Increased intimal hyperplasia after carotid endarterectomy in spontaneously hypertensive rats.

This study evaluated the effects of hypertension on postoperative intimal hyperplasia using a rat carotid endarterectomy (CEA) model with spontaneously hypertensive rats (SHR) and normotensive Sprague-Dawley rats (SD). SHR and SD rats underwent left carotid exposure and CEA via an arteriotomy, scoring and removal of the intima, followed by arteriotomy closure. The rats were then sacrificed two weeks postoperatively. The left carotid artery was harvested and underwent elastin and double immunohistochemical staining. The percent of lumenal stenosis was calculated using morphometric measurements, and stained cells within the intimal hyperplasia were counted. The means and standard deviation of the means were calculated, and the two groups were compared using a 2-sample t test. The systolic blood pressure was 228 +/-35 mm Hg in the SHR group and 108 +/-8 mm Hg in the SD group (p<0.00001). The percent of lumenal stenosis was 82.6 +/-17.1% in the SHR group and 21.2 +/-13.7% in the SD rats (p value <0.0001). The percentage of cells staining for a-SM actin was equal in the SHR group and the SD group (> 91%) but the percentage of these cells staining for BrdU was 38.2 +/-8.4% in the SHR group and 10.7 +/-5.8% in the SD group (p< 0.00001). Hypertension in the SHR rats was associated with an increased lumenal stenosis due to increased intimal hyperplasia. The increased intimal hyperplasia was due to enhanced and accelerated replication of smooth muscle cells. Hypertension may be associated with increased restenosis rates after CEA.

Abdominal aortic aneurysm repair.

Newer, minimally invasive catheter-based endovascular technology utilizing stent grafts are currently being evaluated for abdominal aortic aneurysm (AAA) repair. A retrospective review of all (3 years) consecutive, non-ruptured elective AAA repairs was undertaken to document the results of AAA surgical repair in a modern cohort of patients to allow a contemporary comparison with the evolving endoluminal data. One hundred twenty-one AAAs were identified in a male veteran population. Mean age was 68.5 +/-7.7 years. Medical history review showed hypertension in 55%, heart disease in 73.5%, peripheral vascular disease in 21%, stroke and transient ischemic attacks in 22%, diabetes mellitus in 7%, renal insufficiency in 10%, and smoking history in 80%. The AAA size was documented with ultrasound (5.2 +/-1.3 cm, n=40) and computed tomography (5.6 +/-1.3 cm, n=100). Fifty-nine percent had angiography. Intraoperative end points included an operative time of 165 +/-6.3 minutes from incision to dressing placement. A Dacron tube graft was used in 78%, the remaining were Dacron bifurcated grafts. A suprarenal clamp was used in 8% for proximal aortic control with juxtarenal aneurysms. A pulmonary-artery catheter was placed in 69%. A transverse incision was used in 69% of patients and a midline incision was used in the rest. Estimated blood loss was 1505 +/-103 mL; cell saver blood returned 754 +/-53 mL; crystalloid/Hespan 4771 +/-176 mL; banked packed red blood cells 0.75 +/-0.11 U. Time to extubation was, in the operating room (78.5%), on the day of the operation (5.0%), postoperative day (POD) 1 (12.4%), POD2 (1.7%), POD3 (0.8%), and one case was performed with epidural anesthesia only. Postoperative end points included a 30-day mortality rate of 1.6% (two patients). Postoperative morbidity included wound dehiscence 0.8%; sepsis, urinary tract infection, wound infection, leg ischemia, ischemic colitis, and stroke each had an incidence of 1.6%; myocardial infarction, congestive heart failure, pneumonia, re-operation for suspected bleeding, and ileus or bowel obstruction occurred with an incidence of 3.3%. No significant increase in serum creatinine levels was noted. Time to enteral fluids/nutrition was 3.5 +/-0.08 days. Patients were out of bed to a chair or walking by 1.3 +/-0.06 days postoperatively. The length of stay in the intensive care unit (ICU) was 2.0 +/-0.12 days and postoperative hospital stay was 6.6 +/- 0.33 days. Transfusion requirement for the hospital stay was 1.6 +/-0.2 U per patient. This review highlights a cohort of male veteran patients with significant cardiac co-morbidity who have undergone repair with a conventional open technique and low mortality and morbidity rates. This group had rapid extubation, time to oral intake, and ambulation. In addition, ICU and hospital stays were relatively short.

Increasing levels of dietary homocystine with carotid endarterectomy produced proportionate increases in plasma homocysteine and intimal hyperplasia.

PURPOSE: The role that homocysteine may play in post-carotid endarterectomy (CEA) restenosis due to intimal hyperplasia is not well understood. This study was designed to investigate the effects of different levels of dietary homocystine on: (1) plasma homocysteine; (2) post-CEA intimal hyperplasia; and (3) levels of the methyl donor S-adenosylmethionine (SAM) and its counterpart S-adenosylhomocysteine (SAH) in the homocysteine pathway. METHODS: Male rats were fed specialized diets for 2 weeks pre- and post-CEA. Groups included control (0 homocystine added, n=9), 1.5 (1.5 g/kg homocystine added, n=10), 3.0 (3.0 g/kg homocystine added, n=9), and 4.5 (4.5 g/kg homocystine added, n=11). The rats underwent a surgical carotid endarterectomy. Endpoints included; plasma homocysteine, intimal hyperplasia, replicative index using with alpha-SM actin and BrdU, hepatic SAM levels, SAH levels, and the hepatic activities of methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS). RESULTS: Increasing dietary homocystine produced a proportionate increase in plasma homocysteine and an increase in intimal hyperplasia. Regression analysis of plasma homocysteine levels and intimal hyperplasia showed a significant correlation (r=0.71,P=0.003). Plasma homocysteine levels above 15 microM were associated with significant increases in intimal hyperplasia above 6.5% (P=0.04). Elevation of plasma homocysteine levels to moderate levels (5-25 microM) resulted in significant post-CEA intimal hyperplasia. Cellular analysis of the area of intimal hyperplasia in all diet groups showed comparable amounts of cells positive for alpha-SM actin. However, with increasing levels of dietary homocystine and plasma homocysteine there was an increase in replicative index (P<0.001) as determined by BrdU staining. Increasing dietary homocystine increased plasma homocysteine and was followed by increases in the replicative index thus producing increased intimal hyperplasia and lumenal stenosis. In hepatic measurements the 1.5 and 3.0 g/kg homocystine diets caused: increased liver activity of MTHFR (P=0.03) and decreased hepatic levels of SAM, SAH and SAM/SAH ratios compared to controls. Homocystine treatment did not cause significant alterations in CBS levels (P=0.992). These studies also showed no correlation of the MTHFR and CBS enzymes with plasma homocysteine levels or intimal hyperplasia. However, hepatic levels of SAM showed significant negative correlations with plasma homocysteine (r=-0.58; P=0.006) and with BrdU percentages of cellular proliferation (r=-0.69; P=0.06). CONCLUSION: The degree of post-CEA intimal hyperplasia in a rat model is directly related to the plasma level of homocysteine. The hyperplastic effects of homocysteine may be mediated in part by a physiological insufficiency of methyl donors as shown by decreases in SAM. Thus, increasing levels of plasma homocysteine enhanced and accelerated the smooth muscle cell response after CEA which led to increased intimal hyperplasia and lumenal stenosis.

Surgical complications from hemostatic puncture closure devices.

BACKGROUND: For securing immediate hemostasis following percutaneous arterial catheterization, the Food and Drug Administration has approved three hemostatic puncture closure devices. We reviewed our institutional experience with one device (Angio-Seal). METHODS: A retrospective, single-center, nonrandomized observational study was made of all vascular complications following femoral cardiac catheterization. RESULTS: An immediate mechanical failure of the device was experienced in 34 (8%) patients. Surgical repair was required in 1.6% (7 of 425) of patients following Angio-Seal versus 0.3% (5 of 1662) following routine manual compression (P = 0.004). In 5 patients, the device caused either complete occlusion or stenosis of the femoral artery. The polymer anchor embolized in 1 patient and was retrieved with a balloon catheter at surgery. CONCLUSION: During the first year of utilization of a percutaneous hemostatic closure device following cardiac catheterization, we observed a marked increase in arterial occlusive complications requiring surgical repair. Surgeons must be familiar with the design of these devices to achieve precise repair of surgical complications.

Hyperhomocysteinemia increases intimal hyperplasia in a rat carotid endarterectomy model.

PURPOSE: This preliminary study investigated the ability to elevate the serum homocysteine (H[e]) levels and investigated the increases in postoperative neointimal hyperplasia (IH) in an environment with hyperhomocysteinemia and the resultant restenosis in a rat carotid endarterectomy (CEA) model. METHOD: The 9 rats for the control group were fed rat chow, and the 8 rats for the H(e) group were fed H(e)-supplemented rat chow for 2 weeks before and after CEA. The animals underwent anesthesia, and a left common CEA was performed. After 14 days, the serum H(e) levels were measured and the left carotid artery was harvested and elastin stained. Morphometric measurements were used to calculate the area of stenosis of the lumen. The mean and the standard deviation of the mean were determined. The 2 groups were compared with the Mann-Whitney test and a linear regression model. Three additional rats per group were studied, with carotid artery sectioning with double immunohistochemical staining for 5-bromodeoxyuridine (BrdU) and alpha-smooth muscle (alpha-SM) actin. RESULTS: The serum H(e) level in the H(e) group was 36.32 micromol/L +/- 15.28, and in the control group the level was 5.53 micromol/L +/- 2.06 (P =.0007). IH presented as percent lumen stenosis was 21.89% +/- 4.82% in the H(e) group and 4.82% +/- 1.64% in the control group (P =.0007). The linear regression model of the serum H(e) levels and the percent stenosis showed a linear relationship (r2 =.72). The alpha-SM actin staining revealed that nearly all of the cells in the IH area were of smooth muscle or myofibroblast origin and that 10.1% +/- 2.6% of the cells were stained for BrdU in the control group versus 23% +/- 7.1% in the H(e) group. Also, 9.3% +/- 2.6% of the cells in the IH area were stained for BrdU and for alpha-SM actin versus 19.1% +/- 5. 6% stained for both BrdU and alpha-SM actin in the H(e) group. CONCLUSION: This is the first study to examine IH after CEA and hyperhomocysteinemia in rats. The study shows that the elevation of serum H(e) levels can be obtained by feeding rats modified diets with added H(e). The consistent elevation of serum H(e) levels was associated with more than 4 times the amount of IH after a CEA in a rat model.