Effects of electroacupuncture pretreatment on GABAA receptor of fastigial nucleus and sympathetic nerve activity in rats with myocardial ischemia reperfusion injury / 中国针灸

OBJECTIVE@#To observe the effects of electroacupuncture (EA) pretreatment on cardiac function, sympathetic nerve activity, indexes of myocardial injury and GABAA receptor in fastigial nucleus in rats with myocardial ischemia reperfusion injury (MIRI), and to explore the neuroregulatory mechanism of EA pretreatment in improving MIRI.@*METHODS@#A total of 60 male SD rats were randomly divided into a sham operation group, a model group, an EA group, an agonist group and an agonist+EA group, 12 rats in each group. The MIRI model was established by ligation of the left anterior descending coronary artery. EA was applied at bilateral "Shenmen" (HT 7) and "Tongli" (HT 5) in the EA group and the agonist+EA group, with continuous wave, in frequency of 2 Hz and intensity of 1 mA, 30 min each time, once a day for 7 consecutive days. After intervention, the MIRI model was established. In the agonist group, the muscone (agonist of GABAA receptor, 1 g/L) was injected in fastigial nucleus for 7 consecutive days before modeling, 150 μL each time, once a day. In the agonist+EA group, the muscone was injected in fastigial nucleus 30 min before EA intervention. The data of electrocardiogram was collected by PowerLab standard Ⅱ lead, and ST segment displacement and heart rate variability (HRV) were analyzed; the serum levels of norepinephrine (NE), creatine kinase isoenzyme MB (CK-MB) and cardiac troponin I (cTnI) were detected by ELISA; the myocardial infarction area was measured by TTC staining; the morphology of myocardial tissue was observed by HE staining; the positive expression and mRNA expression of GABAA receptor in fastigial nucleus were detected by immunohistochemistry and real-time PCR.@*RESULTS@#Compared with the sham operation group, in the model group, ST segment displacement and ratio of low frequency to high frequency (LF/HF) of HRV were increased (P<0.01), HRV frequency domain analysis showed enhanced sympathetic nerve excitability, the serum levels of NE, CK-MB and cTnI were increased (P<0.01), the percentage of myocardial infarction area was increased (P<0.01), myocardial fiber was broken and interstitial edema was serious, the positive expression and mRNA expression of GABAA receptor in fastigial nucleus were increased (P<0.01). Compared with the model group, in the EA group, ST segment displacement and LF/HF ratio were decreased (P<0.01), HRV frequency domain analysis showed reduced sympathetic nerve excitability, the serum levels of NE, CK-MB and cTnI were decreased (P<0.01), the percentage of myocardial infarction area was decreased (P<0.01), myocardial fiber breakage and interstitial edema were lightened, the positive expression and mRNA expression of GABAA receptor in fastigial nucleus were decreased (P<0.01). Compared with the EA group, in the agonist group and the agonist+EA group, ST segment displacement and LF/HF ratio were increased (P<0.01), HRV frequency domain analysis showed enhanced sympathetic nerve excitability, the serum levels of NE, CK-MB and cTnI were increased (P<0.01), the percentage of myocardial infarction area was increased (P<0.01), myocardial fiber breakage and interstitial edema were aggravated, the positive expression and mRNA expression of GABAA receptor in fastigial nucleus were increased (P<0.01).@*CONCLUSION@#EA pretreatment can improve the myocardial injury in MIRI rats, and its mechanism may be related to the inhibition of GABAA receptor expression in fastigial nucleus, thereby down-regulating the excitability of sympathetic nerve.

Effect of electroacupuncture preconditioning on the contents of dopamine and 5-hydroxytryptamine in lateral hypothalamus area and cerebellar fastigial nucleus of rats with myocardial ischemia-reperfusion injury / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) preconditioning at heart meridian acupoints on the contents of dopamine (DA) and 5-hydroxytryptamine (5-HT) in lateral hypothalamus area (LHA) and cerebellar fastigial nucleus (FN) in the rats with acute myocardial ischemia-reperfusion injury (MIRI), and explore the role and mechanism of LHA and FN in the effect of EA at heart meridian acupoints against acute MIRI.@*METHODS@#Sixty SD rats were randomly divided into a sham-operation group, a model group, an EA heart meridian group and an EA lung meridian group, 12 rats in each group, as well as an LHA plus heart meridian group (damage of bilateral LHA) and an FN plus heart meridian group (damage of bilateral FN), 6 rats in each one. Three days after nucleus destruction, EA was applied to "Shenmen" (HT 7) and "Tongli" (HT 5) in the EA heart meridian group, the LHA plus heart meridian group and the FN plus heart meridian group and EA was applied to "Taiyuan" (LU 9) and "Lieque" (LU 7) in the EA lung meridian group, with 1 V in stimulating voltage and 2 Hz in frequency, lasting 20 minutes each time, once a day, for consecutively 7 days before model replication. Except in the sham-operation group, MIRI rat models were duplicated by ligation of the left anterior descending branch of the coronary artery in the rest groups. Using Power lab physiological recorder, ST segment displacement value was recorded before modeling, 30 min after ligation and 120 min after reperfusion separately. The high performance liquid chromatography-electrochemical detection and analysis system was adopted to determine the contents of DA and 5-HT in LHA and FN dialysate after rat modeling in each group.@*RESULTS@#In comparison of ST segment displacement value 30 min after ligation and 120 min after reperfusion among groups, the value in the model group was higher than that in the sham-operation group (@*CONCLUSION@#EA preconditioning at heart meridian acupoints can effectively alleviate myocardial injury in acute MIRI rats, during which, DA and 5-HT in LHA and FN may be the important material basis.

Remote preconditioning, perconditioning, and postconditioning: a comparative study of their cardio-protective properties in rat models

OBJECTIVE: Ischemia reperfusion injury is partly responsible for the high mortality associated with induced myocardial injury and the reduction in the full benefit of myocardial reperfusion. Remote ischemic preconditioning, perconditioning, and postconditioning have all been shown to be cardioprotective. However, it is still unknown which one is the most beneficial. To examine this issue, we used adult male Wistar rat ischemia reperfusion models to compare the cardioprotective effect of these three approaches applied on double-sided hind limbs. METHODS: The rats were randomly distributed to the following five groups: sham, ischemia reperfusion, remote preconditioning, remote perconditioning, and remote post-conditioning. The ischemia/reperfusion model was established by sternotomy followed by a 30-min ligation of the left coronary artery and a subsequent 3-h reperfusion. Remote conditioning was induced with three 5-min ischemia/5-min reperfusion cycles of the double-sided hind limbs using a tourniquet. RESULTS: A lower early reperfusion arrhythmia score (1.50 + 0.97) was found in the rats treated with remote perconditioning compared to those in the ischemia reperfusion group (2.33 + 0.71). Meanwhile, reduced infarct size was also observed (15.27 + 5.19% in remote perconditioning, 14.53 + 3.45% in remote preconditioning, and 19.84+5.85% in remote post-conditioning vs. 34.47 + 7.13% in ischemia reperfusion, p<0.05), as well as higher expression levels of the apoptosis-relevant protein Bcl-2/Bax following global (ischemia/reperfusion) injury in in vivo rat heart models (1.255 + 0.053 in remote perconditioning, 1.463 + 0.290 in remote preconditioning, and 1.461 +0.541 in remote post-conditioning vs. 1.003 + 0.159 in ischemia reperfusion, p<0.05). CONCLUSION: Three remote conditioning strategies implemented with episodes of double-sided hind limb ischemia/reperfusion have similar therapeutic potential for cardiac ischemia/reperfusion injury, and remote perconditioning has a greater ability to prevent reperfusion arrhythmia.

Role of verapamil [calcium channel blocker] and lisinopril [angiotensin converting enzyme inhibitor] on myocardial tolerance to acute ischaemia

This work aims to clarify the role of calcium channel blocker [verapamil] and angiotensin-converting enzyme inhibitor [lisinopril] on myocardial ischemia reperfusion injury. The study was done using isolated rabbits hearts and Langendroffs apparatus for recording myocardial contractility, heart rate and coronary flow, also glucose uptake by coronary slices was estimated by glucose enzymatic kit. The work included 4 groups; Group A to study effect of ischemia and reperfusion on mentioned parameters, Group B to study effect of verapamil and lisinopril on tested parameters. Group C to study the effect of 5 minutes pre-ischaemia administration of verapamil and lisinopril on tested parameters and Group D to study the effects of administration of verapamil and lisinopril with reperfusion on parameters mentioned before. Results concluded that global ischaemia decreased the myocardial contractility and heart rate but increases glucose uptake, verapamil is a potent drug used to decrease myocardial contractility, heart rate and increase coronary flow in ischaemic hearts. Lisinopril is a drug of choice to improve contractility and heart rate when administered preischaemic or with reperfusion. Verapamil is a drug of choice to improve coronary flow when administered preischaemic or with reperfusion. There is no preference between the 2 drugs when given preischaemic on increasing glucose uptake. So calcium, angiotensin and O2 free radicals are important mediators of ischaemic reperfusion injury as their modulation by the verapamil and lisinopril significantly improve ischaemia reperfusion induced changes in myocardial contractility, heart rate, coronary flow and glucose uptake

Consideraciones sobre el daño miocárdico por isquemia y reperfusión / Considerations on the myocardial damage due to ischemia and reperfusion

En este artículo, se hacen algunas consideraciones en torno al daño miocárdico debido a déficit de aporte sanguíneo. En realidad, la alteración primordial del síndrome no consiste en la isquemia en sentido electrofisiopatológico, que es un trastorno de la repolarización celular debido a diferentes causas. Dicha alteración constituye más propiamente una despolarización diastólica parcial o lesión, i. e. una reducción moderada del potencial de reposo transmembrana. Caracteriza ésta la fase aguda del síndrome de infarto miocárdico y es responsable de las manifestaciones eléctricas, que aparecen en tal fase: desórdenes del ritmo y de la conducción, así como reducción de la contractilidad de las fibras miocárdicas afectadas. Estos fenómenos se deben a una falla de los mecanismos energéticos del miocardio por alteraciones mitocondriales de los miocitos: reducción temprana de los nucleótidos de nicotinamida adenina, acumulación de calcio ("calcium overload") en las mitocondrias y caída de la fosforilación oxidativa. Tales hechos pueden volver a presentarse, con mayor intensidad, en una fase posterior del síndrome de infarto por reperfusión miocárdica. Su gravedad está relacionada con la duración del período inicial de déficit de aporte sanguíneo al miocardio. Se les pueden agregar las consecuencias de un estrés oxidativo, responsable de la formación de especies reactivas derivadas del oxígeno. Dicho estrés causa daño también en el DNA mitocondrial produciendo mutaciones e inserción y pérdida de secuencias por oxidación de las bases nitrogenadas. Tanto en la fase de isquemia inicial como en la de reperfusión, puede ser muy útil la llamada terapéutica metabólica, p. ej. en su modalidad de las soluciones glucosa-insulina-potasio (G-I-K), que actuarían como acarreadoras de radicales libres derivados del oxígeno. Asimismo los llamados fármacos metabólicos, p. ej. la trimetazidina, los antioxidantes, etc., pueden ser útiles en la fase de reperfusión miocárdica.

In this article, we present some considerations on the myocardial damage due to a deficit of oxygen supply. In fact, this damage properly constitutes a partial diastolic depolarization or injury, i. e., a moderate reduction of the rest transmembrane potential. This phenomenon is characteristic of the acute phase of the myocardial infarction syndrome and is responsible for the main electrical manifestations appearing in this phase: disorders of rhythm and conduction, as well as a reduced contractility of the involved myocardial fibers. All the mentioned phenomena are due to a defect of the myocardial energetic mechanisms, owing to the mitochondrial alterations in myocytes: early reduction of the nicotinamide adenine nucleotides, accumulation of calcium ("calcium overload") into mitochondria, and a drop in oxidative phosphorylation. These changes can present again, more exaggerated, in a following phase of evolution of the myocardial infarction due to myocardial reperfusion. Its severity is related to the duration of the initial ischemia period. Moreover, consequences of the oxidative stress can add producing cellular damage by liberation of reactive oxygen species. Oxidant stress causes also alterations in the mitochondrial DNA, i. e., mutations due to oxidation of nitrogenous bases. During the initial ischemia phase, as well as during reperfusion, metabolic therapy can be very useful as, for example, glucose-insulin-potassium solutions (G-I-K). These could act as scavengers of the free radicals derived from oxygen and avoid or reduce the myocardial damage due to reperfused myocytes. Metabolic drugs, as for example tri-metazidine, antioxidants, etc, can also be used in the myocardial reperfusion phase. (Arch Cardiol Mex 2003; 73:284-290).