Charles C. Marboe

Intracoronary irradiation markedly reduces restenosis after balloon angioplasty in a porcine model

OBJECTIVESnThis study examined the effects of intracoronary irradiation on neointimal proliferation after overstretch balloon angioplasty in a normolipemic swine model of restenosis.nnnBACKGROUNDnRestenosis after percutaneous transluminal coronary angioplasty represents, in part, a proliferative response of vascular smooth muscle at the site of injury. We have previously shown that ionizing radiation, delivered by means of an intracoronary source, causes focal medial fibrosis. We therefore hypothesized that intracoronary irradiation delivered at the time of balloon angioplasty might impair the restenosis process.nnnMETHODSnNineteen juvenile swine underwent coronary angiography; a segment of the coronary artery was chosen as a target for balloon injury. In 10 swine, a ribbon of iridium-192 was positioned at the target segment, and 2,000 cGy was delivered at the vessel wall. Subsequently, overdilation balloon angioplasty was performed at the irradiated segment. In nine control swine, overdilation balloon angioplasty was performed without previous irradiation. Eighteen animals survived and were killed at 30 days. Histopathologic analysis was performed by a pathologist in blinded manner. The area of maximal lumen compromise within the target segment was analyzed by computer-assisted planimetry.nnnRESULTSnIn the control group, mean (+/- SD) neointimal area was 0.84 +/- 0.60 mm2 compared with that in the irradiated group, 0.24 +/- 0.13 mm2 (p = 0.01). In the control group, mean percent area stenosis was 47.6 +/- 20.7%, whereas that in the irradiated group was 17.6 +/- 10.5% (p = 0.001). This represents a 71.4% reduction in neointimal area and a 63.0% reduction in percent area stenosis in the irradiated group. Adjacent coronary segments and surrounding myocardium were unaffected.nnnCONCLUSIONSnIntracoronary irradiation (2,000 cGy) delivered to a target porcine coronary segment before balloon overdilation markedly reduces neointima formation at 30 days and thus significantly impairs the restenosis process.

University of Wisconsin solution for human donor heart preservation: initial clinical experience.

Although in vitro and primate orthotopic transplant experiments have suggested the superiority of University of Wisconsin solution (UWS) compared with crystalloid cardioplegia and saline solution storage for hypothermic heart preservation, concerns about the viscosity and the high potassium concentration of UWS have precluded its use in human cardiac transplantation. To test the safety and efficacy of UWS, 16 patients received hearts arrested with, flushed with, and stored in UWS at 4 degrees C for a mean ischemic time of 153.3 +/- 30.7 minutes. After reperfusion, the hearts contracted vigorously and attained a stable sinus rhythm within 4.0 +/- 2.4 minutes, and the patients were weaned from bypass in 24.5 +/- 8.0 minutes. There was no evidence of acute or chronic ischemic myocardial injury by enzymatic analysis, electrocardiography, or biopsy specimen histology. The results suggest UWS can be safely used, within currently accepted limits of donor ischemic time, to arrest and preserve human hearts for transplantation. Further studies of preservation are required to compare UWS with crystalloid cardioplegia and saline solution storage and to test the ability of UWS to prolong the period of safe donor hypothermic ischemia in clinical heart transplantation.

Normal bronchial healing without bronchial wrapping in canine lung transplantation

The deleterious effect of steroids on bronchial healing in lung transplantation has led to the development of techniques to protect the anastomosis and to the exclusion of steroid-dependent patients from transplantation. The effect of steroids on bronchial healing was tested in a canine single-lung allotransplantation model. Twenty size-matched mongrel dogs (20 to 30 kg) underwent left lung transplantation without anastomotic wrap or direct revascularization. Postoperatively, all received daily doses of cyclosporine (15 mg/kg) and azathioprine (1 mg/kg) and were subdivided into three steroid dosage groups. Group A (n = 10) animals received 1.5 mg/kg of prednisone per day whereas groups B (n = 5) and C (n = 5) received 5.0 mg/kg of prednisone per day for 28 postoperative days. In addition, group C received prednisone (5.0 mg.kg-1.day-1) for 1 month preoperatively. In group A, 8 of 10 dogs survived 28 days without evidence of respiratory compromise, with anastomotic bursting pressure greater than 510 mm Hg. In group B, all 5 dogs survived to 28 days without evidence of respiratory compromise and with intact bronchial anastomoses (bursting pressures greater than 510 mm Hg). In group C, 3 of 5 animals survived to 28 days with intact anastomoses. Histological examination demonstrated normal bronchial healing in all anastomoses. These data suggest that preoperative steroid dependence should not be a contraindication to lung transplantation and that bronchial anastomotic wrapping with vascular tissue may not be essential.

Detection of Multiple Papillary Fibroelastomas of the Tricuspid Valve by Transesophageal Echocardiography

A 66-year-old man without symptoms, referred for the treatment of moderate hypertension, was found to have a right atrial mass by two-dimensional echocardiography. On transesophageal echocardiography two masses were detected on the tricuspid valve, the first one on the posterior leaflet and the second smaller one on the anterior leaflet. These findings were confirmed at surgery. Histologic analysis revealed that the masses represented papillary fibroelastomas.

Chemotherapy and its Effect on Testicular Morphology in Children

Bilateral testicular biopsies were performed on 25 boys between 4 and 16 years old with the diagnosis of acute lymphocytic leukemia after the induction of regression with vincristine and prednisone, followed by cyclic maintenance therapy with a combination of 6-mercaptopurine, methotrexate, L-asparaginase, cyclophosphamide and doxorubicin for 2 years. These drugs were given in accordance with childrens cancer study group protocols. Only 3 boys had positive biopsies (12 per cent), although post-treatment testicular morphology was abnormal in the overwhelming majority. Interstitial fibrosis was present in 16 children (70 per cent), basement membrane thickening in 12 (50 per cent) and, most importantly, a reduction in the tubular fertility index of greater than 50 per cent in 20 (80 per cent). There was no relationship between the abnormal morphology encountered and the age of the patient when treated. Most of these changes may be reversible with time but only a biopsy at a later date can establish the long-term effects of treatment on testicular morphology and, perhaps, help to predict future fertility potential.

Testicular biopsy and occult tumor in acute lymphocytic leukemia

Testicular biopsy has become a routine procedure before discontinuing chemotherapy in male children being treated for acute lymphocytic leukemia (ALL). Before a decision can be made to discontinue multiple drug therapy, all possible sites of occult tumor such as the testis, cerebrospinal fluid, and bone marrow must be sampled. Between December, 1978, and November, 1981, 25 male children underwent testicular biopsies after two or more years of combination chemotherapy at the Babies Hospital, Columbia-Presbyterian Medical Center. Only 3 of the 25 patients (12%) were found to have leukemic infiltrates on histologic sections. Two of 3 patients, however, were noted preoperatively to have either irregular testicular contours or testicular enlargement and induration. Occult testicular infiltration discovered after two or more years of chemotherapy is rare. Most children with a histologically positive biopsy result were at least suspected preoperatively to have testicular involvement.

RENAL PELVIC TUMORS IN CHILDHOOD

A capillary hemangioma in the renal pelvis of a twelve-year-old child is presented. The diagnosis and management of renal pelvic tumors in childhood is reviewed. We believe this pathologic entity should be included in the differential diagnosis of hematuria and ureteropelvic junction obstruction in a child.

Binding of preformed xenoantibodies to porcine bioprosthetic valves

We have investigated whether preformed antibodies against xenoantigens bind to cellular elements remaining on porcine bioprosthetic valves after various methods of preservation. Fresh porcine valves treated with either acetone, 4% formaldehyde, or 0.625% glutaraldehyde, as well as an unfixed valve, were incubated with antiserum against porcine xenoantigens. This serum was prepared using the affinity purification method with porcine lymphocytes as the target. The valves were stained with secondary fluorescein-conjugated antibody against immunoglobulin M or immunoglobulin G and examined under fluorescent microscopy. Intense binding of immunoglobulin M to the endocardium was observed in the unfixed valve as well as in valves fixed in acetone and formaldehyde. Glutaraldehyde fixation eliminated binding of antibody. Binding was not noted within the connective tissue. No binding of antiimmunoglobulin G was noted on the endocardium of any of the sections. Examination of three glutaraldehyde-treated porcine valves explanted from the aortic position after 10 years in situ showed no immunoglobulin deposition. These results demonstrate the elimination of antigenicity to preformed antibodies in the endocardium and connective tissue of glutaraldehyde-preserved porcine valves. The findings may, in part, explain the poor performance of formaldehyde-preserved bioprosthetic xenograft valves in the past and support the use of glutaraldehyde as a preferred agent for preservation of bioprosthetic endovascular materials.