Koray Ak

Genetic Polymorphisms Contribute to Acute Kidney Injury after Coronary Artery Bypass Grafting

BACKGROUND Acute kidney injury is one of the most serious complications after cardiac surgery. Genetic polymorphisms are reported to be associated with postoperative renal impairment. The aim of this study was to investigate the relationship between selected gene polymorphisms and acute kidney injury after cardiac surgery. METHODS Two hundred forty-eight elective coronary artery bypass grafting procedure patients were enrolled in the study. Angiotensin-converting enzyme (ACE) II, ID, and DD, apolipoprotein E (APO E), and angiotensin II type 1 receptor (AGTR1) A1166C genotypes were detected by polymerase chain reaction. Plasma levels of ACE were analyzed by enzyme-linked immunosorbent assay. Acute kidney injury after cardiac surgery was graded according to the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) classification. RESULTS In our study, 21.8% of patients had acute renal impairment after cardiac surgery. Among the 54 patients with acute kidney injury, ACE D allele frequency was 0.620. The plasma levels of ACE were significantly higher in the D allele carriers (P = .018). Three of the 54 patients with acute kidney injury were APO E epsilon 4 allele carriers (P = .002). AGTR1 C allele carriers constituted 46% of all patients with postoperative acute kidney injury. There was no statistically significant difference between A allele homozygotes and C allele carriers with respect to postoperative renal dysfunction (P > .05). CONCLUSIONS The present findings support the hypothesis that ACE I/D and APO E gene polymorphisms may play a role in the development of acute kidney injury after cardiac surgery. However, AGTR1 does not have a unique association with postoperative renal impairment.

Neuroprotective effects of FK-506, l-carnitine and azathioprine on spinal cord ischemia-reperfusion injury

OBJECTIVE In our experimental study, we aimed to test the effect of FK506, azathioprine and L-carnitine on protection of spinal cord injury due to ischemia-reperfusion. METHODS Twenty-seven Sprague-Dawley male rats were randomly divided into five groups. They were subjected to spinal cord ischemia by clamping the abdominal aorta for 45 min. Thirty minutes before the aortic clamping, group I received 0.5 mg/kg FK506, group II received 100 mg/kg L-carnitine, group III received 4 mg/kg azathioprine, the fourth group was the control group and received only normal saline injection intravenously and the last group was the sham group. Neurological status was scored by using the Tarlov scoring system. Sections of the lumbar cord were harvested for histopathological grades (1-4), having regard to percentage of the apoptotic cells. RESULTS Hind-limb motor function had recovered normally 48 h after the operation in all rats which received FK506, azathioprine and L-carnitine prophylactically. In contrast, all rats in the control group had deteriorated to paraplegia by 48 h after the operation (P<0.05). Histopathologic sections in the involved spinal cord segment showed that a greater number of motor neuron cells were preserved and there were less apoptotic cells in the rats that received FK506, azathioprine and L-carnitine than those in control group. CONCLUSIONS These results suggest that prophylactic use of FK506, azathioprine and L-carnitine protects motor neuron cells from ischemic spinal cord injury.

Ischemic preconditioning and nicotinamide in spinal cord protection in an experimental model of transient aortic occlusion.

OBJECTIVES Spinal cord injury is a devastating complication after aortic surgery. The aim of the present study is to examine the effects of ischemic preconditioning (IPC) and nicotinamide containing perfusate in transient aortic occlusion in the rat. METHODS Thirty-two male Spraque-Dawley rats under general anesthesia were randomly assigned to four groups (n=8 in each group). The infrarenal aortas were clamped for 45 min. Groups were as follows: Group 1, undergoing occlusion but receiving no treatment. Group 2, had 5 min of IPC before occlusion. Group 3, received nicotinamide (0.2 ml/l) during the transient occlusion. Group 4, received combined IPC (5 min) and nicotinamide infusion during the transient occlusion. The rats were then allowed for recovery and were tested for their neurological status. All animals were sacrificed at the end of the 48 h and spinal cords also examined histologically. Anti- poly (ADP-ribose) polymerase p85 fragment pAb was used as an immunohistochemical marker for detection of apoptosis. RESULTS In 24 h paraplegia represented as grade 0 and 1 occurred in six animals in Group 1 and two animals in Groups 2 and 3 and one in Group 4. In 48 h six animals in Group 1 and only one animal in Groups 2 and 3 showed a paraplegia. The incidence of neurologic deficit was significantly reduced in animals who had IPC and nicotinamide infusion (P<0.05). At 48 h, combined IPC and nicotinamide showed a significant benefit compared to nicotinamide but not to the IPC alone. Histologic examination of the spinal cords revealed that a neuronal necrosis contributes to acute spinal cord degeneration after a period of aortic occlusion and both nicotinamide and IPC have protective effects against neuronal necrosis. No difference was found among the groups. CONCLUSIONS Both IPC and nicotinamide are beneficial in protection against neurological damage in transient aortic occlusion. IPC alone as expected is significantly beneficial both at 24 and 48 h compared to controls. At 24 h combined nicotinamide and IPC show significant benefit compared to only nicotinamide, but this difference is not maintained at 48 h.

The effects of pulsatile cardiopulmonary bypass on acute kidney injury.

Purpose: Protective effect of pulsatile flow cardiopulmonary bypass (CPB) on the occurrence of acute renal injury is still a matter of debate. The objective of this study was to compare the effects of pulsatile and non-pulsatile cardiopulmonary bypass on kidneys using Urinary neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) as the markers of renal injury. Methods: 85 consecutive patients with normal preoperative renal function were prospectively enrolled in the study. Pulsatile perfusion (Group P) and non-pulsatile perfusion (Group NP) was used in 42 and 43 of the patients, respectively, during aortic cross-clamping period. NGAL and IL-18 were analyzed using ELISA in urine samples obtained preoperatively, and at 2, 12, and 24 h after CPB. Results: There was no significant difference between the groups in terms of perioperative renal function tests. IL-18 levels measured at 12 h after CPB were significantly lower in Group P, compared to Group NP (p<0.05). Urinary NGAL levels measured at 2 and 12 h were higher in Group NP; however, the difference was insignificant. In the subgroup of patients with a cross clamp time ≥45 minutes (pulsatile CPB, group P1, n = 33; non-pulsatile CPB, group NP1, n = 33), IL-18 levels measured at 12 hours after CPB were significantly lower in Group P1. Urinary NGAL concentrations measured at 2 and 12 hours in Group P1 were also significantly lower than that in Group NP1 (p = 0.048 and 0.043, respectively). Conclusions: Low IL-18 and NGAL levels found in the pulsatile perfusion group might suggest the use of pulsatile flow resulted in better kidney protection.

Postoperative Statin Therapy Attenuates the Intensity of Systemic Inflammation and Increases Fibrinolysis After Coronary Artery Bypass Grafting

A total of 25 patients undergoing coronary artery bypass grafting (CABG) were included in the study. Patients received statin (20 mg daily) postoperatively for 2 weeks. All analyses were performed at 2 different time points: preoperatively (group 1) and 2 weeks after operation (group 2). Interleukin (IL)-6, IL-8, plasminogen activator inhibitor 1 (PAI-1), tumor necrosis factor α (TNF-α), tissue plasminogen activator (t-PA) levels, and tissue factor pathway inhibitor (TFPI) were evaluated. Statin treatment caused a significant reduction in the plasma level of PAI-1 (preop: 15.04 ± 0.13 ng/mL vs postop: 13.89 ± 2.14 ng/mL; P < .05) and increased t-PA levels (preop: 109.74 ± 0.13 vs postop: 231.40 ± 1.22 ng/mL; P < .001). Plasma TNF-α and IL-6 levels did not change with treatment. Statin treatment caused a significant reduction in plasma IL-8 level (279.70 ± 3.42 ng/mL vs postop: 207.18 ± 3.63 ng/mL, P < .05), and TFPI (4.87 ± 2.05 ng/mL vs postop: 6.27 ± 1.25 ng/mL; P < .05). The results demonstrate that atorvastatin attenuates systemic inflammatory reaction after cardiac surgery.

Effect of a Low Molecular Weight Heparin Molecule, Dalteparin, on Cellular Apoptosis and Inflammatory Process in an Incisional Wound-Healing Model

PurposeIn this study we aimed to test the effect of a low molecular weight heparin molecule, namely dalteparin, on the inflammation and cellular apoptosis in an incisional wound-healing model in rats.MethodsEighteen male Sprague–Dawley rats were randomly assigned to three groups (n = 6 for each group). Two full-thickness skin incisions were made over cervical and lumbar regions of all rats. Group 1 (sham group) received no treatment, group 2 (control group) received 0.01 ml/g saline subcutaneously 12 h two times daily from 0 to 10th postoperative day, and group 3 (dalteparin group): received 1 IU/g dalteparin subcutaneously two times daily from 0 to 10th postoperative day. A histological evaluation was done by light microscopy. Apoptosis was detected immunohistochemically by anti-poly (ADP-ribose) polymerase p85 fragment pAb.ResultsThe early inflammatory response and related tissue edema were depressed on day 3 in the dalteparin group when compared with those in the other groups (P < 0.05). Fibroblast proliferation was also depressed on day 10 in the dalteparin group compared to the others (P < 0.05). Furthermore, increased apoptosis was detected in the dalteparin group both on day 3 and day 10.ConclusionOur results showed that dalteparin may adversely affect the incisional wound healing by suppressing the early inflammatory process and increasing cellular apoptosis; however, further studies are warranted to confirm the results.

The protective effects of tacrolimus on rat uteri exposed to ischemia-reperfusion injury: a biochemical and histopathologic evaluation

OBJECTIVE To evaluate the effects of the immunosuppressant tacrolimus as an antioxidant and analyze the histopathologic changes in rat uteri exposed to experimental ischemia-reperfusion (I/R) injury. DESIGN Experimental study. SETTING Experimental surgery laboratory in a university. ANIMAL(S) Twenty-eight female rats exposed to experimentally induced uterine I/R injury. INTERVENTION(S) Group I: control group; group II: uterine I/R injury-induced group; group III: pre-ischemia tacrolimus group; group IV: post-ischemia tacrolimus group. MAIN OUTCOME MEASURE(S) Uterine tissue malondialdehyde (MDA) level as a marker of lipid peroxidation and glutathione (GSH) level and superoxide dismutase (SOD) and catalase (CAT) activities as markers of tissue antioxidant capacity; histopathologic examination of all uterine rat tissue. RESULT(S) Following aortic I/R injury, MDA levels were significantly increased whereas GSH levels and CAT and SOD activities were found to be decreased compared with control animals. MDA levels were found to recover prominently after the administration of tacrolimus in both groups III and IV. Administration of tacrolimus improved uterine GSH levels and CAT activity in the tacrolimus-treated groups. CONCLUSION(S) Our results indicate that tacrolimus reduces oxidative damage in rat uteri exposed to I/R injury induced by distal abdominal aortic occlusion. Histologic evaluation reveals that tacrolimus attenuates the inflammatory response and protects the tissue damage induced by I/R injury.

Clopidogrel Provides Significantly Greater Inhibition of Platelet Activity Than Aspirin When Combined With Atorvastatin After Coronary Artery Bypass Grafting: A Prospective Randomized Study:

Objective: We aimed to compare the effects of 2 different antiplatelet agents on platelet activity in patients receiv- ing atorvastatin after coronary artery bypass grafting (CABG). Methods: We prospectively randomized 50 patients undergoing CABG into 2 groups; group 1 started to receive atorvastatin (10 mg) plus clopidogrel (75 mg; C + A, n = 25) and group 2 atorvastatin (10 mg) and acetylsalicylic acid (ASA; 300 mg, ASA + A, n = 25) daily on postoperative day 1 and continued for 6 months after operation. Adenosine diphosphate (ADP)–induced pla- telet aggregation and the expressions of glycoprotein (Gp) IIb, GpIIIa, P-selectin, and fibrinogen (Fg) and low-density lipoprotein (LDL) binding to platelets were assessed preoperatively and at postoperative days 7, 90, and 180. Results: The mean age of the patients was 59.6 ± 7.6 years, and 82% of the patients were males. The combination of C + A markedly inhibited ADP-induced platelet aggregation compared with ASA + A at postoperative days 90 and 180 (52% ± 6.0% vs 56% ± 7.25% and 19.6% ± 3.2% vs 37% ± 4.1%, P = .039 and P = .0001, respectively). The therapy of C + A significantly suppressed the expressions of GpIIIa at postoperative days 7, 90, and 180 (P = .0001, P = .0001, and P = .0001, respectively) and P-selectin at postoperative days 90 and 180 (P = .035 and P = .002, respectively) when compared to ASA + A. The expression of GpIIb was also significantly depressed at postoperative day 180 in group 1 when compared to group 2 (P = .0001). Low-density lipoprotein binding was significantly increased at day 180 postoperatively in both the groups (basal: 42.9% ± 5.6% vs 45.3% ± 4.4% and day 180: 60.3% ± 4.6% vs 61.8% ± 5.7%, P = .0001). Conclusions: Our results demonstrate that the combination of C + A is more effective than that of ASA + A in inhibiting ADP-mediated platelet aggregation and expression of major platelet receptors after CABG.

Blood Cyst of the Right Ventricle Presenting as Recurrent High Fever and Chills in an Adult

Blood cysts are uncommon primary cardiac tumors, frequently encountered in pediatric patients, but extremely rare when found in adults. Due to the considerable risks of embolization and obstruction of the blood flow, surgical removal is preferred. Herein, we report a case of blood cyst of the right ventricle, presenting as recurrent fever and chills in an adult patient.

FK506 to Prevent Lung Injury After Hindlimb Ischemia and Reperfusion in a Rat Model : An Electron Microscopic Study

PurposeHindlimb ischemia and reperfusion leads to lung injury in various animal models. We investigated the effectiveness of FK506, an immunosuppressive agent, which also modulates neutrophilic infiltration, in preventing lung injury after hindlimb ischemia and reperfusion in a rat model.MethodsTwenty-seven male Sprague-Dawley rats were randomized to received FK506 at doses of 0.3 mg/kg, 0.5 mg/kg, or 1 mg/kg body weight per day, or normal saline injections, as pretreatment, and there was also a sham group. On the 4th day, the animals were subjected to 2 h of ischemia induced by a tourniquet, followed by reperfusion of the extremities for 2 h. Lung tissue assays were performed for the lipid peroxidation product malondialdehyde (MDA) and total glutathione (GSH). Lung tissues were also examined histopathologically under light and electron microscopy.ResultsThe MDA levels in the study groups were significantly lower than those in the control group (P < 0.05), but the total GSH levels did not differ significantly among the groups. Histopathologically, there were no significant differences among the groups given different doses of FK506, but there was a significant difference between the control group and all the treatment groups.ConclusionFK506 ameliorates the lung injury associated with ischemia and reperfusion of the lower limbs, and might have an inhibitory effect on the neutrophils that cause remote organ damage.