Myocardial damage by ventricular fibrillation in isolated perfused rat hearts,and its underlying mechanisms

Summary In isolated perfused rat hearts ventricular fibrillation (VF), elicited electrically and persisting further spontaneously, led to an extensive release of creatine kinase (CK). Coronary flow volume and oxygen consumption were increased. In contrast, the CK release was only very small in hearts which were stimulated permanently with rhythmic impulses of 10 Hz, whereas the increase in coronary flow and oxygen consumption was significantly greater. When a relative ischemia was induced by perfusion at a low pressure, the CK release from fibrillating hearts was not greater, but less than at a higher perfusion pressure. It appeared unlikely, therefore, that the CK release from fibrillating hearts was simply due to an oxygen deficiency, although a decrease of ATP and glycogen, and an increase of glucose-6-phosphate and lactate in the myocardium were found. When VF was interrupted by lidocaine, the enzyme leakage was reduced only in the experiments with the higher perfusion pressure. A partial restoration of the myocardial metabolites after 1 h was observed. Findings in maximally ischemic hearts further supported the idea that the enzyme release in fibrillating hearts was not merely due to a lack of oxygen. Complete interruption of the coronary perfusion led to the release of only small CK activities during subsequent coronary reperfusion, whereas the metabolic alterations were more distinct than in fibrillating hearts. Mechanisms responsible for the enzyme release during fibrillation, besides a moderate oxygen deficiency, are discussed.     

Attenuation of reperfusion-induced ventricular fibrillation in the rat isolated hypertrophied heart by preischemic diltiazem treatment

Summary The ability of the calcium antagonist diltiazem to protect against reperfusion-induced arrhythmias in hypertrophied myocardium was studied. Hearts from normotensive and DOCA-salt hypertensive rats were Langendorff perfused and subjected to 10 minutes of stabilization, 10 minutes of left coronary artery occlusion, and 5 minutes of reperfusion. The incidence and duration of ventricular tachycardia (VT) and ventricular fibrillation (VF) during reperfusion were determined and the effects of diltiazem or vehicle (given as a single bolus 3 minutes before coronary artery occlusion) were assessed in hypertrophied and normal hearts. In vehicle-treated (control) hypertrophied hearts, VF incidence was 91% compared with 67% in normal hearts, and the median duration of VF was 272 seconds (mean 207.4±32.3) compared with 27 seconds (mean 110.6±36.6; p<0.05), respectively, suggesting that reperfusion VF is more severe in hypertrophied hearts. In normal hearts, diltiazem 18 µg reduced VT incidence from 92% to 55%, reduced VF from 67% to 27%, and sustained VF from 42% to 9%. In hypertrophied hearts, 18 µg diltiazem reduced the VT incidence from 100% to 58%, reduced VF from 91% to 25% (p<0.01), and sustained VF from 82% to 8% (p<0.01). Median VF duration in this group was reduced to 0 seconds (p<0.05; mean 24.7±22.6). Diltiazem did not significantly affect heart rate or coronary flow rate decreases during ischemia. However, developed tension, at the onset of ischemia, was lower in diltiazem-treated groups than in the control groups. We suggest that the attenuation by diltiazem of reperfusion-induced arrhythmias observed in this model was related to an energy-sparing effect during ischemia. This study shows that diltiazem administered acutely before the onset of ischemia attenuates reperfusion-induced arrhythmias in the hypertrophied myocardium, despite its greater susceptibility to reperfusion-induced arrhythmias.     

Ventricular fibrillation during partial reperfusion following severe myocardial ischemia in the canine model

The authors examined whether partial reperfusion protects against reperfusion ventricular fibrillation (VF) following severe acute myocardial ischemia. Fifty-seven dogs were divided into two groups. In group A (n = 21), the left anterior descending coronary artery was occluded for 10 minutes, followed by full reperfusion. In the remaining 36 dogs (group B), myocardial ischemia was induced by retrograde blood flow (RBF) for 10 minutes. Thereafter, these dogs were divided into three subgroups: in group B1 (n = 10), full reperfusion was made by a carotid-left anterior descending coronary artery bypass; in group B2 (n = 13), partial reperfusion was achieved by collateral flow into the ischemic zone due to stopping RBF; in group B3 (n = 13), RBF was continued for an additional 5 minutes. During 10 minute ischemia, the myocardial blood flow at the ischemic zone measured by the H2 gas-clearance method was 12.3 +/- 2.0 ml/min/100 g in A, 3.4 +/- 0.9 ml/min/100 g in B1, 4.7 +/- 0.6 ml/min/100 g in B2, and 4.7 +/- 0.6 ml/min/100 g in B3 (A vs B1, p less than 0.02; A vs B2 and B3, p less than 0.01). Maximal ST-segment elevation was 11.4 +/- 1.8 mV in A, 28.2 +/- 2.7 mV in B1, 25.1 +/- 3.0 mV in B2, and 27.0 +/- 1.9 mV in B3 (A vs B1, B2, and B3, p less than 0.001). Maximal conduction delay was 48.6 +/- 9.4 ms in A, 106.4 +/- 5.2 ms in B1, 101.6 +/- 9.9 ms in B2, and 91.2 +/- 5.1 ms in B3 (A vs B1, B2, and B3, p less than 0.001). The incidence of reperfusion VF was 14% (3/21) in A, 80% (8/10) in B1, and 69% (9/13) in B2 (A vs B1, p less than 0.001; A vs B2, p less than 0.005). In group B3, VF occurred in only 1 of 13 dogs for the additional 5 minutes. It is concluded that reperfusion VF occurred frequently when ischemia was severe even though the duration of ischemia was short (B1), and that reperfusion VF was not prevented by partial reperfusion when the ischemia was severe (B2).     

Effects of propafenone on pacing-induced ventricular fibrillation and intracellular calcium in rat hearts.

Propafenone is an antiarrhythmic agent with fast sodium channel, calcium channel, and beta-adrenergic receptor blocking properties. The effects of propafenone on arrhythmias, free intracellular calcium and left ventricular performance were studied using perfused rat hearts during (i) pacing-induced ventricular fibrillation and (ii) infusion with 2.65 x 10(-6) M, 5.3 x 10(-6) M and 7.9 x 10(-6) M propafenone hydrochloride (corresponding to approximately 1, 2 and 3 mg kg-1 body weight). A bolus of 1 mg kg-1 propafenone during ventricular fibrillation resulted in a decrease in intracellular calcium, with subsequent conversion to sinus rhythm. In perfused hearts with sinus rhythm propafenone produced a dose-dependent decrease in heart rate and myocardial oxygen consumption together with a rise in left ventricular diastolic pressure, and diastolic [Ca2+]i, indicative of depression of left ventricular function. We conclude that a bolus of propafenone during ventricular fibrillation leads to a decrease in [Ca2+]i preceding conversion to sinus rhythm. In rat hearts with sinus rhythm the depressive effects of propafenone on [Ca2+]i are dose dependent.     

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   

Spectral and correlation analyses of the verapamil-induced conversion of ventricular fibrillation to tachycardia in isolated rat hearts

Ventricular tachycardia (VT) is considered to be the most common precursor of ventricular fibrillation (VF). However, the mechanisms underlying the transition from VT to VF remain unclear. Here, we investigated whether and how perfusion of the heart with verapamil, a blocker of L-type calcium channels, changed the macro-dynamics of the heart between VT and VF. The experiments were performed with Langendorff perfused isolated rat hearts, in which left ventricular pressure and left ventricular cardiomyogram were measured. Sustained VT or VF was induced by burst pacing of the left ventricular muscles. During sustained VF, verapamil perfusion resulted in the conversion of VF to VT. A cross-correlation analysis between left ventricular cardiomyogram and left ventricular pressure revealed that the correlation coefficient was small during VF, but became larger during VT. This study showed that inactivation of L-type Ca(2+) channels occurred during verapamil-induced conversion of pacing-induced sustained VF to VT, and characterized the changes in macro-dynamics of the heart associated with the transition.     

Heterogeneity of ventricular fibrillation dominant frequency during global ischemia in isolated rabbit hearts

Introduction : Ventricular fibrillation (VF) studies show that ECG‐dominant frequency (DF) decreases as ischemia develops. This study investigates the contribution of the principle ischemic metabolic components to this decline. Methods and Results: Rabbit hearts were Langendorff‐perfused at 40 mL/min with Tyrode's solution and loaded with RH237. Epicardial optical action potentials were recorded with a photodiode array (256 sites, 15 × 15 mm). After 60 seconds of VF (induced by burst pacing), global ischemia was produced by low flow (6 mL/min), or the solution changed to impose hypoxia (95% N₂/5% CO₂), low pH_o (6.7, 80% O₂/20% CO₂), or raised [K⁺]_o (8 mM). DF of the optical signals was determined at each site. Conduction velocity (CV), action potential duration (APD90), effective refractory period (ERP), activation threshold, dV/dt_max, and membrane potential were measured in separate experiments during ventricular pacing. During VF, ischemia decreased DF in the left ventricle (LV) (to [58 ± 6]%, P < 0.001), but not the right (RV) ([93 ± 5]%). Raised [K⁺]_o reproduced this DF pattern (LV: [67 ± 12]%, P < 0.001; RV: [95 ± 9]%). LV DF remained elevated in hypoxia or low pH_o. During ventricular pacing, ischemia decreased CV in LV but not RV. Raised [K⁺]_o did not change CV in either ventricle. Ischemia and raised [K⁺]_o shortened APD90 without altering ERP. LV activation threshold increased in both ischemia and raised [K⁺]_o and was associated with diastolic depolarization and decreased dV/dt_max. Conclusions: These results suggest that during VF, decreased ECG DF in global ischemia is largely due to elevated [K⁺]_o affecting the activation thresholds in the LV rather than RV.     

Early recurrence of ventricular fibrillation after successful defibrillation during prolonged global ischemia in isolated rabbit hearts

Introduction: The mechanisms that lower the efficacy of electrical defibrillation during prolonged global ischemia remain unclear.
Methods and Results : Epicardial activation patterns during attempted electrical defibrillation were studied in 18 Langendorff-perfused rabbit hearts at baseline, after 5-minute no-flow global ischemia and after 10-minute reperfusion. DFT₅₀ (voltage required to achieve 50% probability of successful defibrillation) was determined at each stage. Defibrillation was considered successful if postshock sinus/idioventricular rhythm was present. Prolonged global ischemia converted type 1 VF (multiple wandering wavelets) into type 2 VF (repetitive epicardial breakthroughs, REBs). The mean DFT₅₀ after 5-minute ischemia (96 ± 39 V) was significantly lower when compared with that at baseline (154 ± 47 V, P < 0.0001) and after 10-minute reperfusion (145 ± 47 V, P < 0.001). However, the incidence of early (within 10 seconds) VF recurrence after successful shock during prolonged global ischemia (23 of 78, 29.5%) was much higher than that at baseline (2 of 60, 3.3%) and after 10-minute reperfusion (5 of 63, 7.9%; P < 0.0001). Mapping data showed that the VF wavefronts during prolonged global ischemia were initially halted by the shock, followed by one to five ventricular escape beats. These beats then triggered REBs and early VF recurrence. In eight out of 11 episodes, the REBs before and after successful shock arose from the same location near the interventricular septum.
Conclusions : There is a significant reduction of DFT₅₀ during prolonged global ischemia. However, defibrillation appears to fail when the preexisting REBs near the interventricular septum induce early VF recurrence. Shock per se cannot eliminate the substrates of these REBs.     

Acute myocardial ischaemia in the anaesthetised pig: local catecholamine release and its relation to ventricular fibrillation

Summary In anaesthetised open-chest pigs, sequential myocardial samples were obtained before and after occlusion of the distal half of the LAD. These samples were analysed histofluorimetrically to determine the density of catecholamine containing neurones in each sample (quantified morphometrically), and radioenzymatically for total tissue noradrenaline content. Following coronary artery occlusion, 75% of the animals (24 out of 32) died in ventricular fibrillation in the first 30 min, the other 25% (8/32) survived the first 60 min of myocardial ischaemia. Coronary artery occlusion led to a significant reduction in the density of fluorescing fibres in the ischaemic myocardium of animals which fibrillated (from 1.25±0.2% to 0.67±0.10% at 15 min) whereas in the survivors there was no significant change in fluorescing area during the course of the experiment. Animals which fibrillated had a significant reduction in tissue noradrenaline concentration of the ischaemic myocardium (from an initial concentration of 612±72 to 402±64 ng/g ww) within the first 5 min of ischaemia. It is concluded that in this model of myocardial ischaemia, the development of ventricular fibrillation in the early phase seems to be related to the release of noradrenaline from the sympathetic neurones after the onset of myocardial ischaemia.Supported by Deutsche Forschungsgemeinschaft Hi 137/8-1     

Coexistence of two types of ventricular fibrillation during acute regional ischemia in rabbit ventricle

INTRODUCTION: We previously reported that a normal ventricle can demonstrate two types of ventricular fibrillation (VF), depending on the underlying electrophysiologic characteristics at the time of VF induction. We hypothesize that the two types of VF can coexist in acutely ischemic ventricles. METHODS AND RESULTS: Optical mapping studies were performed with di-4ANEPPS in 15 Langendorff-perfused rabbit hearts. Coronary artery branches were ligated to create regional ischemia in 10 hearts. Action potential duration measured to 50% repolarization (APD50) during ischemia showed an area with uniformly shortened APD50 (zone 1), an area with normal or lengthened APD50 (zone 3), and an area in between with an APD50 gradient (zone 2). Ischemia flattened APD restitution (APDR) slope and reduced conduction velocity in zone 1, creating a condition for type II VF. APDR steepened and the conduction velocity changed little in the nonischemic zone (zone 3), creating a condition for type I VF. During induced VF, the dominant frequency in zones 2 and 3 progressively increased after ischemia onset. The dominant frequency in zone 1 (ischemic zone) first decreased and then slightly increased but typically remained less than the dominant frequency in zone 3. The number of wavebreaks increased with time in all three zones (baseline: 4.3 +/- 1.5; 30 min: 11.7 +/- 5.6; 60 min: 15.6 +/- 11 per frame; P < 0.01). CONCLUSION: Two types of VF can coexist during acute regional ischemia. Both ischemic and nonischemic regions develop proarrhythmic changes during regional ischemia, thus contributing to increased ventricular vulnerability to VF and sudden death during acute coronary occlusion.     

Ventricular fibrillation during no-flow global ischemia in isolated rabbit hearts

Introduction: The dominant frequency (DF) during ventricular fibrillation (VF) in Langendorff-perfused guinea pig hearts is higher in left ventricle (LV) than in right ventricle (RV). However, the onset of VF invariably leads to global ischemia. Whether or not a high DF source exists in LV during global ischemia is unknown.
Methods and Results: By using a two-camera optical mapping system, epicardial activation patterns of VF were studied in 12 isolated rabbit hearts during baseline, no-flow global ischemia, and reperfusion. Simultaneous endocardial electrode recording was performed in 4 of the 12 hearts. Optical mapping showed type 1 VF at baseline, with multiple wandering and short-lived wavelets. After the onset of global ischemia, VF showed progressively increased spatiotemporal periodicity. The majority (65%) of VF recorded after 7 minutes of global ischemia showed type 2 VF, containing a single epicardial site with stable (≥3.85 seconds in duration) repetitive activities. Among the 33 sites with these activities, 24 were located near the interventricular septum, and 27 showed an epicardial breakthrough pattern with centrifugal propagation and wavebreaks distant from the focal site. After 10 minutes of global ischemia, the DF was lower on LV epicardium (5.0 ± 1.4 Hz) than on RV epicardium (8.6 ± 2.5 Hz, P < 0.001). However, there was no DF gradient between RV and LV endocardium (9.7 ± 1.0 vs 9.6 ± 0.9 Hz).
Conclusions: VF during prolonged global ischemia is consistent with type 2 VF with a single subepicardial source of rapid activation, mostly near the interventricular septum. The DF in LV is not higher than in RV.     

Bucindolol,a beta blocker,decreased ventricular fibrillation and maintained mechanical function in a pig model of acute myocardial ischemia

Summary Bucindolol is a new beta blocker with marked vasodilatory properties and intrinsic sympathomimetic activity. We tested its potential effect against ventricular fibrillation (VF), in a pig model of acute myocardial ischemia. Bucindolol 6 mg/kg IV was administered in two equally divided doses, the first 30 minutes prior to, and the second 10 minutes after, ligation of the anterior descending coronary artery (CAL) in anesthetized open-chest pigs. Bucindolol decreased the incidence of VF to 1/11 versus 14/16 in the control group (p<0.005). Bucindolol also decreased the duration of ventricular tachycardia, 15±8 seconds versus 104±32 seconds in the control group (p<0.01). Bucindolol maintained LV_maxdP/dt at predrug and pre-CAL values, whereas LV_maxdP/dt was decreased by CAL in the control group. Bucindolol decreased arterial pressure and heart rate. Bucindolol increased blood flow in the peripheral ischemic zone (24.6±1.8% versus 16.2±1.7% (percent of pre-CAL value) in controls, p<0.002), as well as in the nonischemic zones (perlischemic zone: 126.4±6.1% versus 96.7±4.8% in the control group, p<0.0005; remote nonischemic zone: 126.6± 7.1% versus 87.1±4.3% of pre-CAL value in the control group, p<0.0001). Bucindolol had marked antiarrhythmic effects that were associated with beneficial effects on the mechanical function of the left ventricle and on blood flow to the ischemic myocardium.     

Prediction of in-hospital ventricular fibrillation from admission data in acute myocardial infarction

We studied retrospectively 26 readily obtainable clinical and electrocardiographic variables in 22 consecutive patients who experienced primary ventricular fibrillation in association with an episode of acute myocardial infarction. Twenty-eight consecutive patients who had an uncomplicated course after acute myocardial infarction served as controls. The clinical profile of the two groups was similar except that patients who had primary ventricular fibrillation smoked more and had a higher peak creatinine phosphokinase level at the time of infarction. The data was evaluated using univariate and stepwise logistic regression analysis. This analysis demonstrated that patients who developed primary ventricular fibrillation had, on admission (1) more evidence of congestive heart failure (Killip classification), (2) a lower diastolic blood pressure, (3) greater ST-segment elevation, (4) a longer QTc interval, and (5) a less distinguishable J point on the electrocardiogram. This method of logistic analysis that utilizes easily obtainable hospital admission data serves as a preliminary model for prediction of the relative risk of primary ventricular fibrillation in a patient with acute myocardial infarction. The ability to identify patients at risk has important therapeutic implications.     

Fever as a precipitant of idiopathic ventricular fibrillation in patients with normal hearts

INTRODUCTION: Ventricular fibrillation (VF) is the main mechanism of sudden cardiac death. The clinical precipitants of sudden cardiac death due to idiopathic VF are poorly characterized. Emerging evidence implicates triggers originating predominantly from the distal Purkinje arborization and the right ventricular outflow tract. METHODS AND RESULTS: We report three patients without structural heart disease or repolarization abnormalities in whom a febrile illness was the only concurrent disease associated with unexpected sudden cardiac death due to VF storm. An automated defibrillator was implanted in all three patients. In one patient with persistent recurrent VF episodes, mapping demonstrated the origin of these triggers was from the Purkinje arborization of the anterior wall of the right ventricle. Ablation at a site of earliest activation during ectopy, where pace mapping was concordant and Purkinje potential preceded the onset of ventriculogram, resulted in suppression of all arrhythmias. After follow-up of 22, 9, and 18 months in the three patients, no ventricular arrhythmias have been recorded. CONCLUSION: We present a series of patients in whom an apparently benign febrile illness was associated with malignant ventricular arrhythmias in the absence of cardiac disease or other factors known to precipitate sudden cardiac death. Physicians should be aware of this possible phenomenon in cases of febrile illness associated with syncope.     

Prediction of atrial and ventricular fibrillation complicating myocardial infarction from admission data: a prospective study

This study set out to examine prospectively two logistic formulae based on admission clinical data to predict ventricular or atrial fibrillation complicating acute myocardial infarction. A prospective study of 87 consecutive patients with acute transmural myocardial infarction was conducted. The formula for predicting ventricular fibrillation from the diastolic blood pressure, degree of ST-segment elevation, and QTc had a sensitivity of 93%, specificity of 83%, and a predictive value for an abnormal test of 62% (13 of 14 patients who developed ventricular fibrillation were identified). The formula for predicting atrial fibrillation from the age of the patient, a history of heart failure, systolic blood pressure, and four electrocardiographic parameters had a sensitivity of 78%, specificity of 85%, and a predictive value of 67% (14 of 18 patients identified). Our study shows that patients with myocardial infarction who are liable to develop ventricular or atrial fibrillation can be identified on admission from simple clinical data.     

Electrophysiologic characteristics at initiation of ventricular tachycardia and ventricular fibrillation in a canine infarct model

Local ventricular activation time and the conduction time during sinus rhythm at the induction of ventricular tachycardia (VT) and ventricular fibrillation (VF) were investigated using a canine model of chronic myocardial infarction. Of 26 dogs studied, 15 had inducible VT, 10 had inducible VF, and 1 had no inducible arrhythmias. Bipolar local ventricular electrograms were recorded during sinus rhythm from 136 sites in 10 dogs with VT and 164 sites in 11 dogs with VF. Mean activation time in dogs with inducible VT was significantly longer than in dogs with inducible VF. Furthermore, simultaneous local ventricular electrograms were recorded during the induction of VT (74 episodes) or VF (38 episodes) from the infarct border zone at the endocardium (B-EN), the epicardium (B-EP), and normal sites (N-EN, N-EP). During VT induction, the activation time at N-EN and N-EP was significantly longer than during VF induction (N-EN: 94 ± 21, 70 ± 19 ms; N-EP: 83 ± 21, 64 ± 10 ms; p < 0.05). Conduction time was measured at the initiation of VT or VF induced by orthodromic or antidromic pacing. The conduction times of the last paced beat between N-EN and B-EP (35 ± 11, 62 ± 24 ms), N-EN and N-EP (35 ± 12, 14 ± 13 ms), B-EN and B-EP (16 ± 10, 38 ± 25 ms), and B-EP and N-EP (77 ± 27, 44 ± 12 ms) were significantly different in dogs with inducible VT (p < 0.05), but not in dogs with VF. Dispersion of effective refractory period was also observed in dogs with VT. Percent infarct in inducible VT was larger than in inducible VF (VT: 16 ± 5%; VF: 10 ± 2%; p < 0.001). These studies suggest that dogs with inducible VT have prolonged ventricular activation time and significantly different bidirectional conduction time during VT induction. This may serve as a substrate for reentry.     

Role of KATP channels in repetitive induction of ventricular fibrillation.

AIM: Patients with sustained ventricular tachyarrhythmias are at high risk for sudden cardiac death. The mechanisms leading to multiple temporally related episodes of ventricular fibrillation (VF) are not yet fully elucidated, and treatment options are limited. We investigated whether K(ATP)-channels could be involved in triggering VF. METHODS: We determined postarrhythmic changes of monophasic action potentials (MAP) after repetitive induction of VF in 32 Langendorff-perfused rabbit hearts. RESULTS: Postarrhythmic action potential duration (APD) was significantly shorter compared with baseline (100 +/- 12 ms vs. 140 +/- 8 ms, P < 0.05). With increasing numbers of VF and shortening of recovery intervals between VF episodes (2 min) inducibility of VF increased, and abbreviation of APD became more prominent (90 +/- 5 ms vs. 130 +/- 4 ms, P < 0.05). Pre-treatment with the selective K(ATP) blocking agent HMR 1883 led to a significant increase of postarrhythmic APDs compared with control hearts (100 +/- 12 ms vs. 118 +/- 3 ms, P = 0.0013). Moreover, HMR 1883 significantly reduced inducibility of VF and increased the rate of successful defibrillation. CONCLUSIONS: Repetitive episodes of VF result in postarrhythmic abbreviation of APDs, a phenomenon thought to be of potential relevance for incessant tachyarrhythmias in patients. Prevention of postarrhythmic MAP-shortening by HMR 1883 might be useful in suppressing VF.     

Primary angioplasty for isolated right ventricular infarction.

We describe a case of isolated right ventricular infarction that has rarely been diagnosed antemortem. Electrocardiogram showed ST segment elevation in left precordial chest, right precordial chest, and inferior leads, which mimicked those of anterior and inferior left ventricular infarction. Coronary angiography revealed that culprit lesion was totally occluded right coronary artery. Infarcted artery was nondominant right coronary artery with branches supplying only right ventricular wall. Restoration of coronary blood flow was obtained by primary stenting and resulted in prompt ST segment normalization in all leads. Despite extensive right ventricular wall motion abnormality, subsequent right ventricular dysfunction was not observed.     

Delay by a calcium antagonist, amlodipine, of the onset of primary ventricular fibrillation in myocardial ischemia

Summary Calcium antagonists have been reported to counteract the increase by ischemia of vulnerability to ventricular fibrillation. This ability might be especially of interest in the prevention of sudden death subsequent to a major, but transitory, inadequacy between myocardial oxygen requirements and available coronary blood flow produced by exercise, emotion, etc., because death is then not related to irreversible damage of myocardial fibers. This study has been undertaken to examine the protective effect of a calcium antagonist on an animal model of this type of ischemia. This model used complete, but transient occlusion of the left anterior descending coronary artery near its origin during pacing at a constant high rate (180 beats/min) in anesthetized, open-chest pigs, most often resulting in fibrillation within 1–2 minutes after a progressive fall of the electrical fibrillation threshold. Amlodipine was the preferred calcium antagonist for this study because it is only moderately negatively inotropic. The results of the preventive administration of amlodipine was assessed by the time to onset of fibrillation. Amlodipine 0.30 mg/kg prolonged this time by 50–100% (p < 0.05) without appreciable impairment of blood pressure or myocardial contractility. Concurrently, amlodipine delayed the shortening of the monophasic action potential duration, the lengthening of conduction time, and the alterations of ST segments and T waves linked to ischemic depolarization. Consequently, when given experimentally before the occurrence of major, but transitory ischemia, amlodipine protected against fibrillation. Similarly, in clinical settings it ought to delay sudden death that may occur as a result of a major but transitory inadequacy between myocardial oxygen requirements and available coronary blood flow.