Study On The Prevention And Treatment Of Is Chemia Reperfusion Injury In Rats

Acute myocardial infarction or myocardial infarction?AMI or MI?is often referred to as heart attack.It is a disease that occurs when the blood supply is partially interrupted by the heart.The most common reason is the rupture of vulnerable plaques.The resulting ischemia or anoxia leads to injury and potential death of the heart.This is a medical emergency and a major cause of death for men and women all over the world.Revasularization?RV?is the first choice of AMI treatment,including intravenous thrombolysis,percutaneous coronary intervention?PCI?and coronary artery bypass surgery,can obviously improve short-term and long-term prognosis of patients.RV in the treatment of acute myocardial infarction is a landmark in the history of coronary heart disease,and it is an effective and widely used method.Treatment or percutaneous coronary intervention is the most effective treatment for ischemic myocardium,reducing the size of myocardial infarction and the preservation of cardiac function.However,reperfusion may aggravate myocardial injury.This phenomenon is known as"ischemia/reperfusion injury”,which inevitably reduces the therapeutic effect.Due to the infiltration of white blood cells and the production of proinflammatory cytokines,myocardial injury is believed to be the result of a strong inflammatory response.Ventricular arrhythmia is still the main cause of death in patients with acute myocardial infarction during ischemia and reperfusion.These problems can affect the success rate and prognosis of patients,and the function of cardiac muscle cells.Therefore,the mechanism of these problems and how to prevent and treat them become very important.Unfortunately,traditional drug therapy is not effective for the treatment of I/R related inflammation and arrhythmia.Therefore,new treatment interventions are worth considering.If we can prevent such changes or reverse these changes,it may be a new target for clinical treatment of arrhythmia.Recent years,extensive research has been carried out in the field of adjuvant drug therapy.Therefore,now we have various antithrombotic and antiplatelet agents,which have been proven to reduce the main adverse cardiac events in the background of ST-segment elevation myocardial infarction?STEMI?.Aspirin is commonly used in combination with clopidogrel or combination with ticagrelor antiplatelet therapy.Ticagrelor is a cycic three zolouracil,which acts on the platelet P2Y₁₂receptor as an antagonist.It does not need to be transformed into an active metabolite,and it is reversible.In the PLATO trial,compared with clopidogrel,the blood vessel induced mortality was reduced for ticagrelor.For the antiplatelet effect of ticagrelor is more effective for clopidogrel and can rapidly and robustly inhibit platelet aggregation.Many studies show that for ticagrelor can inhibit the balance of equilibrative nucleoside transporter-1?ENT-1?increased plasma concentrations of adenosine,thereby inhibiting platelet function by A2A receptor,and inhibit the healthy volunteers and animal adenosine P2Y₁₂.It is associated with increased plasma concentration of adenosine and cyclic adenosine monophosphate?cAMP?in patients with acute coronary syndrome?ACS?.This effect on adenosine and cAMP may be involved in the so-called pleiotropic effect of the ticagrelor.Animal experimental researches show that,ticagrelor significantly reduce ischemia reperfusion injury,but PCI is the application of ticagrelor surgery can prevent AMI patients after PCI reperfusion arrhythmia and no reflow occurred,there is no clinical research system,so it has important clinical significance in the prevention and treatment of ticagrelor again reperfusion arrhythmia and no reflow effect and mechanism research.In this study,patch clamp technique was used to observe the effect of ticagrelor on the ion channels in ventricular myocytes of AMI reperfusion animal models,and further explore the ionic mechanism of anti arrhythmia.Objective:To study the effect of ticagrelor on cardiac arrhythmia and L type calcium channel in ventricular myocytes of AMI reperfusion animal models,and to explore the ionic mechanism of anti arrhythmia.Methods:24 healthy SD male rats,weighing about 300 g,were randomly divided into sham operation group,ischemia-reperfusion model group and ticagrelor group.Myocardial ischemia reperfusion model was made in rats.Sham was only threaded,without ligation of the anterior descending branch;and two hours before the model of group ticagrelor,the gavage was given to the gastric.During the model,the arrhythmias such as ventricular premature beat,ventricular tachycardia and ventricular fibrillation were observed and recorded.After reperfusion for 120 min in AMI reperfusion animal model,the heart and collagenase II were taken down to decompose rat ventricular myocytes,and then decomposed into single ventricular myocytes.With the patch clamp technique,the L type of calcium current was recorded in the voltage clamp mode by the electrode adsorption,and the G?was reached and the membrane was broken.The effect and mechanism of ticagrelor on L type calcium current of ventricular muscle were investigated by experimental observation.Results:The incidence of arrhythmia:the sham operation group there was only sporadic ventricular contraction,without the occurrence of ventricular tachycardia and ventricular fibrillation;comparing with sham operation group,I/R group showed systolic ventricular premature ventricular tachycardia and ventricular fibrillation and ventricular tachycardia,and ventricular fibrillation rate significantly increased cardiac arrhythmia score increased significantly?P<0.05?;comparing with the I/R group,ticagrelor group,ventricular premature beat and ventricular tachycardia,ventricular fibrillation occurred,but the duration of ventricular premature beat and ventricular tachycardia were shorter than group I/R?P<0.05?,significantly reduced the incidence of arrhythmia score decreased?P<0.05?.Comparing with the sham operation group,I/R group,L type calcium current density was significantly increased?-4.3±0.5,-9.4±0.4,P<0.05,n=10,10 for sham group and I/R group?;comparing with the I/R group,for L type calcium current density ticagrelor group was significantly decreased?the peak current density is-9.4±0.4,-7.1±1.0,P<0.05,n=10,9 for I/R group and ticagrelor group?.By analyzing the current gating characteristics of the channel,it was found that compared with the sham operation group,the I/R group significantly reduced the inactivation process of L-type calcium channel and had no effect on the activation process of L type calcium channel.?half of the inactivated voltages were-26.0±1.1mV,-22.7±0.8mV,P<0.05,and n=10,14 for sham group and I/R group.The activation voltage was-14.9±0.8mV,-13.1±0.7mV,P>0.05,and n=15,15 for sham group and I/R group?.Compared with I/R group,on behalf of ticagrelor group can obviously accelerate the L type calcium channel of the deactivation process,does not affect the activation process of L type calcium channel?half of the inactivated voltages were-22.7±0.8mV,-25.7±0.6mV,P<0.05,n=14,9 for I/R group and ticagrelor group.Half of the activated voltages were-13.1±0.7mV,-13.7±0.7mV,P>0.05,and n=15,9 for I/R group and ticagrelor group?.Conclusions:Ticagrelor can significantly reduce the number of ventricular premature beats during reperfusion,and the duration and incidence of ventricular fibrillation and ventricular tachycardia.Ticagrelor can significantly reduce the increased L-type calcium current during myocardial ischemia and reperfusion,which may be the ionic mechanism of ticagrelor on myocardial ischemia-reperfusion injury.