scholarly journals Antiapoptotic Effect of Simvastatin Ameliorates Myocardial Ischemia/Reperfusion Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Najah R. Hadi ◽  
Fadhil Al-amran ◽  
Maitham Yousif ◽  
Suhaad T. Zamil

Background. Myocardial ischemial reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty, and coronary bypass surgery. Injury of myocardium due to ischemial reperfusion includes cardiac contractile dysfunction, arrhythmias, and irreversible myocytes damage. These changes are considered to be the consequence of imbalance between the formation of oxidants and the availability of endogenous antioxidants in the heart. Objective. This study was undertaken to investigate the potential role of Simvastatin in the amelioration of myocardial I/R injury induced by ligation of coronary artery in a rat model. Materials and Methods. Adult male Swiss Albino rats were randomized into 4 equal groups. Group (1): sham group: rats underwent the same anesthetic and surgical procedures as those in the control group except ligation of LAD coronary artery, group (2): control group: rats were subjected to regional ischemia for 25 min and reperfusion for 2 hours by ligation of LAD coronary artery, group (3): control vehicle group: rats received vehicle of Simvastatin (normal saline) via IP injection and were subjected to regional ischemia for 25 min and reperfusion for 2 hours by ligation of LAD coronary artery, group (4): Simvastatin treated group: rats were pretreated with Simvastatin 1 mg/kg i.p. 1 hr before ligation of LAD coronary artery. At the end of experiment (2 hr of reperfusion), blood samples were collected from the heart for the measurement of plasma level of cardiac troponin I (cTnI). After that the heart was harvested and divided into 3 parts; one part was used for measurement of apoptosis, another part was homogenized for the measurement of tissue tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1α, and the last part for histopathology study. Results. Compared with the sham group, levels of myocardial TNF-α and IL-1β, IL-6, MCP-1, and MIP-1α and plasma cTnI were increased (P<0.05). Histologically, all rats in control group showed significant (P<0.05) cardiac injury. Furthermore, all rats in control group showed significant (P<0.05) apoptosis. Simvastatin significantly counteracted the increase in myocardium level of TNF-α, IL-1B, IL-6, MCP-1 and MIP-1α, plasma cTnI, and apoptosis (P< 0.05). Histological analysis revealed that Simvastatin markedly reduced (P< 0.05) the severity of heart injury in the rats that underwent LAD ligation procedure. Conclusions. The results of the present study reveal that Simvastatin may ameliorate myocardial I/R injury in rats via interfering with inflammatory reactions and apoptosis which were induced by I/R injury.

2017 ◽  
Vol 145 (3-4) ◽  
pp. 153-158 ◽  
Author(s):  
Murat Sadic ◽  
Hasan Atilgan ◽  
Arif Aydin ◽  
Gökhan Koca ◽  
Meliha Korkmaz ◽  
...  

Introduction/Objective. Medical protection of kidneys against ischemia reperfusion injury is very important. Many agents have been used for the protection of ischemia reperfusion renal tissue injury. We aimed to evaluate the radioprotective effect of lycopene on kidneys in ischemia reperfusion injury with histopathological, biochemical, and scintigraphic parameters. Methods. Twenty-one Wistar male albino rats were divided into the following three groups: lycopene, control, and sham group. In the lycopene group, lycopene was started three days before right renal ischemia reperfusion injury and continued for 15 days. In the control group, right renal ischemia reperfusion injury was applied with no medication. In the sham group, neither right renal ischemia reperfusion injury nor medication were applied. On the 15th day, all rats were sacrificed after 99mTc-dimercaptosuccinic acid (DMSA) scintigraphies were taken. Histopathological, biochemical, and scintigraphic evaluations were made. Results. The histopathological score was lower in the lycopene group. In biochemical analysis, myeloperoxidase levels were lower in the lycopene group than in the control group, but not statistically significant. Malondialdehyde and nitrite levels were lower in the lycopene group than in the control group. The postoperative mean 99mTc-DMSA uptake values were 44.82 ? 1.84 in the lycopene group, 38.92 ? 1.17 in the control group, and 50.21 ? 1.35 in the sham group. DMSA uptake values were higher in the lycopene group than in the control group. Conclusion. Lycopene seems to be an effective agent for protection of kidneys in ischemia reperfusion injury as demonstrated by the histopathological, biochemical, and scintigraphic parameters.


2018 ◽  
Vol 6 (4) ◽  
pp. 379-388
Author(s):  
Najah R Hadi ◽  
Fadhil Al-amran

Restoration of blood flow to ischemic myocardium results in the ischemia reperfusion (I/R) injury. This study was undertaken to investigate the potential role of endogenous testosterone in the regional ischemia reperfusion and apoptosis of the male rat hearts. Rats underwent surgical ligation of LAD and subjected to ischemia for 25 min and reperfusion for 40 min, and 2nd underwent surgical castration, left 3wks for recovery, then underwent surgical LAD ligation. Blood samples were collected from the heart for measurement of plasma level of cardiac troponin I (cTn-I). The hearts were harvested, and divided into 3 sections, the 1st for the measurement of cardiac apoptosis level, the 2nd homogenized for measurement of tissue (TNF-α, IL1-β, ICAM-1) and the 3rdwas fixed in 10% formalin for histological examination. Compared with the sham group, levels of tissue TNF-α & IL-1β, ICAM-1 and apoptosis; plasma cTn-I were increased (P<0.05) in the control group, all control group rats showed significant myocardial injury (P<0.05) compared with the sham group. Castration significantly counteracts the increase in myocardial levels of TNF-α, IL-1, ICAM-1, plasma cTn-I and apoptosis (P<0.05). Histological analysis revealed that castration markedly reduced (P<0.05) the severity of the heart injury in the rats underwent the regional ischemia-reperfusion procedure. This study reveals that surgical castration may ameliorate regional I/R injury and apoptosis in the ischemic heart in rats.


Open Medicine ◽  
2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Şafak Ekinci ◽  
Ümit Kaldırım ◽  
Faruk Akyıldız ◽  
Serkan Bilgiç ◽  
Kenan Koca ◽  
...  

AbstractObjective: The aim of this study was to investigate the effect of hypothermia (H) on skeletal ischemia-reperfusion (IR) injury in rats by measuring malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), nitric oxide (NO), and interleukin-1 beta (IL-1β) in muscle, and measureing immunohistochemical- inducible nitric oxide synthase (iNOS) staining of skeletal muscle.Materials and Methods: Eighteen Wistar Albino rats were divided randomly into three groups (sham, IR, hypothermia) (n=6). The sham group had all procedures without the IR period. The lower right extremity of rats in the IR and hypothermia groups was subjected to 2 hours of ischemia and 22 hours of reperfusion by applying a clamp on the common iliac artery and a rubber-band at the level of the lesser trochanter under general anesthesia. Rats in the hypothermia group underwent 4 hours of hypothermia during the first four hours of reperfusion in addition to a 2-hour ischemia and 22-hour reperfusion period. All rats were sacrificed at end of the IR period using a high dose of anesthesia. The tibialis anterior muscles were preserved. Immunohistochemical iNOS staining was performed, and MDA, SOD, GSH-Px, NO, and IL-1β were measured in the muscle.Results: The level of MDA, NO, and IL-1β in muscle was increased in the IR group compared with that in the sham group, but these parameters were decreased in the hypothermia group compared with the IR group. The activities of SOD and GSH-Px in muscle were decreased in the IR group; however, these parameters were increased in the hypothermia group. The score and intensity of iNOS staining of skeletal muscle was dens in IR group, mild in hypothermia group, and weak in sham group.Conclusion: The present study has shown that hypothermia reduced IR injury in the skeletal muscle by decreasing the levels of MDA, NO, and IL-1β, and increasing the activities of SOD and GSH-Px. In addition, hypothermia attenuated the score and intensity of iNOS staining.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maha Sadek El Derh ◽  
Samar Mohamed Abdel Twab ◽  
Mohamed Elgouhary

Abstract Background Off pump coronary artery revascularization (OPCAB) surgeries have benefits over the conventional on pump cardiac surgery, because it avoids the trauma caused by cardiopulmonary bypass (CPB) and minimize aortic manipulation. However, some disadvantages of OPCAB include the concern of ineffective coronary revascularization. Some drugs have shown the ability to protect the myocardium in different studies, by different methods. The usage of intralipid has been shown to make a better functional recovery of the cardiac muscles and help to decrease the myocardial infarct size, it shortens the action potential time, which show polyunsaturated fatty acids diets mechanism as an antiarrhythmic drug, and are associated with low incidence of coronary artery disease. Methods We divided patients into two groups according to the randomization envelopes: intralipid group (group A) received 1.5 ml/kg intralipid 20% through central venous line after sternotomy over 1 h and during infusion, blood pressure, heart rate, and temperature were monitored all through the infusion time. Control group (group B) received normal saline 0.9% in the same volume over the same duration. Results This study showed that infusion of 1.5 ml/kg intralipid after sternotomy in off pump coronary artery revascularization given as preconditioning agent improve the myocardial ischemia reperfusion injury, decrease the need for high doses of nor adrenaline infusion after revascularization, earlier normalization in troponin levels starting 24 h after surgery and higher values of cardiac index were measured in ICU using PICCO. Conclusions This study showed the benefits of infusion of 1.5 ml/kg of intralipid after sternotomy, in preconditioning during OPCABG. Preconditioning with intralipid proved to decrease reperfusion injury in myocardium expressed by improvement in cardiac functions (EF and cardiac index) and normalization of specific cardiac marker (cardiac troponin I).


2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Jingyuan Li ◽  
Negar Motayagheni ◽  
Neusha Barakati ◽  
Mansoureh Eghbali

The prevalence of coronary artery disease in late pregnancy (LP) has increased recently due to significant changes in women’s lifestyle patterns (age, stress, smoking, diabetes and chronic hypertension). Myocardial infarction during LP and the peripartum is associated with significant maternal mortality and morbidity compared to non pregnant women for unclear reasons. We have recently demonstrated that cardiac vulnerability to I/R injury drastically increases in LP rodents, leading to myocardial infarct size ~4 fold greater than in non-pregnant controls. We also discovered that administration of intralipid (an emulsion of soy bean oil, egg yolk phospholipids and glycerol) at reperfusion resulted in ~60% reduction in infarct size of the heart in LP rat subjected to I/R injury. However, the molecular mechanisms underlying intralipid-induced cardioprotection in late pregnancy is not clear. Here we hypothesized that intralipid protects the heart in late pregnancy by regulating the levels of specific microRNAs. The left anterior descending coronary artery was occluded in LP rats (21-22 days of pregnancy) for 45 min followed by 3 hr of reperfusion. One single bolus of PBS (control group) or 20% intralipid (intralipid group) was applied through the femoral vein 5 min before the reperfusion. The hearts of control and intralipid groups were used for microRNA microarray analysis (Ocean Ridge Biosciences). MicroRNA-microarray analysis identified MiR122 as a novel micro-RNA which its expression was strikingly upregulated more than 10 fold in the heart of LP rats in intralipid group compared to control group. miR122 regulates apoptosis in cardiomyocytes subjected to hypoxia/reoxygenation since miR122-overexpression resulted in reduced apoptosis, whereas knockdown of miR122 enhanced apoptosis. Pyruvate kinase isoform M2 (PKM2), which is known to regulate cell apoptosis in the liver, is a direct target of miR122. Our data show that PKM2 and caspase 3 are two targets of miR122 since the expression of PKM2 and capase-3 in the heats subjected to I/R was significantly lower in intralipid group compared to control group in LP. In conclusion intralipid protects the heart in late pregnancy against ischemia/reperfusion injury via inducing miR122 by targeting PKM2.


2017 ◽  
Vol 95 (7) ◽  
pp. 861-865 ◽  
Author(s):  
Neslihan Pınar ◽  
Oya Soylu Karapınar ◽  
Oğuzhan Özcan ◽  
Esin Atik Doğan ◽  
Suphi Bayraktar

The aim of this study was to investigate the antioxidant effects of tempol on ovarian ischemia–reperfusion (I/R) injury in rats. Forty female Wistar albino rats were randomly divided into 5 groups: Group I, sham; Group II, ischemia (I); Group III, I/R; Group IV, I/R + tempol 30 mg/kg i.p; Group V, I/R + tempol 50 mg/kg i.p. Oxidative stress index (OSI) was significantly higher in the ischemia group and the I/R group than in the sham group. Catalase levels were significantly lower in the I/R group than in the I/R + tempol 30 mg/kg i.p. and the I/R + tempol 50 mg/kg i.p. groups. Glutathione peroxidase levels were lower in the I/R group than in the I/R + tempol 30 mg/kg i.p. and the I/R + tempol 50 mg/kg i.p. groups. MDA levels were significantly lower in the I/R + tempol 30 mg/kg i.p. group and the I/R + tempol 50 mg/kg i.p. group than in the I/R group. The levels of the histopathological parameters were significantly decreased in the I/R + tempol 50 mg/kg i.p. group compared with the I/R group. Tempol can be used for reducing ovarian I/R injury.


2017 ◽  
Vol 20 (2) ◽  
pp. 058 ◽  
Author(s):  
Bekir İNAN ◽  
Selma SÖNMEZ ERGÜN ◽  
Asiye NURTEN ◽  
Canan KÜÇÜKGERGİN ◽  
Aslı ZENGİN TÜRKMEN ◽  
...  

Objective: Free radicals and neutrophils are potent sources of ischemia-reperfusion injury (I/R) and they can be limited by the use of exogenous application of some therapeutic agents. The objective of this study was to compare the effects of cilostazol and diltiazem hydrochloride in a rat hind limb model of I/R injury. Methods: Skeletal muscles submitted to 2 hours of ischemia by placing an aneurysm clip to femoral artery and reperfused after 1, 2 and 4 hours. Seventy-two Wistar-Albino rats were randomly divided into mainly four groups according to treatment agents:  Group I (control group) was treated with saline; Group II was treated with diltiazem hydrochloride; Group III was treated with cilostazol in 30% dimethyl sulphoxide; and Group IV was treated with 30% dimethyl sulphoxide intraperitoneally. These four main groups also subdivided into three subgroups according to duration of the reperfusion times.  Blood samples were taken and all rats were sacrificed. Results: Cilostazol-treated groups demonstrated a significant decrease in tissue and serum malondialdehyde (MDA) levels, and tissue myeloperoxidase (MPO ) activity compared with other groups. Increase in serum nitric oxide (NOx) level was significantly higher in all subgroups of cilastazol, diltiazem hydrochloride, and dimethyl sulphoxide groups versus the control group.Conclusion: Although these results suggest the beneficial effects of cilostazol and diltiazem hydrochloride on I/R injury, the effect of cilostazol on I/R injury seems to be more efficient than diltiazem hydrochloride.


Author(s):  
Mohammad Bagher Khosravi ◽  
Mahdi Kahrom ◽  
Mahdi Tahari ◽  
Kambiz Alizadeh ◽  
Ghasem Soltani ◽  
...  

Background: Ischemic postconditioning is a novel strategy for attaining cardioprotection. Remarkable evidence from various in vitro and in vivo animal and human studies have shown significant opioid-induced cardioprotection against myocardial ischemia/reperfusion (I/R) injury. The purpose of this study was to assess the cardioprotective effect of sufentanil against I/R injury after on-pump coronary artery bypass grafting (CABG). Methods: Between June 2016 and July 2017, 80 consecutive patients with triple-vessel disease undergoing on-pump CABG were enrolled in this prospective randomized study. The patients assigned to the sufentanil group received a single dose of sufentanil (0.2 μg/kg diluted with 50 cc of saline) 5 minutes before the removal of the aorta cross-clamp, with the sufentanil injected via a cardioplegia needle into the aortic root. In the control group, the same volume of normal saline was injected as a placebo. Cardiac enzymes, the inotrope score, and the outcome data were compared between the 2 groups. Results: The mean age of the patients was 60.48±7.50 years (range=41–69 y), and men comprised 65.0% of the study population. The levels of CK-MB and cardiac troponin I were significantly lower in the sufentanil group (P<0.001). The amount of inotrope use (P<0.001), the incidence of atrial fibrillation (P=0.014), electrical shock (P=0.007), and the mechanical ventilation time (P<0.001) decreased in the sufentanil group compared with the control group. However, the use of intra-aortic balloon pumps (P=0.247) and the ICU length of stay (P=0.867) were not significantly different between the 2 groups. Conclusion: The injection of a single dose of sufentanil into the aortic root prior to aorta cross-clamp removal diminished cardiac injury during on-pump CABG in our patients.   J Teh Univ Heart Ctr 2019;14(4):177-182   This paper should be cited as: Bagher Khosravi M, Kahrom M, Tahari M, Alizadeh K, Soltani G, Ghanad MA. Effect of the Aortic Root Infusion of Sufentanil on Ischemia-Reperfusion Injury in Patients Undergoing Coronary Artery Bypass Grafting: A Randomized Clinical Trial. J Teh Univ Heart Ctr 2019;14(4):177-182.


2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Fadhil Alamran

Background: Global myocardial ischemia reperfusion (I/R), which is often obligatory during cardiac surgery, induce an inflammatory response in the transplanted heart. Inflammatory reactions in the graft have a pivotal influence on acute as well as long term graft function. Objective: This study was undertaken to investigate the potential role of melatonin and ghrelin in amelioration of I/R injury in the transplanted heart in rat model. Materials and Methods: The rats were randomized into 4 equal groups. Group 1 sham group, rat underwent the same anesthetic and surgical procedure as the control group except for heterotopic heart transplantation, group 2 control group, rats underwent heterotopic heart transplantation and subjected to global ischemia for 30 min and reperfusion for 2 hours, group 3 donor and recipient rats received melatonin 10 mg/kg i.p. 30 min before the transplant procedure and the same dose at the reperfusion, group 4 donor and recipient rats received ghrelin 10 -8 mol/kg i.p. ( 2 doses) 13 & 1 hour before the transplant procedure, the heterotopic heart transplantation is done using the cuff technique in the neck ( the aorta of the donor is anastomosed with the carotid artery of the recipient and the pulmonary artery of the donor to the jugular vein of the recipient). At the end of experiment (2 hr of reperfusion), blood samples were collected from the heart for measurement of plasma level of cardiac troponin I(cTn I). The heart were harvested, the apical side was fixed in 10% formalin for histological examination and the basal side was homogenized for the measurement of tissue tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and intracellular adhesion molecule-1 (ICAM-1). Results: Compared with the sham group, levels of myocardial TNF-α & IL-1β, and ICAM-1; plasma cTn I were increased (p<0.05), Histologically, all induced untreated rats showed significant myocardial injury ( P < 0.05) Both melatonin and ghrelin significantly counteract the increase in myocardium level of TNF-α, IL-1, & ICAM-1 ( P < 0.05). histological analysis revealed that both melatonin and ghrelin markedly reduced ( P < 0.05) the severity of heart injury in the rats underwent transplant procedure. Conclusion: The results of the present study reveal that melatonin and ghrelin may ameliorate I/R injury in the grafted heart in rats via interfering with inflammatory reactions which induced by I/R injury . These findings suggested that both melatonin and ghrelin have a promising graft protective effect against transplant induced global I/R injury.


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