Ilker Kiris

The protective effect of erythropoietin on renal injury induced by abdominal aortic-ischemia-reperfusion in rats.

BACKGROUND Renal injury induced by aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute renal failure following abdominal aortic surgery. The purpose of this study is to examine the effect of erythropoietin on renal injury induced by aortic IR in rats. MATERIAL AND METHODS Twenty-four Wistar-Albino rats were randomized into 3 groups (8 per group). The control group underwent laparotomy and dissection of the infrarenal abdominal aorta without occlusion. The aortic IR group underwent clamping of the infrarenal abdominal aorta for 30 min followed by 60 min of reperfusion. The aortic IR + erythropoietin group underwent the same aortic IR periods and was pretreated with 1000 U/kg subcutaneous erythropoietin 5 min before ischemia. In rat kidney specimens, tissue levels of malondialdehyde (MDA), superoxide dismutase, catalase, and glutathione peroxidase were measured. Histological evaluation of the rat kidney tissues was also done. RESULTS Aortic IR significantly increased the levels of MDA and superoxide dismutase (P < 0.05 versus control). Erythropoietin significantly decreased the levels of MDA, superoxide dismutase, and catalase (P < 0.05 versus aortic IR). Histological evaluation showed that aortic IR significantly increased (P < 0.05 versus control), whereas erythropoietin significantly decreased (P < 0.05 versus aortic IR) the focal glomerular necrosis, dilation of Bowmans capsule, degeneration of tubular epithelium, necrosis in tubular epithelium, interstitial inflammatory infiltration, and congestion of blood vessels. CONCLUSIONS The results indicate that erythropoietin has protective effects on renal injury induced by aortic IR in rats.

Does Continuous Insulin Therapy Reduce Postoperative Supraventricular Tachycardia Incidence After Coronary Artery Bypass Operations in Diabetic Patients

OBJECTIVE To compare continuous insulin infusion (CII) and intermittent subcutaneous insulin therapy for preventing supraventricular tachycardia. The authors propose that continuous insulin therapy is more effective to reduce supraventricular tachycardias. DESIGN A prospective randomized study. SETTING This study was performed in 2 different centers between April 2005 and February 2007: Gülhane Military Medical Academy and University of Süleyman Demirel. PARTICIPANTS Two hundred diabetic patients were included in this prospective randomized study. Patients were divided into 2 groups according to their insulin therapy in 2 different centers. INTERVENTIONS Group 1 included 100 diabetes mellitus (DM) patients, and CIIs were administrated. These patients received a CII infusion titrated per protocol in the perioperative period (Portland protocol). Group 2 also included 100 DM patients, and subcutaneous insulin was injected every 4 hours in a directed attempt to maintain blood glucose levels below 200 mg/dL. Sliding scale dosage of insulin was titrated to each patients glycemic response during the prior 4 hours. MEASUREMENTS AND MAIN RESULTS There were 5 hospital mortalities in the intermittent insulin group. The causes of death were pump failure in 3 patients and ventricular fibrillation in 2 patients. There were 2 hospital mortalities in the CII group (p = 0.044). Thirty-six patients in the intermittent insulin group and 21 patients in the CII group required positive inotropic drugs after cardiopulmonary bypass (p = 0.028). Low cardiac output developed in 28 and 16 patients in the intermittent and CII groups, respectively (p = 0.045). Univariate analysis identified positive inotropic drug requirement (p = 0.011, odds ratio [OR] = 3.41), ejection fraction (EF) (p = 0.001, OR = 0.92), cross-clamp time (p = 0.046, OR = 0.97), left internal mammary artery (p = 0.023, OR = 0.49), chronic obstructive pulmonary disease (COPD) (forced expiratory volume in 1 second <75% of predicted value (p = 0.009, OR = 2.02), intra-aortic balloon pump (p = 0.045, OR = 1.23), body mass index (p = 0.035 OR = 5.60), and CII (p < 0.001, OR = 0.36) as predictors of SVT. Stepwise multivariate analysis confirmed the significance of some of the previously mentioned variables as predictors of SVT. The value of -2 log likelihood of multivariate analyses was 421.504. These were EF (p < 0.001, OR = 0.91), positive inotropic drug requirement (p < 0.001, OR = 3.94), COPD (p = 0.036, OR = 2.11), and CII (p < 0.001, OR = 0.19). CONCLUSION Continuous insulin therapy in the perioperative period reduces infectious complications, such as sternal wound infection and mediastinitis, cardiac mortality caused by pump failure, and the risk of development of supraventricular tachycardias.

Tezosentan reduces the renal injury induced by abdominal aortic ischemia-reperfusion in rats.

BACKGROUND Renal injury induced by aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute renal failure following abdominal aortic surgery. Endothelin (ET) is involved in the development of renal injury induced by aortic IR and tezosentan (R0 61-0612) is a specific ET receptor antagonist. The aim of this study was to examine the effect of tezosentan on renal injury induced by abdominal aortic IR in rats. MATERIAL AND METHODS Twenty-four Wistar-Albino rats were randomized into three groups (eight per group). Control group underwent laparotomy and dissection of the infrarenal abdominal aorta (IAA) without occlusion. The aortic IR group underwent laparotomy and clamping of the IAA for 120 min followed by 120 min of reperfusion. Aortic IR + tezosentan group underwent same aortic IR periods, and received a bolus intravenous injection of 10 mg/kg tezosentan before ischemia plus continuous intravenous infusion of 1 mg/kg/h tezosentan during 120 min ischemia and 120 min reperfusion. At the end of the experiment, blood and kidney tissue specimens were obtained for biochemical analysis. Histological evaluation of the rat kidney tissues was also done. RESULTS Biochemical analysis showed that aortic IR significantly increased (P < 0.05 versus control) while tezosentan significantly decreased (P < 0.05 versus aortic IR) the tissue levels of malondialdehyde, superoxide dismutase, catalase and myeloperoxidase. Histological analyses showed that aortic IR significantly increased (P < 0.05 versus control) while tezosentan significantly decreased (P < 0.05 versus aortic IR) focal glomerular necrosis, dilatation of Bowmans capsule, degeneration of tubular epithelium, necrosis in tubular epithelium and tubular dilatation in the renal tissue samples. CONCLUSION The results of this study indicate that tezosentan reduces renal injury induced by aortic IR in rats. We think that tezosentan exerted this beneficial effect via reducing oxidative stress and lipid peroxidation, inhibition of leukocyte infiltration into renal tissue and acting cytoprotective on renal tubular cells after aortic IR.

β-Glucan Protects against Lung Injury Induced by Abdominal Aortic Ischemia-Reperfusion in Rats

BACKGROUND Aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute lung injury following abdominal aortic surgery. The aim of our study was to examine the effect of β-glucan on lung injury induced by abdominal aortic IR in rats. MATERIAL AND METHODS Thirty-two Wistar-albino rats were randomized into four groups (eight per group) as follows: the control group (sham laparotomy), aortic IR (120 min ischemia and 120 min reperfusion), aortic IR + β-glucan (β-glucan 50 mg/kg/d for 10 d was administered orally before IR), and control + β-glucan. Lung tissue samples were obtained for biochemical analysis. Protein concentrations in bronchoalveolar lavage fluid and lung wet/dry weight ratios were measured. Histologic evaluation of the rat lung tissues was also performed. RESULTS Aortic IR significantly increased the levels of MDA, superoxide dismutase, catalase, and myeloperoxidase (P < 0.05 versus control).Whereas, β-glucan significantly decreased the lung tissue levels of MDA, superoxide dismutase, catalase, myeloperoxidase, (P < 0.05 versus aortic IR), and protein concentration in bronchoalveolar lavage fluid as well as wet/dry lung weight ratio. Histologic evaluation showed that β-glucan attenuated the morphological changes associated with lung injury. CONCLUSIONS The results of this study indicate that β-glucan attenuates lung injury induced by aortic IR in rats. We propose that this protective effect of β-glucan is due to (1) reduced systemic inflammatory response, (2) reduced oxidative stress and lipid peroxidation in the lung tissue, (3) reduced pulmonary microvascular leakage, and (4) inhibition of leukocyte infiltration into the lung tissue.

Iloprost Downregulates Expression of Adhesion Molecules and Reduces Renal Injury Induced by Abdominal Aortic Ischemia-Reperfusion

The aim of this study was to examine the effect of iloprost in renal injury induced by abdominal aortic ischemia-reperfusion (IR) and how it can modulate the expression of adhesion molecules during this effect. Twenty-four Wistar-Albino rats were randomized into three groups (n=8) as follows: control (sham laparotomy), aortic IR (120 min ischemia and 120 min reperfusion), and aortic IR + iloprost (0.45 microg/kg/hr intravenous infusion during 120 min reperfusion). Blood and renal tissue samples were obtained for biochemical analysis. A histological evaluation with both hematoxylin-eosin staining and immunostaining was also done. Biochemical analyses showed that aortic IR significantly increased (p<0.05 vs. control) whereas iloprost significantly decreased (p<0.05 vs. aortic IR) plasma levels of malondialdehyde, P-selectin, intercellular adhesion molecule-1 (ICAM-I), and tissue levels of malondialdehyde and catalase. Histological evaluation with immunostaining showed that aortic IR significantly increased (p<0.05 vs. control) whereas iloprost significantly decreased (p<0.05 vs. aortic IR) the immunoreactivity of P-selectin, tumor necrosis factor-alpha, CD11b, CD18, and ICAM-1. Hematoxylin-eosin staining showed that iloprost also attenuated the morphological changes associated with aortic IR. The results of this study show that iloprost reduces renal injury induced by aortic IR in rats and downregulates expression of adhesion molecules at both the local and systemic levels after aortic IR during this protective effect.

Adrenomedullin attenuates aortic cross-clamping–induced myocardial injury in rats

BACKGROUND In this study we investigate the effects of adrenomedullin on myocardial injury after ischemia-reperfusion (I/R) after abdominal aortic surgery. METHODS Thirty-two Wistar rats were randomized into 4 groups (n = 8) as follows: control group (sham laparotomy), the aortic I/R group, aortic I/R plus adrenomedullin group (underwent aortic I/R periods, and received a bolus intravenous injection of .05 μg/kg/min adrenomedullin), and the control plus adrenomedullin group. RESULTS Biochemical analysis showed that aortic I/R significantly increased (P < .05) the plasma levels of troponin-I and tumor necrosis factor-α, and the myocardial tissue levels of malondialdehyde, superoxide dismutase, catalase, and angiotensin II, whereas aortic I/R plus adrenomedullin significantly decreased these same factors (P < .05). Aortic I/R significantly increased (P < .05) myocardial tissue levels of nitric oxide whereas aortic I/R plus adrenomedullin significantly increased the same factor (P < .05). CONCLUSIONS These results indicate that adrenomedullin has protective effects against myocardial injury induced by abdominal aortic I/R in rats.

The protective effect of adrenomedullin on renal injury, in a model of abdominal aorta cross-clamping.

Renal injury induced by aortic ischemia-reperfusion (IR) is an important factor in the development of postoperative acute renal failure following abdominal aortic surgery. The aim of this study was to examine the effect of adrenomedullin (AM) on kidney injury induced by infrarenal abdominal aortic IR in rats. Thirty-two Wistar Albino rats were randomized into four groups (eight per group) as follows: Control group, IR group (120-minute ischemia and 120-minute reperfusion), IR + AM group (a bolus intravenously of 0.05 µg/kg/min AM), and control + AM group. At the end of the experiment, blood and kidney tissue specimens were obtained for biochemical analysis. Immunohistological evaluation of the rat kidney tissues was also done. IR significantly increased (p < 0.05 vs control group) and AM significantly decreased (p < 0.05 vs. IR group) all of the biochemical parameters. Immunohistological evaluation showed that AM attenuated morphological changes as apoptosis associated with kidney injury. The results of this study indicate that AM attenuates both biochemically and immunohistopathologically kidney injury induced by aortic IR in rats.

Endothelin Receptor Antagonism by Tezosentan Attenuates Lung Injury Induced by Aortic Ischemia–Reperfusion

Tezosentan is a novel dual endothelin receptor antagonist. The purpose of this study was to examine the effect of tezosentan on lung injury induced by abdominal aortic ischemia-reperfusion (IR) in rats. Thirty-two Wistar-albino rats were randomized into four groups (eight per group) as follows: control group (sham laparotomy), aortic IR group (120 min ischemia and 120 min reperfusion), aortic IR + tezosentan group (a bolus intravenous injection of 10 mg/kg tezosentan before ischemia plus continuous intravenous infusion of 1 mg/kg/hr tezosentan during 120 min ischemia and 120 min reperfusion), and control + tezosentan. Blood and lung tissue samples were obtained for biochemical analysis. Protein concentrations in bronchoalveolar lavage fluid and lung wet/dry weight ratios were measured. A histological evaluation was also done. Aortic IR significantly increased (p < 0.05 vs. control group) and tezosentan significantly decreased (p < 0.05 vs. aortic IR group) the plasma level of tumor necrosis factor-alpha; lung tissue levels of malondialdehyde, catalase, and myleperoxidase; and protein concentration in bronchoalveolar lavage fluid and lung wet/dry weight ratio. Histological evaluation showed that tezosentan attenuated the morphological changes associated with lung injury. The results of this study indicate that tezosentan attenuates lung injury induced by aortic IR in rats. We propose that this protective effect of tezosentan is due to (1) reduced systemic inflammatory response, (2) reduced oxidative stress and lipid peroxidation in lung tissue, (3) reduced pulmonary microvascular leakage, and (4) inhibition of leukocyte infiltration into lung tissue.

The Effect of N ω-Nitro- l -Arginine Methyl Ester and l -Arginine on Lung Injury Induced by Abdominal Aortic Occlusion–Reperfusion

PurposeThe aim of this study was to examine the effects of Nω-nitro-l-arginine methyl ester (l-NAME) and l-arginine on lung injury after aortic ischemia–reperfusion (IR).MethodsTwenty-four Wistar-Albino rats were randomized into four groups (n = 6) as follows: Control (sham laparotomy), Aortic IR (30 min ischemia and 120 min reperfusion), l-Arginine (intraperitoneal 100 mg kg−1 live weight)+aortic IR, and l-NAME (intraperitoneal 10 mg kg−1 live weight)+aortic IR. In the lung specimens, the tissue levels of malondialdehyde (MDA), vascular endothelial growth factor (VEGF), and nitric oxide (NO) were measured and a histological examination was done.ResultsAortic IR increased MDA, VEGF, and NO. l-Arginine further significantly increased MDA and NO, and decreased VEGF (P < 0.05 vs aortic IR). l-NAME significantly decreased MDA and NO (P < 0.05 vs l-arginine+aortic IR) and increased VEGF (P < 0.05 vs other groups). A histological examination showed the aortic IR to significantly increase (P < 0.05 vs control) while l-arginine also further increased (P > 0.05 vs aortic IR), whereas l-NAME caused a significant decrease in pulmonary leukocyte infiltration (P < 0.05 vs aortic IR).ConclusionsOur results indicate that l-arginine aggravates the lung injury induced by aortic IR, while l-NAME attenuates it.

Diabetes Mellitusun Koroner Arter Bypass Cerrahisinde Erken Dönem Morbidite ve Mortaliteye Etkisi

SuleymanDemirel Universitesi TIP FAKULTESI DERGISI: 2006 Mart; 13(1) Diabetes Mellitusun Koroner Arter Bypass Cerrahisinde Erken Donem Morbidite ve Mortaliteye Etkisi Ilker Kiris, Şenol Gulmen, Ilker Tekin, Huseyin Okutan Ozet Gunumuzde, koroner arter bypass cerrahisi (KABC) uygulanan hastalarin % 20-30.u diyabetikdir. Bununla birlikte, diabetes mellitus (DM).un KABC sonrasi erken donem mortalite ve morbiditeye olan etkisi tartismalidir. Bu retrospektif calismanin amaci, DM.un KABC uygulanan hastalarda erken donem morbidite ve mortaliteyi anlamli derecede arttirip arttirmadigini arastirmaktir. Haziran 2003 ile Eylul 2005 tarihleri arasinda klinigimizde KABC uygulanan toplam 246 hasta calismaya alindi. Calismaya alinan hastalarin ortalama yasi 59.8 ± 9.75 olup 187.si erkek (% 76) ve 59.u kadin (% 23.9) idi. DM tanisi olan 79 (% 32.1) hasta DM grubunu, diger 167 (% 67.8) hasta da kontrol grubunu olusturdu. Gruplar, postoperatif erken donemde morbidite verileri ve mortalite orani acisindan birbiri ile karsilastirildi. Intra aortik balon pompasi, akut bobrek yetmezligi, multi organ yetmezligi, serebro vaskuler olay, yuzeyel yara yeri enfeksiyonu, sternal dehissens, mediastinit ve mediastinal kanama nedenli reoperasyon oranlari acisindan gruplar birbiri ile karsilastirildiginda istatistiksel olarak anlamli fark bulunmadi (p > 0.05). Mortalite oranlari DM grubunda % 3.7, kontrol grubunda ise %4.7 idi ve aradaki fark istatistiksel olarak anlamli degildi (p > 0.05). Yuzeyel yara yeri enfeksiyonu orani, insulin kullanan diyabetik hastalarda, hem oral antidiyabetik kullanan diyabetik hastalara hem de kontrol grubuna gore anlamli derecede daha yuksekti (p = 0.066). Sonuc olarak, bu calismada, DM.un KABC uygulanan hastalarda erken donem morbidite ve mortaliteyi anlamli derecede arttirmadigini bulduk. KABC, enfeksiyona karsi azami onlemler alinarak, diyabetik olan hastalarda da diyabetik olmayan hastalarda oldugu gibi guvenle uygulanabilir. Anahtar kelimeler: Diabetes mellitus, koroner arter bypass cerrahisi, morbidite, mortalite Abstract Effect of Diabetes Mellitus on Short-Term Morbidity and Mortality in Coronary Artery Bypass Surgery Currently, 15 % to 30 % of the patients that undergo coronary artery bypass grafting (CABG) are diabetics. However, the effect of diabetes mellitus (DM) on short-term morbidity and mortality after CABG iscontroversial. The aim of this retrospective study was to investigate whether DM increases short-term morbidity and mortality after CABG or not. Two-hundred-fourty-eight patients who underwent CABG operations in our clinic between June 2003 and September 2005 were included in the study. Mean age of the patients was 59.8 ± 9.75 and there were 187 male (% 76) and 59 female (% 23.9). Seventy-nine patients (%32.1) were diabetic (DM group) and 167 patients (% 67.8) were nondiabetic (control group). The groups were compared for morbidity data and mortality rates in the postoperative short-term. When the groups were compared for the incidence of intra aortic balloon pumping, acute renal failure, multi organ failure, cerebro vascular complications, superficial wound infection, sternal dehiscence, mediastinitis and reoperation due to mediastinal bleeding, there were no statisticaly significant difference (p > 0.05). Mortality rates in the DM group and the control group were % 3.7 and %4.7, respectively but there were no statisticaly significant difference (p > 0.05). The incidence of superficial wound infection were significantly higher in the patients with insulin-treated DM than both in the patients with oral antidiabetic-treated DM and in the nondiabetic patients (p = 0.066). In conclusion, in this study we found that DM does not significantly increase short-term morbidity and mortality in the patients who undergo CABG. Provided that strict measures are taken against infections, CABG can be performed in diabetic patients as safely as it is being performed in nondiabetic patients. Key words: diabetes mellitus, coronary artery bypass surgery, morbidity, mortality