A comparison of electrically induced cardiac arrest with cardiac arrest produced by coronary occlusion

OBJECTIVE: The present study was undertaken to compare an animal model of electrically induced VF with ischemically induced VF. In a preponderance of models of cardiac arrest and resuscitation in intact animals, ventricular fibrillation (VF) is induced by an alternating current delivered directly to the epicardium or endocardium. Yet, the applicability of such animal models has been challenged for it is not an electrical current alone but rather a current generated in the ischemic myocardium that triggers VF. Accordingly, a potentially more clinically relevant model was investigated in which spontaneous VF followed acute myocardial ischemia. METHODS: Twenty anesthetized pigs were randomized to either electrical fibrillation or myocardial ischemia following transient occlusion of the left anterior descending (LAD) coronary artery. RESULTS: VF was untreated for 7 min in both models after which mechanical ventilation and precordial compression were begun. Defibrillation was attempted after 5 min of CPR in both groups. VF appeared within 5.7+/-2.0 min of LAD occlusion. CONCLUSIONS: A significant increase in the number of post-resuscitation premature ventricular beats and recurrent VF followed ROSC and a significantly greater number of shocks was required for restoration of spontaneous circulation (ROSC) after LAD occlusion. Nevertheless, early post-resuscitation myocardial dysfunction, neurological recovery and 72 h survival were indistinguishable between the two models.     

心肌缺血预适应现象与心肌梗塞临床及预后关系的研究

目的：探讨心肌缺血预适应对心肌梗塞临床及预后的影响。方法：对３８５例心肌梗塞患者的临床及随访资料进行分析，按梗塞前有无心肌缺血表现分为Ａ、Ｂ两组。结果：Ａ组心肌梗塞时心肌坏死范围、心肌酶峰值、心律失常、左心衰竭、室壁瘤形成及病死率均明显低于Ｂ组，而梗塞后心绞痛及再次心肌梗塞的发生率却明显高于Ｂ组。两组差异显著（Ｐ＜０．０５或＜０．０１）。结论：心肌缺血预适应的临床意义有：①使再次缺血的程度减轻。②降低心律失常的发生率，提高室颤阈。③缩小梗塞范围。④维持梗塞后心脏功能。     

缺血预适应对急性心肌梗死合并糖尿病患者预后的影响

目的　探讨心肌缺血预适应对急性心肌梗死合并糖尿病患者临床状况及近期预后的影响。方法　 6 7例确诊为急性心肌梗死同时合并有糖尿病的患者 ,根据心肌梗死发病前 1周内有无心绞痛发作分为缺血预适应组 (2 8例 )和对照组 (39例 ) ,两组基础临床情况类似。观察心肌梗死范围、心肌酶学改变、左室射血分数及住院期间泵衰竭、心源性休克、严重心律失常等心脏事件的发生率和病死率。结果　缺血预适应组患者临床状况及近期预后较好 ,与对照组相比 ,梗死面积小 ,≥ 2个梗死面的检出率低 (32 .1%与 5 6 .4 % ,P <0 .0 5 ) ,血浆CPK、CK MB、cTnT峰值均显著降低 (P <0 .0 1或P <0 .0 5 ) ,且住院期间的泵衰竭发生率(17.9%与 4 1.0 % ,P <0 .0 5 )、心源性休克 (10 .7%与 33.3% ,P <0 .0 5 )、严重心律失常 (14 .3%与 4 6 .2 % ,P<0 .0 1)及住院病死率 (3.6 %与 2 0 .5 % ,P <0 .0 5 )均降低。结论　缺血预适应对急性心肌梗死合并糖尿病的患者有保护作用 ,可以减少心肌梗死面积 ,降低临床并发症的发生率 ,但不能改善左室射血分数与促进心功能的恢复     

Lack of effects of trimetazidine on systemic hemodynamics in patients with coronary artery disease: a placebo-controlled study

Trimetazidine has been shown to improve anginal symptoms and exercise tolerance in patients with coronary artery disease (CAD). To determine the hemodynamic effects of trimetazidine, systemic hemodynamics were studied in 15 patients suffering from CAD (12 male, 3 female, mean age +/- SEM = 58.6 +/- 1.8 years). Cardiac index was determined by thermodilution method. Left ventricular and aortic pressures were measured using micromanometers (Miller Instruments). After basal measurements, patients were randomly given either placebo (n = 5) or one of two therapeutic doses of trimetazidine 1 mg.kg-1 (n = 5) or trimetazidine 1.5 mg.kg-1 (n = 5) in a double-blind procedure. Data were recorded 5, 10 and 20 min after intravenous drug bolus. Throughout the procedure, the evolution of systemic hemodynamic parameters was not statistically different between the three groups, in particular heart rate, cardiac index, systolic, diastolic and mean aortic pressures, end-diastolic ventricular pressure, mean capillary wedge pressure, pulmonary artery pressures or systemic vascular resistances. We conclude that, unlike other antianginal drugs (particularly beta-blockers, nitrates and calcium-channel inhibitors), trimetazidine does not modify systemic hemodynamics in patients with CAD. These results are consistent with a direct effect of trimetazidine on the ischemic myocardial cell previously reported.     

缺血预适应对糖尿病大鼠心肌缺血/再灌注损伤的保护效应

目的 探讨缺血预适应对糖尿病大鼠心肌缺血/再灌注损伤的保护效应.方法 健康雄性大鼠28只,尾静脉注射链脲佐菌素45 mg/kg制备糖尿病大鼠模型,普通饲料喂养4周后随机分为缺血/再灌注（I/R）组和缺血预适应（IP）组.观察两组大鼠缺血前和缺血即刻、缺血15 min、缺血30 min以及再灌注30 min、再灌注2h心电图ST段改变及室性心律失常的发生情况,TTC染色评价心肌细胞坏死情况,TUNEL法检测心肌细胞凋亡情况,免疫组织化学染色法检测心肌组织凋亡相关基因Bcl-2与Bax蛋白表达情况.结果 与I/R组比较,IP组缺血30 min时ST段抬高幅度明显降低[（0.675±0.150）、（0.489±0.161） mV,P＜0.05],室性期前收缩出现时间推迟[（6.47±4.28）、（18.21±5.36） min,t=5.241,P=0.000],室性期前收缩持续时间缩短[（16.71±5.48）、（6.07±4.33） min,t=4.924,P=0.002],室性心动过速、心室颤动发生率显著下降[57.14％ （8/14）与14.29％ （2/14）,x2=5.600,P=0.018;50.00％（7/14）与14.29％（2/14）,x2=4.094,P=0.043],心肌梗死范围缩小[（37.50±11.40）％、（12.50±9.45）％,t=3.211,P=0.006],凋亡指数亦降低[（24.31±3.12）％、（19.01±4.32）％,t=3.227,P=0.006],并伴有凋亡相关蛋白Bcl-2/Bax上调（0.103±0.045、0.221±0.101,t=2.670,P=0.015）.结论 缺血预适应对病程4周糖尿病大鼠心肌缺血/再灌注损伤具有保护效应,其通过上调凋亡相关基因Bcl-2/Bax,减少心肌细胞凋亡.     

Myocardial performance index following electrically induced or ischemically induced cardiac arrest

OBJECTIVES: We sought to investigate the echocardiographic myocardial performance index (MPI) to assess post-resuscitation myocardial function following electrically and ischemically induced ventricular fibrillation (VF). MATERIALS AND METHODS: VF was induced in fourteen anesthetized pigs weighing 38+/-4 kg. VF was induced electrically in seven animals and ischemically, following transient occlusion of the left anterior descending coronary artery (LAD), in the remaining seven animals. VF was untreated for 7 min after which CPR, including precordial compression and mechanical ventilation was begun. Defibrillation was attempted after 5 min of CPR. MPI, ejection fraction (EF) and fractional area change (FAC) were measured hourly during the following 4 h interval post-resuscitation. RESULTS: Five of seven animals were resuscitated in the electrically induced VF group, and four of seven animals in the ischemically induced VF group. No difference in EF and FAC were observed between the two groups. The MPI, however, was significantly greater at 60 min and 120 min post-resuscitation in animals after ischemically induced VF (p<0.05). CONCLUSION: In this model, left ventricular (LV) MPI was a more sensitive and useful quantitative parameter to assess the LV function than the EF and FAC measurements used routinely. MPI measurements indicated that post-resuscitation myocardial dysfunction may be more severe after ischemically induced VF compared to the electrically induced VF.     

优降糖对KATP通道介导缺血预适应心肌再灌注损伤的影响

目的 :探讨优降糖在完整大鼠心脏模型中 ,对 ATP敏感钾通道 (KATP)介导心肌缺血预适应作用的影响。方法 :将 4 4只大鼠随机分为 4组 :心肌缺血预适应组 (IPC组 )、优降糖组 (GL I组 )、优降糖 IPC组 (G P组 )和对照组 (C组 )。心肌缺血预适应由 3次 10分钟缺血和 10分钟再灌注组成。所有大鼠均接受 30分钟缺血和 6 0分钟再灌注。梗死范围由饱和曲利本蓝和红四氮唑蓝染色判定 ,并以坏死区占缺血区的百分比表示。 导联记录心脏室性心律失常。结果 :IPC能显著缩小缺血再灌注后的心肌梗死范围 ,且这种作用能被 KATP通道阻滞剂优降糖完全取消。 IPC可减少缺血再灌注所致的室性心律失常的发生 ,但这种保护作用不能被优降糖所阻断。结论 :优降糖对 KATP介导 IPC的心肌保护作用有影响。     

The cardioprotective effects of preconditioning with endotoxin, but not ischemia, are abolished by a peroxisome proliferator-activated receptor-gamma antagonist

We investigated whether endogenous ligands of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) protect the heart against ischemia-reperfusion (I/R) injury. The selective PPAR-gamma antagonist GW9662 (2-chloro-5-nitrobenzanilide) was used in rat models of 1) regional myocardial I/R, 2) ischemic preconditioning, and 3) delayed cardioprotection by endotoxin. We also investigated the effects of the selective cyclooxygenase-2 inhibitor, parecoxib, on ischemic preconditioning and delayed cardioprotective effects of endotoxin. Male Wistar rats were anesthetized with sodium thiopentone. Animals were subjected to either 15 or 25 min of regional myocardial I/R and pretreated with the PPAR-gamma agonist ciglitazone (0.3 mg/kg), the PPAR-gamma antagonist GW9662 (1 mg/kg), or GW9662 and ciglitazone. Animals were also subjected to either 1) ischemic preconditioning alone, ischemic preconditioning, and pretreated with either GW9662 or parecoxib (20 mg/kg) or 2) lipopolysaccharide (LPS) (1 mg/kg) alone, LPS, and pretreated with ciglitazone, GW9662, or parecoxib (20 mg/kg). Myocardial infarct size was determined by p-nitroblue tetrazolium staining. The PPAR-gamma antagonist GW9662 (1 mg/kg) abolished the cardioprotection afforded by the potent PPAR-gamma agonist ciglitazone (0.3 mg/kg). Neither GW9662 nor parecoxib affected the cardioprotective effects of ischemic preconditioning. Pretreatment with ciglitazone did not provide additional cardioprotection to LPS-treated animals. Both GW9662 and parecoxib abolished the delayed cardioprotective effects of endotoxin. Thus, we propose that 1) endogenous ligands of PPAR-gamma are being generated by myocardial ischemia in sufficient amounts to attenuate myocardial I/R injury, and 2) that cyclooxygenase-2 metabolites contribute to (or even account for) the cardioprotective effects of endotoxin (second window of protection) by acting as endogenous PPAR-gamma ligands.     

曲美他嗪对缺血性心肌病收缩功能不全患者的疗效观察

目的 探讨曲美他嗪对缺血性心肌病(IHD)收缩功能不全患者的疗效.方法 IHD患者90例,随机分为曲美他嗪组48例以及常规治疗组42例.分别于治疗前和治疗6、12个月检测2组患者血脑钠肽(BNP)含量,心脏彩超测量左心室射血分数(LVEF)、左心室舒张末期内径(LVEDD),比较其差异.结果 曲美他嗪组治疗6、12个月与治疗前比较,LVEF、LVEDD、BNP显著降低(F 值分别为6.176、4.590、12.357,P均＜0.01);常规治疗组仅BNP显著降低(F=8.402,P＜0,01).结论 对于 IHD患者,在常规治疗基础上加用曲美他嗪有助于进一步改善心功能,逆转心室重构.     

Propafenone for the treatment of refractory complex ventricular ectopic activity

The results of therapy with propafenone were evaluated in 45 patients with complex ventricular ectopic activity that had been refractory to a mean of 3.8 antiarrhythmic drugs. The cardiac diagnoses were ischemic heart disease (in 16 patients), cardiomyopathy (in 7), mitral valve prolapse (in 7), mitral valve prolapse (in 7), idiopathic ventricular ectopic beats (in 6), valvular heart disease (in 5), and hypertension (in 4). The frequency of ventricular ectopic beats was established after therapy with antiarrhythmic agents had been discontinued. Patients then received propafenone during a dose-ranging protocol. An effective response was defined as a reduction in total ventricular ectopic beats of 80% or more. During dose ranging, therapy failed in four patients because of side effects, in eight because of a reduction in ventricular ectopic beats of less than 80%, and in three because of an aggravation of the arrhythmia. Thirty patients had a reduction in total ventricular ectopic beats of 80% or more. During a mean follow-up of 12.4 months, therapy failed in 1 patient because of sustained ventricular tachycardia and in 7 because of intolerable side effects; 22 patients continued to receive propafenone. PR and QRS intervals were significantly prolonged (P = 0.001), but the corrected QT interval and the heart rate were unchanged. The mean trough plasma level of propafenone associated with an effective response was 756 ng/ml, and that associated with intolerable side effects was 920 ng/ml. Thus, in patients with refractory complex ventricular ectopic beats, propafenone was effective and well tolerated initially in 67% of patients and during long-term administration in 49%, and toxicity was minor in most patients.     

Actions of intravenous magnesium on ventricular arrhythmias caused by acute myocardial infarction

Although the antiarrhythmic properties of magnesium are well recognized, its mechanisms of antiarrhythmic action are poorly understood. This study was designed to characterize the effects of magnesium on ventricular tachyarrhythmias related to acute myocardial infarction (MI) in dogs. When the circumflex coronary artery was occluded repeatedly for 10 min at 30-min intervals, ventricular fibrillation (VF) occurred in 30, 35 and 33% of dogs during occlusions 1, 2 and 3, respectively. Magnesium pretreatment reduced the incidence of VF to 14% during occlusion 3 (P less than .05 compared to occlusions without magnesium pretreatment). Neither the prevalence of ventricular ectopic complexes 24 h after MI nor arrhythmia inducibility 4 days after infarction were significantly altered by i.v. magnesium. Magnesium significantly attenuated the ST segment elevation (an index of ischemic injury) and ventricular conduction slowing caused by MI. Because magnesium has been reported to reverse the effects of hyperkalemia, we evaluated the role of this action by infusing potassium directly into a coronary artery (to mimic ischemia-induced hyperkalemia) and administered i.v. magnesium. Potassium infusion markedly slowed intraventricular conduction, an effect fully reversed by discontinuing potassium administration but unaffected by i.v. magnesium. We conclude that magnesium has antiarrhythmic actions only during the early phases of an experimental MI, and that these actions are associated with attenuation of indices of ischemic injury and conduction slowing. These properties of magnesium are similar to those of calcium antagonists, and suggest that magnesium's calcium antagonist properties may be important in its antiarrhythmic actions.     

Hypercholesterolemia abrogates sevoflurane-induced delayed preconditioning against myocardial infarct in rats by alteration of nitric oxide synthase signaling

The aim of the current study was to determine whether hypercholesterolemia affects the delayed sevoflurane preconditioning against myocardial ischemia-reperfusion (IR) injury and, if so, the underlying mechanism. Male Sprague-Dawley rats fed 2% cholesterol-enriched chow for 8 weeks were subjected to sevoflurane preconditioning (2.4% vol/vol, 1 h) 24 h before myocardial ischemia was induced by occluding the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. The hemodynamic parameters left ventricular developed pressure, left ventricular end-diastolic pressure, and maximal rise/fall rate of left ventricular pressure were continuously monitored, and myocardial infarct size was determined at the end of reperfusion. The protein expression of myocardial nitric oxide synthase (NOS), Bcl-2, and Bad was assessed before ischemia. We found that the left ventricular hemodynamic parameters during the whole IR procedure and the myocardial infarct size did not significantly differ between the normocholesterolemic and hypercholesterolemic control groups. The hemodynamic parameters were all markedly improved during the reperfusion period, and the myocardial infarct size was significantly reduced by delayed sevoflurane preconditioning in normocholesterolemic rats, but all of these improvements were reversed by N-(3-(aminomethyl)benzyl) acetamidine (1400W, 1 mg/kg; i.v., 10 min before ischemia), a selective inducible NOS (iNOS) inhibitor, and 5-hydroxy decanoate sodium (5 mg/kg, i.v., 10 min before ischemia), a mitochondrial ATP-dependent K? channel blocker. Such cardiac improvement induced by delayed sevoflurane preconditioning did not occur in hypercholesterolemic rats and was not exacerbated by 1400W or 5-hydroxy decanoate sodium. The expression of myocardial iNOS was markedly enhanced by delayed sevoflurane preconditioning in normocholesterolemic, but not in hypercholesterolemic rats. The expression of endothelial NOS and Bad did not differ among all groups. The expression of myocardial phosphorylated endothelial NOS, Bcl-2, and phosphorylated Bad in normocholesterolemic rats was not affected by delayed sevoflurane preconditioning but was decreased in the hypercholesterolemic control group, and this was not reversed by sevoflurane, compared with the normocholesterolemic control group. Taken together, these results indicate that sevoflurane preconditioning exerts delayed cardioprotection against IR injury in normocholesterolemic rats, which is blocked by hypercholesterolemia potentially via interference with the iNOS/mitochondrial ATP-dependent K? channel pathway.     

The effects of trimetazidine on left ventricular function and physical exercise tolerance in patients with ischemic cardiomyopathy

Trimetazidine is a new metabolic antiischemic agent, which increases the tolerance of cardiomyocytes to ischemia. The aim of the study was to evaluate the effect of additional trimatazidine therapy in patients with ischemic cardiomyopathy (ICMP) in comparison with standard therapy of cardiac insufficiency. According to the results of the study, trimetazidine improves the clinical status, functional class of cardiac insufficiency, left ventricular ejection fraction, in ICMP patients. Trimetazidine increases physical exercise tolerance according to the results of six-minute walking test. Thus, the optimization of myocardial energetic metabolism may be a promising perspective in the treatment of coronary heart disease with systolic dysfunction.     

Stabilizing microtubules decreases myocardial ischaemia-reperfusion injury

Microtubules are important components of the cytoskeleton that forms the backbone of myocardial architecture, sustaining its form and size. This study investigated whether stabilizing microtubules with paclitaxel (0.1 or 1 μM) could decrease myocardial ischaemia- reperfusion injury, and reduce myocardial infarct size and the incidence of ischaemic ventricular arrhythmia. Isolated rat hearts were used, with arrhythmia induced by regional ischaemia and myocardial infarcts induced by ischaemia-reperfusion. In these ex vivo rat models, paclitaxel decreased myocardial ischaemia-reperfusion injury, significantly reducing the incidence and severity of ischaemic ventricular arrhythmia and significantly decreasing infarct size.     

Idiopathic Recurrent Parasystolic Ventricular Tachycardia in a Child

An asymptomatic 3¹/₂-year-old boy demonstrated parasystolic ventricular tachycardia with AV dis-sociation, early sinus capture beats, marked variability in coupling intervals between conducted and ectopic beats, fusion beats, and interectopic intervals which were multiples of the ectopic cycle length. The arrhythmia initially responded to quinidine, reappeared over an 11-month observation period, and finally was suppressed at a high quinidine dose. An invasive and noninvasive work-up failed to demonstrate organic heart disease.     

Increase in heart rate precedes episodes of ventricular tachycardia and ventricular fibrillation in patients with implantable cardioverter defibrillators: analysis of spontaneous ventricular tachycardia database

Patients with heart disease and decreased heart rate variability (HRV) have an increased risk of all-cause mortality as well as arrhythmic death. The question of acute changes in HRV immediately preceding arrhythmic events remains unanswered. We analyzed data from patients with implantable cardioverter defibrillators who had ventricular tachycardia (VT) or ventricular fibrillation (VF) detected by the device. The device stores 1,000 consecutive RR intervals preceding the arrhythmic event detection and before device interrogation. Compared to this control segment, the mean heart rate (HR) increased prior to the arrhythmic event for both VT (88.5 vs 72.7 beats/min, P < 0.0005) and VF (85.4 vs 73.3 beats/min, P < 0.05) patients. No difference in HRV (as analyzed by a time-domain, frequency-domain [fast Fourier transform], and a nonlinear technique) has been detected. We estimated the amount of ectopic beats from the number of RR intervals that differed from the preceding RR interval by > 10%. The frequency of such beats was significantly higher in the prearrhythmic data segments than in the control segments for VT (10.7 vs 6.6/50 beats, P < 0.05) although not for VF (9.8 vs 6.1/50 beats, NS). We conclude that the HR and frequency of ectopic beats are higher prior to onset of the arrhythmic events, although HRV does not change markedly. These results are consistent with sympathetic activation being the predominant autonomic change prior to VT/VF onset in this patient population.     

Myocardial effects of ventricular fibrillation in the isolated rat heart.

OBJECTIVE: Ventricular fibrillation (VF) is known to increase myocardial oxygen requirements and to alter coronary vascular physiology. However, the significance of these effects during cardiac arrest and resuscitation is not well understood. A model was developed in the isolated rat heart to investigate the myocardial effects of VF during a simulated episode of cardiac arrest and resuscitation. We hypothesized that VF would intensify the severity of myocardial ischemia and consequently accentuate postischemic myocardial dysfunction. DESIGN: Prospective and randomized. SETTING: Research laboratory. SUBJECTS: Twenty Sprague-Dawley rats. INTERVENTIONS: Hearts were harvested and perfused at a constant flow rate of 10 mL/min using a modified Krebs-Henseleit solution equilibrated with 95% oxygen and 5% CO2. In five hearts, VF was induced by a 0.05-mA current delivered to the right ventricular endocardium. The perfusate flow was then stopped for a 10-min interval and resumed at 20% of baseline flow for another 10 mins. After 20 mins of VF, the perfusate flow was returned to baseline and a sinus rhythm reestablished by epicardial electrical shocks. The studies were randomized and included three additional groups to control for the effects of ischemia without VF (n = 5), the effects of VF without ischemia (n = 5), and the stability of the preparation (n = 5). MEASUREMENTS AND MAIN RESULTS: Isovolumic indices of left ventricular function were obtained using a latex balloon advanced through the mitral valve and distended to an end-diastolic pressure of 10 mm Hg. The coronary effluent was collected from the right ventricular cavity. VF during myocardial ischemia was associated with a higher coronary effluent PCO2, increased coronary vascular resistance, and development of ischemic contracture as indicated by increases in left ventricular pressure from 9+/-3 to 33+/-6 mm Hg (p < .05). After defibrillation, contractility and relaxation rapidly returned to baseline values, whereas the isovolumic end-diastolic pressure remained elevated for 20 mins. These changes were much less prominent when ischemia was not accompanied by VF. CONCLUSIONS: These findings indicate that VF may adversely affect myocardial ischemia by hastening the development of ischemic contracture, increasing coronary vascular resistance, and favoring the development of diastolic pump failure early after resuscitation from cardiac arrest.     

Ischemic postconditioning of the myocardium: a new method of heart protection against reperfusion damage

AIM: To examine effects of ischemic postconditioning on persistent ventricular fibrillation (VF) induced by reperfusion on the model of isolated rat heart. MATERIAL AND METHODS: Isolated by Langendorf hearts (n = 46) were ischemized for 30 min with following reperfusion. Hearts with persisting VF (n = 11) persisting to reperfusion minute 15 were randomized into two groups: control (n = 6)--reperfusion without interventions, study group on postconditioning (n = 5)--2 min global ischemia followed by reperfusion. Left ventricular pressure, heart rate, coronary blood flow were registered continuously. RESULTS: VF converted to a regular rhythm in all the hearts exposed to postconditioning. Regular contractions were made by all the postconditioned hearts in the course of further reperfusion. None of the control hearts had normal rhythm in the end of the experiment. In the end of reperfusion pulse left ventricular pressure of the postconditioned hearts was lower than that in hearts without persistent VF. CONCLUSION: Ischemic postconditioining exerts an arrhythmic effect in relation to persistent reperfusion ventricular tachyarrhythmias. Postconditioning may serve a new strategy for myocardial protection.     

The nitroderivative of aspirin, NCX 4016, reduces infarct size caused by myocardial ischemia-reperfusion in the anesthetized rat

NCX 4016, a nitro-ester of aspirin endowed with antithrombotic activity, appears to have clinical potential in treating cardiac complications related to coronary insufficiency. This compound has been shown to improve postischemic ventricular dysfunction and to reduce myocardial infarct size in the rabbit. The cardioprotection conferred by NCX 4016 (10, 30, and 100 mg/kg) and aspirin (ASA, 54 mg/kg) was evaluated in anesthetized rats subjected to 30 min of myocardial ischemia followed by 120 min of reperfusion (MI/R). Drugs were given orally for 5 consecutive days. NCX 4016 displayed remarkable cardioprotection in rats subjected to MI/R as was evident in the reduction of ventricular premature beats and in the incidence of ventricular tachycardia and fibrillation; they were reduced dose dependently and correlated with survival of all rats treated with the higher dose of NCX 4016. In these animals, infarct size was restricted proportionally to the dose of NCX 4016 associated with diminution of both plasma creatine phosphokinase and cardiac myeloperoxidase activities. ASA showed only a minor degree of protection against MI/R damage. Rats treated with N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) demonstrated aggravated myocardial damage in terms of arrhythmias, mortality, and infarct size. Supplementation of nitric oxide (NO) with NCX 4016 (100 mg/kg) greatly reduced the worsening effect caused by L-NAME. The beneficial effects of NCX 4016 appear to derive in large part from the NO moiety, which modulates a number of cellular events leading to inflammation, obstruction of the coronary microcirculation, arrhythmias, and myocardial necrosis.     

舒芬太尼预处理对大鼠心肌缺血再灌注损伤的影响

目的探索舒芬太尼预处理对大鼠心肌缺血再灌注损伤的作用。方法健康雄性SD大白鼠50只,随机分为5组。采用结扎左冠状动脉前降支30分钟再灌注90分钟的方法制备心肌缺血再灌注模型。I/R组为缺血再灌注对比组,IPC组为缺血预处理组,SPC组为舒芬太尼预处理组,将其分为三个亚组,低剂量组(LS组0.20μg/kg);中剂量组(MS组2.0μg/kg);高剂量组(HS组5.0μg/kg)。应用Even’s blue-TTC法检测心肌梗死范围,以梗死区心肌重量/缺血区心肌重量(IS/AAR%)来表示。于实验结束时(再灌注末),利用硫代巴比妥酸反应法(TBA)测定MDA浓度,利用黄嘌呤氧化酶法测定SOD活性。结果与1/R组比较,IPC组与SPC三个亚组的心肌梗死面积(IS/AAR)均有降低,其中舒芬太尼预处理组(SPC)三个亚组相互比较中,高剂量(HS)组IS/AAR的降低最为明显。与1/R组比较,IPC组及SPC三个亚组的MDA浓度均有下降,SOD活性均有升高。结论舒芬太尼预处理可减轻大鼠心肌缺血再灌注损伤,减少心肌梗死面积,抑制氧化产物的增加,提高机体的抗氧化能力,且呈剂量依赖性。