Injury In Rat Myocardium Research Articles

Effects of propofol on LC3II and mTOR/p-mTOR expression during ischemia-reperfusion myocardium injury in rats with type 2 diabetes mellitus.

To investigate the effects of propofol on myocardial ischemia reperfusion in rats with type 2 diabetes, male adult rats were divided into five groups: Sham-operation (CC), ischemia-reperfusion (CI), low-dose propofol (LP), moderate-dose propofol (MP) and high-dose propofol (HP). The LP, MP and HP groups were administered with 6, 12 and 24 mg/kg/h propofol, respectively, prior to occlusion. Heart rate (HR), left ventricular systolic pressure (LVSP) and the rate (dp/dt max) of left ventricular pressure rise in early systole (±dp/dt max) were recorded. The role of autophagy was also studied by measuring the levels of superoxide dismutase (SOD), malondialdehyde (MDA), autophagy marker protein LC3II, mammalian target of rapamycin (mTOR)/phosphorylate (p)-mTOR and cardiac troponin T (cTnT). The myocardial morphological features were assessed using light and electron microscopy. The present results demonstrated that the HR, LVSP, +dp/dt and -dp/dt levels in the propofol groups (LP, MP and HP) were significantly increased (P<0.05) when compared with the CI group. The myocardial cells in the MP group showed mild edematous changes and partially dissolved mitochondrial cristae and membrane rupture. SOD, cTnT and MDA levels were significantly decreased (P<0.05), mTOR expression decreased significantly (P<0.05) and p-mTOR expression increased significantly in the MP group (P<0.05). The present study demonstrated the protective effects of propofol in T2DM rats exhibiting MIRI, with an optimal protective effect at an infusion rate of 12 mg/kg/h. Additionally, the results revealed that propofol led to significant reductions in LC3II and mTOR serum levels and the inhibition of autophagy in myocardial cells.

Changes in Autophagy Levels in Rat Myocardium During Exercise Preconditioning-Initiated Cardioprotective Effects.

The role of autophagy in the cardioprotection conferred by ischemic preconditioning (IPC) has been well described. This study aimed to investigate the changes in autophagy levels during the cardioprotective effects initiated by exercise preconditioning (EP).Rats were randomly divided into 4 groups: group C (control), group EP, group EE (exhaustive exercise), and group EP + EE (EP pretreatment at 0.5 hours before EE). The EP protocol included 4 periods of 10 minutes of treadmill running each at 30 m/minute with intervening 10 minute periods of rest. Hematoxylin-basic fuchsin-picric acid (HBFP) staining and plasma levels of cardiac troponin I (cTnI) were used to evaluate the ischemia-hypoxia injury in rat myocardium. Alteration levels in several autophagy proteins in the left ventricular myocardium were analyzed by Western blot. The phasic alterations of autophagy levels during EP-initiated cardioprotective phase were also examined.Compared with group C, the ischemia-hypoxia positive areas and IOD value in HBFP-staining and cTnI plasma levels increased significantly in group EE. Compared with group EE, the ischemia-hypoxia injury was markedly attenuated in group EP + EE. Compared with group C, the LC3-II/LC3-I ratio, a marker of autophagosome formation, was reduced in group EE, but the LC3-II/LC3-I ratio remained unaltered in group EP + EE. Furthermore, the LC3-II/LC3-I ratio increased significantly at 2 hours during the cardioprotective phase after EP.These results suggest that the activated autophagy level during the EP-initiated cardioprotective phase may be partly involved in the cardioprotective effects by maintaining a normal autophagy basal level during the subsequent exhaustive exercise in rat myocardium.

The protective effects of Tanacetum parthenium extract on CCl4-induced myocardium injury in rats

The protective effects of Tanacetum parthenium extract on CCl4-induced myocardium injury in rats

E0178 Differential expression of N-Myc downstream regulated gene 2 (Ndrg2) in the rat heart after ischaemia/reperfusion injury

AimsIt has been shown that Ndrg2 (N-Myc downstream-regulated gene 2), a Myc-repressed gene, is markedly expressed in heart. Ndrg2 can act as a stress responsor under hypoxia and is necessary...

Experimental study on thrombopoietin providing protection against adriamycin-induced oxidative damage of myocardial cell in rats

Objective To inwst the antagonistic effect of thrombopoietin on adriamycin induced myocardium injury in rats and explore the mechanism.Methods 32 Wistar rats were randomized into four groups(n=8):Control group,ADM group,ADM+TPOL group and ADM+TPOH group.All agents were given by intraperitoneal injection.The control group was given saline.While the other three groups were given adriamycin at the dosage of20mg/kg.TPO group were injected TPO at the dosages of 10μg/kg or 30μg/kg three times on alternale days.ELISA was used to detect the concentration of CK-MB and cTnI in the serum of rats.The change of cardiocyte ultrastructure was observed by the electron microscope,and pathological change Was observed by immunohistochemistry staining.The expression level of 8- hydroxy-2'-deoxyguanosin(8-OHdG)produced by DNA oxidative damage in myocard tissue were detected.IPP6.0 software was used to detect IOD and calculate the 8-OHdG index.Results The energy of CK-MB and cTNI of TPO group was obviously lower than that in ADM group(P<0.01).The ultragtrueture of cardiocyte in the ADM group Wag damaged more severely than that in TPO group.Pathological Score,IOD and 8-OHdG index of TPO groups were lower than ADM group(P<0.05).These indexes had no significant statistics difference between ADM+TPOL group and ADM+TPOH group.Conclusions TPO can provide heart protection by antagonizing oxidative damage of myocardial cell induced by edriamycin. Key words: Thrombopoietin/PD; Cardiomyopathies; Myocytes,cardiac/DE; Oxidative stress

Protective effects of N-acetylcysteine in isoproterenol-induced myocardium injury in rats

Isoproterenol (ISO) has been found to cause severe injury in the myocardium. The aim of this study was to investigate the protective effects of N-acetylcysteine (NAC) on ISO-induced myocardial injury in rats and its underlying mechanisms. Fouty male Wistar rats were randomly divided into four groups: control, ISO, NAC, and ISO + NAC group. Myocardial histopathological observation were performed; The activities of creatine kinase isoenzyme-MB (CK-MB) and lactate dehydrogenase (LDH) were examined; Myocardium TNF-alphaand IL-1beta gene expressions were examined by RT-PCR analysis; Myocardial expressions of TNF-alphaand IL-1betaproteins were observed by immunohistochemical assay and western blotting analysis. The myocardial injury induced by ISO was significantly reduced by the treatment of NAC as judged by the reduction of myocardial necrosis. Compared with ISO group, rats pre-injected with NAC showed a significant decrease in the activities of cardiac marker enzymes such as CK-MB and LDH in serum. NAC inhibits the pro-inflammatory factors expressions (TNF-alphaand IL-1beta) stimulated by ISO. In conclusion, NAC exerts significant cardio-protective effects against ISO-induced myocardial injury in rats, likely regulating pro-inflammatory factors expressions.

Mitochondrial ATP-sensitive potassium channels and mitochondrial protein kinase C: sometimes it's good to have a close neighbor

the fine study by Jiang et al. ([8][1]) in this issue of the American Journal of Physiology Heart and Circulatory Physiology is an important milestone in the ongoing studies on the role of the mitochondrial ATP-sensitive K+ (mitoKATP) channels in myocardial ischemia. It is not particularly

Preventive effect of Breviscapus Injection on chronic hypoxic myocardium injury in rats

To study the preventive effect of Breviscapus Injection on the chronic hypoxic myocardium injury in rats and its mechanism. Transmission electron microscope and biochemical analysis were used to assay the therapeutic effect of Breviscapus Injection in rat model induced by 4 week's hypoxia. The contents of malondialdehyde (MDA) and Ca(2+) in the homogenate of myocardial tissue of the hypoxic rats were significantly higher than those of the control rats. The activities of superoxide dismutase (SOD), nitric oxide synthase (NOS) in the homogenate of myocardial tissue and the plasmic NO levels of the hypoxic rats were significantly lower than those of the control rats. Breviscapus Injection reduced the contents of MDA and Ca(2+), and increased the levels of SOD, NOS and NO. Ultrastructural examination revealed that the injuries of the ultrastructure of heart in hypoxic rats were improved by treatment with Breviscapus Injection. Breviscapus Injection can effectively prevent and treat the hypoxia-induced myocardial damage. One of its mechanisms may relate to its adjusting NO level, anti-damaging of free radicals and inhibiting calcium overload.

Lipopolysaccharide pretreatment attenuates myocardial infarct size: A possible mechanism involving heat shock protein 70-inhibitory κBα complex and attenuation of nuclear factor κB

Objective: Lipopolysaccharide pretreatment is known to reduce myocardial infarct size, but the mechanism has not been elucidated. We hypothesized that heat shock protein 70, induced by lipopolysaccharide pretreatment, formed complexes with inhibitory κBα, thereby inhibiting degradation and attenuating activation of nuclear factor κB and cellular injury in rat myocardium. Methods: Fifteen Sprague-Dawley rats were given saline solution (control group) or lipopolysaccharide. After 48 hours, 5 hearts in each group were excised without ischemia for examination of heat shock protein 70 and inhibitory κBα levels and detection of heat shock protein 70-inhibitory κBα complexes. Myocardium from the remaining 10 rats in each group was exposed to 30 minutes of ischemia and 30 minutes of reperfusion (n = 5) to evaluate nuclear factor κB activity or to 24 hours of reperfusion (n = 5) to evaluate infarct size. Results: Infarct size was reduced in the lipopolysaccharide group (P <.05). Nuclear factor κB was activated in the control ischemia group and attenuated in the lipopolysaccharide group (P <.05). Heat shock protein 70 levels were increased in the lipopolysaccharide group (P <.05), but inhibitory κBα levels were similar in both groups. Heat shock protein 70-inhibitory κBα complexes were detected only in the lipopolysaccharide group. Colocalization of the 2 proteins was observed in the lipopolysaccharide group. Conclusions: Heat shock protein 70, induced by lipopolysaccharide pretreatment, forms complexes with inhibitory κBα and attenuates activation of nuclear factor κB and myocardial infarct size. Our results suggest that attenuation of nuclear factor κB through a mechanism forming heat shock protein 70-inhibitory κBα complexes might protect the myocardium from ischemia-reperfusion injury.J Thorac Cardiovasc Surg 2002;124:933-41

Role of protein kinase C in mitochondrial KATP channel-mediated protection against Ca2+ overload injury in rat myocardium.

Growing evidence exists that ATP-sensitive mitochondrial potassium channels (MitoKATP channel) are a major contributor to the cardiac protection against ischemia. Given the importance of mitochondria in the cardiac cell, we tested whether the potent and specific opener of the MitoKATP channel diazoxide attenuates the lethal injury associated with Ca2+overload. The specific aims of this study were to test whether protection by diazoxide is mediated by MitoKATP channels; whether diazoxide mimics the effects of Ca2+ preconditioning; and whether diazoxide reduces Ca2+ paradox (PD) injury via protein kinase C (PKC) signaling pathways. Langendorff-perfused rat hearts were subjected to the Ca2+ PD (10 minutes of Ca2+ depletion followed by 10 minutes of Ca2+ repletion). The effects of the MitoKATP channel and other interventions on functional, biochemical, and pathological changes in hearts subjected to Ca2+ PD were assessed. In hearts treated with 80 micromol/L diazoxide, left ventricular end-diastolic pressure and coronary flow were significantly preserved after Ca2+ PD; peak lactate dehydrogenase release was also significantly decreased, although ATP content was less depleted. The cellular structures were well preserved, including mitochondria and intercalated disks in diazoxide-treated hearts compared with nontreated Ca2+ PD hearts. The salutary effects of diazoxide on the Ca2+ PD injury were similar to those in hearts that underwent Ca2+ preconditioning or pretreatment with phorbol 12-myristate 13-acetate before Ca2+ PD. The addition of sodium 5-hydroxydecanoate, a specific MitoKATP channel inhibitor, or chelerythrine chloride, a PKC inhibitor, during diazoxide pretreatment completely abolished the beneficial effects of diazoxide on the Ca2+ PD. Blockade of Ca2+ entry during diazoxide treatment by inhibiting L-type Ca2+ channel with verapamil or nifedipine also completely reversed the beneficial effects of diazoxide on the Ca2+ PD. PKC-delta was translocated to the mitochondria, intercalated disks, and nuclei of myocytes in diazoxide-pretreated hearts, and PKC-alpha and PKC-epsilon were translocated to sarcolemma and intercalated disks, respectively. This study suggests that the effect of the MitoKATP channel is mediated by PKC-mediated signaling pathway.

The effects of Danshen's effective component on reperfusion injury in rat myocardium

The effects of Danshen's effective component on reperfusion injury in rat myocardium

Freeze-thaw injury of rat heart across an intact diaphragm: a new model for the study of the response of myocardium to injury.

A new method for producing a circumscribed injury in rat myocardium is described. It utilises laparotomy and freeze-thawing across an intact diaphragm. Morbidity and mortality are negligible because the chest and pericardial cavities, the major coronary vessels, and the major branches of the conduction system remain intact. The size and location of the injury are reproducible and its sharp delineation facilitates accurate collection of samples from areas of interest. The myocytes are killed in the area of injury, whereas the capillary, nerve and connective tissue cells are killed centrally but preserved peripherally in a perimeter zone of injury in which capillaries remain patent. The reparative activities are initiated at the border between injured and uninjured myocardium; as they progress over the ensuing 6 weeks, the volume of damaged myocardium diminishes rapidly leaving only a rim of subepicardial scar tissue, and the thickness of ventricular muscle between the scar and endocardium returns almost completely to its pre-injury width. The mechanisms involved in the repair process are being investigated.

Effect of diltiazem, Ca++ channel blocking agent, on the anoxic injury in rat myocardium . Dept. of Pathology, University of Cincinnati Medical Center, Cincinnati, OH 45267

Effect of diltiazem, Ca++ channel blocking agent, on the anoxic injury in rat myocardium . Dept. of Pathology, University of Cincinnati Medical Center, Cincinnati, OH 45267