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Biomedical subjects

R L Hardesty

Publications and source records attributed to R L Hardesty.

At least 145 records · Page 8Linked to original sources

Vascular endothelial cell HLA-DR antigen and myocyte necrosis in human allograft rejection.

Endomyocardial biopsies were obtained from patients who had received a human heart allograft. The biopsies were stained with a monoclonal antibody to the HLA-DR framework structure and the presence of HLA-DR was determined by an immunoperoxidase staining procedure. An increase in the concentration of HLA-DR on the vascular endothelium was detected shortly after transplantation. Low concentrations of endothelial DR were rarely (1/13) associated with myocyte necrosis. Eleven of 36 biopsies having an increased concentration of vascular endothelial cell DR antigen had myocyte necrosis. This study established that rejection is associated with an increase in HLA-DR antigens on the vascular endothelial cells.

Biopsy↗

Procurement for combined heart-lung transplantation. Bilateral thoracotomy with sternal transection, cardiopulmonary bypass, and profound hypothermia.

A bilateral thoracotomy with cardiopulmonary bypass and profound hypothermia has become our preferred method of procurement of organs for combined heart-lung transplantation and has replaced the sternotomy without cardiopulmonary bypass as initially used. This technique has provided good exposure and has facilitated dissection and hemostasis of the posterior aspect of the middle mediastinum.

Adolescent↗

General surgical complications in heart and heart-lung transplantation.

One hundred forty-three patients underwent cardiac transplantation from 1980 to 1985; 122 received a heart, 19 received a heart-lung, and two received a heart-liver transplant. All patients received immunosuppression with prednisone and cyclosporine. General surgical complications have developed since transplantation in 40 patients (28%). Of these, 17 patients have required surgery: exploratory laparotomy (10 patients), inguinal or ventral herniorrhaphy (two patients), repair of false aneurysm of the femoral artery (two patients), repair of lymphocele of the groin (two patients), and incision and drainage of a perirectal abscess (one patient). Of the 10 patients who required laparotomy, three underwent sigmoid resection for a perforated sigmoid diverticulum (all survived), two underwent small bowel resection for perforation (both died), two had free intraperitoneal air with no site of perforation found (one died), one underwent a cholecystostomy and one a cholecystectomy for acute calculous cholecystitis (one died), and one underwent an elective pyloroplasty for gastric outlet obstruction secondary to vagus nerve injury during heart-lung transplantation and survived. All patients who underwent elective surgery survived. Six patients died without operation and at autopsy were found to have unrecognized general surgical complications including pancreatitis (three patients), cecal ulceration with sepsis (two patients), and jejunal perforation secondary to peritoneal dialysis (one patient). Eleven other patients had severe abdominal pain and five had gastrointestinal hemorrhage not requiring operation. Proper management of these patients includes early and aggressive diagnosis of conditions requiring operative intervention, strict attention to surgical technique, and careful titration of dose of immunosuppressive drugs. The 28% incidence of general surgical complications associated with heart and heart-lung transplantation emphasizes the role of the general surgeon in the management of these complex patients.

Adolescent↗

Use of autoperfusion for distant procurement of heart-lung allografts.

Heart-lung transplantation has been limited to on-site organ procurement because current methods of lung preservation are unreliable for periods in excess of one hour. A method of dynamic heart-lung preservation has been evaluated as a possible means for distant procurement for human transplantation. Canine and bovine heart-lung blocks were removed and preserved by autoperfusion for periods of two to nine hours. The key features of the method included normothermic coronary autoperfusion with donor blood by an autoregulating beating heart, and a stabilizing reservoir bag interposed between the donor aorta and the right atrium. The reservoir is positioned one meter above the aortic valve, and determines the pressure in the aorta. Flow from the bag to the right heart dictates venous return, pulmonary blood flow, and ventricular stroke volume. The lungs are ventilated with room air and 5% to 10% of CO2, at 4 liters/minute. Normothermia is ensured by immersion of the heart-lungs block in a temperature controlled crystalloid bath. Eleven canine and eight bovine heart-lung blocks were evaluated for two to nine hours. Lung function was excellent during this period, and cardiac output did not decline from pre-harvest levels. Five heart-lung allografts were transplanted after an average of four hours of autoperfusion and all functioned satisfactorily. All animals could be weaned from the extracorporeal circulation support. Two to three hours later, cardiac outputs and arterial pO2 were normal. The peak airway pressures averaged 29 cm H2O.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Heart-liver transplantation in a patient with familial hypercholesterolaemia.

A girl aged 6 years 9 months with severe heart disease secondary to homozygous familial hypercholesterolaemia underwent orthotopic cardiac transplantation and her liver was replaced with the liver of the same donor. In the first 10 weeks after transplantation serum cholesterol fell to 270 mg/dl from preoperative concentrations of more than 1000 mg/dl.

Child↗

Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy.

Post-transplant lymphomas or other lymphoproliferative lesions, which were usually associated with Epstein-Barr virus infections, developed in 8, 4, 3, and 2 recipients, respectively, of cadaveric kidney, liver, heart, and heart-lung homografts. Reduction or discontinuance of immunosuppression caused regression of the lesions, often without subsequent rejection of the grafts. Chemotherapy and irradiation were not valuable. The findings may influence policies about treating other kinds of post-transplantation neoplasms.

Adolescent↗

Repair of an iatrogenic aortoatrial fistula.

A patient with uncommon potential to contain the extraluminal path of an aortic perforation, due to adhesions from previous operation, survived perforation of the ascending aorta and creation of an aortoatrial fistula at cardiac catheterization. The method of repair is described and discussed herein.

Aorta↗

Venous bypass in clinical liver transplantation.

A venous bypass technique (BP) that does not require the use of systemic anticoagulation is used routinely at our institution in all adult patients during the anhepatic phase of liver transplantation (LT). Complete cardiopulmonary profiles were obtained in a subset of 28 consecutive cases. During the anhepatic phase while on bypass, mean arterial pressure, central venous pressure, and pulmonary arterial wedge pressure were maintained at prehepatectomy levels. Oxygen consumption fell secondary to a decrease in temperature and the removal of the liver. Consequently, cardiac index fell without an increase in arterial-venous O2 content difference, reflecting adequate tissue oxygenation. Compared with 63 patients in a previous series given LT without bypass (NBP), the 57 total BP patients experienced better postoperative renal function (p less than 0.001), required less blood use during surgery (p less than 0.01), and had better survival 30 days after LT. The equivalency of 90-day survival in these groups results from the lack of effect of BP on the long-term survival of patients considered at high risk for metabolic reasons. BP patients at high risk for technical considerations, however, survived LT whereas NBP patients did not. BP offers other advantages important in establishing LT as a service-oriented procedure.

Adult↗

Powerful but limited immunosuppression for cardiac transplantation with cyclosporins and low-dose steroid.

Cyclosporin and low-dose prednisone provide powerful but limited immunosuppression for orthotopic cardiac transplantation. Optimal long-term survival was possible only with rescue therapy using rabbit antithymocyte globulin (RATG) when myocyte necrosis could not be reversed with pulse steroid therapy. The continued absence of rejection following rescue therapy with RATG in six of the last 19 patients is responsible for the improved 79% cumulative survival rate at 9 months compared to the 61% cumulative survival rate at 1 year for the initial 23 patients. The difference is that among the latter group, seven patients had persistent histologic rejection with focal myocyte necrosis which was not reversed with pulse therapy of steroids (hydrocortisone) or an increased dose of maintenance prednisone (30 to 40 mg/day). Three of these seven died of acute rejection within 3 months and four died between 8 and 13 months. Consequently, the cumulative survival rate of these 23 patients at 2 years was 41%. The projected 2 year cumulative survival rate of the 19 patients should not decrease greatly, as new episodes of rejection have not occurred beyond 3 months in either group.

Adolescent↗

A flexible procedure for multiple cadaveric organ procurement.

Techniques have been developed which permit removal of the kidneys, liver, heart and other organs from the same donor without jeopardy to any of the individual grafts. The guiding principle is avoidance with all organs of warm ischemia. This is achieved by carefully timed and controlled infusion of cold solutions into anatomic regions, the limits of which are defined by preliminary dissection.

Cadaver↗

Targeted blood levels of cyclosporin for cardiac transplantation.

Forty-nine patients have undergone cardiac transplantation since July, 1982, and have been treated with maintenance cyclosporin and low-dose prednisone, 15 to 20 mg. Cyclosporin dose has been targeted to a whole-blood level of 1,000 ng/ml as measured by radioimmune assay. The actuarial survival rate in this group of patients has been 79% at 12 months and 71% at 21 months. Histologic rejection has occurred at all blood levels of cyclosporin, as has significant nephrotoxicity. The hepatic toxicity encountered has been more a clinical nuisance than significant problem. The administered dose of cyclosporin required to reach a target of 1,000 ng/ml has varied between 2 and 30 mg/kg/day. The average perioperative and late serum creatinine levels were 1.2 and 1.49 mg/dl and occurred with cyclosporin levels of 1,078 and 1,068 ng/ml, respectively. Late cyclosporin toxicity has persisted despite reduction in the dose of cyclosporin below the targeted 1,000 ng/ml. Some method of blood level monitoring is necessary in patients receiving cyclosporin immune suppression to assure adequacy of the administered dose. The 1,000 ng/ml target has provided adequate immune suppression. Significant nephrotoxicity has not correlated with the blood level measured.

Bilirubin↗

The effects of cardiovascular drugs on the defibrillation threshold and the pathological effects on the heart using an automatic implantable defibrillator.

Internal defibrillating leads were implanted in 6 dogs through a left thoracotomy and in 6 pigs through a subxiphoid approach. The effects of digoxin (0.04 mg per kilogram of body weight), procainamide (15 mg per kilogram), and propranolol (0.2 mg per kilogram) on the defibrillation threshold was determined 30 to 60 minutes following intravenous administration. Resultant blood levels were equal to or greater than therapeutic levels. Individually these drugs resulted in no appreciable change in the defibrillation threshold from baseline. Pathological study of the myocardium obtained from 6 dogs that underwent more than two hundred shocks each did not demonstrate any abnormality. The 6 pigs were reliably defibrillated, this indicating that thoracotomy is not required for successful implantation. The automatic implantable defibrillator is not the definitive treatment for recurrent ventricular arrhythmias, but is a practical regimen of therapy for a select group of high-risk, out-of-hospital patients. These observations advance our knowledge of the use of this device and give more assurance for future implantation in this select group of patients.

Animals↗

Changes in lung function after routine exposure manipulations during thoracotomy.

The effect of manual retraction and bronchial occlusion upon right lung function during a 2-hr thoracotomy was evaluated in sheep. Group 1 (seven sheep) underwent manual lung retraction. Group 2 (seven sheep) underwent right bronchial occlusion. Group 3 (seven sheep) served as controls. Radioisotopic indicators (51Cr-RBC, 125I-albumin, [14C]urea, 3H2O) were used to assess changes in capillary permeability-surface area product (PS-urea), extravascular lung water (VE), and intravascular blood volume (Vv). Lung water was further quantified by gravimetric technique. Pulmonary vascular resistance increased following thoracotomy in both groups (34% Group 1, 66% Group 2) and compliance decreased (16% Group 1, 33% Group 2). Mean right lung shunt increased in Group 1 from 17 to 37% (P less than 0.05) and for Group 2 from 18 to 36% (P less than 0.02). A reduction (greater than 25%) in both groups for PS-urea and VE occurred (P less than 0.05). The fall in PS-urea and VE and the increase in PVR indicate a reduction in the right lung perfusion for both groups. It is concluded that a similar marked reduction in ventilation, perfusion, and V/Q occurred after reexpansion whether the lung was retracted or the bronchus occluded.

Animals↗

Principles of multiple organ procurement from cadaver donors.

The need for cadaveric organs other than kidneys for transplantation is increasing. Principles and techniques that allow their procurement without jeopardizing renal recovery are outlined. These include utilization of brain dead donors, careful donor selection, and surgery which minimizes warm ischema while avoiding iatrogenic injury. Utilizing this approach, a variety of combinations of organs have been removed and transplanted resulting in satisfactory functional results.

Cadaver↗

Midline pericardial cyst in the posterior mediastinum: sonographic and computed tomographic correlation.

A chest radiograph revealed an incidental finding of a large mediastinal mass located in the midline posterior to the lower aspect of the heart. The computed tomogram and sonographic examinations of the chest showed the mass to be cystic in nature, contiguous with the heart, and anterior to the displaced distal esophagus. At surgery this proved to be a pericardial cyst. The unusual location of this entity, which has never before been documented, now behooves us to include pericardial cyst and diverticulum in the differential diagnosis of mediastinal masses, posterior to the heart.

Female↗