Effect of transplantation of bone marrow stem cells on myocardial infarction size in a rabbit model

BACKGROUND:Intravenous transplantation has been regarded as a most safe method in stem cell therapies.There is evidence showing the homing of bone marrow stem cells(BMSCs) into the injured sites,and thus these cells can be used in the treatment of acute myocardial infarction(Ml).This study aimed to investigate the effect of intravenous and epicardial transplantion of BMSCs on myocardial infarction size in a rabbit model.METHODS:A total of 60 New Zealand rabbits were randomly divided into three groups:control group,epicardium group(group Ⅰ) and ear vein group(group Ⅱ).The BMSCs were collected from the tibial plateau in group Ⅰ and group Ⅱ,cultured and labeled.In the three groups,rabbits underwent thoracotomy and ligation of the middle left anterior descending artery.The elevation of ST segment>0.2 mV lasting for 30 minutes on the lead Ⅱ and Ⅲ of electrocardiogram suggested successful introduction of myocardial infarction.Two weeks after myocardial infarction,rabbits in group Ⅰ were treated with autogenous BMSCs at the infarct region and those in group Ⅱ received intravenous transplantation of BMSCs.In the control group,rabbits were treated with PBS following thoracotomy.Four weeks after myocardial infarction,the heart was collected from all rabbits and the infarct size was calculated.The heart was cut into sections followed by HE staining and calculation of infarct size with an image system.RESULTS:In groups Ⅰ and Ⅱ,the infarct size was significantly reduced after transplantation with BMSCs when compared with the control group(P<0.05).However,there was no significant difference in the infarct size between groups Ⅰ and Ⅱ(P>0.05).CONCLUSION:Transplantation of BMSCs has therapeutic effect on Ml.Moreover,epicardial and intravenous transplantation of BMSCs has comparable therapeutic efficacy on myocardial infarction.

Effects of nicorandil on myocardial infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention:study design and protocol for the randomized controlled trial

Previous studies have shown that nicorandil has a protective effect on cardiomyocytes.However,there is no study to investigate whether perioperative intravenous nicorandil can further reduce the myocardial infarct size in patients with ST-segment elevation myocardial infarction(STEMI)compared to the current standard of percutaneous coronary intervention(PCI)regimen.The CHANGE(China-Administration of Nicorandil Group)study is a multicenter,prospective,randomized,double-blind and parallel-controlled clinical study of STEMI patients undergoing primary PCI in China,aiming to evaluate the efficacy and safety of intravenous nicorandil in ameliorating the myocardial infarct size in STEMI patients undergoing primary PCI and provide evidence-based support for myocardial protection strategies of STEMI patients.

Significance of neuroglobin in serum of acute atherosclerotic cerebral infarction patients

This study sought to examine neuroglobin （NGB） in the serum of acute cerebral infarction patients with double-antibody sandwich enzyme-linked immunosorbent assay to identify all risk factors, calculate infarct size, assess neurological impairment, and analyze the relation between NGB and each of these factors. The double-antibody sandwich assay indicated that levels of NGB in serum were unaltered within 6 hours following acute cerebral infarction compared with normal levels. NGB levels then underwent a distinct change, peaking at 24 hours then returning to normal levels in 72 hours. The results suggest that the level of NGB might be related to infarct size and low-density lipoprotein at 24 hours after acute cerebral infarction. There were no significant differences in neurological impairment scores and infarct size at different periods following infarction. The findings indicated that the level of NGB in serum of acute cerebral infarction patients was correlated with infarct time.

To investigate the effects of butylphthalide on reducing neuronal apoptosis in rats with cerebral infarction by inhibiting the JNK/P38 MAPK signaling pathway

Objective:To investigate the effects of butylphthalide on reducing neuronal apoptosis in rats with cerebral infarction by inhibiting the JNK/P38 MAPK signaling pathway.Methods:Forty-eight SD male rats were divided into DZ group(control group),CI group(model group)and NBP group(butylphthalide group).Rats in CI group and NBP group were used to establish cerebral infarction models.NBP group used NBP.The solution(80 mg/(kg?d))was administered orally,and the remaining two groups were administered with the same volume of peanut oil.After 14 consecutive days of treatment,the Zea Longa score was used to evaluate the neurological function of DZ,CI and NBP rats.Scoring,TTC staining was used to observe the cerebral infarction volume of rats in DZ group,CI group and NBP group,HE staining was used to observe the pathological morphology of brain tissue in DZ group,CI group and NBP group.Neuronal apoptosis,Western blot was used to detect the expression of p-JNK and p-p38MAPK in brain tissues of DZ group,CI group and NBP group.Results:The neurological function of the rats in the CI group was higher than that in the DZ group,and the difference was statistically significant(P<0.05).The neurological function score of the rats in the NBP group was reduced compared with the CI group,and the difference was statistically significant(P<0.05).The cerebral infarction volume in the group was 35.56%higher than that in the DZ group,and the difference was statistically significant(P<0.05).The minor infarct volume in the NBP group was 21.59%,which was less than that in the CI group,and the difference was statistically significant(P<0.05).Nerve cells are neatly sorted,with a large number.The gap between blood vessels and interstitial tissue in the CI group is enlarged,the cells are severely contracted,and the neuron structure is incomplete.Compared with the CI group,the NBP group has reduced neuron contraction and increased number;The dead nerve cells were brown.The apoptosis rate of nerve cells in the CI group was 79.65%higher than that in the DZ group was 5.82%.The difference was statistically significant(P<0.05).The nerve cell apoptosis rate in the NBP group was 30.23%.Compared with CI group,the difference was statistically significant(P<0.05);Western blot results showed that p-JNK and p-p38MAPK protein expression in CI group was higher than that in DZ group,and the difference was statistically significant(P<0.05).The levels of p-JNK and p-p38MAPK proteins in the NBP group were lower than those in the CI group.There was statistically significant(P<0.05).Conclusion:Butylphthalide can improve neurological damage,reduce apoptotic nerve cells,and reduce infarct volume in rats with cerebral infarction,which is related to the inhibition of JNK/P38 MAPK pathway expression.

The effect of an adaptation to hypoxia on cardiac tolerance to ischemia/reperfusion

The acute myocardial infarction(AMI)and sudden cardiac death(SCD),both associated with acute cardiac ischemia,are one of the leading causes of adult death in economically developed countries.The development of new approaches for the treatment and prevention of AMI and SCD remains the highest priority for medicine.A study on the cardiovascular effects of chronic hypoxia(CH)may contribute to the development of these methods.Chronic hypoxia exerts both positive and adverse effects.The positive effects are the infarct-reducing,vasoprotective,and antiarrhythmic effects,which can lead to the improvement of cardiac contractility in reperfusion.The adverse effects are pulmonary hypertension and right ventricular hypertrophy.This review presents a comprehensive overview of how CH enhances cardiac tolerance to ischemia/reperfusion.It is an in-depth analysis of the published data on the underlying mechanisms,which can lead to future development of the cardioprotective effect of CH.A better understanding of the CH-activated protective signaling pathways may contribute to new therapeutic approaches in an increase of cardiac tolerance to ischemia/reperfusion.

Human neural stem cells promote proliferation of endogenous neural stem cells and enhance angiogenesis in ischemic rat brain

Transplantation of human neural stem cells into the dentate gyrus or ventricle of rodents has been reportedly to enhance neurogenesis. In this study, we examined endogenous stem cell proliferation and angiogenesis in the ischemic rat brain after the transplantation of human neural stem cells. Focal cerebral ischemia in the rat brain was induced by middle cerebral artery occlusion. Human neural stem cells were transplanted into the subventricular zone. The behavioral performance of human neural stem cells-treated ischemic rats was significantly improved and cerebral infarct volumes were reduced compared to those in untreated animals. Numerous transplanted human neural stem cells were alive and preferentially localized to the ipsilateral ischemic hemisphere. Furthermore, 5-bromo-2′-deoxyuridine-labeled endogenous neural stem cells were observed in the subventricular zone and hippocampus, where they differentiated into cells immunoreactive for the neural markers doublecortin, neuronal nuclear antigen Neu N, and astrocyte marker glial fibrillary acidic protein in human neural stem cells-treated rats, but not in the untreated ischemic animals. The number of 5-bromo-2′-deoxyuridine-positive ？ anti-von Willebrand factor-positive proliferating endothelial cells was higher in the ischemic boundary zone of human neural stem cells-treated rats than in controls. Finally, transplantation of human neural stem cells in the brains of rats with focal cerebral ischemia promoted the proliferation of endogenous neural stem cells and their differentiation into mature neural-like cells, and enhanced angiogenesis. This study provides valuable insights into the effect of human neural stem cell transplantation on focal cerebral ischemia, which can be applied to the development of an effective therapy for stroke.

Three hours continuous injection of adenosine improved left ventricular function and infarct size in patients with ST-segment elevation myocardial infarction

Background The definitive treatment for myocardial ischemia is reperfusion. However, reperfusion injury has the potential to cause additional reversible and irreversible damage to the myocardium. One likely candidate for a cardioprotection is adenosine. The present study aimed at investigating the effect of intravenous adenosine on clinical outcomes in patients with ST-segment elevation myocardial infarction （STEMI） undergoing primary percutaneous coronary intervention （PCI）. Methods Patients with STEMI within 12 hours from the onset of symptoms were randomized by 1：1：1 ratio to receive either adenosine 50μg-kg-1.min-1 （low-dose group, n=31）, or 70 μg.kg-1.min1 （high-dose group, n=32）, or saline 1 ml/min （control group, n=27） for three hours. Drugs were given to the patients immediately after the guide wire crossed the culprit lesion. Recurrence of no-reflow, TIMI flow grade （TFG） and TIMI myocardial perfusion grade （TMPG）, and collateral circulation were recorded. The postoperative and preoperative ST segment elevation sum of 18-lead electrocardiogram （ECG） and their ratio （STsum-post/STsum-pre） were recorded, as well as the peak time and peak value of CK-MB enzyme. Serial cardiac echo and myocardial perfusion imaging were performed at 24 hours and 6 months post-stenting. The primary endpoint was left ventricular function, and infarct size. The secondary end-point was the occurrence of cardiac and non-cardiac death, non-fatal myocardial infarction, and heart failure. Results A total of 90 STEMI patients were studied. No-reflow immediately after stent procedure was seen in 11 （35.5%） patients in the control group, significantly different from 6.3% in the low-dose group or 3.7% in the high-dose group （both P=0.001）. STsum-post/STsum-pre in the low-dose and high-dose groups was significantly different from the control group （low-dose group vs. control group, P=0.003 and high-dose group vs. control group, P=0.001）, without a dose-dependent pattern （P=0.238）. The peak value of CK-MB enzyme was significantly reduced in the high-dose group compared to the control group （P=-0.024）. Compared to the left ventricular ejection fraction （LVEF） in control group, LVEF in the low-dose group increased by 5.8% at 24 hours （P=0.012） and by 10.9% at 6 months （P=0,007）, LVEF in the high-dose group increased by 9.5% at 24 hours （P=0.001） and by 10.0% at 6 months （P=0.001）, respectively. Significant reduction of infarct size by 24.2% was detected in the high-dose group vs. low-dose or control groups （P=0.008）. There was no significant difference regarding secondary endpoints at 6 months among the treated groups. Cardiac function by NYHA classification in both the low-dose and the high-dose groups was improved significantly （P=0.013, P=0.016）. Conclusion Intravenous adenosine administration might significantly reduce the recurrence of no-reflow, with resultant improved left ventricular systolic function. High-dose adenosine was further associated with significant reduction of infarct size.

The Effect of Hypercapnic Acidosis Preconditioning on Rabbit Myocardium

This study observed the protective effect of hypercapnic acidosis preconditioning on rabbit heart suffered from ischemia-reperfusion injury. Hypercapnic acidosis was established in animals with mechanical hypoventilation before ischemia-reperfusion. Thirty-two rabbits were randomly divided into 4 groups, with each having 8 aminals in term of the degree of acidification： hypercapnic acidosis group A （group A）, hypercapnic acidosis group B （group B）, hypercapnic acidosis group C （group C）, ischemia and reperfusion group （group IR）. Animals in group IR were ventilated normally （tidal volume： 15 mL/kg, breathing rate 35 bpm）. The PETCO2 was maintained at the level of 40-50 mmHg for 30 min. Animals in groups A, B, C received low-frequency, low-volume ventilation to achieve hypercarbonic acidosis and the target levels of PETCO2 were 75-85 ,65-75, 55-65 mmHg, respectively, with levels being maintained for 5 min. The animals then were ventilated normally to lower PETCO2 to 40-50 mmHg. The left anterior branch artery of all the animals was ligated for 30 min and reperfused for 180 min. Then the infarct size was calculated. The cardiomyocytes were morphologically observed and ECG and hemodynamics were monitored on continuous basis. Acid-base balance was measured during procedure. Our results showed that the infarct size was （48.5±11.5）% of the risk area in the control group and （42.4±7.9）% in group C （P〉0.05）. Mean infarct size was significantly smaller in group B （34.5%±9.4%） （P〈0.05 vs control group） and group A （31.0%±9.1%） （P〈0.01 vs control group）. It is concluded that HA-preconditioning can effectively protect the myocardium.

Ischemic Conditioning-Mediated Myocardial Protection in Relation to Duration of Coronary Occlusion

Background: Myocardial ischemia is a dynamic process whereby a cascade of events is initiated to stimulate transition from reversible to irreversible cellular injury. Non-pharmacologic approaches to cellular protection, such as ischemic conditioning, delay onset of cellular injury in most organs in a host of animal species;however the degree of protection is limited to rather short durations of ischemia. In the present study, we examined whether protection afforded by ischemic conditioning could be extended beyond currently established limits of coronary occlusion in an in situ animal model. Methods: Rabbits (n = 106) were exposed to 30-, 60-, 120-, 180-, 240-, or 360-min coronary occlusion followed by 180-min coronary reperfusion (i.e. non-conditioned control groups). Ischemic conditioned rabbits were pre-treated by ischemic conditioning (i.e. 2-cycles of 5-min coronary occlusion and 5-min reperfusion) prior to a prolonged period of ischemia as described above. Area at risk (AR; by fluorescent microparticles) and area of necrosis (AN;by tetrazolium staining) were quantified by planimetry. Serum troponin I levels were assessed at baseline (i.e. before experimental protocol) and at the end of the experiment. Results: Changes in heart rate and hemodyamic indices were similar for all groups regardless of duration of ischemia and regardless of treatment (i.e. non-conditioned vs. ischemic conditioned). Infarcts (as percent AR) were markedly smaller (~35%) in ischemic conditioned rabbits (vs. controls) for the 30-min coronary occlusion group. With longer durations of coronary occlusion (60-, 120-, 180-, 240-min) infarcts were smaller (~20%) in ischemic conditioned groups but protection afforded was not statistically significant. With 360-min coronary occlusion, infarct size was the same for both treatment groups. Serum troponin I levels were greater in relation to infarct size as expected but no differences were detected between treatments regardless of ischemic duration. Conclusions: Ischemic conditioning limits infarct development;however, protection is limited when the duration of ischemia is extended beyond 4 hours. These findings provide further support for the concept that ischemic conditioning can delay, but does not limit myocyte necrosis. Underlying mechanisms for cellular protection remain to be established.

MECHANISMS INVOLVED IN THE REDUCTION OF INFARCT SIZE BY ACE INHIBITIOR AFTER LEFT CORONARY ARTERY LIGATION IN RATS

The contribution of the inhibition of angiotensin Ⅱ (ANGⅡ) synthesis and bradykinin (BK) breakdown to the effects of ACE inhibition on infarct size, cardiac hypertrophy and blood supply to the marginal zone of the infarcted area