Use of the isolated perfused kidney model to assess the acute pharmacologic effects of cyclosporine and its vehicle, cremophor EL.

"Nephrotoxicity" secondary to cyclosporine and its clinically used vehicle, Cremophor EL, was examined in the isolated perfused rat kidney model. This model allows the serial determination of renal hemodynamic and tubular functional studies over a 3-hr duration using a normothermic, low hematocrit (13-15%) perfusion system. Initial studies indicated that the addition of small quantities of Cremophor EL resulted in marked renal vasoconstriction with decreased renal blood flow and deterioration in renal tubular function. These effects were highly significant and were of the same magnitude whether or not cyclosporine was present in the system. Cyclosporine was therefore examined after being dissolved in another vehicle, methanol. A 10% (v/v) amount of plasma was necessary in the perfusate to prevent significant adsorption of cyclosporine to the perfusion apparatus. Cyclosporine at concentrations below 100 ng/ml resulted in minor changes in renal hemodynamics. Beginning at 100 ng/ml glomerular filtration rate dropped significantly and renal vascular resistance increased three-fold. Fractional excretion of sodium significantly increased and the urine:plasma inulin ratio significantly decreased. We conclude that the clinically used drug vehicle, Cremophor EL, has significantly adverse effects on renal hemodynamics and tubular function. In addition, CsA causes similar renal toxicity in a dose-dependent fashion. Simultaneous administration of these two nephrotoxic agents could contribute to the high incidence of acute renal failure seen after transplantation. These observations suggest that an alternate vehicle with less renal toxicity might significantly decrease the incidence of this clinical problem.

Insertion and recovery of a new retrievable vena caval filter. Work in progress.

A new retrievable inferior vena cava (IVC) filter was tested in nine pigs. Insertion was through a 14 French sheath using both the femoral and jugular approaches. All insertions were successful, and there was a 100% postinsertion IVC patency rate (8/8 pigs at one week and 1/1 pig at one month). Addition of an apical hook to the filter design allowed transjugular retrieval of two filters at one week postinsertion. Three of nine filters migrated to the upper IVC. The filter's design allows paraxial blood flow despite trapped thrombus and inhibits filter tilting. In vitro, the filter captured 95% to 100% of 5 X 5 mm clots. If problems with migration can be solved, the new filter may provide effective short- and long-term prophylaxis against pulmonary embolism.

Use of freshly isolated capillary endothelial cells for the immediate establishment of a monolayer on a vascular graft at surgery.

Endothelial seeding of vascular graft surfaces may lead to a less thrombogenic surface. We examined the feasibility of using microvessel endothelial cells derived from human fat for seeding purposes. Human fat was treated with collagenase for 24 minutes, washed, and purified in a Percoll gradient separation. This yielded 1.25 +/- 0.45 X 10(6) cells/gm of fat. After a 1-hour incubation on plasma-coated Dacron, 2.8 +/- 1.5 X 10(4) cells remained firmly adherent to the surface. When exposed to flow for 2 hours at a shear stress of 0 to 80 dyne/cm2, between 50% and 100% of the initially adherent cells remained adherent. Statistical analysis of this data failed to demonstrate a strong relationship between the number of adherent cells and the shear rate. Scanning electron microscopy demonstrated endothelial cells in various stages of attachment to the plasma-coated Dacron. Although most cells were still round and only focally attached to the surface, some cells were maximally flattened, forming cell-to-cell contact. Because of the high cell yield and the firm adherence characteristics, we conclude that microvessel endothelial cells may offer the possibility for confluent endothelial cell seeding of a graft at the time of surgical implantation without the need for cell culture.

Transvenous catheter pulmonary embolectomy.

Acute cardiovascular collapse in the hospitalized patient is associated with a high mortality rate and remains a therapeutic dilemma. Survival could be improved in the subgroup of patients with massive pulmonary thromboembolism if prompt surgical intervention is undertaken. This report presents the cases of two patients with cardiovascular collapse who survived transvenous catheter pulmonary embolectomy (herein described in detail). This procedure can be performed in any hospital with angiographic facilities and personnel trained in the technique. In our opinion it is the procedure of choice in patients with refractory cardiovascular collapse from massive pulmonary thromboembolism.

Complications encountered with the use of the Greenfield filter.

The Greenfield filter can be used with a low complication rate provided one adheres to certain principles. First, preoperative venography to define the inferior vena caval anatomy will help avoid difficulties associated with anatomic variations. At the time the study is carried out, it would be extremely useful if the radiologist places a radiopaque marker at the level of the renal veins. This will ensure that filters will be placed in the infrarenal position when appropriate, thus preventing occasional inadvertent discharge, particularly into the right renal vein. Second, use of a guide wire greatly facilitates passage of the introducer and accurate intracaval positioning. Third, intraoperative technical errors must be recognized and promptly corrected. Finally, meticulous postoperative follow-up is essential, and recurrent embolism or any change in filter position requires repeat roentgenography of the vena cava to guide appropriate corrective treatment.

Long-term follow-up of reoperative carotid surgery.

BACKGROUND: We examined our long-term results of carotid reoperation to identify risk factors for morbidity and secondary recurrence. METHODS: Medical record review revealed 27 patients had reoperative surgery for recurrent stenosis. Demographics, operative details, pathology, clinical outcome, and follow-up imaging results were reviewed. RESULTS: No neurologic deficits and no mortalities were noted perioperatively. Long-term follow-up (average 54 months) revealed an 85% 5-year and 29% 10-year estimated survival. The 5- and 10-year estimated neurologic event rates were 15% and 35%, respectively. These included 3 ipsilateral strokes and 1 ipsilateral TIA; only the TIA involved secondary restenosis. Follow-up imaging revealed a 21% incidence of secondary restenosis, occurring more frequently in patients with hyperlipidemia (P < 0.05) and previous contralateral endarterectomy (P < 0.05). CONCLUSIONS: (1) Reoperation provides long-term protection from stroke due to recurrent stenosis. (2) Secondary restenosis rates appear higher than those for primary surgery. (3) Hyperlipidemia and contralateral endarterectomy are risk factors for secondary restenosis.

Origin of cells that line damaged native blood vessels following endothelial cell transplantation.

Endothelial cell (EC) transplantation has been proposed as a method to reduce the thrombogenicity of both vascular grafts as well as injured native blood vessels. While techniques have been developed to establish EC monolayers on these surfaces, a major question that remains is whether the cells that exist on the blood flow surface are the same cells placed on the surface at the time of transplantation. We have developed an intravital fluorescent staining technique that permits isolated, autologous, fat-derived microvascular endothelial cells (MVEC) to be labeled and subsequently detected following their transplantation. In our study, rat abdominal aortas (AA) were injured with a 3F embolectomy catheter, and the injured surfaces were immediately treated with fluorescently labeled MVEC. Five days after transplantation, AA were evaluated by both scanning electron and fluorescence microscopy. Results of scanning electron microscopy showed the existence of nonthrombogenic regions in the areas of injury, and fluorescence microscopy of the identical areas established that these cells contained fluorescent dye. Our results indicate that the cells that line these injured areas of native vessels are the same cells that were originally transplanted. Our intravital fluorescence technique provides a method to trace the origin and disposition of transplanted cells on the vascular surfaces.

Comparison of Doppler US and CT angiography for evaluation of renal artery stenosis.

RATIONALE AND OBJECTIVES: The authors compared Doppler ultrasound (US) with computed tomographic (CT) angiography in the evaluation of stenosis of the main renal artery. MATERIALS AND METHODS: Fifty-six patients who had undergone conventional angiography of the renal arteries participated in a prospective comparison of Doppler US (45 patients) and CT angiography (52 patients). US evaluation included both the main renal artery and segmental renal arteries. RESULTS: There were 27 main renal arteries with at least 50% stenosis in 20 patients. In 36 patients, there was no significant stenosis. All cases of main renal artery stenosis detected with Doppler US of the segmental arteries were also identified with Doppler US of the main renal artery. The by-artery sensitivity (63%) of US of the main renal artery was greater than that (33%) of US of the segmental arteries. CT angiography was more sensitive (96%) than Doppler US (63%) in the detection of stenosis, but the specificity of CT (88%) was similar to that of US (89%). The difference in the area under the receiver operating characteristic curve (AUC) between CT (AUC = 0.94) and US (AUC = 0.82) was statistically significant (P = .038). CONCLUSION: Doppler US of the main renal artery is more sensitive than Doppler US of segmental arteries in the detection of stenosis. CT angiography is more accurate than Doppler US in the evaluation of renal artery stenosis.

Risk of pulmonary embolus with inferior vena cava thrombosis.

The authors have evaluated the risk of pulmonary embolism both as a primary event or as a secondary embolus despite adequate anticoagulation in 39 patients with phlebographically documented inferior vena caval (IVC) thrombosis. Twenty-six of these patients had thrombi characterized as free floating, and 13 had thrombi that were adherent to the IVC wall without a free-floating component. The incidence of initial pulmonary embolism confirmed by either pulmonary arteriography or high probability ventilation-perfusion lung scanning was 50 per cent (13/26) in those patients with free-floating IVC thrombi, but 15 per cent (2/13) in those with closely adherent mural thrombi (P less than 0.05). Pulmonary embolism despite adequate anticoagulation occurred in 27 per cent (7/26) of patients with free-floating clots, but in only 17 per cent (1/8) of cases with adherent thrombi (P greater than 0.05). These data strongly suggest that patients with documented free-floating inferior vena caval thrombi are at a significant risk for pulmonary embolism as an initial event and perhaps also as a recurrent embolus, even in the presence of adequate anticoagulation. When such thrombi are identified, the overall incidence of pulmonary embolus is high and conventional anticoagulant treatment with heparin may not be sufficient.

Renal autotransplantation and extracorporeal reconstruction for complicated benign and malignant diseases of the urinary tract.

Renal autotransplantation was performed in five patients and extracorporeal vascular reconstruction was required in two of these cases. One had a carcinoma of the mid-ureter with a solitary kidney. Two patients had ureteral injury. One was iatrogenic from a prior operation, and the other had intrinsic ureteral disease secondary to schistosomiasis. The fourth patient had renovascular hypertension with disease extension into the interlobar renal arteries and a single kidney. The final patient had a large, renal arteriovenous malformation and polycystic kidneys. All have functioning grafts at follow-up ranging from 10 to 36 months. There is no evidence of tumor recurrence after 30 months in the patient with ureteral malignancy. The patient with renovascular hypertension has adequate blood pressure control with medication 12 months after surgery. His creatinine which had risen in the post-operative period to 4.2 mg/dl, has returned to its pre-operative valve of 1.8 mg/dl. None of the other four patients had any post-operative decline in renal function. These cases illustrate that the technique of nephrectomy, extracorporeal surgery, and renal autotransplantation can be applied to a variety of benign and malignant diseases of the kidney and ureter not amenable to conventional in-situ correction, thus allowing maximal preservation of renal parenchyma. We also have demonstrated that the procedure can be successfully performed in the presence of significant infectious risk (Case 2: indwelling nephrostomy), and retroperitoneal infection (Case 3: schistosomiasis). We feel that this procedure is currently underutilized.(ABSTRACT TRUNCATED AT 250 WORDS)

Axillo-internal carotid artery bypass in the treatment of neck metastases.

The initial surgical management of neck metastases from head and neck cancer may be complicated if the tumor mass invades the carotid vessels. Acute carotid ligation is associated with a high stroke rate. Consequently preservation of flow to the internal carotid artery is desirable. We will describe two patients in whom preservation of flow was accomplished with the use of a saphenous vein bypass from the axillary artery to the internal carotid artery. The technique is described and has several advantages. First, it preserves flow to the internal carotid artery; second, it allows radical excision of tumor without compromising the margins of resection; and finally, at least one suture line and most of the graft are outside the field of radiation and remote from the wound closure. We believe that this technique is useful in the management of patients with disease that has metastasized to the neck.

Cultured and immediately procured endothelial cells: current and future clinical applications.

Great progress has been made in the last several years in our ability to culture human endothelial cells. In addition, techniques to immediately procure and utilize these cells have also been developed. The purpose of this paper is to present an overview of the current and potential uses of these cells in both vascular and nonvascular conditions. It is likely that endothelial cells will be used in a variety of applications in the near future. Immediately procured and cultured cells will be used to resurface vascular prosthetic grafts. They may also be used on the surface of vessels following procedures such as balloon angioplasty or atherectomy. In addition, they may be placed upon the surface of implantable devices such as expandable stents. Through the mechanism of genetic engineering, these cells may be modified to produce proteins, which may modify thrombogenicity and perhaps decrease the rate of recurrent stenosis by influencing cellular hyperplasia. Genetically modified endothelial cells also have great potential in nonvascular disease. Their contact with circulating blood makes them an ideal cell for production of proteins to correct systemic conditions such as the insulin deficiency found in diabetes mellitus. The application of endothelial cell biology in both vascular and nonvascular science represents one of the most exciting fields of research active today.

Role of selective arteriography in the diagnosis of a ruptured middle colic artery aneurysm.

A case of a ruptured middle colic artery is reported. The diagnosis was initially overlooked and eventually made by selective arteriography. Aneurysms of visceral arteries are rare and rupture of them even more infrequent. Awareness of this potentially fatal and treatable entity should enable early detection by selective visceral arteriography. The roles of embolization and surgery in the management of visceral aneurysms are discussed.

Role of thrombin in endothelial cell monolayer repair in vitro.

PURPOSE: We examined the effect of thrombin on human iliac artery endothelial cell monolayer repair and proliferation after denuding vascular injury. METHODS: Human iliac artery endothelial cell monolayer repair was determined by scrape wounding confluent monolayers and measuring the advancement of the cells into the wounded area for 3 days. Proliferation studies involved plating human iliac artery endothelial cells at one tenth confluence and counting the increase in cell number every 2 days for a 2-week period. Proliferation during monolayer repair was examined by determining bromodeoxyuridine uptake in cells located at the leading edge of a scrape-wounded monolayer. RESULTS: Thrombin (1 to 8 U/ml) inhibited human iliac artery endothelial cell monolayer repair in a concentration-related, reversible manner. The effect was augmented by decreasing serum concentration and was independent of the presence of endothelial cell growth supplement. Inactivation of thrombin's proteolytic site with diisopropylfluorophosphate eliminated its effect on monolayer repair. Thrombin (0.5 to 8 U/ml) inhibited human iliac artery endothelial cell proliferation in a dose-related manner. This effect was augmented by decreasing serum concentration. Finally, thrombin (4 U/ml) inhibited the proliferative response of cells located at the leading edge of wounded monolayers compared with control groups. CONCLUSION: Thrombin inhibits human arterial endothelial cell monolayer repair and proliferation after denuding vascular injury.

Treatment of iatrogenic femoral artery injuries with ultrasound-guided compression.

Iatrogenic injuries of the groin are becoming more common after increasingly sophisticated vascular intervention. These injuries are accurately detected by duplex and color Doppler ultrasonography. Recent treatment of these lesions by ultrasound-guided compression repair (UGCR) has been described. During a 1-year period we identified 18 femoral artery injuries, including 17 pseudoaneurysms and one arteriovenous fistula. Three of the pseudoaneurysms thrombosed spontaneously before attempted treatment. The remaining 15 lesions underwent a trial of UGCR. Successful closure was accomplished in 10 patients (56%). Seven of these lesions were successfully treated during the initial session, and thrombosis was accomplished after repeat compression in three additional lesions. Three patients who were given anticoagulants had a failed UGCR, but their pseudoaneurysms thrombosed after administration of anticoagulants was discontinued. Two patients had failed UGCR and required operation. Seven (88%) of eight patients who were not given anticoagulants were successfully treated. In contrast only two (29%) of seven patients given therapeutic doses of anticoagulant medication were successfully treated by the technique. There was no statistical difference between mean pseudoaneurysm diameter, mean width and length of pseudoaneurysm neck, or depth of pseudoaneurysm neck from skin surface in patients in whom successful initial closure was achieved when compared with those patients in whom the initial attempt failed. UGCR is a safe, simple, noninvasive technique that can be used to treat many femoral artery injuries that traditionally were treated with surgery. The technique can be applied by any laboratory that has the necessary ultrasonography equipment and is currently the method of choice for treating uncomplicated iatrogenic femoral artery injuries at our institution.