The present study further investigates evidence for lipid peroxidation in atherosclerotic aortic tissue by determining the activity of antioxidant enzymes and concentrations of lipid peroxide fluorochromes in abdominal aortas from 15 patients with abdominal aortic aneurysms (AAA), an additional 7 patients with ruptured abdominal aneurysms, and 12 patients with atherosclerotic occlusive disease (AOD). Aortas from nonatherosclerotic organ donors served as nondiseased controls. Cu, Zn-superoxide dismutase (Cu,Zn-SOD) activities in AAA and AOD tissues were 16% and 25% of control activity, respectively. Mn-SOD activity in diseased aortae were about 65% of controls. CuZn-SOD protein in AAA and AOD was 56% and 100% of controls, respectively, resulting in significantly lower CuZn-SOD specific activity in these tissues. Ruptured AAA tissue also had low SOD activity and protein. Glutathione peroxidase (GPx) activity in AAA and AOD aortas was 70% and 65% of controls, respectively, and glutathione reductase (GR) activity in AAA and AOD aortas was 80% and 65% of control activities, respectively. These results were associated with significantly higher lipid peroxide fluorochromes, expressed as U/g aorta, in both groups of atherosclerotic aortas than in controls. AOD aortas had 33% higher fluorescence than AAA aortas, but the highest levels were seen in ruptured AAA. These data further support the involvement of free radicals and lipid peroxidation in atherosclerotic aortic disease, but do not indicate that these mechanisms are specifically involved in aneurysm formation versus development of occlusive disease.
A patient with large left lower pole renal cell carcinoma in a solitary kidney is presented. The patient was treated by partial nephrectomy and autotransplantation using splenic arterial and venous anastomoses. The potential for reducing operative morbidity compared with autotransplantation to the iliac fossa is discussed.
We evaluated the effects of alcohol ingestion on aortic lipid concentrations in 15 pair-fed Sprague-Dawley rats divided into three groups of five animals each. Control rats were fed a liquid diet, with 36% of their energy provided by maltose-dextrin for 28 days, and the remaining two groups of rats were fed an equivalent proportion of their energy as alcohol for 28 days or 18 months. Alcohol-fed rats exhaled significantly greater quantities of ethane than did controls at 28 days and 18 months. Serum cholesterol levels increased by 40% and triglyceride levels increased by 80%, but phospholipid levels remained unchanged in alcohol-fed rats compared with controls. Aortic concentrations of cholesterol and phospholipids increased twofold and threefold, respectively, in alcohol-fed rats, with a corresponding alteration of the cholesterol-phospholipid ratio at both time intervals. Tissue triglyceride levels were only elevated at 28 days, and no differences in aortic lipid peroxide levels were detected between alcohol-fed rats and controls. The results of the study indicate that alcohol ingestion increases aortic cholesterol, phospholipid, and triglyceride levels at 28 days and cholesterol and phospholipid but not triglyceride levels at 18 months. The mechanisms underlying the accumulation of lipids in aortic tissue need further elucidation.
Lipid peroxidation may play a significant role in the initiation and progression of atherosclerotic plaque. Freshly harvested normal and atherosclerotic human aortic tissue, coronary arteries and explanted vein grafts were snap frozen at −70°C. Folch reagent (chloroform - methanol 2:1, v/v) was used to extract lipids from the homogenates. These extracts were assayed for cholesterol, phospholipid and triglyceride content. Lipid peroxide complexes in vessels were measured fluorometrically. Atherosclerotic plaque from patients with aortic aneurysmal and occlusive disease and coronary artery disease contained significantly greater amounts of cholesterol (15.54±9.71 vs 3.39±1.14 mg/g tissue) than controls (p<0.01). Lipid peroxide fluorochromes were similarly elevated in all atherosclerotic tissue (4.159±1.065 vs 3.087±0.497 fluoro units/g tissue) compared to control (p<0.01) with significant elevations in saphenous vein grafts and occlusive aortic disease. Although lipid peroxidation and lipid accumulation occur in close association in atherosclerotic plaque, the role of lipid peroxides in the pathogenesis of atherosclerosis remains to be determined.
Although the growth and rupture of abdominal aortic aneurysms are commonly explained by Laplace's law, the final events that precede aneurysm rupture are not fully understood. Local excrescences within the wall of abdominal aortic aneurysms were observed in four of five patients studied with preoperative CT scanning, and were removed from six patients at the time of surgery. These protrusions were filled with thrombus, and on histologic examination marked attenuation of the aortic wall, focal loss of elastic fibers, and inflammatory cell infiltrates of lymphocytes, plasma cells, and occasional multinucleate giant cells were seen. The presence of these blebs and their microscopic characteristics suggest their potential as a mechanism for rupture and recognition of this deformity by use of abdominal CT scanning may indicate the necessity for prompt surgical intervention. Further careful clinicopathologic correlation is required to clearly establish these localized defects in the aneurysm wall as a cause for rupture.
Altered trace elements and ascorbic acid metabolism have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, their role in the disease process, or the effect of atherosclerosis on their tissue levels within plaque, is poorly understood. The present study analyzes the concentrations of Fe, Cu, Zn, and Mn, and ascorbic acid and superoxide dismutase (SOD) activity in tissue samples from 29 patients with abdominal aortic aneurysms (AAA) and 14 patients with atherosclerotic occlusive disease (AOD). It was observed that the Fe and Mn concentrations in AAA and AOD tissue were higher than the levels in nondiseased control aorta, whereas Cu and Zn levels in AAA and AOD tissue were similar to the levels in controls. The Zn:Cu ratio was significantly lower in the AAA tissue in comparison to both AOD and control tissue. In addition, AAA and AOD tissue had low ascorbic acid levels and low Cu,Zn-SOD activity with Cu,Zn-SOD:Mn-SOD ratios of 0.27 and 0.19, respectively, compared to a ratio of 3.20 in control aorta. These data indicate that aorta affected by aneurysms and occlusive disease have altered trace element and ascorbic acid concentrations, as well as low Cu,Zn-SOD activity. Although these observations do not directly support the hypothesis that AAA is associated with aortic Cu deficiency they do suggest a role for oxygen radicals or increased lipid peroxidation in occlusive and aneurysmal disease of the aorta.
We performed 33 carotid endarterectomies in 29 patients for recurrent carotid stenosis. The interval between the initial and second operations ranged from six weeks to 11 years with a mean of 56 months. Three types of pathologic lesions were identified: (1) recurrent atherosclerosis (RA), (2) neointimal fibromuscular hyperplasia (NFH), and (3) lesions with elements of both RA and NFH (complex lesions). Histologic examination of early-recurring lesions (less than three years) revealed NFH in 17 patients and one complex lesion. Late-recurring lesions (three years or later) were due to atherosclerosis in eight vessels, NFH in four, and both RA and NFH in three. Focal neurologic symptoms occurred in 25 (76%) of 33 vessels, and an embolic source could be identified in 16 (64%) of 25 patients. Embolic events rather than reduced blood flow due to progressive stenosis are more frequent causes of symptoms in patients with recurrent carotid stenosis than was formerly believed.
Perioperative care and anesthetic management of donor and recipient animals are crucial factors in studies involving experimental liver transplantation in the pig. Prevention of unacceptably high morbidity and mortality in the transplant recipients requires meticulous attention to anesthesia, preoperative and postoperative care. Liver transplant surgeries were performed using 15 pairs of pigs. Six of the transplant recipients were anesthetized with halothane plus 50% nitrous oxide (N2O) and oxygen (O2), and nine with isoflurane plus 50% N2O in O2. Arterial blood pressure, total anesthetic time, time of interruption of vena cava blood flow, and fluids administered, as well as length of survival were among the parameters measured and compared for the two groups. No deaths were attributed to either anesthetic technique. However, the isoflurane group had slightly higher blood pressure intraoperatively, better long range survival, and relatively rapid recoveries when compared to the halothane group. Because of these findings and the reported low rate of isoflurane metabolism and low resultant potential for formation of toxic metabolites when compared to halothane metabolism, we have elected to use the isoflurane-50% N2O regimen for this procedure.
Considerable interest in experimental liver transplantation has been generated recently due to improvements in the results of clinical liver transplantation efforts. An operative technique for orthotopic porcine liver transplantation is presented which represents modifications of and improvements to previously published techniques. Salient features of the technique include (1) use of a diaphragmatic cuff for the suprahepatic inferior vena cava anastomosis, (2) use of a splenojugular shunt, (3) omission of caval shunts, and (4) use of isoflurane as the primary anesthetic agent. This operative technique has provided excellent survival rates in our transplanted animals.
Description d'une technique amelioree pour l'anastomose de la veine cave lors de la transplantation orthotopique de foie. La methode a ete appliquee dans 50 cas chez l'animal (porc) et dans 11 cas cliniques