Perioperative microemboli and platelet aggregation in patients undergoing carotid endarterectomy.

In carotid endarterectomy (CEA) patients, platelet aggregation is increased despite heparinization. We investigated whether this phenomenon correlates with the occurrence of perioperative microemboli. Of 27 CEA patients, 18 (67%) used aspirin and 9 also used clopidogrel. Blood was collected at multiple time points before, during, and after CEA. Platelet aggregation and P-selectin expression were determined. Transcranial Doppler monitoring was used to measure microemboli. Platelet aggregation showed a significant increase 5 minutes postheparinization compared with preheparinization (19.7 +/- 2.8% vs 8.9 +/- 0.9% in the aspirin group and 22.5 +/- 4.4% vs 8.7 +/- 1.2% in the clopidogrel group; p < .01 and p < .05, respectively). P-selectin expression showed a tendency to increase postheparinization in both groups (p = .07 and p = .09, respectively). The number of microemboli ranged from 0 to 50. Clopidogrel patients displayed fewer microemboli than aspirin patients (4.1 +/- 2.3 vs 17.6 +/- 18.2; p < .01). Patients with a high number of microemboli displayed had a tendency toward higher baseline platelet aggregation than patients with a low number of microemboli (p = .08). In conclusion, platelet aggregation is transiently increased during CEA despite the administration of antiplatelet agents. Clopidogrel is associated with a decreased number of perioperative microemboli. The exact relationships between these findings, postoperative microemboli formation, and the risk for thromboembolic complications after CEA remain to be determined.

Angiostatin inhibits experimental liver fibrosis in mice.

BACKGROUND AND AIMS: Liver fibrosis is a response to chronic hepatic damage, which ultimately leads to liver failure and necessitates liver transplantation. A characteristic of fibrosis is pathological vessel growth. This type of angiogenesis may contribute to the disturbance of hepatocyte perfusion dynamics and lead to aggravation of disease. We hypothesized that angiostatin can inhibit pathological vessel growth and, consequently, the development of hepatic fibrosis. METHODS: Hepatic fibrosis was induced by injection of carbon tetrachloride for 5 weeks. Angiostatin mice received carbon tetrachloride for 5 weeks and angiostatin during weeks 4 and 5. After 5 weeks, immunohistochemistry for endothelial cell marker von Willebrand factor and for cell proliferation was performed. Angiogenesis was quantified by counting the number of immunopositive microvessels. Also, the relative fibrotic surface was determined using Sirius Red histostaining and computer image analysis. RESULTS: Immunohistochemistry revealed increased expression for von Willebrand factor in fibrotic livers. Immunopositive microvessels were localized in fibrotic areas surrounding larger vessels and in emerging fibrotic septa. Angiostatin reduced the number of immunopositive microvessels by 69% (p<0.001). In addition, angiostatin reduced the relative fibrotic area in the liver by 63+/-0.1% (p<0.001). Finally, angiostatin treatment was not associated with differences in cell proliferation. CONCLUSIONS: Angiostatin inhibits the development of pathological angiogenesis and liver fibrosis in mice. These results warrant further evaluation of angiostatin as an antifibrotic agent, potentially contributing to the deferment of liver transplantation and reduced recurrence of fibrotic disease in the transplanted liver.

Intravital analysis of microcirculation in the regenerating mouse liver.

BACKGROUND: Liver tissue remodeling after surgery includes development of new hepatic microvasculature. Although various endothelial growth factors have been shown to play a role in liver tissue repair, the functional consequences of rapid endothelial cell proliferation are unknown. To determine the influence of endothelial cell proliferation on vessel functionality, we have analyzed the in vivo morphology of microvasculature in the regenerating liver. MATERIALS AND METHODS: Mice were subjected to 70% partial hepatectomy (PH) and at 24, 48, 96 h, 7 and 14 days post PH underwent intravital microscopy of the exposed liver remnant. Intrahepatic microvessels were visualized with fluoresceine-labeled dextran. Recorded parameters were: functional vessel length (VL), functional vessel diameter (VD), hepatic cell plate width (PW), and functional vessel surface area (FVSA). RESULTS: VL showed a transient decrease (17-31%) after PH. PW was significantly increased in the regenerating liver. VD significantly increased on days 1 and 2 post PH. On days 4, 7, and 14, VD returned to normal. In contrast, FVSA remained within normal range until day 14 post PH. CONCLUSIONS: Despite changes in vessel length and hepatic cell plate width in the early regenerating liver, functional vessel surface area remains normal until day 14 post PH. These changes may indicate compensatory vascular growth mechanisms to ensure adequate hepatocyte perfusion during liver regeneration. Better understanding of functional variations during physiological liver regeneration may be of use in liver conditions characterized by defective regeneration, e.g., cirrhosis.