has shown that while hypertension contributes to increased morbidity and mortality in the early postoperative period and an increased rate of progression of atherosclerosis, neither diabetes nor hypertension appeared to influence the one- to two-year results of coronary revascularization.

Allogeneic unresponsiveness to orthotopic cardiac transplants in DL-A-identical radiation chimeras.

Nine Cooperstown beagles of known DL-A genotypes were exposed to supralethal total-body irradiation and received bone-marrow allografts from DL-A-identical donors. Four to 5 months later, the resulting chimeras received orthotopic cardiac allografts from their corresponding donors of marrow. Six chimeras died of operative complications in the immediate postoperative period. The other 3 chimeras survived from 173 to 547 days; 1 dog died at 173 days as a result of right-sided heart failure, secondary to stenosis at the site of the pulmonary artery anastomosis. The other two recipients continue to be active and healthy at 545 and 547 days. The results indicate that dogs can be rendered specifically tolerant to orthotopic cardiac allografts by supralethal total-body irradiation and the transplantation of marrow obtained from the prospective allograft donor.