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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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    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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    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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    Neuroprotective effect of N-acetylcysteine and hypothermia on the spinal cord ischemia-reperfusion injury
    (Elsevier Sci Ltd, 2003) Cakir, O; Erdem, K; Oruc, A; Kilinc, N; Eren, N
    The purpose of this study was to investigate the effect of N-acetylcysteine (NAC) on spinal cord ischemia-reperfusion (I-R) in rabbits. Thirty rabbits were divided into five equal groups, group I (sham-operated, no I-R), group II (control, only I-R), group III (I-R + NAC), group IV (I-R + hypothermia), group V (I-R + NAC + hypothermia). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the aortic bifurcation. Forty-eight hours postoperatively, the motor function of the lower limbs was evaluated in each animal according to Tarlov Score. Spinal cord samples were taken to evaluate the histopathological changes. The sham-operated rabbits (group I) showed no neurologic deficit (Score = 4). Paraplegia (Score = 0) developed in all rabbits in the control group (group II). Administration of 50 mg/kg of NAC (group III) resulted in significant reduction of motor dysfunction (Score = 3.1 +/- 1.3, p = 0.002). Application of hypothermia alone (group IV) showed significant recovery of motor functions (Score = 3.0 +/- 1.1, p = 0.002), and combination of hypothermia and 50 mg/kg of NAC (group V) showed complete recovery of lower limb motor function (Score = 4, p = 0.001). Histologic examination of the spinal cord in rabbits with paraplegia revealed several injured neurons. The cords of animals with no motor function deficits showed only minimal cellular infiltrates in the gray matter, and there was good preservation of nerve cells. NAC showed protective effects of the spinal cord. Moderate hypothermia alone also showed protective effects. Combined use of NAC and hypothermia resulted in highly significant recovery of spinal cord function. (C) 2003 The International Society for Cardiovascular Surgery. Published by Elsevier Ltd. All rights reserved.
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    A young adult with coronary artery and jugular vein thrombosis
    (Springer-Verlag, 2002) Çakir, M; Ayyildiz, O; Oruc, A; Eren, N
    Protein C and protein S deficiencies increase the risk of thromboembolic events. We report a case of combined protein C and S deficiency in a young woman, with resulted in acute myocardial infarction and asymptomatic jugular vein thrombosis. The patient was treated successfully with coronary artery hypass graft surgery and systemic anticoagulation. Our report emphasizes that a combined deficiency of protein C and S may be a high risk factor for arterial thromboembolic events in young adults.