急性心肌缺血犬心室颤动时的左室心内膜电图

目的　探讨急性心肌缺血心室颤动 (室颤 )的形成机理。方法　经开胸结扎冠状动脉前降支或经皮腔内冠状动脉成形术球囊堵塞前降支 ,造成 4只犬心肌缺血室颤模型。经股动脉插入4极电极导管 ,顶端置于左室心尖部 ,同步记录体表心电图、左室心尖部单极和双极心内膜电图。结果　 4只犬均发生室颤。其中 2只犬在室颤发生 1～ 3min时 ,双极心内膜电图显示幅度、形状、频率规则的R波 ;另 2只犬也显示相当规律的R波。随着室颤持续时间的延长 ,心内膜电图的规律性逐渐消失。结论　研究提示 ,心室内存在多个相对独立而性质和形状不一的折返环是室颤形成的机理之一。     

Dissociation between cardiac cyclic AMP and myocardial contractility induced by verapamil, calcium and magnesium ions.

Isolated, perfused rat hearts were used to study the effects of verapamil, excess calcium ions or excess magnesium ions on changes in heart cyclic AMP and myocardial force of contraction. Verapamil caused a dose-dependent decrease in force of contraction and a nondose-related reduction in cyclic AMP. Perfusion of hearts with medium containing 5 mM calcium produced a significant rise in cyclic AMP, but no change in contractile force. The depressant effects of verapamil on contractility and cyclic AMP were reversed by 5mM calcium; excess calcium in the perfusion fluid also containing verapamil prevented the myocardial depressant effects of verapamil. Acutely elevating the magnesium concentration in the perfusion medium decreased force of contraction, accentuated the negative inotropic effect of verapamil, but did not decrease cyclic AMP or enhance the verapamil-induced reduction in cyclic AMP.     

Prevention of ventricular fibrillation by metoprolol in a pig model of acute myocardial ischaemia: absence of a major arrhythmogenic role for cyclic AMP

Absence of a Major Arrhythmogenic Role for Cyclic AMP. Journal of Molecular and Cellular Cardiology (1986) 18, 375-387. We examined the mechanism whereby beta-adrenoceptor antagonism exerts an antiarrhythmic effect in early myocardial ischaemia. Ligation of the anterior descending coronary artery in the anaesthetized open-chest pig resulted in severe transmural anteroseptal ischaemia. Blood flow in the mid-ischaemic zone 20 min after ligation was decreased to 5.7 +/- 0.7% of the preligation control value. Epicardial ST-segment deflections of 6.7 +/- 0.4 mV were recorded over this zone. A distinct phase of ventricular arrhythmias was evident about 10 to 30 min after ligation. A high incidence of ventricular fibrillation (14/16 pigs) was associated with a circumstantial increase in levels of cyclic AMP in ischaemic tissue. Twenty minute values were: 1.10 +/- 0.06, P less than 0.05 v. the non-ischaemic tissue level of 0.86 +/- 0.05 nmol/g. Propranolol 3 mg/kg IV, metoprolol 20 mg/kg IV or sotalol 10 mg/kg IV were given between 30 min prior to and 10 min after ligation. Adequate beta-adrenoceptor antagonism by each agent could be proven. Metoprolol decreased the incidence of ventricular fibrillation (2/13, P less than 0.0005 v. control group), while propranolol or sotalol did not. All three beta-antagonists decreased tissue levels of cyclic AMP prior to ligation. However, the temporary increase in ischaemic tissue after ligation could not be prevented. Furthermore, cyclic AMP in ischaemic tissue 20 min after ligation was higher in the metoprolol group than in the propranolol or sotalol group (0.94 +/- 0.04 v. 0.81 +/- 0.02 P less than 0.05, and 0.79 +/- 0.03 nmol/g P less than 0.01, respectively). Blood flow in the mid-ischaemic zone of the metoprolol group was increased to 8.6 +/- 0.6% of preligation control value (P less than 0.0001 v. control group). In contrast, blood flow in the mid-ischaemic zone of the propranolol or sotalol group was decreased. Metoprolol also reduced epicardial ST-segment deflections over the mid-ischaemic zone to 3.5 +/- 0.2 mV (P less than 0.0001 v. control group). ST-segment deflections in the propranolol group were increased. The mechanism whereby metoprolol prevented ventricular fibrillation may be explained by a decrease in the severity of ischaemia but not in terms of changes of tissue levels of cyclic AMP.     

A fast Fourier transform analysis of coronary reperfusion-induced ventricular fibrillation and the modification by dibutyryl cyclic AMP in a cat model.

To investigate the effect of dibutyryl cyclic AMP (dbcAMP) on ventricular fibrillation after coronary reperfusion, the proximal portion of the anterior descending branch of left coronary artery was reperfused 20 min after ligation in 24 cats. McFee X Y Z electrocardiograms were recorded and ventricular fibrillation was analyzed using a fast Fourier transform analysis (FFT). Ventricular fibrillation occurred in 20 of 24 cases. Sixty seconds after the occurrence of ventricular fibrillation, an intracardiac infusion of dbcAMP was administered. Nine of the 20 were defibrillated and converted to sinus rhythm or junctional rhythm after the administration of dbcAMP. The amplitude and frequency of the main power spectrum of the ventricular fibrillation waves were analyzed by FFT before and after the infusion of saline or dbcAMP. In the saline group there was no significant change in FFT. However, in the dbcAMP group, the amplitude increased significantly from 0.036 +/- 0.015 (MV--2) to 0.054 +/- 0.013 (MV--2) (p < 0.01) and the frequency decreased significantly from 4.22 +/- 1.37 (Hz) to 1.33 +/- 0.91 (Hz) (p < 0.01). Those results indicate that dbcAMP increased the amplitude and decreased the frequency of the main power spectrum of ventricular fibrillation analyzed by FFT. These distinctive changes in FFT analysis were associated with defibrillation in 9 of 20 cases.     

阿司咪唑中毒致多形室性心动过速、心室颤动一例

患者女性 ,5 0岁 ,因头晕、心悸入院。入院前 16ｈ内患者间断服用阿司咪唑 (息斯敏 ,西安杨森制药有限公司 )共35 0ｍｇ ,1ｈ后感头晕 ,恶心 ,2ｈ后症状加重并感阵发性心悸 ,气促 ,无晕厥。入院时血压 12 0 / 75ｍｍＨｇ (1ｍｍＨｇ =0 133ｋＰａ) ,心率 80次 /ｍｉｎ ,心律齐 ,无杂音。心电图示窦性心律 ,偶发室性早搏 (室早 ) ,ＱＴ间期延长为 0 6 0ｓ,急查电解质示血清钾 3 2ｍｍｏｌ/Ｌ ,临床诊断为阿司咪唑中毒。入院后立即洗胃 ,补钾 ,1ｈ后心电监护示频发多源室早 ,5ｍｉｎ后转为尖端扭转性室性心动过速 (Ｔｄｐ) ,继而转为心室颤…     

Hypokalaemia and ventricular fibrillation in acute myocardial infarction.

Serum potassium concentrations obtained on admission to hospital were inversely related to the incidence of ventricular fibrillation in 289 women and 785 men with acute myocardial infarction, 92 of whom developed ventricular fibrillation. Hypokalaemia (serum potassium concentration less than or equal to 3.5 mmol/l) was found in 122 patients (11.4%). The incidence of ventricular fibrillation was significantly greater in patients with hypokalaemia compared with those classified as normokalaemic (serum potassium concentration greater than or equal to 3.6 mmol/l) (17.2% v 7.4%). The increased risk of ventricular fibrillation in the hypokalaemic group was about the same for women and men. While they were in hospital patients with hypokalaemia developed ventricular fibrillation significantly earlier than did normokalaemic patients (median 0.3 hours v 7 hours). Hypokalaemia was more common in women (17.3%) than in men (9.2%), and 55% of the hypokalaemic patients had been treated with diuretics before admission compared with 22% of the normokalaemic group. Hypokalaemia on admission to hospital predicts an increased likelihood and early occurrence of ventricular fibrillation in patients with acute myocardial infarction.     

Myocardial norepinephrine and cyclic amp concentration following myocardial ischemia--relation to ventricular fibrillation and sudden death

This study was designed to investigate the relationships of myocardial concentrations of norepinephrine (NE) and cyclic AMP (c-AMP) to the development of ventricular fibrillation (VF) with reference to the effects of a premedication of dibutyryl cyclic AMP (DBC-AMP) and propranolol in dogs with experimental myocardial infarction. Myocardial specimens were obtained serially from the ischemic and the non-ischemic zones by mini-drill biopsy, and NE and c-AMP levels were determined by high-performance liquid chromatography and radioimmunoassay, respectively. Before the occurrence of VF, myocardial NE increased in both the ischemic and the non-ischemic zones, and c-AMP increased significantly in the ischemic zone but did not in the non-ischemic zone. In dogs premedicated with DBC-AMP an increase of c-AMP was observed in both the ischemic and the non-ischemic zones in association with an increased incidence of VF. On the other hand, no significant increase of myocardial c-AMP was observed in both the ischemic and the non-ischemic zones of propranolol-premedicated dogs which were free from VF. A significant increase of myocardial c-AMP in the ischemic zone was observed in dogs which suffered from VF in spite of the premedication of propranolol. The incidence of VF was significantly reduced by 26.5% in dogs pretreated with propranolol. No significant changes in myocardial norepinephrine and c-AMP were observed in dogs which were free from VF throughout the experiments.     

Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure.

Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.     

急性心肌梗死后快速刺激诱发心室颤动的“混沌机制”的研究

目的探讨急性心肌梗死后心室颤动（室颤）的发病机制，观察室颤过程中“混沌”的非线性动力学特征，为临床预防急性心肌梗死后室颠的发生提供理论依据。方法2003—06～2005—12对中国医科大学附属第二医院心内科制造的急性心肌梗死模型，快速起搏刺激犬的在体心肌并诱发室颤，用64导心外膜标测系统记录室颤过程中心肌的电生理学参数，观察激动周期的动态改变。结果急性心肌梗死时，诱发室颤的刺激间期明显提高；快速刺激诱发室颤的过程中，激动周期呈现倍周期分叉、准周期乃致混沌等非线性动力学特征，其Poincar＇e作图为环状结构。结论心肌急性缺血导致室颤的阅值明显升高；室颤是由于系统呈现倍周期分叉、准周期乃致混沌而导致。     

Dibutyryl cyclic AMP attenuates lung responses induced by endotoxin in conscious sheep.

Dibutyryl cyclic AMP (DBcAMP) could inhibit the production of prostanoids and modulate the pulmonary vascular responses induced by endotoxin. Diffuse lung injury after endotoxemia in sheep is accompanied by the production of prostanoids and an increase in endothelial permeability. To determine whether exogenous DBcAMP could prevent the endotoxin responses, we measured pulmonary hemodynamics, gas exchange, and lung lymph responses to an intravenous infusion of Escherichia coli endotoxin (1.0 micrograms/kg over 30 min) in unanesthetized sheep in the presence and absence of DBcAMP (30 micrograms/kg/min) infused intravenously for 6 h beginning 1 h before endotoxin infusion or for 4.5 h after 30 min of treatment with endotoxin infusion. We also measured circulating leukocytes and lung lymph and plasma concentrations of thromboxane B2 (TXB2) and prostacyclin (6-keto-PGF1 alpha) metabolites by radioimmunoassay. DBcAMP infusion before endotoxin infusion decreased endotoxin-induced pulmonary hypertension and hypoxemia and markedly attenuated the increased lung lymph flow and lymph protein clearance. DBcAMP after endotoxin only attenuated the increased lung lymph flow and lymph protein clearance. DBcAMP treatment both before and after endotoxin infusion blocked endotoxin-induced increases in lung lymph and plasma TXB2 and 6-keto-PGF1 alpha. DBcAMP did not affect the number of circulating leukocytes. Although DBcAMP alone did not affect the pulmonary and systemic hemodynamics and lung lymph balance, the potential that DBcAMP directly modulates the pulmonary vascular responses to endotoxin as a vasodilator could be expected. We conclude that DBcAMP infusion attenuates lung dysfunction caused by endotoxemia, possibly by preventing prostanoid release and modulating the pulmonary vascular responses.     

急性心肌梗死后快速刺激诱发心室颤动的"混沌机制"的研究

目的探讨急性心肌梗死后心室颤动(室颤)的发病机制,观察室颤过程中“混沌”的非线性动力学特征,为临床预防急性心肌梗死后室颤的发生提供理论依据。方法2003-06～2005-12对中国医科大学附属第二医院心内科制造的急性心肌梗死模型,快速起搏刺激犬的在体心肌并诱发室颤,用64导心外膜标测系统记录室颤过程中心肌的电生理学参数,观察激动周期的动态改变。结果急性心肌梗死时,诱发室颤的刺激间期明显提高;快速刺激诱发室颤的过程中,激动周期呈现倍周期分叉、准周期乃致混沌等非线性动力学特征,其Poincare作图为环状结构。结论心肌急性缺血导致室颤的阈值明显升高;室颤是由于系统呈现倍周期分叉、准周期乃致混沌而导致。     

Effects of cardiotoxic doses of adrenergic amines on myocardial cyclic AMP.

The role of beta-adrenergic activation in the cardiotoxicity of adrenergic amines was assessed by measuring rat myocardial cyclic AMP at various times after subcutaneous injection of necrosis-inducing amounts of isoproterenol, phenylephrine or epinephrine in the presence and in the absence of the phosphodiesterase inhibitor aminophylline. The β-adrenergic agonist isoproterenol (5.25 mg/kg) increased myocardial cyclic AMP at 1 h to 147% of control and in the presence of aminophylline (75 mg/kg) to 261% of control as compared to 146% for aminophylline alone. Propranolol (6.25 mg/kg) blocked isoproterenol-induced increases in cyclic AMP. Neither the α-adrenergic agonist phenylephrine (15 mg/kg) nor epinephrine (4 mg/kg), which has both α- and β-adrenergic properties, increased myocardial cyclic AMP above control levels even in the presence of aminophylline. With α-adrenergic blockade by tolazoline (15 mg/kg) or phenoxybenzamine (2 mg/kg), combined administration of epinephrine and aminophylline caused an increase of the myocardial cyclic AMP content to 163% and 173%, respectively, of that of control rats. These results suggest that in the intact rat, cyclic AMP-mediated myocardial stimulation is an important factor in the cardiotoxicity of isoproterenol but not of phenylephrine, while the beta-adrenergic component of epinephrine cardiotoxicity is unmasked only in the presence of α-adrenergic blockade.     

Increase of cyclic AMP levels induced by isoproterenol in cultured and non-cultured chick embryonic hearts.

Cyclic AMP levels were determined in young (day 4) and old (day 16) embryonic chick hearts, fresh and cultured. The 4-day hearts contained 33.6±2.2 pmol/mg protein, and isoproterenol (5 × 10^?5m) elevated this to 118.9±1.5. When they were organ-cultured for 7 days, the cyclic AMP level decreased markedly to about 6.0 pmol/mg protein. Isoproterenol caused a large rise to 37.7±4.7. When cells were separated by trypsin and cultivated in vitro for days, their cyclic AMP levels were lowered to 5.6±1.4, and isoproterenol raised the level to 28.8±2.0 pmol/mg protein. The 16-day hearts contained 11.7±1.5 pmol/mg protein, and isoproterenol elevated this to 22.0±1.5. When old hearts were organ-cultured, their cyclic AMP level decreased somewhat to about 5.3 pmol/mg protein, and isoproterenol raised it to 17.9±2.0. When cells were separated by trypsin and placed into cell culture for 7 days, their cyclic AMP levels were low, about 4.4 pmol/mg protein, and isoproterenol raised the level to about 23.6. The results indicated that: (a) Young hearts in situ have a high cyclic AMP level. (b) Young and old hearts placed into organ and cell culture have low cyclic AMP levels, and isoproterenol is capable of producing very large increases. (c) Beta-adrenergic receptors are present in the young hearts. (d) Beta-adrenergic receptors of young and old hearts are retained in culture. (e) There seems to be no relationship between basal intracellular cyclic AMP levels and membrane electrical properties.     

Hypokalaemia and ventricular fibrillation in acute myocardial infarction

Serum potassium concentrations obtained on admission to hospital were inversely related to the incidence of ventricular fibrillation in 289 women and 785 men with acute myocardial infarction, 92 of whom developed ventricular fibrillation. Hypokalaemia (serum potassium concentration less than or equal to 3.5 mmol/l) was found in 122 patients (11.4%). The incidence of ventricular fibrillation was significantly greater in patients with hypokalaemia compared with those classified as normokalaemic (serum potassium concentration greater than or equal to 3.6 mmol/l) (17.2% v 7.4%). The increased risk of ventricular fibrillation in the hypokalaemic group was about the same for women and men. While they were in hospital patients with hypokalaemia developed ventricular fibrillation significantly earlier than did normokalaemic patients (median 0.3 hours v 7 hours). Hypokalaemia was more common in women (17.3%) than in men (9.2%), and 55% of the hypokalaemic patients had been treated with diuretics before admission compared with 22% of the normokalaemic group. Hypokalaemia on admission to hospital predicts an increased likelihood and early occurrence of ventricular fibrillation in patients with acute myocardial infarction.     

Characteristics and prognosis of ventricular tachycardia induced by atrial fibrillation]

The aim of this study was to evaluate the clinical significance of ventricular tachycardia (VT) induced by atrial pacing. A group of 145 patients with spontaneous and induced VT was studied. Twenty-four VTs were induced by atrial stimulation (Group I) and 121 by ventricular stimulation (Group II). The underlying cardiac disease was comparable in the two groups (ejection fraction 32 +/- 14% versus 34 +/- 17%). Spontaneous bi-tachycardias, syncope and VT induced by exercise testing were more common in Group I. The prognosis was worse with 7 cardiac deaths in Group I versus 23 in Group II; recurrences of VT were commoner in group I. In this group, an electrophysiological (branch to branch or fascicular reentry) or clinical mechanism (ischaemia or poor haemodynamic status) could usually be demonstrated. Some cases of idiopathic VT were also observed in young patients. These results suggest that atrial stimulation should be performed routinely during electrophysiological studies of VT because the induction of VT by this method is not uncommon (16%). In addition, these cases of VT usually have a precise mechanism and a poor prognosis and, therefore, an appropriate treatment should be given.     

Beta-adrenergic stimulation of myocardial cyclic AMP in endotoxic rats

Sympathetic nervous system activity and myocardial response to adrenergic stimulation were studied in the rat during endotoxicosis. Plasma glucose concentration, adrenal norepinephrine (NE) and epinephrine (E) content, spleen NE content, and myocardial NE and cAMP content were analyzed in fed rats given saline or endotoxin (ETOX, 16.7 mg/kg). Values were determined at various times during a 6-hour period or at the agonal stage of shock. Myocardial cAMP content was reduced by 1 hour, recovered at 4 hours, and was again depressed at the agonal stage. In addition, isoproterenol-stimulated cAMP production in ventricular slices from ETOX rats was attenuated by 3 hours after administration. These data suggest that myocardial beta-adrenergic receptor mechanisms are altered during endotoxicosis, which may account for reports of decreased functional responsiveness to catecholamines under similar conditions. At 1 hour after ETOX, adrenal NE did not change, but E was depleted and remained low throughout the period. By 2 hours, spleen NE was also found depleted. Myocardial NE did not change until the agonal stage, when it was severely depressed. This implies that there may be nonuniform activation (duration and/or intensity) of sympathetic pathways during endotoxicosis.     

Initiation of ventricular fibrillation by supraventricular beats in patients with acute myocardial infarction.

The role of supraventricular extrasystoles in the initiation of ventricular arrhythmia was studied in 72 consecutive patients who developed primary ventricular fibrillation during the acute phase of myocardial infarction. In six patients (8%), a total of 12 episodes of ventricular fibrillation and 16 episodes of ventricular tachycardia were initiated by supraventricular extrasystoles. Ventricular fibrillation and tachycardia were initiated by single supraventricular extrasystoles in 16 and by salvos greater than or equal to two beats in 12 episodes. The RR coupling interval of the supraventricular impulse immediately preceding ventricular tachycardia ranged from 240 to 420 ms (mean 356 (62)) and was characteristic of R-on-T (prematurity index less than 1) in 63% of episodes. Average peak serum creatine kinase activity in the six patients in whom ventricular tachycardia was initiated by a supraventricular extrasystole was 1275 units compared with 720 units in the remaining 66 patients. Five of these six patients later showed evidence of pump failure. Lignocaine or procainamide or both suppressed the ventricular arrhythmia in five of the six patients. The initiation of ventricular fibrillation or tachycardia by supraventricular extrasystoles in acute myocardial infarction is not uncommon and may reflect the increased vulnerability of the heart after a large infarct. These arrhythmias may respond to drugs that suppress ventricular irritability.