Electrophysiologic effects of volatile anesthetics,sevoflurane and halothane,in a canine myocardial infarction model

The effects of sevoflurane and halothane on the effective refractory period (ERP) and ventricular activation were examined in a canine myocardial infarction model. Sevoflurane (1 MAC) reduced the heart rate and prolonged ERP in both normal and infarcted zones. A prolongation of ERP with sevoflurane was observed also during atrial pacing at a fixed rate, but the effect was less than during sinus rhythm. Sevoflurane either further delayed or blocked the delayed activation entirely in the infarcted zones with only slight effects on the activation of the normal zones. Halothane (1 MAC) prolonged ERP during sinus rhythm and atrial pacing, but to a lesser extent during the latter. Halothane also depressed ventricular activation in the infarcted zone during atrial pacing. In conclusion, sevoflurane as well as halothane selectively depresed the delayed activation and the prolongation of ERP in myocardial infarction, which may inhibit ventricular arrhythmias in myocardial infarction.     

Beta-blockade by sotalol in early myocardial infarction decreases ventricular arrhythmias without increasing left ventricular volume

Although early beta-blockade in acute myocardial infarction (AMI) may have potential benefits owing to an anti-arrhythmic effect and limitation of infarct size, the haemodynamic effects are not well characterised. Accordingly, we studied the effects of intravenous beta-blockade by sotalol in AMI, commencing a mean of 6 hours after the onset of chest pain, with particular reference to systemic haemodynamic changes and left ventricular (LV) volumes. Thirty patients were randomised to a control group or to sotalol therapy starting with 40 mg and increasing to 120 mg, followed by the maximal dose tolerated every 6 hours for 72 hours. Sotalol reduced heart rate and mean blood pressure without elevating pulmonary wedge pressure or increasing enzymatic infarct size. Sotalol also decreased the incidence of ventricular tachycardia (P less than 0.001). An important new finding was that there was no increase in the LV volume measured by radionuclide techniques. Therefore intravenous sotalol safely achieved its beneficial effects without causing LV dilatation.     

Left ventricular dysfunction in a canine model of chronic cyanosis

States of low cardiac output frequently complicate the postoperative course of patients undergoing repair of cyanotic congenital heart lesions. The relative contribution of chronic cyanosis alone to the postoperative deterioration in left ventricular function remains unknown. To study the effects of chronic cyanosis on left ventricular function, nine dogs underwent inferior vena cava-to-left atrial anastomosis, a model that minimizes abnormal left ventricular hemodynamic loads. After at least 6 months of chronic cyanosis (mean arterial pO2 of 44 mm Hg and mean hematocrit of 61%), the dogs were instrumented with ultrasonic dimension transducers and micromanometers for collection of left ventricular pressure-dimension data. Studies were performed 7 to 10 days after recovery from instrumentation while the dogs were awake and alert. Nine normal dogs were also instrumented and served as controls. Pressure and dimension data were collected during transient vena cava occlusions before and after the combined administration of propranolol and atropine to produce autonomic blockade. Contractile function as measured by dP/dt, ejection fraction, and the stroke work-end diastolic length relationship was decreased by autonomic blockade to a similar extent in both normal and cyanotic dogs. After autonomic blockade, normal dogs were able to maintain stroke volume and cardiac index by utilization of Frank-Starling reserves (increased left ventricular end diastolic volume). In contrast, dogs with cyanosis were unable to maintain stroke volume and cardiac index or to increase left ventricular end diastolic volume after autonomic blockade. Dogs with cyanosis had reduced ventricular diastolic compliance, and they more fully used Frank-Starling reserves to maintain normal stroke volume and cardiac index in the control state when compared with normal dogs. The diminished preload reserves of the cyanotic dogs limited systolic performance (stroke volume and cardiac index) only at reduced levels of contractility produced by autonomic blockade.     

吸入麻醉药预处理对兔心肌缺血再灌注中心肌细胞凋亡的影响

目的：探讨异氟醚、七氟醚、地氟醚预处理对心肌缺血再灌注过程中心肌细胞凋亡的影响。方法：48只新西兰白兔随机分成6组（n=8)：假手术对照组（P组）、心肌缺血再灌注对照组（IR组）、缺血预处理组（IP组）、异氟醚预处理组（I组）、七氟醚预处理组（S组）、地氟醚预处理组（D组）。除P组外，每组均接受左冠脉前降支3h阻断和3h再灌注。IP组在缺血前接受连续3次每次缺血5min、再灌注5min的预处理，吸入药预处理组在缺血前分别吸入1MAC的异氟醚、七氟醚或地氟醚30min后洗脱15min。取心肌缺血区边缘组织用琼脂糖电泳检测DNA梯带的形成，用流式细胞仪测凋亡指数（AI）。结果：心肌梗死范围占缺血范围的百分比及AI，IP、I、S及D组较IR组显著减少（P＜0．05）。IR组DNA梯带的形成明显，IP、I、S、D组减弱、变模糊。结论：异氟醚、七氟醚、地氟醚预处理能抑制心肌缺血再灌注所致的心肌细胞凋亡。     

Antifibrillatory effects of volatile anesthetics in acute occlusion/reperfusion arrhythmias

Halothane, enflurane, and isoflurane were evaluated for antifibrillatory efficacy and compared with lidocaine, propranolol, procainamide, and verapamil in a canine acute left anterior descending (LAD) coronary artery occlusion/reperfusion model with basal pentobarbital anesthesia. Of the antiarrhythmic drugs, only verapamil prevented ventricular fibrillation during occlusion and reperfusion. Halothane 1% inspired after 15 min showed similar protection. Enflurane 2.5% inspired after 15 min resulted in significant protection but caused hypotension after occlusion in 4 of 17 dogs. Isoflurane 1.7% inspired after 15 min showed intermediate results. At inspired concentrations of 0.5% and 1.25%, respectively, halothane and enflurane protected against ventricular fibrillation without hypotension. It is concluded that the volatile anesthetics have antifibrillatory effects in this canine model but differ in their ability to cause hypotension in the presence of proximal LAD coronary artery occlusion.     

Surgical management of sustained ventricular arrhythmias presenting within eight weeks of acute myocardial infarction

When it occurs after a recent (less than eight weeks) myocardial infarction, sustained ventricular tachycardia (VT) or fibrillation (VF) has resulted in a high one-year mortality despite antiarrhythmic drug therapy. We have operated on 29 patients with this syndrome either on an emergency basis because they had medically refractory VT or VF (19 patients) or electively if they had persistent congestive heart failure or angina and VT or VF (10 patients). Ages ranged from 36 to 82 years (mean, 60 years), and the mean left ventricular ejection fraction was 31 +/- 13%. Each patient had failed a trial of one or more (average, four) antiarrhythmic drugs and because of VT, required electrical cardioversion on an average of five occasions. Intraoperative mapping was complicated by multiple VT morphologies (9 patients), the rapid degeneration of VT to VF (5 patients), and the inability to induce VT reliably (5 patients). Subendocardial excision was performed at the site of the earliest electrical activity, or if no single site could be identified, a wide subendocardial excision of all visible scar was performed. There were 4 perioperative deaths (14%). All operative survivors underwent postoperative electrophysiological studies. Twenty of them required no further antiarrhythmic therapy, but 5 patients required drug therapy because of either spontaneous (2 patients) or electrically induced (3 patients) VT. During follow-up (average, 16 months) of these 25 patients, there have been 3 late deaths, 2 of them sudden. Two of the 3 late deaths were those of patients taking antiarrhythmic drugs. Our results demonstrate the effectiveness of early operative intervention when sustained ventricular arrhythmias complicate recovery after myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms of ventricular arrhythmias induced by myocardial contusion: a high-resolution mapping study in left ventricular rabbit heart

BACKGROUND: The aims of the Langendorff-perfused rabbit heart study were to evaluate the arrhythmogenic consequences of myocardial contusion and to determine the mechanism of arrhythmia. METHODS: Six hearts were in the control group, and 24 hearts (intact heart protocol) were submitted to one of four different contusion kinetic energies (75, 100, 150, or 200 millijoules [mJ]; n = 6). Occurrence of arrhythmia, of an electrically silent area (i.e., area with no electrical activity), and of line of fixed conduction block were reported before and for 1 h after contusion. In 16 hearts (frozen hearts) submitted to cryoprocedure and contusion impact of 100 or 200 mJ, ventricular conduction velocities, anisotropic ratio, wavelengths, ventricular effective refractory period, and its dispersion were measured before and for 1 h after contusion. Using high-resolution mapping, arrhythmias were recorded and analyzed. RESULTS: The intact heart study showed that the number and seriousness of contusion-induced arrhythmias increased with increasing contusion kinetic energy, as did the number of electrically silent areas (five of six ventricular fibrillations and five of six electrically silent areas at 200 mJ). In the frozen heart study, immediately after contusion ventricular effective refractory periods were shortened and dispersed, and wavelengths were also shortened. The arrhythmia analysis showed that all ventricular tachycardias but one were based on reentry developed around an electrically silent area or a line of fixed conduction block. CONCLUSIONS: Myocardial contusion has direct arrhythmogenic effects, and the seriousness of arrhythmia increases with the level of contusion kinetic energy. The mechanism of arrhythmia was mainly based on reentrant circuit around a fixed obstacle.     

Surgical management of refractory ventricular arrhythmias in patients with prior inferior myocardial infarction. A preliminary report

Most reports of operations for ventricular arrhythmia have dealt with patients with anterior myocardial infarction. Patients with previous remote inferior myocardial infarction and recurrent ventricular tachycardia or fibrillation are a difficult subset of patients to treat with surgical ablative procedures. Over a 2 year period, 11 patients with prior inferior myocardial infarction and drug-refractory ventricular tachycardia or fibrillation underwent elective operation to control the arrhythmia. Five patients had monomorphic ventricular tachycardia. Three of these five patients had localized endocardial resection and/or cryoablative procedures when the ventricular tachycardia was well localized intraoperatively. In the remaining two patients, ventricular tachycardia was noninducible intraoperatively, and the patients underwent extensive endocardial resection and mitral valve replacement because of sites suspected near the posterior papillary muscle from preoperative catheter mapping. None of these five patients had inducible ventricular tachycardia postoperatively, and all are clinically free of the arrhythmia over a 24 month follow-up period. One patient with two morphologies of ventricular tachycardia previously had an unsuccessful blind endocardial resection. She underwent map-directed cryoablation of both sites of ventricular tachycardia. Postoperatively, the patient was free of inducible arrhythmia and has been asymptomatic over 8 months. Five patients had pleomorphic ventricular tachycardia or fibrillation that could not be electrically localized. One patient with ventricular fibrillation underwent extensive endocardial resection, but the posterior papillary muscle was spared. Postoperative electrophysiological study was positive. The patient has had no clinical ventricular arrhythmias on a regimen of amiodarone, however. Two patients had extensive endocardial resection and mitral valve replacement. One died early in the postoperative course and the other is clinically well. The remaining two patients had an encircling endocardial ventriculotomy. Both are clinically stable although one had inducible ventricular fibrillation postoperatively. We conclude that well-defined monomorphic ventricular tachycardia in patients with a previous inferior myocardial infarction can be successfully treated with localized endocardial resection and/or cryoablation. However, patients with poorly localized monomorphic ventricular tachycardia or pleomorphic ventricular tachycardia or fibrillation may require more extensive procedures. The role of posterior papillary muscle sacrifice with mitral valve replacement remains undefined.(ABSTRACT TRUNCATED AT 400 WORDS)     

吸入麻醉药预处理的心肌保护机制

吸入麻醉药对心肌具有预处理作用,这为围手术期心肌保护的研究和应用提供了新方法.目前有关吸入麻醉药预处理的机制尚未完全阐明,此文综述了吸入麻醉药在活性氧产生、细胞内信号转导、ATP敏感性钾通道开放及细胞凋亡通路调节等方面的研究进展.     

挥发性麻醉药后处理保护缺血/再灌注心肌的研究进展

缺血后处理（ischemic postconditioning）是近年来提出的一种新的心肌保护方法,即心肌缺血后在长时间的再灌注之前,进行的数次短暂再灌注／缺血的循环。实验证明后处理对缺血心肌确有显著的保护作用。挥发性麻醉药后处理也可以发挥同样的保护效应,其机制比较复杂,远未阐明,现就其保护作用的机制作一综述。     

Influence of volatile anesthetics on myocardial contractility in vivo: desflurane versus isoflurane

The direct effects of desflurane on myocardial contractility in vivo have not been characterized. Therefore, the purpose of this investigation was to systematically examine the effects of desflurane on myocardial contractile function and compare these actions to equianesthetic concentrations of isoflurane in chronically instrumented dogs. Contractility was evaluated using an established index of inotropic state, the preload recruitable stroke work (PRSW) versus end-diastolic segment length (EDL) relationship. Since autonomic nervous system tone may influence the hemodynamic effects of the volatile anesthetics in vivo, experiments were performed in the presence of pharmacologic blockade of the autonomic nervous system. Two groups of experiments were performed with seven dogs instrumented for measurement of aortic and left ventricular pressure, the maximum rate of increase of left ventricular pressure (dP/dt), subendocardial segment length, coronary blood flow velocity, and cardiac output. After autonomic nervous system blockade, ventricular pressure-segment length loops were generated using preload reduction via partial inferior vena caval occlusion. The PRSW versus EDL relation was calculated from the pressure-length loops. Dogs were then anesthetized with 1.0 or 1.5 MAC desflurane or isoflurane in a random fashion, and measurements were repeated after 30 min of equilibration at each anesthetic concentration. The PRSW versus EDL slope reflected similar changes in contractile state when desflurane or isoflurane was administered (53 +/- 4 during control to 26 +/- 4 erg.cm-2 x 10(-3).mm-1 at 1.5 MAC desflurane, and 57 +/- 5 during control to 31 +/- 3 erg.cm-2 x 10(-2).mm-1 at 1.5 MAC isoflurane). In conclusion, desflurane and isoflurane produced equivalent direct decreases in myocardial contractility.     

Treatment of cardiac arrhythmias in patients with acute myocardial infarction

Cardiac arrhythmias and conduction disturbances are commonly observed in patients with acute myocardial infarction. The available data suggest the administration of prophylactic lidocaine, either through a large intramuscular dose (300 mg), which is particularly suited for out-patient situations, or through intravenous loading doses followed by a constant lidocaine infusion. Patients with ventricular arrhythmia should be treated with direct-current countershock if hemodynamic deterioration is present. Drug therapy for patients with ventricular arrhythmias who are resistant to lidocaine include procainamide, bretylium, or intravenous amiodarone (experimental drug).Treatment of atrioventricular block in acute infarction depends on the site of atrioventricular block, the infarct location, and the hemodynamic status. Generally, atrioventricular block associated with inferior infarction and normal hemodynamic states generally does not require insertion of a pacemaker. In contrast, patients with anterior myocardial infarction and Mobitz II or third degree atrioventricular block should be treated with emergent temporary insertion of a pacemaker. In addition, prophylactic pacing is clearly indicated for those with acute myocardial infarction complicated by the bifascicular block pattern or first degree atrioventricular block and new onset bundle branch block.     

Cardioprotection by placenta-derived stromal cells in a murine myocardial infarction model

Background

Autologous cells for cell therapy of ischemic cardiomyopathy often display age- and disease-related functional impairment, whereas an allogenic immunotolerant cell product would allow off-the-shelf application of uncompromised donor cells. We investigated the cardiac regeneration potential of a novel, clinical-grade placenta-derived human stromal cell product (PLX-PAD).

Methods

PLX-PAD cells derived from human donor placentas and expanded in a three-dimensional bioreactor system were tested for surface marker expression, proangiogenic, anti-inflammatory, and immunomodulatory properties in vitro. In BALB/C mice, the left anterior descending artery was ligated and PLX-PAD cells (n = 10) or vehicle (n = 10) were injected in the infarct border zone. Four weeks later, heart function was analyzed by two-dimensional and M-mode echocardiography. Scar size, microvessel density, extracellular matrix composition, myocyte apoptosis, and PLX-PAD cell retention were studied by histology.

Results

In vitro, PLX-PAD cells displayed both proangiogenesis and anti-inflammatory properties, represented by the secretion of both vascular endothelial growth factor and angiopoietin-1 that was upregulated by hypoxia, as well as by the capacity to suppress T-cell proliferation and augment IL-10 secretion when co-cultured with peripheral blood mononuclear cells. Compared with control mice, PLX-PAD-treated hearts had better contractile function, smaller infarct size, greater regional left ventricular wall thickness, and less apoptosis after 4 wk. PLX-PAD stimulated both angiogenesis and arteriogenesis in the infarct border zone, and periostin expression was upregulated in PLX-PAD-treated hearts.

Conclusions

Clinical-grade PLX-PAD cells exert beneficial effects on ischemic myocardium that are associated with improved contractile function, and may be suitable for further evaluation aiming at clinical pilot trials of cardiac cell therapy.     

Inhibition of E-selectin-mediated leukocyte adhesion by volatile anesthetics in a static condition

Purpose Leukocyte recruitment from blood vessels to inflamed tissues is the central step in the process of inflammation. This may cause damage of the inflamed tissues in the case of severe inflammatory conditions such as ischemia reperfusion or graft rejection. Adhesion molecules, such as E-selectin, are induced on activated endothelium and play an important role in this process. Volatile anesthetics protect tissues or organs in such conditions, and inhibition of leukocyte adhesion by anesthetics has been implicated. However, little is known about how the anesthetics act on individual adhesion molecules. We examined the effects of volatile anesthetics on E-selectin mediated leukocyte adhesion in a static condition using HL-60 cells, a granulocyte cell line, and E-selectin-coated plates as well as cytokine-activated human umbilical vein endothelial cells (HUVEC).Methods The adhesion assay was carried out by overlaying fluorescence-labeled HL-60 cells on E-selectin-coated plates or cytokine-activated HUVEC. E-selectin in the coated plates or activated HUVEC were quantified by enzyme-linked immunosorbent assay. E-selectin in the activated HUVEC was analyzed by immunoblot.Results Isoflurane and sevoflurane concentration-dependently suppressed adhesion of HL-60 cells to E-selectin-coated plates. Although isoflurane did not change the amount of expression, or the molecular weight of E-selectin in the activated HUVEC, it significantly suppressed HL-60 cell adhesion to activated HUVEC.Conclusion Volatile anesthetics suppress E-selectin-mediated cell adhesion in a static condition without changing the expression of E-selectin. A role for E-selectin in the organ protection by volatile anesthetics is suggested.