Faruk Metin Çomu

Dexmedetomidine protects against lipid peroxidation and erythrocyte deformability alterations in experimental hepatic ischemia reperfusion injury.

Background : Hepatic ischemia–reperfusion injury is a common clinical problem in hepatic surgery and transplantation. Several cellular and tissue structural and functional alterations are observed in such injury. The aim of this study was to evaluate the effect of dexmedetomidine on lipid peroxidation and erythrocyte deformability during ischemia–reperfusion injury in rats. Methods : Twenty-four Wistar Albino rats were randomly separated into three groups as control (C), ischemia–reperfusion injury (I/R) and dexmedetomidine group (I/R-D). Ischemia was induced with portal clampage for 45 min and reperfusion period was 45 min after declampage. Group I/R-D received dexmedetomidine 100 µg/kg i.p. 30 min before portal clampage. Serum malondialdehyde and superoxide dismutase activities to document lipid peroxidation and erythrocyte deformability index were investigated. Results : Serum superoxide dismutase and malondialdehyde activity levels were significantly higher and erythrocyte deformability index was decreased in hepatic ischemia–reperfusion group. However, these changes were observed to be prevented with dexmedetomidine treatment when given before portal clampage. Conclusion : These findings clearly indicate that erythrocyte deformability index is decreased in hepatic ischemia reperfusion injury and has a potential role to prevent these alterations. The protective effect of dexmedetomidine on hepatic I/R injury is also decreased lipid peroxidation. Further experimental and clinical investigations may clarify the molecular mechanisms and clinical significance of these findings.

The effect of hypothermia on splanchnic flows and lung in a two-hit hemorrhagic shock model.

BACKGROUND To evaluate the effect of hypothermia on bacterial translocation, splanchnic vascular flow, lung tissue weight, and levels of malondialdehyde (MDA) and nitric oxide (NO) in a two-hit model of hemorrhagic shock. METHODS Thirty rats were randomly allocated into three groups of 10 rats each. In the control group (group C), rats were treated without hemorrhage, and normothermia (37 degrees C) was maintained. In the mild hypothermia group (group MH), rats were subjected to volume-controlled hemorrhage (2 mL/100g) and a rectal temperature of 34 degrees C was maintained. In the normothermic group (group NT), rats were treated as in group MH, except for hypothermia. Seventy-two hours after hemorrhagic shock (first insult), Pseudomonas aeuruginosa was administered intratracheally as a second insult. Finally, mesenteric vascular flow patterns were recorded. Bacterial translocation was studied from tissue samples of spleen, liver, and mesenteric lymph nodes. Blood samples were obtained to evaluate the possible presence of bacteria in the bloodstream. Lung tissue weight ratio, MDA, and NO levels in lung tissue were assessed. RESULTS Renal, mesenteric, and portal venous flow rates were found to be lower in groups MH and NT in comparison with group C. Blood flow profiles were lower in group NT than in group MH (P<0.05). Bacterial translocation was not observed in group C, and it was detected more often in group NT than in group MH. Lung weight ratio was found to be higher in group NT compared with groups MH and C. Although it did not reach the level of statistical significance, MDA level in the control group was lower than that in the NT group (P=0.085). CONCLUSION Hypothermia corrected mesenteric blood flow and decreased the occurrence of bacterial translocation in the two-hit model of hemorrhagic shock and tracheal inoculaton of P. aeruginosa.

Gender-related alerations in erythrocyte mechanical activities under desflurane or sevoflurane anesthesia

Alterations in erythrocyte mechanical activities under the influence of anesthesia have been observed and discussed among the responsible factors for the deterioration of tissue and organ perfusion related to anesthetic procedures.21 female and 17 male Swiss Albino rats were used. Female (f) and male (m) rats were divided into 3 groups; control (f (n=7); m (n=5)), sevoflurane treated group (f (n=7); m (n=5)), desflurane treated group (f (n=7); m (n=7)). 2% of sevoflurane or 6% desflurane were applied to the rats with inhalation in an adjustable cage for one hour. The deformability indexes of the erythrocytes were measured by a laser diffractometer (Myrenne Rheodyne SSD). Sevoflurane anesthesia has improved the deformability of erythrocytes in male rats (p<0.05) whereas there were not any significant changes in female rats. Desflurane has improved the deformability of erythrocytes in both gender significantly (p<0.05). Volatil anesthetic agents sevofluran and desflurane has improved the mechanical properties of the erythrocytes in male rats compared to their controls. However, these changes were not significant with sevoflurane in females. The results in male rats may be due to the effects of testosterone on the flexibility of the erythrocytes leading them to tolerate to the environmental changes. These results reveal that the inhalation anesthetics like sevoflurane and desflurane are appropriate anesthetics which can improve the deformability of erythrocytes during surgery.

Effects of alprostadil and iloprost on renal, lung, and skeletal muscle injury following hindlimb ischemia–reperfusion injury in rats

Objectives To evaluate the effects of alprostadil (prostaglandin [PGE1] analog) and iloprost (prostacyclin [PGI2] analog) on renal, lung, and skeletal muscle tissues after ischemia reperfusion (I/R) injury in an experimental rat model. Materials and methods Wistar albino rats underwent 2 hours of ischemia via infrarenal aorta clamping with subsequent 2 hours of reperfusion. Alprostadil and iloprost were given starting simultaneously with the reperfusion period. Effects of agents on renal, lung, and skeletal muscle (gastrocnemius) tissue specimens were examined. Results Renal medullary congestion, cytoplasmic swelling, and mean tubular dilatation scores were significantly lower in the alprostadil-treated group than those found in the I/R-only group (P<0.0001, P=0.015, and P<0.01, respectively). Polymorphonuclear leukocyte infiltration, pulmonary partial destruction, consolidation, alveolar edema, and hemorrhage scores were significantly lower in alprostadil- and iloprost-treated groups (P=0.017 and P=0.001; P<0.01 and P<0.0001). Polymorphonuclear leukocyte infiltration scores in skeletal muscle tissue were significantly lower in the iloprost-treated group than the scores found in the nontreated I/R group (P<0.0001). Conclusion Alprostadil and iloprost significantly reduce lung tissue I/R injury. Alprostadil has more prominent protective effects against renal I/R injury, while iloprost is superior in terms of protecting the skeletal muscle tissue against I/R injury.

Effect of picroside II on erythrocyte deformability and lipid peroxidation in rats subjected to hind limb ischemia reperfusion injury.

Background Ischemia reperfusion injury (I/R) in hind limb is a frequent and important clinical phenomenon. Many structural and functional damages are observed in cells and tissues in these kinds of injuries. In this study, we aimed to evaluate the effect of picroside II on lipid peroxidation and erythrocyte deformability during I/R in rats. Methods Rats were randomly divided into four groups – each containing six animals (sham, I/R, sham + picroside II, and I/R + picroside II). The infrarenal section of the abdominal aorta was occluded with an atraumatic microvascular clamp in I/R groups. The clamp was removed after 120 minutes and reperfusion was provided for a further 120 minutes. Picroside II (10 mg·kg−1) was administered intraperitoneally to the animals in the appropriate groups (sham + picroside II, I/R + picroside II groups). All rats were euthanized by intraperitoneal administration of ketamine (100 mg·kg−1) and taking blood from the abdominal aorta. Erythrocytes were extracted from heparinized complete blood samples. Buffer (PT) and then erythrocytes (PE) were passed through the filtration system and the changes in pressure were measured to investigate the role of serum malondialdehyde and nitric oxide (NO) in lipid peroxidation and erythrocyte deformability index. Results Deformability index was significantly increased in the I/R group compared to groups sham, sham + picroside-II, and I/R + picroside-II (P<0.0001, P<0.0001, and P=0.007). Malondialdehyde (MDA) and NO levels were evaluated. MDA level and NO activity were also higher in the I/R group than in the other groups. Picroside II treatment before hind limb I/R prevented these changes. Conclusion These results support that deformability of erythrocytes is decreased in I/R injury and picroside II plays a critical role to prevent these alterations. Further experimental and clinical studies are needed to evaluate and clarify the molecular mechanisms of action and clinical importance of these findings.

The effect of levosimendan on myocardial ischemia–reperfusion injury in streptozotocin-induced diabetic rats

Objective Ischemia/reperfusion (I/R) injury is an important cause of myocardial damage by means of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine the potential cardio protective effects of levosimendan in a diabetic rat model of myocardial I/R injury. Methods A total of 18 streptozotocin-induced diabetic Wistar Albino rats (55 mg/kg) were randomly divided into three equal groups as follows: the diabetic I/R group (DIR) in which myocardial I/R was induced following left thoracotomy, by ligating the left anterior descending coronary artery for 60 min, followed by 2 h of reperfusion; the diabetic I/R levosimendan group (DIRL), which underwent I/R by the same method while taking levosimendan intraperitoneal 12 µg kg−1; and the diabetic control group (DC) which underwent sham operations without tightening of the coronary sutures. As a control group (C), six healthy age-matched Wistar Albino rats underwent sham operations similar to the DC group. Two hours after the operation, the rats were sacrificed and the myocardial tissue samples were examined by light microscopy for evidence of myonecrosis and inflammatory cell infiltration. Results Myonecrosis findings were significantly different among groups (p=0.008). Myonecrosis was more pronounced in the DIR group compared with the C, DC, and DIRL groups (p=0.001, p=0.007 and p=0.037, respectively). Similarly, the degree of inflammatory cell infiltration showed significant difference among groups (p<0.0001). Compared with C, DC, and DIRL groups, the inflammatory cell infiltration was significantly higher among the DIR group (p<0.0001, p<0.0001, and p=0.020, respectively). Also, myocardial tissue edema was significantly different among groups (p=0.006). The light microscopic myocardial tissue edema levels were significantly higher in the DIR group than the C, DC, and DIRL groups (p=0.001, p=0.037, and p=0.014, respectively). Conclusion Taken together, our data indicate that levosimendan may be helpful in reducing myocardial necrosis, myocardial inflammation, and myocardial tissue edema resulting from ischemia–reperfusion injury.

Effect of Sevoflurane and Desflurane on Erythrocyte Deformability during Ischaemia-Reperfusion Injury of Lower Extremity in Diabetic Rats

Aim: It is known that blood viscosity and erythrocyte aggregation are increased and erythrocyte deformability is decreased in diabetic patients. Ischemia reperfusion injury (I/R) in lower extremity is a frequent and important clinical phenomenon. Blood rheology is known to be affected by numerous factor including anaesthetic drugs. Accordingly, we aimed to investigate the effects of sevoflurane and desflurane on erythrocyte deformability in infrarenal aorta of diabetic rats undergoing I/R Materials and methods: In this study, 30 male Wistar albino rats. After the effects of chronic diabetes encountered diabetic rats were randomly assigned into diabetic control (group DC), diabetic I/R group (group D-I/R), diabetic I/R group with desflurane (group D-I/R-D), and diabetic I/R group with sevoflurane (group D-I/R-S) groups. Another 6 rats without diabetes were assigned as control group (group C). 4 weeks after the injection of streptozotocin diabetic rats were anaesthetized by desflurane 6% or sevoflurane 2% at a dose by which minimal alveolar concentration (MAC) for rats would be one. The drugs were given for 4 hours within 100% oxygen at a rate of 4L.min 1 . Erythrocyte samples were obtained from heparinized whole blood samples. Measurements for deformability were conducted on erythrocyte suspensions within serum physiologic tamponized with phosphate. Results: Deformability index was significantly increased in diabetic rats (p<0.001), however, it was similar in GroupD-I/R, GroupDI/R-D and GroupD-I/R-S (p=0.570, p=0.951 respectively). It was significantly increased in GroupD-I/R,D-I/R-D and D-I/R-S when compared to GroupDC (p=0.001, p=0.004, p=0.001 respectively). Relative resistance was increased in diabeticand I/R models. Conclusion: Neither sevoflurane nor desflurane caused a negative effect on erythrocyte deformability in infrarenal aorta of diabetic rats undergoing I/R diabetic rats. However these findings should be further investigated in larger and more detailed studies.

Protective effect of hypothermia in a blunt thoracic trauma and hemorrhagic shock model.

BACKGROUND The aim of this study was to investigate the effect of volume-controlled hemorrhage and hypothermia on rats with blunt chest trauma, evaluating bacterial translocation (BT), lung tissue malondialdehyde (MDA), nitric oxide (NO) levels, and erythrocyte deformability (ED). METHODS In our study, 10 animals each were included in 6 groups. Groups were as follows: a group with blunt chest trauma only (Group T), a group with hemorrhage only (Group H), a normothermic group with comorbidity of trauma and hemorrhage (Group NT), a mild hypothermic group with trauma and hemorrhage (Group MH), a moderate hypothermic group with trauma and hemorrhage (Group MoH), and a control group (Group C). Sodium pentobarbital (50 mg/kg, intraperitoneally) anesthesia was administered. Thoracic trauma was generated using kinetic energy at the middle of the chest (2.45 J). Stage 3 hemorrhagic shock was initiated. After 24 hours, the rats were killed and red blood cell deformability, BT development in the liver, spleen, and mesenteric lymph nodes, and NO and MDA levels in lung tissue, kept at -80°C, were measured. RESULTS In Groups MH and MoH, there was no difference in ED values, though they were lower than those in Group NT (p<0.05). BT was more prevalent in Group NT than in the other groups. In Group NT, the growth of BT was greater than in other groups (p<0.05). The level of NO in Group H was higher than in the control group (p<0.05). In Group MoH, the level of MDA was lower than in Group MH (p<0.05). CONCLUSION Hypothermia seems to demonstrate protective effects on ED and BT by reducing oxidative stress. The protective effects of therapeutic hypothermia on ED may be due to the effect of reducing NO and/or MDA. There was no difference in effect between mild and moderate hypothermia in terms of the formation of ED and BT.

Effects of lornoxicam and intravenous ibuprofen on erythrocyte deformability and hepatic and renal blood flow in rats

Background Change in blood supply is held responsible for anesthesia-related abnormal tissue and organ perfusion. Decreased erythrocyte deformability and increased aggregation may be detected after surgery performed under general anesthesia. It was shown that nonsteroidal anti-inflammatory drugs decrease erythrocyte deformability. Lornoxicam and/or intravenous (iv) ibuprofen are commonly preferred analgesic agents for postoperative pain management. In this study, we aimed to investigate the effects of lornoxicam (2 mg/kg, iv) and ibuprofen (30 mg/kg, iv) on erythrocyte deformability, as well as hepatic and renal blood flows, in male rats. Methods Eighteen male Wistar albino rats were randomly divided into three groups as follows: iv lornoxicam-treated group (Group L), iv ibuprofen-treated group (Group İ), and control group (Group C). Drug administration was carried out by the iv route in all groups except Group C. Hepatic and renal blood flows were studied by laser Doppler, and euthanasia was performed via intra-abdominal blood uptake. Erythrocyte deformability was measured using a constant-flow filtrometry system. Results Lornoxicam and ibuprofen increased the relative resistance, which is an indicator of erythrocyte deformability, of rats (P=0.016). Comparison of the results from Group L and Group I revealed no statistically significant differences (P=0.694), although the erythrocyte deformability levels in Group L and Group I were statistically higher than the results observed in Group C (P=0.018 and P=0.008, respectively). Hepatic and renal blood flows were significantly lower than the same in Group C. Conclusion We believe that lornoxicam and ibuprofen may lead to functional disorders related to renal and liver tissue perfusion secondary to both decreased blood flow and erythrocyte deformability. Further studies regarding these issues are thought to be essential.