地昔帕明对心肌缺血后交感神经重构和室颤阈值的影响

目的: 研究地昔帕明对大鼠急性心肌缺血后交感神经重构和室颤阈值的影响,并探讨交感神经重构与室颤阈值的关系。方法: 将60只SD大鼠随机分为3组,每组各20只:即心肌缺血组:夹闭左冠状动脉前降支30 min;地昔帕明组:先单次静脉给予地昔帕明0.8 mg/kg,5 min后夹闭左冠状动脉前降支30 min及假手术组:仅开胸但不夹闭左冠状动脉。喂养1周后,开胸测定室颤阈值。用免疫组化染色法检测大鼠心室肌中生长相关蛋白43（GAP43）和酪氨酸羟化酶（TH）阳性神经纤维的分布和密度,并用RT-PCR测定梗死周边区GAP43和TH mRNA表达的水平。 结果: 地昔帕明组的室颤阈值(11.0±2.65)V较心肌缺血组(7.2±1.30)V显著增高（P<0.05）;与假手术组的(13.0±2.12)V比较无明显差异。心肌缺血组GAP43和TH阳性神经纤维的分布紊乱,密度明显高于地昔帕明组和假手术组（P<0.05）。与心肌缺血组相比,地昔帕明组GAP43和TH mRNA表达的水平显著降低（P<0.05）。结论: 地昔帕明可改善心肌缺血后交感神经重构,提高室颤阈值,增加缺血心脏的电稳定性。     

Cardiopulmonary bypass in a model of acute myocardial infarction and cardiac arrest

Cardiopulmonary bypass (CPB) reperfusion has demonstrated improved resuscitation rates in ventricular fibrillation cardiac arrest models. To investigate the effectiveness of CPB reperfusion in an ischemic cardiac arrest setting, simulating the clinical scenario of myocardial ischemia preceding sudden cardiac death, we developed a canine model of acute myocardial infarction followed by ventricular fibrillation. Sixteen dogs were randomly assigned to two groups. Group 1 (eight) had ventricular fibrillation induced without left anterior descending coronary artery occlusion. Group 2 (eight) had a thrombogenic copper coil placed in the left anterior descending artery and showed ECG evidence of acute myocardial infarction before induction of ventricular fibrillation. CPR commenced after eight minutes of ventricular fibrillation. Epinephrine 0.05 mg/kg and NaHCO3 1.0 mEq/kg were administered at ten minutes. CPB was begun at 12 minutes and continued for one hour. Myocardial ischemic and necrotic areas were determined in four-hour survivors by dual histochemical staining. All animals were resuscitated; all eight group 1 and six of eight group 2 animals survived to four hours. With the onset of CPB, coronary perfusion pressures increased significantly by 68.6 +/- 31.8 (SD) mm Hg in group 1 and 56.2 +/- 34.6 mm Hg in group 2 over those obtained with CPR (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of nitroglycerin on vulnerability to ventricular fibrillation during myocardial ischemia and reperfusion.

The effect of nitroglycerin on vulnerability to ventricular fibrillation was examined in 44 chloralose-anesthetized dogs. In 19 animals ventricular fibrillation threshold was measured before and during a 10 minute period of occlusion of the left anterior descending coronary artery followed by abrupt release of occlusion. Fibrillation threshold was determined using the single stimulus and train of stimuli methods. The influence of nitroglycerin on vulnerability was assessed with and without prevention of the drug's hypotensive effect by intravenous injection of phenylephrine. In the nonischemic myocardium, infusion of nitroglycerin alone or in combination with phenylephrine did not alter the ventricular fibrillation threshold. However, during both coronary occlusion and reperfusion, administration of nitroglycerin alone afforded partial protection against vulnerability to ventricular fibrillation. Nearly complete protection was imparted by combined administration of nitroglycerin and phenylephrine. The incidence of spontaneous ventricular fibrillation during reperfusion was significantly reduced by combined administration of nitroglycerin and phenylephrine. It is concluded that infusion of nitroglycerin decreases susceptibility to ventricular fibrillation during both acute myocardial ischemia and reperfusion and that this beneficial action is substantially enhanced when the drug's hypotensive effect is prevented.     

Exercise training after experimental myocardial infarction increases the ventricular fibrillation threshold before and after the onset of reinfarction in the isolated rat heart

Previous work has shown that exercise training increases the ventricular fibrillation threshold of the isolated perfused rat heart. The aim of our study was to determine whether exercise training that begins after myocardial infarction can similarly increase the ventricular fibrillation threshold. Rats that had suffered an experimental myocardial infarction were subject to a running training program. Thereafter, the ventricular fibrillation threshold was measured before and after the onset of acute reinfarction induced by a second coronary artery ligation. Ventricular fibrillation thresholds were significantly elevated in trained rats during normoxia (13.7 +/- 2.2 vs. 4.7 +/- 0.8 mA, p less than 0.01) and during acute ischemia (6.8 +/- 1.6 vs. 3.0 +/- 0.7 mA, p less than 0.02). The myocardial cyclic AMP level was lower in the nonischemic zone of the trained hearts (0.21 +/- 0.01 vs. 0.28 +/- 0.01 nmol/g, p less than 0.05), which also had lower cyclic AMP levels after epinephrine challenge (0.50 +/- 0.05 vs. 0.73 +/- 0.09 nmol/g, p less than 0.01; 1.41 +/- 0.11 vs. 1.85 +/- 0.09 nmol/g, p less than 0.02 after epinephrine 10(-7) M and 5 x 10(-6) M injection, trained vs. untrained). Both propranolol 10(-6) M and epinephrine 5 x 10(-7) M attenuated the difference in ventricular fibrillation thresholds before and after second coronary artery ligation and eliminated any difference in cyclic AMP content of both the nonischemic and ischemic myocardial tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of sulfinpyrazone on ventricular vulnerability in the normal and the ischemic heart

The effects of sulfinpyrazone were studied in 33 chloralose-anesthetized dogs. Ventricular fibrillation thresholds, mid diastolic thresholds and duration of the effective refractory period were determined in the normal heart after intravenous administration of sulfinpyrazone, 30 mg/kg body weight. The drug significantly raised the ventricular fibrillation threshold by 24 percent and the mid diastolic threshold by 36 percent and prolonged the effective refractory period by seven percent. The influence of sulfinpyrazone during acute myocardial ischemia was evaluated before and during a 10 minute occlusion of the left anterior descending coronary artery and after abrupt release of the occlusion. Although the drug afforded significant protection during coronary occlusion, it had no effect on the ventricular fibrillation threshold after reperfusion. Because potent cardiocardiac reflexes are elicited during ischemia, the influence of sulfinpyrazone on the ventricular fibrillation threshold was studied during norepinephrine infusion. Sulfinpyrazone attenuated the reduction of the ventricular fibrillation threshold during sympathetic humoral stimulation. Its effect was additive to beta adrenergic blockade with practolol and membrane stabilization with lidocaine. This investigation suggests that sulfinpyrazone exerts significant effects on ventricular vulnerability of both the normal and the ischemic myocardium. Further studies are needed to elucidate its precise mechanism of action.     

老年大鼠急性心肌梗死模型的制备

目的:建立一种稳定可重复的老年大鼠急性心肌梗死动物模型。方法:老年Wistar雄性大鼠乌拉坦麻醉后,气管切开插管,连通呼吸机,左侧3、4肋间开胸后结扎左冠状动脉前降支,收紧结扎线当时出现前降支支配区域心肌变苍白或发绀,心电图ST段抬高≥0.2 mV或T波高耸形成单峰融合波,提示结扎成功。结果:60只老年大鼠,死亡6只,成功制备54只,模型制备成功率90%,22只出现心室纤颤(室颤),其中3只死亡,室颤发生率36.7%,室颤死亡占总死亡的50%。结论:正确使用麻醉药、顺利气管插管、准确结扎冠状动脉及减少术中出血与肺损伤是制模成功的基础,本文建立的方法简单、有效,为研究老年急性心肌梗死提供了新的手段。     

The effects of antiplatelet agents in the prevention of ventricular tachyarrhythmias during acute myocardial ischemia in rats.

Experiments were performed in rat models to study the effectiveness of various antiplatelet agents in the prevention of ventricular tachyarrhythmias during acute myocardial ischemia. The time to the onset of ST-segment elevation and initiating ventricular arrhythmias, frequency and incidence of ventricular arrhythmias, and mortality rates were observed during acute myocardial ischemia (20 minutes) induced by ligation of the proximal left anterior descending coronary artery (LAD) in anesthetized rats. Four groups were studied: Control group (n = 10, not pretreated); Aspirin pretreated group (n = 10, 300 mg/kg p.o. for 1 wk); Ticlopidine pretreated group (n = 10, 200 mg/kg p.o. for 1 wk); and Abciximab (Platelet glycoprotein IIb/IIIa receptor antagonist) pretreated group (n = 10, 2 mg/kg i.v. 10-20 minutes before an experiment). No significant difference was observed in the time to the onset of ST-segment elevation and ventricular arrhythmias between the groups. The incidence of ventricular tachycardia (VT) in the abciximab group was significantly lower than in the control group (p < 0.05) and ventricular fibrillation (VF) in the aspirin and ticlopidine group was significantly lower than in the control group (p < 0.05). The mortality rate in the ticlopidine group was significantly lower than in the control group (p < 0.01). This study suggests aspirin, ticlopidine, and abciximab can effectively prevent VT or VF during acute myocardial ischemia induced by nonthrombotic occlusion and its antiarrhythmic effect may lead to prolonged survival.     

Spontaneous and electrically induced ventricular arrhythmias during acute ischemia superimposed on 2 week old canine myocardial infarction

The arrhythmogenic effect of acute reversible myocardial ischemia before and 2 weeks after experimental myocardial infarction was investigated in 37 dogs that underwent reversible 10 min occlusion of the first major marginal branch of the left circumflex coronary artery. Subsequently, 24 of the dogs underwent experimental myocardial infarction with permanent left anterior descending coronary ligation, and 13 dogs served as sham-operated controls. Two weeks later, an open chest programmed electrical stimulation was performed in the 13 sham-operated and 24 postinfarction dogs to determine its accuracy in predicting the ventricular arrhythmias that develop during a subsequent episode of acute reversible ischemia. After programmed electrical stimulation, the left circumflex marginal branch was reversibly occluded for 10 min at the same site. The incidence of spontaneous ventricular fibrillation during reversible left circumflex marginal coronary occlusion did not differ from the first to the second study in sham-operated dogs, whereas in the postinfarction dogs, it increased from 13% before infarction to 54% after infarction (p = 0.005). The outcome of programmed electrical stimulation predicted spontaneous ventricular arrhythmias during coronary occlusion in only 21% of the postinfarction dogs. The accuracy of programmed electrical stimulation was 42% and its predictive value was 47% in detecting the dogs with spontaneous ventricular fibrillation. Regional myocardial blood flow measurements by microsphere technique identified the severity of reversible ischemia in the infarct border and periinfarction zones as a correlate of spontaneous ventricular fibrillation during coronary occlusion. In contrast, total infarct size correlated with electrically induced but not with spontaneous ventricular arrhythmias.     

Comparative effects of the opioids fentanyl and buprenorphine on ventricular vulnerability during acute coronary artery occlusion

Fentanyl, a mu selective opioid agonist in wide clinical use, raises the ventricular fibrillation threshold in the normal canine myocardium. We have previously shown that this effect is amplified by haemorrhagic stress. In order to determine if mu receptor activation is antifibrillatory during acute myocardial ischaemia, we compared the effects of two mu selective agents, fentanyl and buprenorphine, in open chest chloralose anaesthetised dogs. Each drug was administered intravenously in two doses 1 h apart (fentanyl 30 micrograms.kg-1.dose; buprenorphine 0.3 mg.kg-1.dose). Ventricular fibrillation threshold was measured during right ventricular pacing using the single stimulus technique. The threshold was determined before and during a 10 min left anterior descending coronary artery occlusion. Prior to fentanyl administration, ventricular fibrillation threshold decreased from a control value of 19(SEM 2) mA to 12(1) mA during coronary artery occlusion. After the first dose of this drug an attenuation in the ischaemia induced fall in fibrillation threshold from 23(4) mA to 15(2) mA was observed. After the second dose of fentanyl the decline in fibrillation threshold was significantly blunted at 22(4) mA during control and 18(3) mA during occlusion, p less than 0.05 compared to no drug. In an additional series of experiments atropine sulphate abolished the antifibrillatory action of fentanyl, indicating that vagal efferent activation is responsible for the protective effect of the drug during acute myocardial ischaemia. This is in contrast with its mode of action during haemorrhage, when it enhances vagal afferent inhibition of sympathetic tone, and atropine pretreatment is without effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of beta-adrenergic inhibition on scar formation after myocardial infarction

In view of clinical interest in the efficacy of beta-adrenergic blockade during acute myocardial infarction (AMI), we have determined the long-term effect of therapy on scar formation after experimental myocardial ischemia. Intact anesthetized dogs underwent acute occlusion of the left anterior descending coronary artery, by means of a balloon catheter, which permitted monitoring of the aortic-peripheral coronary artery pressure gradient during the 4-hour period of balloon inflation. Practolol administration was begun 15 minutes after the onset of ischemia in group A. Control animals (group B) received procainamide to approximate the antiarrhythmic action of beta blockade. Only group A exhibited significant reduction in the ST segments during acute ischemia. Chronic therapy was maintained for 1 month and the mature scar formed in the myocardium was assessed after 4 months. The extent of subendocardial scar was similar in both groups but subepicardial scar formation was significantly less in group A. There was also a significant decrease in the percentage of total myocardium involved with scar in this treatment group. Although thinning of the left ventricular wall was similar for both groups in the central scar region, this process was significantly reduced at the lateral margin in group A. Thus, specific beta-receptor blockade during acute myocardial ischemia and sustained during the repair process can result in a reduced quantity and altered distribution of mature scar.     

Effect of thromboxane synthetase inhibition on vulnerability to ventricular arrhythmia following coronary occlusion

Release of thromboxane (TXA2) during acute myocardial infarction may be an important contributing factor in the genesis of ventricular fibrillation (VF). We assessed the effect of selective TXA2 inhibition on vulnerability to VF after total occlusion of the anterior descending coronary artery in chloralose-anesthetized cats. Animals were pretreated with vehicle or with CGS-13080, a TXA2 synthetase inhibitor, 3.0 or 9.0 mg/kg intravenously. There was an apparent dose-dependent protective effect following CGS-13080 administration, in which the decrease in VF threshold following coronary occlusion was attenuated. Also, the incidence of spontaneous ventricular arrhythmia in the first 30 minutes after occlusion was reduced by two thirds in the 9.0 mg/kg CGS-13080 group compared to the vehicle-treated animals. This protective effect does not appear to be due to a change in hemodynamics, effective refractory periods, or extent of ischemia. TXA2 released during coronary occlusion appears to be arrhythmogenic, and inhibiting its synthesis may be protective.     

Efficacy of diltiazem in two experimental feline models of sudden cardiac death

The potential role of calcium entry blockers in the prevention of life-threatening arrhythmias associated with acute myocardial ischemia and reperfusion is still controversial. In 98 anesthetized cats, the effect of diltiazem was examined in two experimental models. In protocol I, ventricular tachycardia or fibrillation was consistently induced by the interaction between a 2 minute coronary artery occlusion and a 30 second left stellate ganglion stimulation. After three trials under control conditions, if the same pattern of arrhythmia was induced, the drug under study was administered and three additional trials were performed. In 16 animals the administration of saline solution did not modify the pattern of arrhythmias. In contrast, diltiazem (0.1 mg/kg body weight plus 0.2 mg/kg per h) abolished both ventricular tachycardia and fibrillation that had occurred in 64 and 36%, respectively, of the cats in the control state. In protocol II, a 20 minute coronary artery occlusion was released in three groups; one served as the control group, one received diltiazem 15 minutes before occlusion and one received diltiazem 3 minutes before reperfusion. The incidence of reperfusion ventricular fibrillation was 62% (16 of 26) in the control group. It was significantly (p less than 0.05) reduced by diltiazem administered before the occlusion to 25% (4 of 16), whereas it was not affected when diltiazem was administered just before reperfusion (7 [47%] of 15). These results indicate that diltiazem exerts a striking protective effect against the malignant arrhythmias induced by the combination of acute myocardial ischemia and sympathetic hyperactivity. Diltiazem was also effective in reducing the incidence of life-threatening reperfusion arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of procainamide on fibrillation threshold of normal and ischemic ventricles

The effect of procainamide on ventricular fibrillation threshold was studied in anesthetized open chest hearts in 12 dogs without coronary occlusion and in 11 dogs during acute coronary occlusion. The minimal current required to induce ventricular fibrillation was determined by delivering a train of rapid rectangular pulses (100/sec) to the ventricle during its vulnerable period. Procainamide was administered as a single intravenous injection in a dose of 10 to 20 mg/kg body weight. Blood levels of the drug reached their peak immediately, fell to therapeutic levels (5 to 10 μg/ml) within about 30 minutes and then remained at those levels up to 80 minutes after the injection. The effect of procainamide on the fibrillation threshold correlated with procainamide blood levels. The increase, peak level and decrease in blood concentration paralleled changes in fibrillation threshold. Procainamide at therapeutic blood levels increased the mean fibrillation threshold from the control value of 16 to 30 ma (88 percent increase) in the normal ventricles. The effect was less pronounced during acute coronary occlusion, and the mean fibrillation threshold increased from 8 to 13 ma (63 percent increase) at therapeutic procainamide blood levels. In addition, procainamide failed to produce complete reversion of the decreased fibrillation threshold to the normal value during acute myocardial ischemia.     

Combination of a Calcium Antagonist, Verapamil, with an Angiotensin Converting Enzyme Inhibitor, Trandolapril, in Experimental Myocardial Ischemia and Reperfusion: Antiarrhythmic and Hemodynamic Effects of Chronic Oral Pretreatment

The combination of a calcium antagonist with an angiotensin-converting enzyme (ACE) inhibitor is increasingly used in the therapy of hypertension, but there are no experimental data supporting the use of this combination in acute myocardial ischemia and reperfusion. We tested the effects of oral pretreatment in a pig model, paying special attention to arrhythmias and adverse hemodynamic effects. Pigs received verapamil 240 mg + trandolapril 4 mg, verapamil 240 mg, or placebo orally once daily for 10 days, after which a coronary artery was ligated for 20 minutes and then allowed to reperfuse. The ventricular fibrillation threshold (VFT) was measured during ischemia to assess the vulnerability of the heart to ventricular fibrillation, whereas spontaneous tachyarrhythmias were monitored during reperfusion. Regional left ventricular (LV) blood flow was measured with radioactive microspheres. During the ischemic period, both the combination of verapamil plus trandolapril, and verapamil alone, prevented a fall in the VFT, indicating antiarrhythmic activity. The combination maintained LV contractile activity and cardiac output (CO) at preligation levels, whereas verapamil alone decreased cardiac output. During reperfusion, verapamil plus trandolapril prevented spontaneous ventricular tachyarrhythmias and increased blood flow in the reperfused zone. In contrast, verapamil was not antiarrhythmic and decreased CO. Thus the addition of the ACE inhibitor trandolapril to the calcium antagonist verapamil resulted in antiarrhythmic activity during ischemia and reperfusion, and produced a better hemodynamic profile.     

Calcium antagonists and acute myocardial ischemia: Comparative effects of gallopamil and nifedipine on ischemia-induced and reperfusion-induced ventricular arrhythmias,epicardial conduction times,and ventricular fibrillation thresholds

Summary The comparative effects of the calcium-antagonists gallopamil and nifedipine on ischemia-induced and reperfusion-induced ventricular arrhythmias, particularly ventricular fibrillation (VF), were assessed in a total of 40 mongrel dogs in two experimental preparations. In part I of the study, changes in the time course of spontaneous ventricular arrhythmias and VF parallel to changes in epicardial conduction following acute coronary artery occlusion lasting 20 minutes and followed by subsequent reperfusion were determined. In part II, repeated coronary artery occlusions (20 min) followed by reperfusion (60 min) were performed, and changes in ventricular fibrillation threshold (VFT) were assessed. Gallopamil proved to be highly effective in preventing ventricular arrhythmias and VF following coronary artery occlusion. Simultaneously, peak epicardial conduction delay was reduced. The ischemia-induced fall in VFT occurring during the first few minutes after occlusion (phase Ia) was significantly reduced. In contrast, nifedipine failed to influence the incidence of ventricular arrhythmias and VF. Following reperfusion, neither drug reduced the incidence of VF nor the associated fall in VFT at the onset of reperfusion. The time course of recovery of epicardial conduction was not affected by either drug. However, the increase in the VFT during the early postreperfusion period was significantly enhanced by both agents. The effects of gallopamil were more pronounced than those of nifedipine. Delayed reperfusion ventricular arrhythmias arising 5 to 10 minutes after release of coronary artery obstruction were significantly reduced by gallopamil whereas nifedipine proved ineffective. The results show that calcium antagonists display direct antiarrhythmic and cardioprotective actions in acute transient myocardial ischemia. The different effectiveness of gallopamil compared to nifedipine can be explained by differences in electrophysiological properties of the drugs. Enhanced ventricular vulnerability following acute transient coronary artery occlusion and subsequent release of coronary artery obstruction, first described by Tennant and Wiggers [1], has been extensively investigated over the past decade in a variety of experimental and clinical settings. However, the basic mechanisms underlying ischemia- and reperfusion-induced ventricular arrhythmias and ventricular fibrillation (VF) have not yet been fully elucidated. Furthermore, the results of pharmacological approaches to prevent ventricular arrhythmic activity are conflicting. The present study aimed to evaluate the antiarrhythmic efficacy of calcium antagonists in acute myocardial ischemia and reperfusion. We have examined the effects of gallopamil and nifedipine on the time course of ventricular arrhythmias during the first 20 minutes after acute coronary artery occlusion and subsequent reperfusion. We have studied the underlying mechanisms by mapping epicardial conduction and by assessing the electrically induced ventricular fibrillation threshold (VFT) both within and outside ischemic areas.     

Effects of ethmozine on ventricular fibrillation threshold in acute occlusion of the coronary artery in dogs

In experiments on dogs with acute left descending coronary artery occlusion, ethmozine (3 mg/kg) was tested for effects on the threshold of ventricular fibrillation occurring as a result of high-frequency electric stimulation. Two hours after occlusion, the fibrillation threshold became significantly lower than the control values. Ethmozine used in this period enhanced the ventricular fibrillation threshold in some experiments and diminished it in the others. Four hours following the occlusion, the fibrillation threshold did not differ from the control ones. Ethmozine given in this period caused a significant increase in the ventricular fibrillation threshold. It was concluded that 4 hours after the onset of experimental myocardial infarction are the minimal time period following which administration of ethmozine failed to decrease electric stability of the heart.     

Relationship between sympathetic neural activity, coronary dynamics, and vulnerability to ventricular fibrillation during myocardial ischemia and reperfusion

The relationship between neural sympathetic discharge and vulnerability to ventricular fibrillation during myocardial ischemia and reperfusion was studied in 26 chloralose-anesthetized dogs. Preganglionic cardiac sympathetic impulse activity and ventricular fibrillation thresholds were separately determined before and during a 10-minute period of left anterior descending coronary artery occlusion and during release-reperfusion. Within 2 minutes of occlusion the ventricular fibrillation threshold was significantly decreased (from 25 +/- 1.3 to 16 +/- 2.3 mA, p less than 0.05) corresponding with the period of maximal activation of cardiac sympathetic preganglionic fibers (from 4.4 +/- 0.2 to 6.3 +/- 0.5 impulses/sec). Coronary sinus blood flow and oxygen tension decreased significantly. All these changes persisted for 5 to 6 minutes, thereafter returning to control levels despite continued obstruction of the coronary artery. A transient but significant reduction in ventricular fibrillation threshold also occurred with release of the occlusion but was unaccompanied by increases in sympathetic neural discharge. Bilateral stellectomy completely prevented the ventricular fibrillation threshold changes observed during coronary artery occlusion. However, there was no change in coronary sinus oxygen tension or blood flow. During reperfusion, stellectomy increased rather than decreased vulnerability to ventricular fibrillation. Stellectomy augmented the reactive hyperemic response to release-reperfusion. These findings indicate that enhanced cardiac sympathetic neural activity contributes to ventricular vulnerability associated with coronary artery obstruction. An opposite action results during release-reperfusion. Cardiac sympathetic neural discharge, by reducing the magnitude of reactive hyperemic response through influence on coronary vascular tone, exerts an antifibrillatory effect.     

缺血预适应对糖尿病大鼠再灌注心肌的保护作用

目的　通过建立大鼠缺血预适应 (IP)模型 ,探讨IP对缺血 再灌注 (I/P)糖尿病大鼠心肌的保护作用。方法　在SD大鼠腹腔内注射链佐星 (6 0mg/kg)制造糖尿病大鼠模型。 2d后 ,随机时刻测定血糖 ,将血糖≥ 11.1mmol/L定为糖尿病大鼠 2 2只 ,另外 2 2只血糖正常鼠为非糖尿病鼠。 2周后 ,麻醉大鼠 ,结扎和放松冠状动脉左前降支(LAD)复制IP和I/P模型。将 44只大鼠分为IP糖尿病大鼠组 (DIP组 )、IP非糖尿病大鼠组 (NDIP组 )、非IP糖尿病大鼠组 (DNIP组 )和非IP非糖尿病大鼠组 (NDNIP组 )各 11只。记录II导联心电图。取心脏切片染色 ,计算心肌缺血范围和心肌坏死范围。结果　各组间心肌缺血范围无显著差异 (P >0 .0 5 )。DIP组心肌坏死范围较DNIP组明显减小 (P <0 .0 1)。DNIP组室性心律失常增多 ,尤其心室颤动较其他各组显著增多 (P <0 .0 1)。结论　缺血预适应可以减轻糖尿病大鼠随后较长时间缺血 再灌注对心肌的严重损害 ,能减少心肌坏死范围和降低心室颤动的发生率。     

Electrophysiologic actions and antifibrillatory efficacy of subacute left stellectomy in a conscious, post-infarction canine model of ischemic ventricular fibrillation

The autonomic nervous system appears to modulate ventricular arrhythmias associated with acute myocardial ischemia. This study investigated the electrophysiologic effects and antifibrillatory actions of subacute left stellectomy in a conscious, post-infarction canine model of sudden cardiac death. Twenty-two dogs with a previous anterior wall myocardial infarction and inducible ventricular arrhythmias were randomized to undergo either left stellectomy (n = 12) or remain as sham-denervated controls (n = 10). Five to 7 days post left stellectomy, there were no significant changes in heart rate, electrocardiographic intervals or ventricular refractoriness compared to sham-denervated controls. Acute posterolateral ischemia was produced in left stellectomy and sham-denervated dogs by anodal current-induced thrombosis via a previously positioned electrode in the left circumflex coronary artery. Ventricular fibrillation developed within 1 hour of the onset of ischemia (early ventricular fibrillation) in 3/12 (25%) left stellectomy dogs versus 8/10 (80%) sham-denervated controls (P less than 0.05). However, 24-hour mortality rate was 5/12 (42%) after left stellectomy versus 8/10 (80%) after sham denervation (P = 0.072). Small differences in regional myocardial norepinephrine content, which is a marker for neuronal integrity, occurred in the mid-posterolateral and mid-anteroseptal regions of the left ventricle after left stellectomy. Overall norepinephrine concentration after left stellectomy was 409.70 +/- 9.90 ng/g vs 428.07 +/- 10.84 ng/g in sham controls (P = NS). In summary, subacute left stellectomy significantly reduces the incidence of ventricular fibrillation occurring within 1 hour of the onset of acute posterolateral ischemia at a distance to a previous myocardial infarction in conscious dogs, and tends to reduce the ischemic post-infarction mortality at 24 hours after the onset of ischemia. This protective effect of left stellectomy is not due to any alteration in cardiac electrophysiologic parameters measured prior to the development of acute posterolateral ischemia, nor is it related to regional denervation as determined by myocardial tissue concentration of residual norepinephrine.     

急性心肌缺血家兔心室易损期和心室颤动阈的变化

目的观察急性心肌缺血对心肌易损性的影响。方法采用程序电刺激方法测定家兔心室颤动阈(VFT)、心室易损期(VVP)和有效不应期(ERP)。结果 急性心肌缺血时VFT降低,VVP延长,ERP缩短。VFT的迅速降低发生于冠状动脉结扎1分钟左右,结扎5分钟VFT降低幅度最大,由对照值10.55±1.54V降为6.39±1.19V(P相似文献