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    Does sodium nitroprusside reduce lung injury under cardiopulmonary bypass?
    (Elsevier Science Bv, 2003) Cakir, O; Oruc, A; Eren, S; Buyukbayram, H; Erdinc, L; Eren, N
    Objective: We hypothesized that direct pulmonary arterial infusion of sodium nitroprusside (SNP) would ameliorate lung injury under cardiopulmonary bypass. Methods: Experiments were performed on 12 adult mongrel dogs of both sexes weighing 20-28 kg. The animals were randomly divided into two groups of six animals each. All animals were subjected to total cardiopulmonary bypass (CPB) and moderate hypothermia (28degreesC core temperature). During total CPB, the aorta was clamped together with the pulmonary artery to prevent any antegrade flow to the lungs. After cardioplegic arrest for 120 min, the animals were rewarmed, weaned from CPB, and their condition stabilized for another 90 min. After the release of the aortic cross-clamp, the dogs received either a 5% glucose solution as a placebo (group I) or SNP (0.5 mug/kg per min) (group II), both infused into the pulmonary arterial line. The infusion was stopped after 60 min. To measure lung tissue malondialdehyde (MDA), water content and polymorphonuclear leukocytes count, lung tissue samples were taken before CPB and after weaning from CPB. In addition, alveolar-arterial oxygen difference (AaDO(2)) for tissue oxygenation was calculated by obtaining arterial blood gas samples. Results: Values of MDA before CPB of 42.0 +/- 5.3 nmol/g of tissue rose to 67.6 +/- 5.7 nmol/g of tissue after weaning from CPB in group I (P = 0.028). In group II MDA values also increased from 43.1 +/- 4.3 to 52.4 +/- 5.7 nmol MDA/g of tissue after weaning from CPB (P = 0.046). The MDA increase in group II after CPB was found to be significantly lower than that for group I (P = 0.004). The wet-to-dry lung weight ratio in the sodium nitroprusside group was 5.1 +/- 0.2, significantly lower than in the control group (6.8 +/- 0.4), (P = 0.01). AaDO(2) increased significantly in group I (P = 0.028). There was no statistically significant difference (P = 0.065) between groups I and II. During histopathological examination it was observed that neutrophil counts in the lung parenchyma rose significantly after CPB in both groups. The increase in group I was significantly larger than that in group II (P < 0.001). Conclusions: The results represented in our study indicate that pulmonary arterial infusion of sodium nitroprusside during reperfusion can reduce lung injury under cardiopulmonary bypass. (C) 2003 Elsevier Science B.V. All rights reserved.
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    The effect of aprotinin on ischemia-reperfusion injury in an in situ normothermic ischemic lung model
    (Elsevier Science Bv, 2003) Eren, S; Esme, H; Balci, AE; Cakir, O; Buyukbayram, H; Eren, MN; Erdinc, L
    Objectives: In the context of the physiopathology of damage due to ischemic preservation and reperfusion injury following preservation, we aimed to demonstrate the positive effects of the addition of aprotinin, a serine protease inhibitor, to low potassium dextran (LPD), used as a single-flush solution in normothermic ischemic animal models, on lung protection and the prevention of reperfusion injury. Methods: In the study, 21 New Zealand white rabbits were used as experimental subjects. The subjects were ventilated with the assistance of a manual mechanical ventilator at 30 breaths/min and 10 ml/kg tidal volume. Lung protection solution was supplied to the pulmonary artery via a catheter. After applying the solution, ischemia was carried out for 120 min. At the end of this period, reperfusion was carried out for 90 min. The subjects were divided into three groups of seven subjects each. In the control group, pulmonary perfusion solution was not employed, whereas in the second group LPD was employed, and in the third group LPD and aprotinin (LPD + A) were perfused. Blood gas analysis, bronchoalveolar lavage (BAL) fluid examination, tissue malondialdehyde (MDA) level analysis and morphological examinations were performed. Results: The LPD + A group showed the significantly highest levels of oxygenation at the 15th and 60th minutes of reperfusion (297 +/- 76.7 and 327 +/- 97.4 mmHg) in comparison to the LPD (157 +/- 20.6 and 170 +/- 53.6 mmHg) and control (64 +/- 8.4 and 59 +/- 7.2 mmHg) groups (P < 0.001). The LPD + A group showed the significantly lowest levels of alveolar-arterial oxygen difference at the 60th minute of reperfusion (389 +/- 15 mmHg) in comparison to the LPD (478 +/- 19 mmHg) and control (542 + 23) groups (P < 0.001). The BAL fluid neutrophil percentage was significantly lower in the LPD + A group (22 +/- 2.4%) compared to the LPD (31 +/- 6.1%) and control (38 2.4%) groups. MDA levels were significantly lower in the LPD + A group (119.8 +/- 5.3 nmol MDA/g) when compared to the LPD (145.06 +/- 9.5 nmol MDA/g) and control (147.3 +/- 3.9 nmol MDA/g) groups (P < 0.05). Morphological examinations revealed pathological lesions and alveolar hemorrhaging in all samples, with the LPD + A group having statistically more significant levels than the LPD and control groups (P < 0.005). The LPD + A group had a significantly lower percentage of pathological lesions and alveolar hemorrhage grade values than the LPD and control groups (P < 0.005). Conclusions: It was observed that the addition of aprotinin to LPD solution as a pulmonary flush solution in an in situ normothermic ischemic lung model prevents reperfusion injury by means of various mechanisms and also protects the morphological, functional and biochemical integrity of the lung. In our view, therefore, the addition of aprotinin to lung protection solution will provide positive results in lung transplantation protocols. (C) 2002 Elsevier Science B.V. All rights reserved.
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    Effects of N-acetylcysteine on pulmonary function in patients undergoing coronary artery bypass surgery with cardiopulmonary bypass
    (Sage Publications Ltd, 2003) Eren, N; Çakir, Ö; Oruc, A; Kaya, Z; Erdinc, L
    Cardiopulmonary bypass (CPB) has been implicated in causing poor pulmonary gas exchange postoperatively in patients undergoing coronary artery bypass grafting (CABG) procedures. In this prospective, randomized, double-blind, placebo-controlled study, we examined the pulmonary effects of N-acetylcysteine (NAC) in patients undergoing CABG. Twenty patients undergoing elective CABG and early tracheal extubation were randomized into two groups. Group I (ten patients) received a physiologic salt solution as a placebo in a continuous intravenous infusion for one hour before CPB and 24 hours after CPB; Group II (ten patients) received 100 mg/ kg NAC intravenously for one hour before CPB and 40 mg/kg/day at 24 hours after CPB. Perioperative hemodynamic and pulmonary data were recorded. Postoperative tracheal extubation was accomplished at the earliest appropriate time. The postoperative clinical course was similar in the two groups. Both groups exhibited significant postoperative increases in A-a oxygen gradient (p < 0.01), but patients in Group II exhibited significantly lower increases in postoperative A-a oxygen gradient (p < 0.006). Other hemodynamic and pulmonary data (pulmonary capillary wedge pressure, pulmonary vascular resistance (PVR), cardiac index (CI), shunt flow, dynamic lung compliance and static lung compliance) exhibited no differences between the groups. There was no significant difference in terms of intubation time. The malondialdehyde (MDA) increase in Group II following CPB was found to be significantly lower than in Group I (p = 0.043). This clinical study reveals that administration of NAC to patients undergoing elective CABG with CPB improves systemic oxygenation. There was no effect in other pulmonary parameters and in terms of intubation time.
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    The evaluation of the role of microwave and vitamins on rat eyes related to lipid peroxidation and tissue damage
    (Taylor & Francis Ltd, 2002) Akdag, MZ; Sert, C; Erdinc, L; Dasdag, S; Buyukbayram, H; Celik, MS; Cakmak, SS
    In the present study, the effect of low-intensity microwave radiation on rat eyes and the protective effect of some vitamins against the damage induced by microwave was investigated. 32 Wistar-albino female rats were divided into four groups (1 Control, 3 Experimental) (n=8). The rats of first experimental group were exposed to 9450 MHz microwave (2.65 mW/cm(2)) for one hour a day during 21 days. In addition to exposure with MW as first experimental group, Vitamin E and Vitamin C (150 mg/kg/day) were injected intraperitoneally to second and third experimental groups respectively during last seven days of exposure. The eyes of rats were examined daily after MW and sham exposure by an ophthalmologist biomicroscopically. After completed 21 days exposure period the rats were sacrificed under ketalar anesthesia. The rat eyes were enucleated for histopathological examination and Malondialdehyde (MDA) assay. Sero hemoragic dark brown secretion was observed in rats' conjunctiva of fist and second experimental groups after biomicroscopic examination. However, no damage was detected in the third group. Vacuolization, pleomorphism between cells and increasing of cell layers in lens fibers of all experimental groups were observed histopathologically. In the cornea of experimental groups, cellular loss, shape and size differences among cells and lack of polarity were noticed. Slight edema, congestion, desquamation in epithelial cells, separation between layers in some areas and alteration in pigment cells of retina were also determined in experimental group rats. The MDA (Malondialdehyde) levels of all experimental groups increased significantly compared to control group (P<0.05). However, no significant differences among experimental groups were observed at MDA levels (P>0.05). The temperature differences of all experimental groups were found to be significant compared to control group (P<0.05). Finally, it was determined that low-intensity long-term microwave exposure caused histopathologic alternations and lipid peroxidations on rat eyes.
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    N-acetylcysteine reduces lung reperfusion injury after deep hypothermia and total circulatory arrest
    (Wiley, 2004) Çakir, Ö; Oruc, A; Kaya, S; Eren, N; Yildiz, F; Erdinc, L
    Objective: We hypothesized that the use of N-acetylcysteine would ameliorate the lung reper-fusion injury observed after deep hypothermia and total circulatory arrest (DHTSA). Methods: Experiments were carried out on 12 adult mongrel dogs of either sex weighing 25 to 30 kg. The animals were randomly divided into two groups of six animals each. All animals were cooled to an esophageal temperature of 15 degreesC during 30 minutes and underwent 60 minutes of DHTSA, followed by the reinstitution of cardiopulmonary bypass (CPB) and rewarming. Before rewarming, while 100 mL physiologic saline solution was added into the pump in group 1, 50 mg/kg N-acetylcysteine(NAC) was given in group II. Heart rate, mean arterial pressure, pulmonar arterial pressure, left atrial pressure, central venous pressure, and cardiac output were recorded. To measure lung tissue malondialdehyde (MDA), water content and polymorphonuclear leukocytes (PMNs) count, lung tissue samples were taken before CPB and after weaning CPB. In addition, alveolar-arterial oxygen difference (AaDO(2))for tissue oxygenation was calculated by obtaining arterial blood gas samples. Dynamic lung compliance (DLC) was measured before CPB and after CPB. Results: MDA levels before CPB of 44.2 +/- 3.9 nmol/g tissue rose to 76.6 +/- 5.6 nmol/g tissue after weaning CPB in group I (p = 0.004). In group II also, the MDA levels increased from 43.5 +/- 4.2 to 57.4 +/- 5.6 nmol MDA/g tissue after weaning CPB (p = 0.006). The MDA increase in group 11 after CPB was found to be significantly lower than in group I (p = 0.006). The wet-to-dry lung weight ratio in the NAC group was 5.1 +/- 0.2, significantly less than in the control group (5.9 +/- 0.3), (p = 0.004). AaDO(2) significantly increased in the group I and II (p = 0.002 and p = 0.002, respectively); this elevation in group I was significant than in group II (p = 0.044). In histopathological examination, it was observed that neutrophil counts in the lung parenchyma rose significantly after CPB in both groups (p < 0.001). The increase in group I was significantly larger than group II (p < 0.001). Conclusions: Results represented in our study indicate that addition of NAC into the pump after DHTSA can reduce lung reperfusion injury.
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    The role of enzymatic antioxidant defense system and lipid peroxidation on gentamicin nephrotoxicity in rat renal tissues
    (Mbr Press Inc, 1998) Isik, FB; Erdinc, L; Mete, N; Erdinc, M; Ketani, MA; Yokus, B
    The activities of antioxidant enzymes, superoxide dismutase (SOD), Glutathione peroxidase (GSH-Px) and catalase (CAT), and the levels of malondialdehyde (MDA), an end product of lipid peroxidation, in kidney tissues were measured in rats treated with gentamicin alone (100 mg/kg/day subcutaneously (s.c.)) for 10 days or gentamicin together with vitamin E (300 mg/kg/day intraperitoneally (i.p)) for 10 days. Gentamicin caused depression in activities of the antioxidant enzymes (SOD, GSH-Px, CAT)) and elevation in MDA levels. These effects were highly significant when compared to the effects of placebo in control group (P < 0.001). Vitamin E was found to be ineffective for preventing gentamicin induced nephrotoxicity as determined both functionally and histopathologically. Although there was a borderline decrease of MDA levels (p < 0.05) in rats taking vitamin E, there was no difference in the activities of antioxidant enzymes between the rats taking gentamicin with or without vitamin E. Our finding suggests that gentamicin nephrotoxicity causes a decrease in the activities of antioxidant enzymes and an increase in the level of lipid peroxidation, and vitamin E do not has any preventive effect against gentamicin nephrotoxicity.