Mechanical determinants of graft kinking.

Vascular grafts can be twisted inadvertently during implantation. If twisted excessively, they may kink and obstruct flow. In this study, in vitro experiments were performed to identify the mechanical factors that determine graft kinking. These included graft material, graft length, graft diameter, graft wall thickness, perfusion pressure, and flow rate. Six-millimeter-diameter saphenous veins were obtained from humans at autopsy. Six-millimeter standard-wall and 6-mm thin-wall polytetrafluoroethylene (PTFE) grafts also were obtained. Both fixed-length and stretchable PTFE grafts were examined. Grafts 15, 30, 50, and 70 cm in length were evaluated. Finally, PTFE grafts 4, 6, 8, 10, 12, and 14 mm in diameter were studied to determine the effect of diameter. The vessels were mounted horizontally in vitro and were perfused with saline at 50, 100, or 150 mmHg pressure at low (49 mL/min), medium (105 mL/min), and high (239 mL/min) flow rates. Each graft was twisted 90 degrees, then subjected to perfusion for 15 sec. Pressure and flow were interrupted, and an additional 90 degrees twist was imposed for another 15 sec. This sequence was repeated until a visible kink developed. We conclude from our results that, when constructing a bypass, particular care should be taken with vein, short grafts, thin-wall grafts, and large-diameter grafts, as these are especially susceptible to kinking.

Sustained expression of high levels of human factor IX from human cells implanted within an immunoisolation device into athymic rodents.

Immunoisolation of allogeneic cells within a membrane-bound device is a unique approach for gene therapy. We employed an immunoisolation device that protects allograft, but not xenograft, cells from destruction, to implant a human fibroblast line (MSU 1.2) in athymic rodents. Cells, transduced with the MFG-human factor IX retroviral vector, and expressing 0.9 microg/10(6) cells/day in vitro, were implanted in rats (four 40-microl devices, each containing 2 x 10(7) cells, two subcutaneously, two in epididymal fat) and in mice (two 20-microl devices, each containing 2 x 10(6) cells, subcutaneously). Plasma factor IX levels increased for 50 days, reaching maxima of 203 ng/ml (rat) and 597 ng/ml (mouse), and both continued at greater than 100 ng/ml for more than 140 days. A clone derived from the transduced cells, making 5 microg of factor IX/10(6) cells/day, was implanted within a device (one 20-microl device containing 2.5 x 10(6) cells), or without a device (1 x 10(7) cells implanted freely), either subcutaneously or in epididymal fat. The freely implanted cells expressed transiently, reaching more than 100 ng/ml in each site by day 4, but dropped to zero by day 20 (subcutaneous) or day 90 (epididymal fat). In devices, levels gradually increased to 100 ng/ml (subcutaneous) or 300 ng/ml (epididymal fat), remaining high for more than 100 days. These results show long-term, high-level expression of a human protein: (1) when cells are implanted within a cell transplantation device, but not when the cells are freely implanted, and (2) from a transgene driven by a viral promoter. An alloprotective device will enable the use of cloned cell lines that can be subjected to stringent quality control assessment that is impossible to achieve with autologous approaches.

Selective use of the intensive care unit following carotid endarterectomy.

The purpose of this study was to develop criteria by which selected patients can be observed solely on the ward following carotid endarterectomy (CEA). One hundred consecutive CEA patients were retrospectively reviewed. Preoperative medical conditions were identified, and the postanesthesia recovery room course was reviewed in an attempt to predict the need for intensive care unit (ICU) level care. Forty-four of our 100 patients developed perioperative complications or conditions that required some intervention. Conditions included hypertension in 23, hypotension in nine, arrhythmias in six, and myocardial ischemia in two. Complications included nonfatal cerebrovascular accident (CVA) in one, fatal CVA in one, and postoperative bleeding in two. Sixteen patients required ICU level intervention (hypertension in five, hypotension in five, arrhythmias in two, nonfatal CVA in one, fatal CVA in one, and postoperative bleeding in two. Fifteen of the 16 were identified in the recovery room. Fifty-three patients had a medical history of significant hypertension (42), cardiac disease (27), and/or recent CVA (seven). Thirty-six (68%) of these patients required perioperative intervention in some form; 12 (23%) required ICU level therapy. Eight of 47 (17%) patients without a significant medical history required intervention; only four (9%) required ICU level care. All eight patients were identified in recovery. Only 16 of 100 CEA patients required ICU level care. Fifteen of 16 were identified in recovery. Certain patients identified in the recovery room can be followed safely in a less intense and costly setting.