The effect of per os colchicine administration in combination with fenofibrate and N-acetylcysteine on triglyceride levels and the development of atherosclerotic lesions in cholesterol-fed rabbits.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease promoted by pro-inflammatory cytokines produced by NOD-, LRR- and pyrin domain-containing protein 3 (NLRP 3) inflammasome. Colchicine is an anti-inflammatory agent that inhibits inflammasome's action and stabilizes atherosclerotic lesions. N-acetylcysteine (NAC) reduces low-density lipoprotein (LDL) oxidation, metalloproteinase levels, and foam cell count and volume. Fenofibrate also has antioxidant, anti-inflammatory, and anticoagulant properties while also having a beneficial effect on the vasomotor function of the endothelium. The purpose of this study is to investigate the effect of per os colchicine administration in combination with fenofibrate and NAC on triglyceride levels and the development of atherosclerotic lesions in cholesterol-fed rabbits. MATERIALS AND METHODS: Twenty-eight male, 2 months old New Zealand White rabbits were separated into four groups and were fed with different types of diet for 7 weeks: standard, cholesterol 1% w/w, cholesterol 1% w/w plus colchicine 2 mg/kg body weight plus 250 mg/kg body weight/day fenofibrate, and cholesterol 1% w/w plus colchicine 2 mg/kg body weight plus 15 mg/kg body weight/day NAC. Blood samples were drawn from all animals. Lipid profiles were assessed, and interleukin 6 (IL-6) measurements were performed using an enzyme-linked immunosorbent assay (ELISA) kit. Histologic examination was performed on aorta specimens stained with eosin and hematoxylin. Aortic intimal thickness was evaluated using image analysis. RESULTS: Colchicine administration in combination with fenofibrate or NAC statistically significantly reduced the extent of atherosclerotic lesions in aortic preparations. Co-administration of colchicine with NAC has a stronger anti-atherogenic effect than the colchicine plus fenofibrate regimen. Triglerycide levels were decreased in the colchicine plus fenofibrate group and the colchicine plus NAC group at the end of the experiment (p < 0.05), whereas the Cholesterol group had increased levels. A favorable significant lower concentration of IL-6 was detected in the colchicine plus NAC group vs. the other groups. CONCLUSIONS: In an experimental rabbit model, it appears that colchicine statistically significantly reduces the development of atherosclerosis of the aorta, especially in combination with NAC. Colchicine, as an NLRP3 inflammasome inhibitor, and NAC, as an agent that directly targets IL-6 signaling, can reduce the inflammatory risk. Fenofibrate enhances the attenuating role of colchicine on triglyceride levels. Clinical studies should investigate whether similar effects can be observed in humans.

Cardiac allograft vasculopathy after heart transplantation: current prevention and treatment strategies.

OBJECTIVE: Cardiac allograft vasculopathy (CAV) is a leading cause of mortality in heart transplantation patients. Despite optimal immunosuppression therapy, the rate of CAV post-transplantation remains high. In this review, we gathered all recent studies as well as experimental evidence focusing on the prevention and treatment strategies regarding CAV after heart transplantation. MATERIALS AND METHODS: A complete literature survey was performed using the PubMed database search to gather available information regarding prevention and treatment strategies of CAV after heart transplantation. RESULTS: Several non-immune and immune factors have been linked to CAV such as ischemic reperfusion injury, metabolic disorders, cytomegalovirus infection, coronary endothelial dysfunction, injury and inflammation respectively. Serial coronary angiography combined with intravascular ultrasound is currently the method of choice for detecting early disease. Biomarkers and noninvasive imaging can also assist in the early identification of CAV. Treatment strategies such as mammalian target of rapamycin inhibitors proceed to grow, but prevention remains the objective. CONCLUSIONS: Early detection is the key to therapy management. It enables early identification and diagnosis of patients with CAV, who would gain the most from prompt treatment. Further investigation is needed to elucidate the multifactorial pathophysiological process of CAV, develop detection methods and find treatments that prevent or slow disease progression.

Progress in the management of type I thoracoabdominal and descending thoracic aortic aneurysms.

We reviewed our categorization of patients at high risk for neurologic complications in the repair of descending thoracic and thoracoabdominal aortic aneurysm in which we used cerebrospinal fluid drainage and distal aortic perfusion (adjuncts). A total of 409 patients were operated on by one surgeon for descending thoracic or thoracoabdominal aortic aneurysm between 1992 and 1997. Of these patients, 232 had total descending thoracic or type I thoracoabdominal aortic aneurysm, 131 (56%) of whom were operated on with adjuncts. These patients were compared to 101 nonadjunct patients for demographic variables, intraoperative variables, blood product consumption, and neurologic status. In 131 consecutive patients with adjuncts, all but one awoke from anesthesia without neurologic deficit. In nonadjunct patients, however, neurologic deficit occurred in 6 of 101 (6%) (p < 0.003). The adjunct group had more preoperative renal insufficiency (p < 0.05), an established risk factor for neurologic deficit (odds ratio = 2.2 in published studies). All other risk factors for neurologic deficit occurred with comparable frequency in both groups. We conclude that the introduction of adjuncts has dramatically reduced the neurologic risk associated with type I thoracoabdominal or total descending thoracic aortic repair. Previously considered high risk for neurologic complications, these aneurysms can now be reclassified as low risk in surgery accompanied by adjuncts. Future investigations will focus on type II thoracoabdominal aortic aneurysm as the major source of neurologic morbidity.

Effect of extended cross-clamp time during thoracoabdominal aortic aneurysm repair.

BACKGROUND: In previous studies of the neurologic outcome of patients undergoing thoracoabdominal aortic aneurysm repair with the simple cross-clamp technique, cross-clamp time of greater than 30 minutes was identified as an important risk factor. We retrospectively examined the effect of clamp time of 30 minutes or greater on outcome for patients undergoing repair with the addition of surgical adjuncts. METHODS: Between February 1991 and June 1996 we operated on 370 patients for thoracoabdominal or descending thoracic aortic aneurysm. Two hundred seventy-one of these patients with cross-clamp times of 30 minutes or greater were included in this study. One hundred twelve patients underwent simple cross-clamp repair, whereas 159 were operated on with the surgical adjuncts of distal aortic perfusion and cerebrospinal fluid drainage. RESULTS: By multivariate analysis, acute dissection, surgical adjuncts, and aneurysm extent proved most significant in overall patient outcome. The overall rate of early neurologic deficits was 23 of 271 (8.5%). For highest risk patients with type II thoracoabdominal aortic aneurysms, the rate of neurologic deficits was 11 of 29 (38%) for cross-clamp versus 6 of 82 (7.3%) for adjunct operation patients (odds ratio = 0.13; p < 0.001). CONCLUSIONS: The adjuncts of cerebrospinal fluid drainage and distal aortic perfusion decreased the risk of extended cross-clamp time during thoracoabdominal aortic aneurysm repair, particularly for highest risk type II.

Thoracic and thoracoabdominal aortic aneurysm repair using cardiopulmonary bypass, profound hypothermia, and circulatory arrest via left side of the chest incision.

PURPOSE: Although some authors advocate hypothermic circulatory arrest for spinal cord protection in descending thoracic and thoracoabdominal repair, this method has been associated with high morbidity and mortality rates in other studies. The safety and effectiveness of this surgical adjunct were evaluated. METHODS: Between February 1991 and April 1997, 409 patients underwent thoracic or thoracoabdominal aortic repair. Because of an inability to gain proximal aortic control because of anatomic or technical difficulty, hypothermic circulatory arrest was used in 21 patients (4.9%). Thirteen patients were men, 8 were women, and the median age was 57 (range, 21 to 81 years). Four patients (19%) had Marfan's syndrome, and 1 had aortitis. Seven patients (33%) had aortic dissection (4 chronic type A, 2 chronic type B, 1 acute B), and 1 had aortic laceration. All but 6 patients had hypertension. Fifteen patients (73%) were operated on for repair of the distal arch and descending thoracic aorta, 4 (19%) for repair of the distal arch and thoracoabdominal aorta, and 2 for repair of either the thoracoabdominal or descending thoracic aorta alone. Surgery for 9 patients (43%) also included bypass grafts to the subclavian or innominate arteries. Six operations (29%) were urgent. RESULTS: The overall 30-day mortality rate was 29% (6 of 21 patients). Among urgent patients, the mortality rate was 50% (3 of 6 patients) versus 20% (3 of 15) for elective patients. Of the remaining 15 patients, renal failure occurred in 1 (7%) and heart failure in 2 (13%). Ten patients (67%) had pulmonary complications. Encephalopathy occurred in 5 patients (33%) and stroke in 2 (13%), and spinal cord neurologic deficit developed in 2 (13%). The median recovery was 28 days (range, 10 to 157 days). CONCLUSION: Hypothermic circulatory arrest did not reduce the incidence of deaths and morbidity to a rate comparable with our conventional methods. We recommend the judicious application of this method in rare instances when proximal control is not feasible or catastrophic intraoperative bleeding leave the surgeon with no other option.

Operation for acute and chronic aortic dissection: recent outcome with regard to neurologic deficit and early death.

BACKGROUND: We reviewed our experience in the repair of acute and chronic aortic dissection with regard to early neurologic deficit and death. METHODS: Between February 1991 and June 1996, we performed 206 operations on 195 patients for aortic dissection. Ascending or arch repair, or a combination (type A dissection) was performed on 92 of 206 patients (45%); 44 of 92 (48%) were acute dissection and 48 of 92 (52%) were chronic. Descending or thoracoabdominal repair (type B dissection) was performed on 114 of 206 patients (55%); 22 of 114 (19%) were acute and 92 of 114 (81%) were chronic. RESULTS: Among type A cases, strokes occurred in 6 of 92 patients (7%) overall; 4 of 44 (9%) were acute cases and 2 of 48 (4%) were chronic (p < 0.34). Early deaths for type A were 11 of 92 (12%) overall; 9 of 44 (20%) acute and 2 of 48 (4%) chronic (p < 0.02). In type B cases, neurologic complications were 15 of 114 (13%) overall; 7 of 22 (32%) were acute cases and 8 of 92 (9%) were chronic (p < 0.004). Early deaths for type B were 12 of 114 (11%) overall; 3 of 22 (14%) acute and 9 of 92 (10%) chronic (p < 0.6). Preoperative hypotension was significant in acute type A patients, with strokes in 2 of 7 (29%) hypotensives compared with 2 of 37 (5%) normotensives (p < 0.05) and early death in 4 of 7 (57%) hypotensives versus 5 of 37 (14%) normotensives (p < 0.009). CONCLUSIONS: Morbidity and mortality for repair of chronic dissection types A and B were acceptable. Preoperative hypotension in acute type A dissection was a major predisposing factor toward stroke (29% versus 5%, p < 0.05). Acute type B dissection had acceptable mortality (14%) but a high rate of neurologic complications (32%).

Importance of intercostal artery reattachment during thoracoabdominal aortic aneurysm repair.

PURPOSE: We studied the relationship of neurologic deficit to ligation, reimplantation, and preexisting occlusion of intercostal arteries to determine which arteries and consequent management are most critical to outcome in thoracoabdominal aortic aneurysm repair. METHODS: From February 1991 to July 1996, 343 patients with thoracoabdominal aortic aneurysms underwent repair by one surgeon. In this study, only Crawford types I, II, and III (n = 264) were considered. Of these, 110 (42%) were type I, 116 (44%) type II, and 38 (14%) type III. The adjuncts of distal aortic perfusion and cerebrospinal fluid drainage were used in 164 patients (62%). Data were analyzed by contingency table and by multiple logistic regression. RESULTS: Early neurologic deficit occurred in 23 patients (8.7%), and late deficit in 10 patients (3.8%). Neurologic deficit in patients with at least one reimplantation and no ligation of arteries T11 or T12 occurred in 19 of 147 (12.9%). Neurologic deficit for occlusion of the same arteries occurred in 11 of 111 (9.9%), whereas for ligation of T11 and T12 neurologic deficit occurred in three of six (50%; reimplantation, p < 0.03; occlusion, p < 0.006). In addition, reimplantation of intercostal arteries T9 or T10 was significantly associated with reduced late neurologic deficit in multivariate analysis (p = 0.05). No other intercostal artery status was associated with modification of the neurologic deficit rate. Multivariate analysis showed type II aneurysms and acute dissections to be significantly associated with an increased risk of postoperative neurologic deficit (p < 0.0009, 0.002, respectively). Adjuncts were protective (p < 0.007), most often in types II and III (14.1% neurologic deficit in type II with adjunct, 35.3% without; 0% in type III with adjunct, 20% without). CONCLUSION: Patients with patent arteries at the T11/T12 level have highly variable outcomes depending on whether the arteries are reattached or ligated. Our data suggest that reimplantation of thoracic intercostal arteries T11 and T12 is indicated when these arteries are patent. Reimplantation of T9 and T10 lowers the risk of late neurologic deficit, probably by decreasing the spinal cord's vulnerability to changes in blood and cerebrospinal fluid pressure in the days after surgery. Adjuncts lower overall risk and provide adequate time for targeted intercostal artery reimplantation.

Impact of distal aortic and visceral perfusion on liver function during thoracoabdominal and descending thoracic aortic repair.

PURPOSE: We examined the impact of distal aortic and visceral perfusion on liver function during thoracoabdominal and descending thoracic aortic repair. METHODS: Between January 1991 and July 1996, 367 patients underwent thoracoabdominal and descending thoracic aortic repair. Baseline and postoperative total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, fibrinogen, prothrombin time (PT), and partial thromboplastin time (PTT) were measured for 286 patients. We examined the impact of distal aortic and direct visceral perfusion on liver function-related clinical laboratory values. Univariate and multivariate statistical methods for categorical and continuous variables were used. RESULTS: In categorical analysis, type II thoracoabdominal aortic aneurysm, history of hepatitis, and emergency presentation had a statistically significant multivariate association with abnormal laboratory values. In continuous-distributed multivariate data analysis, type II thoracoabdominal aortic aneurysm and visceral perfusion were statistically significant predictors of postoperative alkaline phosphatase, PT, and PTT. Type II aneurysms increased postoperative liver function-related laboratory values significantly above other aneurysm types (alkaline phosphatase, +114 IU, p < 0.0001; PT, +1.99 seconds, p < 0.02; PTT, +6.7 seconds, p < 0.03). Visceral perfusion was associated with a concomitant decrease (alkaline phosphatase, -101.2 IU, p < 0.0001; PT, -1.8 seconds, p < 0.07; PTT, -5.6 seconds, p < 0.02). CONCLUSIONS: Visceral perfusion negates the rise in postoperative liver function-related clinical laboratory values associated with type II thoracoabdominal aortic aneurysm repair.

Staged repair of extensive aortic aneurysm: improved neurologic outcome.

OBJECTIVE: We reviewed the adjuncts for brain and spinal cord protection and modifications of operative techniques. SUMMARY BACKGROUND DATA: Two-staged repair--the "elephant trunk" technique--has provided the means for successful repair of massive aortic aneurysms, although historically morbidity has been high. METHODS: Between February 1991 and February 1996, we operated on 512 patients for thoracic aortic aneurysm. Preoperative, intraoperative, or postoperative predictors of morbid outcomes were studied in 63 patients treated with the elephant trunk technique. Data were analyzed by contingency table methods. RESULTS: After stage 1, there were no strokes among patients who received retrograde cerebral perfusion (0 of 53), two strokes occurred among patients who did not receive retrograde cerebral perfusion (2 of 10 [20%]), and early mortality occurred in 4 of the 63 patients (6%). Interval mortality occurred in 6 of 59 patients (10%); 3 (50%) of these 6 deaths were due to distal aortic aneurysm rupture. Thirty-eight patients have undergone stage two repair thus far. There was no incidence of neurologic deficit after stage 2, and early mortality occurred in 1 of the 38 patients (3%). CONCLUSIONS: Extensive aortic aneurysm can be successfully treated using the elephant trunk technique. In this group of patients, retrograde cerebral perfusion eliminated neurologic complications.

Observations on delayed neurologic deficit after thoracoabdominal aortic aneurysm repair.

PURPOSE: To describe the phenomenon of delayed-onset neurologic deficit after thoraco-abdominal aortic aneurysm repair and to discuss management of this type of deficit in a case series. METHODS: Since September 1992 we have used cerebrospinal fluid drainage and distal aortic perfusion routinely to reduce the risk of neurologic deficit in thoracoabdominal aortic aneurysm patients. All patent intercostal arteries were reattached when this was technically feasible. Delayed neurologic complications occurred in eight patients who underwent operation for thoracoabdominal aortic aneurysm between September 1992 and March 1997, between 1 and 14 days after awakening from anesthesia. All patients had immediate cerebrospinal fluid drainage on recognition of their symptoms. RESULTS: Patients were evaluated by an independent neurologist and were classified by a modified Tarlov score between 0 and 5. All eight patients improved at least two points by discharge. The mean change in Tarlov score from onset to discharge was 2.4 +/- 1.1 (p = 0.008). CONCLUSIONS: Cerebrospinal fluid drainage significantly improved late-onset neurologic deficit that occurred between 1 day and 2 weeks after operation in our series. Immediate drainage should be considered when signs of neurologic deficit first begin to appear.

Mucopolysaccharidosis presenting as pediatric multiple aortic aneurysm: first reported case.

Within the pediatric population, the rare aortic aneurysm is most often brought on by congenital cardiovascular malformation or connective tissue disorder, trauma, inflammatory disease, or infection. Thus our 8-year-old patient who had multiple aortic aneurysms and evidence of mucopolysaccharidosis presented a doubly unique case. Three and one-half months after the patient underwent emergency aortic valve replacement, we performed resection and graft replacement of both her descending thoracic aorta and thoracoabdominal aorta. Histologic analysis of the aneurysm wall displayed severe medial degeneration with large deposits of acid mucopolysaccharides. Subsequent evaluation, although negative for connective tissue disorders, showed glycosaminoglycans, chondroitin sulfate, and heparan sulfate in the patient's urine. These findings are diagnostic for a heterogeneous group of storage diseases termed mucopolysaccharidoses, although testing of the patient's cultured fibroblasts failed to reveal any specific previously described enzymatic defect. After reviewing the literature, we believe that this is the first known successfully treated pediatric aortic aneurysm associated with mucopolysaccharidosis.

Cerebral spinal fluid drainage and distal aortic perfusion decrease the incidence of neurological deficit: the results of 343 descending and thoracoabdominal aortic aneurysm repairs.

OBJECTIVE: We reviewed our experience of 343 descending and thoracoabdominal aortic aneurysm repairs to determine the impact of the adjuncts distal aortic perfusion and cerebral spinal fluid drainage on neurological deficit and death. MATERIALS AND METHODS: Between January 1991 and March 1996, 104 (30%) patients were operated for thoracoabdominal aortic aneurysm type I, 118 (34%) for type II, 68 (20%) for type III or type IV, and 53 (15%) for descending thoracic type. Before September 1992, simple cross-clamp was used for 94 (27%) patients. After September 1992, adjuncts were used for 186 (54%) patients. RESULTS: Overall neurological deficit was 33/343 (10%). Neurological deficit for simple cross-clamp patients compared to adjunct patients was 15/94 (16%) vs. 12/186 (7%) (O.R. 0.36, p < 0.01). For types I and II the incidence was 11/52 (21%) vs. 12/141 (9%) (O.R. 0.35, p < 0.02) and for type II, nine out of 22 (41%) vs. 11/85 (13%) (O.R. 0.21, p < 0.003). Overall 30-day mortality was 43/343 (13%), including patients presenting with rupture. Excluding these patients, overall 30-day mortality was 33/322 (10%). CONCLUSION: Cerebral spinal fluid drainage and distal aortic perfusion decreased the incidence of neurological deficit and were particularly effective for patients at highest risk with type II thoracoabdominal aortic aneurysm.

Impact of retrograde cerebral perfusion on ascending aortic and arch aneurysm repair.

PURPOSE: The effect of retrograde cerebral perfusion on the incidence of stroke and death among patients undergoing repair of aneurysms of the ascending aorta and transverse arch was determined. MATERIALS AND METHODS: Between January 1991 and March 1995, 161 patients were operated on for aneurysms of the ascending aorta and transverse arch. Thirty-three of the patients (20%) had an aneurysm of the ascending aorta only and 128 (80%) had aneurysms of both the ascending aorta and the transverse arch. All the patients underwent cardiopulmonary bypass, profound hypothermia, and circulatory arrest, and 120 (74%) also underwent retrograde cerebral perfusion. Median pump time was 143 minutes (range, 21 to 461 minutes). Median circulatory arrest time was 42 minutes (range, 8 to 111 minutes), and median myocardial ischemic time was 71 minutes (range, 14 to 306 minutes). RESULTS: The overall 30-day mortality rate was 6% (9 patients) and the incidence of stroke was 4% (7 patients). The use of retrograde cerebral perfusion demonstrated a protective effect against stroke (3 of 120 patients, or 3%) compared with no retrograde cerebral perfusion (4 of 41 patients, or 9%; odds ratio, 0.24; confidence interval, 0.06 to 0.99; p < 0.049). This was most significant in patients more than 70 years of age; none of the 36 elderly patients who received retrograde cerebral perfusion had a stroke, compared with 3 of the 13 (23%) who did not (p < 0.003). Only pump time was associated with an increased risk of stroke (odds ratio, 1.01; 95% confidence interval, 1.00 to 1.02; p < 0.005). Pump time also was associated with increased mortality (odds ratio, 1.01; 95% confidence interval, 1.00 to 1.02; p < 0.008). CONCLUSION: Retrograde cerebral perfusion decreased the incidence of stroke in patients undergoing repair of aneurysms of the ascending aorta and transverse arch.

Predictive factors for acute renal failure in thoracic and thoracoabdominal aortic aneurysm surgery.

PURPOSE: The purpose of this study was to analyze the factors associated with acute renal failure in total descending thoracic and thoracoabdominal aortic aneurysm surgery. METHODS: A total of 234 patients underwent thoracoabdominal aortic aneurysm or total descending thoracic aneurysm repair between January 1991 and January 1994. Eighty-five women and 149 men were evaluated. The median age was 67 years (range 8 to 88 years). Seventy-seven patients had type I thoracoabdominal aortic aneurysm, 99 had type II, 51 had type III or IV, and 7 had total descending thoracic aneurysm. Factors such as age, sex, aneurysm type, and visceral and distal aortic perfusion were examined with univariate fourfold table and multivariate logistic regression analysis. RESULTS: Acute renal failure, defined as an increase in serum creatinine by 1 mg/dl per day for two consecutive days after surgery, occurred in 41 (17.5%) of 234 patients. Thirty-six (15%) of 234 patients required dialysis. Twenty (49%) of 41 patients with acute renal failure died. Of the 21 survivors with renal failure, renal failure resolved in 18 (86%) within 30 days of surgery. The univariate odds ratio of death, given acute renal failure, was 6.7 (95% confidence interval [CI] 3.2 to 14.2, p < 0.0001). No significant association was found between the probability of acute renal failure and age, sex, hypertension, right renal artery reattachment, or renal bypass. Factors associated with increased risk of acute renal failure in multivariate analysis were visceral perfusion (odds ratio [OR] = 3.6 95%, CI 1.2 to 11.0, p < 0.02), left renal artery reattachment (OR = 4.4 95%, CI 1.6 to 11.9, p < 0.004), preoperative creatinine > or = 2.8 mg/dl (OR = 10.3, 95% CI 12.0 to 411.8, p < 0.0001), and simple clamp technique (OR = 3.4 95%, CI 1.07 to 10.76, p < 0.04). Direct univariate correlation was seen between preoperative creatinine and acute renal failure (OR = 3.2 per mg/dl increase, 95% CI 2.7 to 10.1, p < 0.0001). CONCLUSION: Postoperative acute renal failure after thoracoabdominal and total descending thoracic aortic aneurysm surgery is associated with preoperative creatinine level, visceral perfusion, left renal artery reattachment, and simple cross-clamp technique.

Low-dose heparin treatment does not inhibit SW480 human colon cancer growth and metastasis in vivo.

We investigated heparin effects on the biological behavior of SW480 human colon adenocarcinoma cells in vivo. Tumor growth, pathological features, metastatic potential and karyotype, were studied after the twelve week low-dose heparin treatment of nude mice subcutaneously injected with SW480 cells. A non statistically significant increase in tumor growth was observed (0.05 < p < 0.1, compared to the control group). No differences in tumor histology and karyotype were detected. Two of the six heparin-treated animals exhibited an increase in tumor vascularization. Metastasis to the lungs and liver was not inhibited. These results do not support the role of heparin in the prevention of the in vivo growth and metastasis of SW 480 colon cancer cells.

Cerebrospinal fluid drainage and distal aortic perfusion: reducing neurologic complications in repair of thoracoabdominal aortic aneurysm types I and II.

PURPOSE: This study was conducted to evaluate the role of cerebrospinal fluid (CSF) drainage and distal aortic perfusion (DAP) in the prevention of postoperative neurologic complications for high-risk patients who had undergone type I and type II thoracoabdominal aortic aneurysm (TAAA) repair. METHODS: CSF drainage and DAP were used as an adjunct in the treatment of 94 patients with TAAA (31 type I, 63 type II) between September 1992 and December 1994; 67 were men and 27 were women. The median age was 64 years (range, 28 to 88 years). Aortic dissection occurred in 35 of 94 patients (37%). Thirty-six of 94 patients (38%) had previously undergone proximal aortic surgery. All patients underwent intraoperative DAP and perioperative CSF drainage. Median aortic cross-clamp time was 67 minutes (range, 20 to 131 minutes). RESULTS: The 30-day survival rate was 90% (85 of 94 patients). Early neurologic complications occurred in 5 of 94 patients (5%), and late neurologic complications occurred in 3 of 94 patients (3%). We compared the neurologic complications of our current group of 94 patients with the data from 42 patients (control group) who also underwent repair of TAAA type I and type II with only simple cross-clamp and without CSF drainage or DAP. Both groups were treated by the senior author (HJS) at the same institution. Total neurologic complications for the current group occurred in 8 of 94 patients (9%) versus 8 of 42 patients (19%) for the control group (p=0.090). Neurologic complications for patients with type II TAAA occurred in 8 of 63 patients (13%) versus 17 of 42 patients (41%) (p=0.014). For all patients with aortic clamp times >or=45 minutes, neurologic complications occurred in 7 of 55 (13%) versus 7 of 18 (39%) (p=0.033). CONCLUSION: The period of risk during aortic cross-clamp time is reduced with the adjuncts of CSF drainage and DAP, which significantly lower the incidence of neurologic complications after repair of TAAA types I and II.

In vitro effects of heparin on SW480 tumor cell-matrix interaction.

We investigated the in vitro effects of heparin on the growth and interaction of SW480 colon adenocarcinoma cells with the extracellular matrix proteins laminin, fibronectin and collagen IV. Cell adhesion assays were performed in wells precoated with the proteins mentioned. Tumor cell migration and invasiveness were assayed in Transwell cell culture chambers. SW480 cell adhesion to the matrix proteins and migration to laminin/fibronectin precoated filters were inhibited by heparin in a dose- dependent manner, whereas cell growth and invasion through collagen IV gel were not affected. Our results suggest that heparin influences the SW480 cell-matrix interaction in vitro and inhibits crucial steps of the metastatic process in an experimental model.

Retrograde cerebral perfusion during profound hypothermia and circulatory arrest in pigs.

The purpose of this study was to evaluate the use of retrograde cerebral perfusion via the superior vena cava during profound hypothermia and circulatory arrest (CA) in pigs. In three groups of 5 pigs each, group A (control) underwent cardiopulmonary bypass and normothermic CA for 1 hour, group B underwent cardiopulmonary bypass, profound hypothermia, and CA (15 degrees C nasopharyngeal) for 1 hour, and group C underwent the same procedure as group B plus retrograde cerebral perfusion. In group A none awoke. In group B, 2 of 5 did not awake and 3 of 5 awoke unable to stand, 2 with perceptive hind limb movement and 1 moving all extremities. In group C all awoke, 4 of 5 able to stand and 1 of 5 unable to stand but moving all limbs. In neurologic evaluation group B had significantly lower Tarlov scores than group C (p = 0.0090). Group B mean wake-up time, plus or minus standard error of the mean, was 124.6 +/- 4.6 minutes versus 29.2 +/- 5.1 in group C (p = 0.0090). In group B late phase CA cerebral blood flow dropped 30.9% +/- 4.8%, but in group C it rose 24.7% +/- 9.3% (p = 0.0007, pooled variance t test, two-tailed). In group B late phase CA brain oxygenation decreased 46.0% +/- 13.9% but it increased 26.1% +/- 5.4% in group C (p = 0.0013). This difference was reduced somewhat during rewarming (B, -21.2% +/- 14.9%; C, 16.4% +/- 4.7%; p = 0.043). Group B rewarming jugular venous O2 saturation was 30.8% +/- 2.5% versus 56.0% +/- 4.4% in group C (p = 0.0011). We conclude that in pigs retrograde cerebral perfusion combined with profound hypothermia during CA significantly reduces neurologic dysfunction, providing superior brain protection.

Repeat replacement of aortic valve bioprosthesis.

We describe a safe and simple technique for replacing an aortic valve bioprosthesis in a patient who also had a previously implanted ascending aortic graft and multiple coronary artery bypass grafts. This method allows for isolated valve replacement without removal of the ascending aortic graft or alteration of the coronary artery bypass graft attachments.