Protection of saphenous vein graft from arterial pressure: an experimental study.

BACKGROUND: Reoperations for bypass surgery increase the need for new grafts. We investigated early changes in both the normal human saphenous vein and in ectatic varicose veins externally supported by PTFE (polytetrafluoroethylene) graft and exposed to arterial pressure in an IN VITRO non-pulsatile flow model. MATERIAL AND METHODS: A total of 24 saphenous vein pieces (11 of them normal, the other 13 with varicosities) with a length of 6 centimeters were divided into equal parts; half of these parts were wrapped in PTFE grafts. All vein parts were placed in a perfusion circuit. Tissue biopsies were obtained from the vein segments. Light and electron microscopy examinations were performed, and endothelial continuity, elastic laminate continuity, medial connective tissue uniformity, medial smooth muscle uniformity, and adventitial connective tissue uniformity parameters were identified. RESULTS: All parameters in the PTFE protected vein groups were better. The fewest morphological changes among all four groups were detected in the vein walls from normal veins with PTFE protection. There was no significant difference in endothelial continuity and adventitial connective tissue uniformity between the normal vein group and the varicose vein group with PTFE protection. CONCLUSIONS: It is suggested that supporting vein grafts externally with PTFE sufficiently protects the vein walls against damage from exposure to arterial pressure. If varicose veins are used as arterial grafts, supporting them with PTFE may be useful because of the good protection of endothelial and medial connective tissues, resulting in similar parameters to those of normal vein walls.

Serine protease inhibitor aprotinin ameliorates renal injury in a rat model of ischemia-perfusion injury.

BACKGROUND: Renal ischemia-reperfusion (I/R) injury may occur after renal transplantation, thoracoabdominal aortic surgery, and renal artery interventions. OBJECTIVE: To investigate the therapeutic effects of aprotinin on tissue protection against I/R injury in a rat model. N-acetylcysteine (NAC), a potent antioxidant, was also tested to assess the experimental model. MATERIALS AND METHODS: Twenty-four rats were categorized into 3 groups of 8 rats each: those receiving isotonic sodium chloride solution (control group); NAC, 150 mg/kg; and aprotinin, 40,000 KIU/kg. The animals underwent unilateral nephrectomy after 60 minutes of warm ischemia and 60 minutes of reperfusion of the kidney. Malondialdehyde, a lipid peroxidation marker, and antioxidant glutathione levels were measured in the kidney parenchyma. Tissue samples were obtained for histologic analysis. RESULTS: Compared with the control group, the NAC group demonstrated significantly low levels of malondialdehyde (P = .04) and high levels of glutathione (P = .01). At histopathologic analysis, less acute tubular necrosis (ATN) and cellular swelling was noted in the NAC group (P = .002 and P = .005, respectively). In the aprotinin group, histopathologic analysis revealed less tissue damage in terms of ATN (P < .001, cellular swelling (P < .001), and vacuolysis (P = .002). Compared with the NAC group, ATN (P = .01), vacuolysis (P = .04), and congestion (P = .05) were significantly less in the aprotinin group. CONCLUSIONS: Our results suggest that administration of aprotinin attenuates renal I/R injury. This observation has potential application for kidney preservation for transplantation, for aortic surgery, and for renal artery interventions by protecting cells from free radical damage.

Attenuation of acute lung injury following lower limb ischemia/reperfusion: the pharmacological approach.

AIM: The purpose of this study was to examine the effects of N-acetylcysteine (NAC), calcium dobesilate (DOBE) and aprotinin on the amelioration of lung damage following ischemia/reperfusion injury in a rat hind limb model. A well known antioxidant dimethyl-sulfoxide (DMSO) was also tested for comparison. METHODS: Ischemia was induced in the lower limb for 4 h by vascular clamping and followed by 1 h of reperfusion. Lung injury was evaluated in 5 groups as a saline (control), DMSO, NAC, DOBE and aprotinin group. Plasma creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances (TBARS) as well as lung tissue TBARS levels were measured. Lung tissue samples were taken for histological examination. P<0.005 was considered statistically significant. RESULTS: Plasma TBARS values were found to be significantly lower in the DMSO (P<0.005), NAC (P<0.005) and aprotinin (P<0.005) groups compared to the control group. Lung TBARS values were significantly lower in the DMSO, NAC, DOBE and aprotinin groups compared to the control group (P<0.001, P<0.001, P<0.001). Also in the aprotinin group lung TBARS values were found to be significantly lower compared to DMSO (P<0.001), NAC (P<0.001) and DOBE (P<0.001) groups. Histological examination showed less prominent peribronchial leukostasis (P<0.005) and interstitial leukostasis (P<0.005) in all drug groups compared to the control group. CONCLUSION: These observations indicate that DOBE and NAC, which are known to have antioxidant properties and aprotinin, a serine proteinase inhibitor, acted effectively on the prevention of lung injury in a rat hind limb ischemia/reperfusion model. The reason why aprotinin exerts a more protective effect than the other drugs is not clear, however, its clinical use may have the dual advantage of hemostasis and lung protection in surgical practice.

The effects of clopidogrel and calcium dobesilate on intimal hyperplasia following vascular injury.

BACKGROUND: Neo-intimal hyperplasia is one of the most common causes of failure of arterial patency following cardiovascular interventions. It has been proposed that clopidogrel and calcium dobesilate may play an important role in the amelioration of intimal hyperplasia. The aim of this study is to examine the effect of these agents on intimal hyperplasia occurring after experimental balloon catheter injury. MATERIAL AND METHODS: Twenty-four male New Zealand rabbits were divided into three groups. Endothelial injury was caused by introducing a 2.5 x 20 mm balloon angioplasty-catheter into the left iliac artery. After the procedure, clopidogrel (25 mg/kg/day/orally) or calcium dobesilate (100 mg/kg/day/orally) were given for 2 weeks. Eight rabbits were given a placebo and served as controls. The contralateral non-injured iliac arteries of the control group were considered as normal iliac artery samples. Iliac artery specimens were examined planimetrically and the intima/media ratio was obtained for each vessel. RESULTS: In the control group, the intima/media ratio was still significantly higher (p < 0.05) than the contralateral normal artery 14 days after the balloon catheter injury. In the clopidogrel and calcium dobesilate groups, this ratio had significantly decreased when compared with the control group (p < 0.05). No significant difference was found when the clopidogrel and calcium dobesilate groups were compared. CONCLUSION: The anti-agregant agent clopidogrel, and the venous endothelial regulator calcium dobesilate, ameliorate intimal hyperplasia after experimentally induced vascular injury in rabbit iliac arteries.

Histopathological and immunohistochemical detection of protective effects of University of Wisconsin solution supplemented with iloprost on donor lung damage.

OBJECTIVE: Histopathological evaluation and immunohistochemical markers of surfactant B and CD34 were used to detect alveolar type II cell and pulmonary endothelial cell damage in order to assess the efficacy on donor lung protection of University of Wisconsin (UW) solution supplementation with iloprost. METHODS: Twelve rats were divided into two groups: UW solution was used alone in group I, and UW iloprost solution in group II. Lung samples were taken at regular intervals for pathological examination to evaluate alveolar cell integrity with hematoxylin and eosin staining. Preservation, of alveolar type II cell and pulmonary endothelial cells was assessed using surfactant B and CD34 immunomarkers, respectively. RESULTS: In both groups, alveolar integrity, surfactant, and CD34 revealed time-dependent, progressive damage, although this deterioration was less apparent among the iloprost-supplemented group. Alveolar integrity was better preserved at 4, 6, 8, 12, and 48 hours among group II rate. Surfactant staining showed significantly more deterioration at 12 and 24 hours in group I. Similarly, CD34 demonstrated significantly more injury at 6, 12, 24, and 48 hours in group I. CONCLUSION: Although progressive lung tissue damage assessed by histopathological and immunohistochemical methods was observed in both groups, our findings suggest less deterioration in the iloprost-supplemented group.

Calcium dobesilate ameliorates lung injury following lower limb ischemia/reperfusion.

We examined the effects of calcium dobesilate on ameliorating the lung damage following ischemia-reperfusion injury in skeletal muscle of rats. A well known antioxidant, dimethyl sulfoxide, was also tested for comparison. The study included three groups: normal saline, dimethyl sulfoxide and calcium dobesilate. Plasma bicarbonate, creatine kinase, lactate dehydrogenase, thiobarbituric acid reactive substances (TBARS), as well as muscle and lung tissue TBARS levels were measured. Lung tissue samples were taken for histological examination. The dimethyl sulfoxide group showed significant amelioration of plasma (p = 0.004), skeletal muscle (p = 0.006) and lung TBARS (p = 0.004) levels, compared with controls. Calcium dobesilate-treated rats showed significantly low level muscle (p = 0.025) and lung TBARS (p = 0.004), compared with the control group. The extent of lung injury according to the histological findings was less in the dimethyl sulfoxide (p = 0.004) and calcium dobesilate (p = 0.003) groups. These observations indicated that calcium dobesilate acted effectively in the prevention of lung damage following ischemia-reperfusion injury in the rat skeletal muscle.