Saratin, an inhibitor of von Willebrand factor-dependent platelet adhesion, decreases platelet aggregation and intimal hyperplasia in a rat carotid endarterectomy model.

PURPOSE: Post-carotid endarterectomy, thrombosis, and intimal hyperplasia may be decreased by the inhibition of platelet adhesion and activation. In this study, a novel agent, saratin, was used to inhibit platelet-to-collagen adhesion in a rat carotid endarterectomy model. Saratin is a recombinant protein isolated from the saliva of the medicinal leech Hirudo medicinalis, which is thought to act by binding to collagen, and inhibits von Willebrand factor-collagen interaction under conditions of increased shear and therefore, the adherence and activation of platelets at the vessel wall. Saratin has the advantage of being a nonsystemic, site-specific topical application. METHODS: A rat carotid endarterectomy model was used in which an open technique with arteriotomy and intimectomy was used. Saratin was applied to the endarterectomized surface of the carotid artery before arterial closure. End point measurements included platelet adhesion, thrombosis rate, intimal hyperplasia development, bleeding times, and platelet counts. Electron micrographs of carotid arteries were used for quantitative analysis of platelet aggregation and platelet counts. Intimal hyperplasia and thrombosis were assessed with computer-assisted morphometric analysis of elastin-stained carotid artery sections with direct measurement of the intimal hyperplasia area. RESULTS: The topical application of saratin significantly decreased platelet adhesion compared with controls at 3 hours after carotid endarterectomy (64 +/- 17 vs 155 +/- 33 platelets per grid, P = .05), and 24 hours after carotid endarterectomy (35 +/- 11 vs 149 +/- 37 platelets per grid, P = .0110), respectively. A percent luminal stenosis, as a measure of intimal hyperplasia, was significantly decreased with saratin application compared with controls (10.9% +/- 1.8% vs 29.8% +/- 6.8%, P = .0042). This decrease in intimal hyperplasia formation correlated with the inhibition of platelet adhesion. Thirty-three percent of control arteries were found to be thrombosed 2 weeks after carotid endarterectomy compared with a 0% thrombosis rate in the saratin-treated group (P = .0156). No increased bleeding was encountered along the arterial suture line in the saratin group. Bleeding times and systemic platelet counts were not found to change significantly in the saratin-treated rats compared with control rats at 3 and 24 hours after endarterectomy. CONCLUSION: Saratin significantly decreased platelet adhesion, intimal hyperplasia, luminal stenosis, and thrombosis after carotid endarterectomy in rats. Saratin did not increase suture line bleeding or bleeding times, and did not decrease platelet counts. Saratin may serve as a topical agent to be used for the site-specific inhibition of thrombosis and intimal hyperplasia after vascular manipulation.

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.

Surfing-related ocular injuries.

PURPOSE: This report evaluates the clinical characteristics of surfing-related ocular trauma to learn the nature of such injuries and propose possible preventive measures. METHODS: The authors reviewed 11 cases of surfing-related eye injuries caused by direct trauma from the surfboard, studying their mechanism of injury, the associated ocular complications, and the anatomic and visual outcomes of surgical repair. RESULTS: Surfing-related ocular injuries occurred exclusively in young males (mean age, 24.8 years; range, 14-37 years). The mechanism of injury most frequently responsible was impact with the sharp nose of the surfboard following a fall. Serious posterior segment complications were observed in all 11 patients, with nine patients suffering ruptured globes. Despite immediate medical attention, five patients did not recover ambulatory levels of visual acuity (>5/200). CONCLUSIONS: Surfing-related ocular trauma presenting to the retinal specialist typically leaves the patient with a permanent visual disability. Important factors contributing to these high-velocity injuries include the sharply pointed nose of the surfboard and the leash keeping the surfer in close proximity to the board following a fall. A simple modification in surfboard design such as blunting the sharp nose of the surfboard, or appropriate protective guards fitted over the surfboard nose, should lessen the severity of such injuries.

Retinopathy of prematurity: incidence and severity in Hawaii.

Because survival of low birth-weight infants requiring intensive care has improved recently, particularly since the advent of exogenous surfactant therapy, we reviewed our experience at Kapiolani Medical Center for Women and Children (KMCWC) from 1989 to 1991 to determine if the incidence of retinopathy of prematurity (ROP), a serious long-term complication, had also increased. During this 3-year period, threshold disease, the ROP stage in which cryosurgery is recommended, occurred only in infants < or = 1000 grams. Seventy-four infants < or = 1000 grams were diagnosed with ROP of any stage. Sixteen eyes (9 infants) reached threshold; 14 were treated with cryosurgery. Six of these eyes have useful vision on follow up; 8 do not. Exogenous surfactant therapy had no significant effect on ROP incidence or severity in our series. Although ROP incidence did not increase during this review period, it remains a serious problem in high-risk premature infants in our Newborn Intensive Care Unit.

Role of chorioretinal biopsy in inflammatory eye disease.

Two patients who had similar clinical presentations of bilateral multiple chorioretinal lesions and needed a correct diagnosis underwent chorioretinal biopsy. The biopsy from one patient demonstrated mainly a B cell infiltrate in choroidal and subretinal nodules, while the biopsy from the second patient showed mainly macrophages in the retina. These findings directed the therapeutic approach taken in each patient. Although chorioretinal biopsy is an invasive procedure with the potential for serious complications, the resultant finding may aid in the diagnosis and guide the subsequent management of certain patients presenting with serious ocular findings of undefined etiology.

Intraocular pressure during enflurane and neurolept anesthesia in adult patients undergoing ophthalmic surgery.

The effects of neurolept and enflurane anesthesia on intraocular pressure (IOP) were studied in 20 patients undergoing elective ophthalmic surgery. Ten received neurolept and ten enflurane anesthesia. Continuous EEG tracings recorded the level of anesthesia. IOP was measured before and at intervals during anesthesia at varying concentrations of enflurane and incremental doses of fentanyl. During level I neurolept anesthesia IOP increased from control values of 18.10 +/- 0.93 mm Hg (mean +/- SEM) to 19.50 +/- 1.65 mm Hg, but decreased to 14.55 +/- 0.84 mm Hg during level II and to 12.29 +/- 1.13 mm Hg during level III anesthesia. During enflurane anesthesia IOP decreased from control values of 19.00 +/- 1.44 mm Hg (mean +/- SEM) to 14.50 +/- 1.60 mm Hg during level, I, 14.10 +/- 1.04 mm Hg during level II, and 11.60 +/- 1.46 mm Hg during level III anesthesia. The increase in IOP during neurolept level I anesthesia was not statistically significant but the decreases in IOP from control values during levels II and III anesthesia were statistically significant. Decreases in IOP from control values were statistically significant at all levels of enflurance anesthesia. There was, however, no statistical significance between the differences in IOP values during levels II and III neurolept anesthesia, nor between levels I, II, and III enflurane anesthesia. The differences in the mean IOP values between neurolept and enflurane anesthesia were statistically significant only during EEG level I anesthesia.

Mesoectodermal dysgenesis: familial iris anomaly.

A family is described with hypoplasia of the anterior iris stroma, no angle anomalies, and no glaucoma. The pedigree is suggestive of an autosomal dominant mode of inheritance. This is compared to the main peripheral malformations of the anterior chamber cleavage syndrome and other disease entities with similar iris changes. The pedigree represents a point on the continuum of mesoectodermal dysgenesis or anterior chamber cleavage syndrome.