Heritable anisotropy associated with cognitive impairments among patients with schizophrenia and their non-psychotic relatives in multiplex families.

BACKGROUND: To test the functional implications of impaired white matter (WM) connectivity among patients with schizophrenia and their relatives, we examined the heritability of fractional anisotropy (FA) measured on diffusion tensor imaging data acquired in Pittsburgh and Philadelphia, and its association with cognitive performance in a unique sample of 175 multigenerational non-psychotic relatives of 23 multiplex schizophrenia families and 240 unrelated controls (total = 438). METHODS: We examined polygenic inheritance (h2r) of FA in 24 WM tracts bilaterally, and also pleiotropy to test whether heritability of FA in multiple WM tracts is secondary to genetic correlation among tracts using the Sequential Oligogenic Linkage Analysis Routines. Partial correlation tests examined the correlation of FA with performance on eight cognitive domains on the Penn Computerized Neurocognitive Battery, controlling for age, sex, site and mother's education, followed by multiple comparison corrections. RESULTS: Significant total additive genetic heritability of FA was observed in all three-categories of WM tracts (association, commissural and projection fibers), in total 33/48 tracts. There were significant genetic correlations in 40% of tracts. Diagnostic group main effects were observed only in tracts with significantly heritable FA. Correlation of FA with neurocognitive impairments was observed mainly in heritable tracts. CONCLUSIONS: Our data show significant heritability of all three-types of tracts among relatives of schizophrenia. Significant heritability of FA of multiple tracts was not entirely due to genetic correlations among the tracts. Diagnostic group main effect and correlation with neurocognitive performance were mainly restricted to tracts with heritable FA suggesting shared genetic effects on these traits.

Contemporary management of aortic branch compromise resulting from acute aortic dissection.

PURPOSE: In an earlier report, we documented the incidence and impact of aortic branch compromise complicating acute aortic dissection (AD) over a 21-year interval (1965-1986). In the current study, management of peripheral vascular complications (PVCs) of AD over the past decade was reviewed. METHODS: Medical records of patients treated for AD over the interval January 1, 1990, to December 31, 1999, were reviewed. Patients with branch compromise confirmed with radiography or operation and patients with spinal cord ischemia that was based on results of a physical examination defined the study group. Comparisons between subgroups with and without PVC over a 30-year interval were analyzed with the chi(2) test. RESULTS: A total of 187 patients (101 proximal and 86 distal) were treated for AD over the study interval. A total of 53 (28%) of these patients had clinical evidence of organ or limb malperfusion (7 cerebral, 3 upper extremity, 5 spinal cord, 11 mesenteric, 12 renal, and 24 lower extremity [sites inclusive]), and one of three (17 patients) of these underwent specific peripheral vascular intervention. The remaining 65% (36) of the PVC group had complete or partial malperfusion resolution after central aortic therapy (medical or surgical) alone. Open techniques for treating PVC included aortic fenestration (9), femorofemoral grafting (2), and aortofemoral grafting (1). All had favorable outcomes with no mortality. Endovascular procedures in five patients included abdominal aortic fenestration (3) or stenting of the renal (2), mesenteric (2), and iliac (1) arteries with clinical success in three patients and two deaths. The in-hospital mortality rate for the entire group of 187 patients was 18% (15% for proximal aortic operation, 8% in medically treated patients). The presence of aortic branch compromise was not a statistically significant predictor of the patient mortality rate (23% with and 16% without; P =.26). Overall mortality rate in the current study (18% vs 37%; P =.000006) and the mortality rate with PVC (23% vs 51%; P =.001), in particular with mesenteric ischemia (36% vs 87%; P =.026), decreased significantly when compared with prior experience. CONCLUSIONS: The overall mortality rate from AD during the past decade has decreased significantly. Similar trends were noted in patients with PVCs, a previously identified high-risk subgroup. Increased awareness and prompt, specific management of PVCs, in particular when visceral ischemia is present, have contributed to improved outcomes in patients with AD.

The effect of combined arterial hemodynamics on saphenous venous endothelial nitric oxide production.

INTRODUCTION: Evidence exists that an ideal bypass conduit should have a functional endothelial cell surface combined with mechanical properties similar to those of native arteries. We hypothesized that the effect of combined arterial levels of pulsatile shear stress, flow, and cyclic strain would enhance saphenous venous endothelial cell nitric oxide (NO) production, and that variations in these "ideal" conditions could impair this function. We studied NO production as a measure of endothelial function in response to different hemodynamic conditions. METHODS: Human adult saphenous venous endothelial cells were cultured in 10-cm silicone tubes, similar in diameter (5 mm) and compliance (6%) to a medium-caliber peripheral artery (eg, popliteal). Tube cultures were exposed to arterial conditions: a combined pressure (120/80 mm/Hg; mean, 100 mm/Hg), flow (mean, 115 mL/min) and cyclic strain (2%), with a resultant pulsatile shear stress of 4.8 to 9.4 dyne/cm2 (mean, 7.1). Identical tube cultures were used to study variations in these conditions. Modifications of the system included a noncompliant system, a model with nonpulsatile flow, and a final group exposed to pulsatile pressure with no flow. NO levels were measured with a fluorometric nitrite assay of conditioned media collected at 0, 0.25, 0.5, 1, 2, and 4 hours. Experimental groups were compared with cells exposed to nonpulsatile, nonpressurized low flow (shear stress 0.1 dyne/cm2) and static cultures. RESULTS: All experimental groups had greater rates of NO production than cells under static conditions (P <.05). Cells exposed to ideal conditions produced the greatest levels of NO. Independent decreases in compliance, flow, and pulsatility resulted in significantly lower rates of NO production than those in the group with these conditions intact (vs noncompliant P <.05, vs nonflow P <.05, and vs nonpulsatile P <.05). CONCLUSIONS: Our results show that in the absence of physiologically normal pulsatility, cyclic strain, and volume flow, endothelial NO production does not reach the levels seen under ideal conditions. Pulsatile flow and compliance (producing flow with cyclic stretch) play a key role in NO production by vascular endothelium in a three-dimensional hemodynamically active model. This correlates biologically with clinical experience linking graft inflow and runoff and the mechanical properties of the conduit to long-term patency.

An in vitro cell culture system to study the influence of external pneumatic compression on endothelial function.

PURPOSE: External pneumatic compression (EPC) is an effective means of prophylaxis against deep venous thrombosis. However, its mechanism remains poorly understood. Understanding of the biological consequences of EPC is an important goal for optimizing performance of the EPC-generating device and providing guidance for clinical use. We present a new in vitro cell culture system (Venous Flow Simulator) that simulates blood flow and vessel collapse conditions during EPC, and we examine the influence of these factors on endothelial cell (EC) fibrinolytic activity and vasomotor function. METHODS: An in vitro cell culture system was designed to replicate the hemodynamic shear stress and vessel wall strain associated with induced blood flow during different modes of EPC. Human umbilical vein endothelial cells were cultured in the system and subjected to intermittent flow, vessel collapse, or a combination of the two. The biologic response was assessed through changes in EC morphology and the expression of fibrinolytic factors tissue plasminogen activator, plasminogen activator inhibitor type 1, profibrinolytic receptor (annexin II), and vasomotor factors endothelial nitric oxide synthase and endothelin-1. RESULTS: The cells remained attached and viable after being subjected to intermittent pulsatile flow (F) and tube compression (C). In F and F + C, cells aligned in the direction of flow after 6 hours. Northern blot analysis of messenger RNA shows that there is an upregulation of tissue plasminogen activator expression (1.95 +/- 0.19 in F and 2.45 +/- 0.46 in FC) and endothelial nitric oxide synthase expression (2.08 +/- 0.25 in F and 2.11 +/- 0.21 in FC). Plasminogen activator inhibitor type 1, annexin II, and endothelin 1 show no significant change under any experimental conditions. The results also show that pulsatile flow, more than vessel compression, influences EC morphology and function. CONCLUSION: Effects on ECs of intermittent flow and vessel collapse, either individually or simultaneously, were simulated with an in vitro system of new design. Initial results show that intermittent flow associated with EPC upregulates EC fibrinolytic potential and influences factors altering vasomotor tone. The system will facilitate future studies of EC function during EPC.

Clinical outcome of internal iliac artery occlusions during endovascular treatment of aortoiliac aneurysmal diseases.

PURPOSE: To determine the clinical outcome of hypogastric artery occlusion in patients who underwent endovascular treatment of aortoiliac aneurysmal disease. MATERIAL AND METHODS: From January 1994 to March 1998, 94 patients underwent endovascular treatment of aneurysmal diseases involving the infra-abdominal aorta or iliac arteries. Preoperative and intraoperative radiologic data were reviewed. Discharge summaries, clinic visits, and phone calls formed the basis for clinical follow-up, with a mean follow-up period of 7.3 months (range, 1-24 months). RESULTS: Because of the anatomy of the aneurysms, 28 patients required occlusion of one or more hypogastric arteries. One of the 28 patients died of unrelated causes before follow-up. Seven (26%) of the remaining 27 patients developed symptoms attributable to the hypogastric artery occlusions. Five patients developed new buttock or thigh claudication; of these five patients, three with initially mild symptoms noted complete or near complete resolution of symptoms upon follow-up. One patient with originally significant claudication at 2-year follow-up noted near resolution of symptoms. The other patient with severe pain did not improve significantly on final 1-year follow-up before his death (of unrelated causes). Other clinical complications were worsening sexual function in one patient and a nonhealing sacral decubitus ulcer that developed in a debilitated patient in the postoperative setting, which required surgery. No bowel ischemia was observed. CONCLUSION: When treating aortoiliac aneurysmal disease through an endovascular approach, the occlusion of internal iliac artery is often necessary but carries with it a small but finite chance of morbidity.

Utility and reliability of endovascular aortouniiliac with femorofemoral crossover graft for aortoiliac aneurysmal disease.

OBJECTIVE: The purpose of this study was to determine the early efficacy of endovascular aortouniiliac stent grafts with femorofemoral bypass graft in the treatment of aortoiliac aneurysmal disease. METHODS: We analyzed 51 consecutive patients from January 1997 to March 1999 with a mean follow-up of 15.8 months. Patients ranged in age from 44 to 93 years (mean, 75 years) with a mean aortic aneurysm diameter of 6.2 cm. Technical success was achieved in 50 patients; one patient required conversion to open repair intraoperatively. We placed 28 custom-made and 22 commercial devices. The mean operative time was 223 minutes. The endograft was extended to the external iliac artery in 42% of cases. The contralateral common iliac artery was occluded using either a closed covered stent or intraluminal coils. RESULTS: The median hospital stay was 4 days with an average intensive care unit stay of 0.25 days. There were no operative mortalities. Two patients died during follow-up from unrelated conditions. Endoleaks occurred in 11 patients (22%); seven patients (14%) required intervention (four catheter based, three operative). Other complications occurred in 38% of patients but were largely remote or wound related. One femorofemoral bypass graft occluded immediately postoperatively as a result of an intraprocedural external iliac dissection yielding a 98% primary patency and 100% secondary patency. Clinical success was achieved in 88% of patients. CONCLUSIONS: These data suggest that this strategy represents a reliable method of repair of aortoiliac aneurysmal disease and extends the capability of an endoluminal approach to patients with complex iliac anatomy.

The response of adult human saphenous vein endothelial cells to combined pressurized pulsatile flow and cyclic strain, in vitro.

Adult human saphenous vein endothelial cells (HVEC) were cultured in a compliant tubular device and evaluated by Northern hybridization for the effects of combined pressurized pulsatile flow and cyclic strain on the expression of mRNAs for endothelin-1 (ET-1), endothelial cell nitric oxide synthase (ecNOS), tissue plasminogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1). The hemodynamic environment was designed to mimic shear stress conditions at the distal anastomosis of a saphenous vein graft, a common site of intimal proliferation. Steady-state mRNA levels in experimental tubes were expressed relative to that in controls. No changes were observed in ET-1 mRNA after 1 and 24 hr, but a 50% decrease in experimental cultures was observed after 48 hr in the vascular simulating device. Similar results were obtained for ecNOS mRNA, although a subgroup (4 of 11) showed a significant decrease (>50%) by 24 hr. For tPA mRNA, no change was observed after 1 hr, but a significant decrease (>60%) was measured after 24 hr and no message was detectable after 48 hr. Steady-state levels for PAI-1 mRNA remained unchanged through 48 hr of treatment. These results show that pressure, pulsatile flow, and cyclic strain, when applied in concert, differentially alter vasoactive and fibrinolytic functions in HVEC. Moreover, the dramatic decrease in steady-state levels of tPA mRNA is consistent with a shift toward an increased thrombotic state.

Surgical renal artery reconstruction without contrast arteriography: the role of clinical profiling and magnetic resonance angiography.

PURPOSE: Contrast arteriography is the accepted gold standard for diagnosis and treatment planning in patients with atherosclerotic renovascular disease (RVD). In this study, the results of a selective policy of surgical renal artery reconstruction (RAR) with magnetic resonance angiography (MRA) as the sole preoperative imaging modality are reviewed. METHODS: From May 1993 to May 1998, 25 patients underwent RAR after clinical evaluation, and aortic/renal MRA performed with a gadolinium-enhanced and 3-dimensional phase contrast technique. Clinical presentations suggested severe RVD in all patients and included poorly controlled hypertension (16 patients), hospitalization for hypertensive crises and/or acute pulmonary edema (13), and deterioration of renal function within one year of operation (15). Thirteen patients had associated aortic pathologic conditions (12 aneurysms, 1 aortoiliac occlusive disease), and eight of these patients also underwent noncontrast computed tomography scans. Significant renal dysfunction (serum creatinine level, >/=2.0 mg/dL) was present in all but 4 patients with 14 of 25 patients having extreme (creatinine level, >/=3.0 mg/dL) dysfunction. RESULTS: Hemodynamically significant RVD in the main renal artery was verified at operation in 37 of 38 reconstructed main renal arteries (24/25 patients). A single accessory renal artery was missed by MRA. RAR was comprehensive (bilateral or unilateral to a single-functioning kidney) in 21 of 25 patients and consisted of hepatorenal bypass graft (3 patients), combined aortic and RAR (13 patients), isolated transaortic endarterectomy (8 patients), and aortorenal bypass graft (1 patient). Early improvement in both hypertension control and/or renal function was noted in 21 of 25 patients without operative deaths or postoperative renal failure. Sustained favorable functional results at follow-up, ranging from 5 months to 4 years, were noted in 19 of 25 patients. CONCLUSION: MRA is an adequate preoperative imaging modality in selected patients before RAR. This strategy is best applied in circumstances where the clinical presentation suggests hemodynamically significant bilateral RVD and/or in patients at substantial risk of complications from contrast angiography.

The effects of external compression on venous blood flow and tissue deformation in the lower leg.

External pneumatic compression of the lower legs is effective as prophylaxis against deep vein thrombosis. In a typical application, inflatable cuffs are wrapped around the patient's legs and periodically inflated to prevent stasis, accelerate venous blood flow, and enhance fibrinolysis. The purpose of this study was to examine the stress distribution within the tissues, and the corresponding venous blood flow and intravascular shear stress with different external compression modalities. A two-dimensional finite element analysis (FEA) was used to determine venous collapse as a function of internal (venous) pressure and the magnitude and spatial distribution of external (surface) pressure. Using the one-dimensional equations governing flow in a collapsible tube and the relations for venous collapse from the FEA, blood flow resulting from external compression was simulated. Tests were conducted to compare circumferentially symmetric (C) and asymmetric (A) compression and to examine distributions of pressure along the limb. Results show that A compression produces greater vessel collapse and generates larger blood flow velocities and shear stresses than C compression. The differences between axially uniform and graded-sequential compression are less marked than previously found, with uniform compression providing slightly greater peak flow velocities and shear stresses. The major advantage of graded-sequential compression is found at midcalf. Strains at the lumenal border are approximately 20 percent at an external pressure of 50 mmHg (6650 Pa) with all compression modalities.

Quality assessment and vascular disease: the analytic imperatives confronting vascular surgeons in the new era.

Vascular Surgery is poised at the edge of a rare moment in medical care. Energy, intelligence, innovation, and resources are available to improve greatly the methods of vascular disease correction. Precedent exists for the overzealous application of technologies. Poor study design and inadequate tracking of outcomes can dilute the value, discredit a critical therapy, and undermine proper patient selection. The proper analysis of our new technologies will be obtained only through well-organized studies, information systems, and informed organizational oversight. Our analysis must extend beyond procedure-specific outcomes to include quality of life issues measured in a validated and relevant fashion. The present and future of vascular disease therapeutics must reside under the control of those who have devoted their lives to its theory and practice.

Initial experience with endovascular aneurysm repair: comparison of early results with outcome of conventional open repair.

PURPOSE: To determine the safety, effectiveness, and problems encountered with endovascular repair of abdominal aortic aneurysm (AAA). Initial experience with endoluminal stent grafts was examined and compared with outcome for a matched concurrent control group undergoing conventional operative repair of AAA. METHODS: Over a 3-year period, 30 patients underwent attempts at endovascular repair of infrarenal AAA. Of the 28 (93%) successfully implanted endografts, 8 were tube endografts, 8 bifurcated grafts, and 12 aortouniiliac grafts combined with femorofemoral bypass. Most of the procedures were performed in the past year because the availability of bifurcated and aortoiliac endografts markedly expanded the percentage of patients with AAA who might be treated with endoluminal methods. The follow-up period ranged from 1 to 44 months, with a mean value of 11 months. RESULTS: Endovascular procedures demonstrated significant advantages with respect to reduced blood loss (408 versus 1287 ml), use of an intensive care unit (0.1 versus 1.75 days), length of hospitalization (3.9 versus 10.3 days), and quicker recovery (11 versus 47 days). Although the total number of postoperative complications was identical for the two groups, the nature of the complications differed considerably. Local and vascular complications characteristic of endovascular repair could frequently be corrected at the time of the procedure and tended to be less severe than systemic or remote complications, which predominated among the open surgical repair group. On an intent-to-treat basis, 23 (77%) of the 30 AAAs were successfully managed with endoluminal repair. The seven (23%) failures were attributable to two immediate conversions caused by access problems, three persistent endoleaks, one late conversion caused by AAA expansion, and one late rupture. CONCLUSIONS: Although less definitive than those for conventional operations, these early results suggest that endovascular AAA repair offers considerable benefits for appropriate patients. The results justify continued application of this method of AAA repair, particularly in the treatment of older persons at high risk.

Telemedicine in vascular surgery: feasibility of digital imaging for remote management of wounds.

PURPOSE: Telemedicine coupled with digital photography could potentially improve the quality of outpatient wound care and decrease medical cost by allowing home care nurses to electronically transmit images of patients' wounds to treating surgeons. To determine the feasibility of this technology, we compared bedside wound examination by onsite surgeons with viewing digital images of wounds by remote surgeons. METHODS: Over 6 weeks, 38 wounds in 24 inpatients were photographed with a Kodak DC50 digital camera (resolution 756 x 504 pixels/in2). Agreements regarding wound description (edema, erythema, cellulitis, necrosis, gangrene, ischemia, and granulation) and wound management (presence of healing problems, need for emergent evaluation, need for antibiotics, and need for hospitalization) were calculated among onsite surgeons and between onsite and remote surgeons. Sensitivity and specificity of remote wound diagnosis compared with bedside examination were calculated. Potential correlates of agreement, level of surgical training, certainty of diagnosis, and wound type were evaluated by multivariate analysis. RESULTS: Agreement between onsite and remote surgeons (66% to 95% for wound description and 64% to 95% for wound management) matched agreement among onsite surgeons (64% to 85% for wound description and 63% to 91% for wound management). Moreover, when onsite agreement was low (i.e., 64% for erythema) agreement between onsite and remote surgeons was similarly low (i.e., 66% for erythema). Sensitivity of remote diagnosis ranged from 78% (gangrene) to 98% (presence of wound healing problem), whereas specificity ranged from 27% (erythema) to 100% (ischemia). Agreement was influenced by wound type (p < 0.01) but not by certainty of diagnosis (p > 0.01) or level of surgical training (p > 0.01). CONCLUSIONS: Wound evaluation on the basis of viewing digital images is comparable with standard wound examination and renders similar diagnoses and treatment in the majority of cases. Digital imaging for remote wound management is feasible and holds significant promise for improving outpatient vascular wound care.

Mesenteric shunting decreases visceral ischemia during thoracoabdominal aneurysm repair.

PURPOSE: A technique to decrease visceral ischemic time during thoracoabdominal aneurysm (TAA) repair is reported. METHODS: A 10 mm Dacron side-arm graft is attached to the aortic prosthesis and positioned immediately distal to the planned proximal thoracic aortic anastomosis. On completion of the anastomosis, a 16 to 22 Fr perfusion catheter is attached to the side-arm graft and inserted into the orifice of the celiac axis or superior mesenteric artery. The cross-clamp is then placed on the aortic graft distal to the mesenteric side-arm graft. Pulsatile arterial perfusion is thus established to the visceral circulation while intercostal anastomoses or reconstruction of celiac, superior mesenteric, and right renal arteries is performed. Visceral ischemic time and the rise in end-tidal Pco2 after reconstruction of the visceral vessels in patients with mesenteric shunting was compared with a control group matched for aneurysm extent and treated immediately before use of the mesenteric shunt technique. RESULTS: Between July and Oct, 1996, the technique was applied in 15 patients undergoing type I, II, or III TAA repair with a clamp and sew technique. The mean decrease in systolic arterial pressure was 12.5 +/- 8.5 mm Hg, with a concomitant rise in end-tidal Pco2 (mean, 6.9 +/- 5.8 mm Hg), after perfusion was established through the mesenteric shunt. Mean time to establishment of visceral perfusion through the shunt was 25.5 +/- 4.4 minutes; the resultant decrement in visceral ischemic time averaged 31.3 minutes (i.e., until celiac, superior mesenteric, and right renal arteries were reconstructed). Compared with controls, patients with shunts had a significantly decreased (6.9 +/- 5.8 versus 21.6 +/- 8.4 mm Hg; p = 0.0003) rise in end-tidal CO2 on completion of visceral vessel reconstruction. CONCLUSIONS: In-line mesenteric shunting is a simple method to decrease visceral ischemia during TAA repair, and it is adaptable to clamp and sew or partial bypass and distal perfusion operative techniques.

Clinical experience with epidural cooling for spinal cord protection during thoracic and thoracoabdominal aneurysm repair.

PURPOSE: This report summarizes our experience with epidural cooling (EC) to achieve regional spinal cord hypothermia and thereby decrease the risk of spinal cord ischemic injury during the course of descending thoracic aneurysm (TA) and thoracoabdominal aneurysm (TAA) repair. METHODS: During the interval July 1993 to Dec. 1995, 70 patients underwent TA (n = 9, 13%) or TAA (n = 61) (type I, 24 [34%], type II, 11 [15%], type III, 26 [37%]) repair using the EC technique. The latter was accomplished by continuous infusion of normal saline (4 degrees C) into a T11-12 epidural catheter; an intrathecal catheter was placed at the L3-4 level for monitoring of cerebrospinal fluid temperature (CSFT) and pressure (CSFP). All operations (one exception, atriofemoral bypass) were performed with the clamp-and-sew technique, and 50% of patients had preservation of intercostal vessels at proximal or distal anastomoses (30%) or by separate inclusion button (20%). Neurologic outcome was compared with a published predictive model for the incidence of neurologic deficits after TAA repair and with a matched (Type IV excluded) consecutive, control group (n = 55) who underwent TAA repair in the period 1990 to 1993 before use of EC. RESULTS: EC was successful in all patients, with a 1442 +/- 718 ml mean (range, 200 to 3500 ml) volume of infusate; CSFT was reduced to a mean of 24 degrees +/- 3 degrees C during aortic cross-clamping with maintenance of core temperature of 34 degrees +/- 0.8 +/- C. Mean CSFP increased from baseline values of 13 +/- 8 mm Hg to 31 +/- 6 mm Hg during cross-clamp. Seven patients (10%) died within 60 days of surgery, but all survived long enough for evaluation of neurologic deficits. The EC group and control group were well-matched with respect to mean age, incidence of acute presentations/aortic dissection/aneurysm rupture, TAA type distribution, and aortic cross-clamp times. Two lower extremity neurologic deficits (2.9%) were observed in the EC patients and 13 (23%) in the control group (p < 0.0001). Observed and predicted deficits in the EC patients were 2.9% and 20.0% (p = 0.001), and for the control group 23% and 17.8% (p = 0.48). In considering EC and control patients (n = 115), variables associated with postoperative neurologic deficit were prolonged (> 60 min) visceral aortic cross-clamp time (relative risk, 4.4; 95% CI, 1.2 to 16.5; p = 0.02) and lack of epidural cooling (relative risk, 9.8; 95% CI, 2 to 48; p = 0.005). CONCLUSION: EC is a safe and effective technique to increase the ischemic tolerance of the spinal cord during TA or TAA repair. When used in conjunction with a clamp-and-sew technique and a strategy of selective intercostal reanastomosis, EC has significantly reduced the incidence of neurologic deficits after TAA repair.

Magnetic resonance angiography in the management of lower extremity arterial occlusive disease: a prospective study.

PURPOSE: We conducted a prospective study to clarify the clinical utility of magnetic resonance angiography (MRA) in the treatment of patients with lower extremity arterial occlusive disease. METHODS: During the interval of September 1993 through March 1995, 79 patients (43% claudicants, 57% limb-threatening ischemia) were studied with both MRA and contrast arteriography (ANGIO) and underwent intervention with either balloon angioplasty (9%), surgical inflow (28%), or outflow (63%) procedures. MRA and ANGIO were interpreted by separate blinded vascular radiologists, and arterial segments from the pelvis to the foot were graded as normal or with increasing degrees of mild (25% to 50%), moderate (51% to 75%), or severe (75% to 99%) stenosis or occlusion. Treatment plans were formulated by the attending surgeon and were based initially on hemodynamic, clinical, and MRA data and thereafter with ANGIO. Additional study surgeons formulated independent and specific treatment plans based on MRA or ANGIO alone. Indexes of agreement (beyond chance) for arterial segments depicted by MRA and ANGIO were assessed (kappa value), and treatment plans formulated were compared (chi-square). RESULTS: Precise agreement (%) and the percent of major discrepancies (segment classified as normal/mild stenosis on one study and severe stenosis/occlusion on the other) between MRA and ANGIO for respective arterial segments was as follows: common and external iliacs (n = 256) 77/3.5; superficial femoral and above-knee popliteal (n = 255) 73/6.7; below-knee popliteal (n = 131) 84/3.8; infrapopliteal runoff vessels (n = 864) 74/12.4; pedal vessels (n = 111) 69/19.8 Kappa values indicated moderate agreement (between MRA and ANGIO) beyond chance for all arterial segments. Treatment plans formulated by the attending surgeon, the MRA surgeon, and the ANGIO surgeon agreed in more than 85% of cases. Inability of MRA to assess the significance of inflow disease and inadequate detail of tibial/pedal vessels were the principal deficiencies of MRA in those cases where it was considered an inadequate examination. CONCLUSION: These findings suggest MRA and ANGIO are nearly equivalent examinations in the demonstration of infrainguinal vascular anatomy. MRA is an adequate preoperative imaging study (and may replace ANGIO), particularly in those circumstances when the risk of ANGIO is increased or when clinical and hemodynamic evaluation predict the likelihood of straightforward aortofemoral or femoral-popliteal reconstruction.

Coagulation changes during thoracoabdominal aneurysm repair.

PURPOSE: The cause of coagulopathic hemorrhage during thoracoabdominal aneurysm (TAA) repair has not been well defined in human studies. We investigated changes in the coagulation system associated with supraceliac versus infrarenal cross-clamping to address this critical issue. METHODS: Blood levels of fibrinogen, the prothrombin fragment F1.2, D-dimer, and factors II, V, VII, VIII, IX, X, XI, and XII were analyzed in 19 patients with TAAs and four patients with abdominal aortic aneurysms (AAAs) at: (A) induction; (B) 30 minutes into supraceliac (TAA) or infrarenal (AAA) clamping; (C) 30 minutes after release of supraceliac or infrarenal clamps; and (D) immediately after surgery. Preoperative and intraoperative variables, including but not limited to aneurysm type, pathologic findings, comorbid conditions, clamp times, volume and timing of blood products, and clinical outcome, were prospectively recorded. Significance was determined by analysis of variance, Student's t test, and univariate linear regression. RESULTS: Levels of fibrinogen and factors II, V, VIII, VIII, IX, X, XI, and XII decreased (p < 0.05) at time B versus time A and returned to near baseline by time D. D-dimer and F1.2 increased starting at time B and reached significance (p < 0.05) by time D. Data points were compared for the TAA and AAA groups. Although AAA groups demonstrated a trend to factor activity reduction and increased fibrinolysis, the effect was much less pronounced than in TAA and did not approach significance. No correlation of coagulation change with clamping time was present; however, visceral clamping times were all less than 65 minutes (mean, 44 minutes). Blood and factor replacement was initiated after time B. Univariate regression analysis of factor level versus total blood replacement demonstrated a significant (p < 0.04) correlation between the reduction in the levels of factors II, V, VII, VIII, X, and XII, and the increase in the level of D-dimer at time B and subsequent total blood replacement. CONCLUSIONS: Thoracoabdominal aneurysm repair is associated with a reduction in clotting factor activity and an increase in fibrinolytic function, which occurs after placement of the supraceliac clamp. Explanations include visceral ischemia or a greater and longer ischemic tissue burden as the likely cause of coagulation alterations. Total blood replacement during TAA procedures was correlated to the degree of factor reduction and fibrinolysis at the time of visceral cross-clamping. An aggressive approach to early blood component replacement and to coagulation monitoring could lessen blood loss during TAA repair and avoid potentially disastrous bleeding complications.

Diagnosis and treatment of thoracic aortic intramural hematoma.

PURPOSE: This report reviews our recent experience with nine patients who had intramural hematoma of the thoracic aorta. METHODS: This was a retrospective study of all patients who had intramural hematoma at our institution from 1989 to 1994. Patients who had identifiable intimal flap, tear, or penetrating aortic ulcer were excluded from the study. RESULTS: Among these nine elderly patients (mean age, 76 years), the most common presentation was chest or back pain. Intramural hematoma was diagnosed by a variety of high-resolution imaging techniques. The descending thoracic aorta alone was involved in seven patients, whereas the ascending aorta was affected in the other two patients. One patient had evidence of an aneurysm (5.0 cm diameter) in the region of the hematoma. All patients were initially managed nonsurgically with blood pressure control. Both patients who had ascending aortic involvement had progression of aortic hematoma, which resulted in death in one case and in successful surgery in the other. Six of the seven patients who had descending aortic involvement alone were successfully managed without aortic surgery. The patient who had intramural hematoma and associated aortic aneurysm, however, had severe, recurrent pain and underwent successful aortic replacement. Another patient had recurrent pain associated with hypertension, but was successfully managed nonsurgically with antihypertensive therapy. All eight survivors are doing well at a median follow-up of 19 months. CONCLUSIONS: Intramural hematoma appears to be a distinct entity, although overlap with aortic dissection or penetrating aortic ulcer exists. Aggressive control of blood pressure with intensive care unit monitoring has been our initial management. Patients who have involvement of the descending thoracic aorta alone can frequently be managed without surgery in the absence of coexisting aneurysmal dilatation or disease progression. Our experience suggests that a more aggressive approach with early surgery is warranted in patients who have ascending aortic involvement or those who have coexisting aneurysm and intramural hematoma.

Characteristics of vascular wall cells subjected to dynamic cyclic strain and fluid shear conditions in vitro.

We recently developed an in vitro silicone rubber tubular apparatus, the vascular simulating device (VSD), which simulates pressure, flow, and strain characteristics of peripheral arteries (Benbrahim et al., 1994, J. Vasc. Surg. 20, 184-194). In this report, we tested the ability of silicone rubber surfaces to support the growth and differentiation of endothelial cells (EC) and smooth muscle cells (SMC) and studied the effects of arterial levels of pressure, flow, and strain on these properties. Human umbilical and saphenous vein EC and bovine aortic EC and SMC were cultured on coated and uncoated silicone rubber in flat and tubular configurations (6 mm inner diameter) and on tissue culture plastic (TCP). Attachment, growth, and differentiation were compared on these surfaces. In addition, the effects of arterial pressure, flow, and strain conditions on adhesion and subsequent growth and differentiation were studied in the tubular configuration. Attachment and growth of vascular wall cells on fibronectin-coated silicone rubber was similar to that obtained on TCP. Application of arterial levels of pressure, flow, and strain did not alter adhesion of the cells to the tubes. Subsequent passage of these cells demonstrated that attachment, growth, and differentiation (uptake of LDL and expression of factor VIII-related antigen by EC and expression of muscle-specific actin by SMC) were similar in cells derived from experimental and control tubes which were not subjected to arterial conditions. Finally, mRNA expression of specific "housekeeping" genes was similar in cells isolated from experimental and control tubes. We conclude that the VSD supports the culture of viable and differentiated EC and SMC. These experiments demonstrate that it is possible to evaluate the effects of arterial strain and fluid shear on vascular wall cells in vitro, in a configuration similar to the blood vessel wall.

Renal artery reconstruction for the preservation of renal function.

PURPOSE: We reviewed a 13-year experience with an emphasis on long-term survival and renal function response when renal artery reconstruction (RAR) was performed primarily for the preservation or restoration of renal function in patients who had atherosclerotic renovascular disease. METHODS: From January 1, 1980, to June 30, 1993, 139 patients underwent RAR for renal function salvage and were retrospectively reviewed. Inclusion criteria were either preoperative serum creatinine level > 2.0 mg/dl (67% of patients) or RAR to the entire functioning renal mass irrespective of baseline renal function. Patient survival was calculated by life-table methods. Cox regression analysis was used to determine relative risk (RR) estimates for the late outcomes of continued deterioration of renal function and late survival after RAR. A logistic regression model was used to evaluate variables associated with perioperative complications. RESULTS: Clinical characteristics of the cohort were notable for advanced cardiac (history of congestive heart failure, 27%; angina, 22%; previous myocardial infarction, 19%) and renal disease (serum creatinine level < 2.0 mg/dl, 33%; 2.0 mg/dl to 3.0 mg/dl, 40%, > 3.0 mg/dl, 27%). Cardiac disease was the principle cause of early (6 of 11 operative deaths) and late death. Operative management consisted of aortorenal bypass in 47%, extraanatomic bypass in 45%, and endarterectomy in 8%; 45% of patients required combined aortic and RAR. The operative mortality rate was 8%; significant perioperative renal dysfunction occurred in 10%. Major operative morbidity was associated with increasing azotemia (RR = 2.1; p = 0.001; 95% confidence interval [CI], 1.3 to 4.7 for each 1.0 mg/dl increase in baseline creatinine level). Of those patients who had a baseline creatinine level > or = 2.0 mg/dl, 54% had > or = 20% reduction in creatinine level after RAR. Late follow-up data were available for 87% of operative survivors at a mean duration of 4 years (range, 6 weeks to 12.6 years). Actuarial survival at 5 years was 52% +/- 5%. Continued deterioration in renal function occurred in 24% of patients who survived operation, and eventual dialysis was required in 15%. Deterioration of renal function after RAR was associated with increasing levels of preoperative creatinine (RR = 1.6; 95% CI, 1.2 to 1.8; p = 0.001 for each 1.0 mg/dl increment in baseline creatinine level), and inversely related to early postoperative improvement in creatinine level (RR = 0.41; 95% CI, 0.2 to 0.9; p = 0.04). CONCLUSIONS: Intervention before major deterioration in renal function and an aggressive posture toward the frequently associated coronary artery disease are necessary to improve long-term results when RAR is performed for renal function salvage.