Ischemic Ventricular Fibrillation Research Articles

Autonomic control of heart rate: pharmacological and nonpharmacological modulation.

The evidence of the predictive value of autonomic markers has generated a growing interest for interventions able to influence autonomic control of heart rate. The hypothesis is that an increase in cardiac vagal activity as detected by an increase in heart rate variability (HRV) or baroreflex sensitivity (BRS) may be beneficial in the ischemic heart. Numerous experimental data support the hypothesis that augmenting vagal activity might be protective against lethal ischemic arrhythmias. Among them is the evidence that ventricular fibrillation during acute myocardial ischemia may be largely prevented by electrical stimulation of the right cervical vagus or by pharmacological stimulation of cholinergic receptors with oxotremorine. There is an inherent danger in the so far unwarranted assumption that modification of HRV or BRS translates directly in cardiac protection. This may or may not be the case. It should be remembered that the true target is the improvement in cardiac electrical stability and that BRS or HRV are just markers of autonomic activity. Low dose scopolamine increases HRV in patients with a prior myocardial infarction. This observation, combined with the evidence that elevated cardiac vagal activity during acute myocardial ischemia is antifibrillatory, has generated the hypothesis that scopolamine might be protective after MI. We tested low dose scopolamine in a clinically relevant experimental preparation for sudden death in which other vagomimetic interventions are effective and found that this intervention does indeed increase cardiac vagal markers but has minimal antifibrillatory effects. This is in contrast to exercise training that in the same experimental model had a marked effect on both BRS and HRV and at the same time provided strong protection from ischemic ventricular fibrillation. Thus, based on the current knowledge it seems appropriate to call for caution before attributing excessive importance to changes in "markers" of vagal activity in the absence of clearcut evidence for a causal relation with an antifibrillatory effect.

Regional expansion during myocardial ischemia predicts ventricular fibrillation and coronary reocclusion.

Primary ventricular fibrillation (VF) complicating acute myocardial infarction is associated with occluded infarction-related arteries. The relationship between VF during ischemia and spontaneous coronary reocclusion was analyzed in 48 anesthetized pigs submitted to 48 min of coronary ligation and 6 h of reflow. Reocclusion was associated with ischemic VF (6 of 11 animals with VF but only 6 of 37 without it had reocclusion) but not with reperfusion arrhythmias, the size of the ischemic area, the magnitude of electrocardiogram changes or contractile dysfunction during ischemia, or the severity of intimal injury at the occlusion site. The increase in end-diastolic length in the ischemic region during coronary occlusion was associated with ischemic VF (15 min after occlusion, end-diastolic length was 116 +/- 2 and 111 +/- 1% of baseline in animals with or without presenting subsequent VF, respectively) and was retained by multiple logistic regression analysis as the only independent predictor of ischemic VF and reocclusion. Thus ischemic VF is strongly associated with an increased rate of spontaneous coronary reocclusion during subsequent reperfusion. Acute expansion of ischemic myocardium appears as a prominent determinant of both ischemic VF and reocclusion.

Efficacy of a beta-adrenergic receptor antagonist, propranolol, in preventing ischaemic ventricular fibrillation: dependence on heart rate and ischaemia duration.

To investigate the prevention of ventricular fibrillation with a beta-adrenergic receptor (beta-AR) antagonist in anaesthetized, open-chest pigs in a model of ischaemia, intended to reproduce what happens either in anginal attack or in the first hour of infarction. Ventricular fibrillation threshold (VFT) was determined with trains of diastolic stimuli of 100 ms duration delivered by a subepicardial electrode inserted in the area subjected to ischaemia. Ischaemia was obtained by the complete occlusion of the left anterior descending coronary artery, either near its origin during brief but increasing periods (30, 60, 90, 120, 150, 180, 240, 300 s), or half-way from its origin for a much longer time (more than 60 min). During transient proximal occlusion and isoprenaline infusion (0.25 microgram/kg/min), propranolol (50 micrograms/kg plus 2 micrograms/kg/min) attenuated both tachycardia and the fall in VFT to 0 mA. The shortening of MAP duration accompanying depolarization of the fibres was concurrently slowed down, and time to fibrillation prolonged (122 +/- 15 to 262 +/- 14 s, p < 0.001). In the absence of isoprenaline infusion, propranolol exerted similar effects, but to a lesser degree, in proportion to heart rate dependent on sympathetic activity. In contrast, it became unable to raise VFT before and during ischaemia, when heart rate was kept constant by pacing. After persistent midportion occlusion, significant differences in VFT were found only at the 5th min, depending on whether heart rate was accelerated by isoprenaline (0.8 +/- 0.2 mA), left normal (1.8 +/- 0.3 mA) or slowed down by propranolol (1.6 +/- 0.3 mA). Later on, especially after 15 and 25 min of ischaemia, VFT, which was below 1.0 mA, did not appear to be influenced by the activation or blockade of beta-ARs: spontaneous fibrillations were observed in the same number in this period with or without the administration of propranolol. Beyond 30 min after occlusion, the rise in VFT, subsequent to the first irreversible cell damage, also occurred in the same way. The prevention of ischaemic ventricular fibrillation by a beta-AR antagonist, judged from VFT, is easily checked experimentally when ischaemia is only transitory, especially if sympathetic activity is high. The maintenance of VFT at a relatively high level is essentially related to the depressant effect on the sinus rate. The same animal model does not give support to an effective protection in the first hour of infarction. However, the control of heart rate may also be beneficial in these circumstances by attenuating systemic haemodynamic disorders.

Coronary Venous Hypertension Prevents the Formation of the Electrophysiological Arrhythmogenic Substrate of Acute Ischemia in the Dog: Salutary Effects of Preserved Myocardial Hydration

Coronary venous hypertension induced by partial coronary sinus obstruction (CSO) in the dog, prevents or delays the predictable ventricular fibrillation (VF) of the early phase of acute ischemia. Also, CSO acting presumably through enhanced myocardial hydration, normalizes the inhomogenous extracellular potassium ([K+]o) accumulation, a major factor in producing the electrophysiological disparities, characteristic of arrhythmogenic substrate. To further clarify the mechanism of early ischemic VF prevention in dogs, radioactive microspheres were used to evaluate regional perfusion changes, resulting from CSO sufficient to raise the coronary sinus pressure to 40 mmHg, before and during ischemia induced by double coronary artery occlusion (CAO) (n=5). Also, global or regional unipolar electrogram mapping was used to assess changes of epicardial ventricular activation times (AT) and sequence and activation recovery intervals (ARI) during CSO, CAO and combined CSO and CAO, induced in random order (n=8). CSO did not affect regional perfusion nor improved collateral blood flow during ischemia. With CSO, AT shortened modestly over time (0.41±1.1 ms/min,r=0.85,P<0.05) and ARI transiently decreased by up to 5.5%. With CAO, AT became variably delayed and isochrone map distortions were indicative of localized conduction delays or blocks, consistent with elevated [K+]o. In contrast, when CAO was preceded by CSO, AT delays were homogenous and normal activation sequence was preserved. Also, whereas with CAO, ARI shortened unequally over the ischemic region by as much as 43% at individual sites (average of 38.3±6.8 ms,P<0.001), with combined CSO and CAO, ARI shortening was less pronounced and more homogenous (26.1±5.6 ms,P<0.05), not exceeding 29% at any site. Thus, in accordance with previous findings of enhanced [K+]ohomogeneity, coronary venous hypertension reduces the disparities of activation and refractoriness of ischemia attributable, at least in part, to disparate [K+]oaccumulation. Since no collateral blood flow improvement could be identified, the salutary electrophysiological effects of CSO may reflect a more homogenous extracellular environment, due to preservation of normal microvascular pressure (Pmv) and sustained filtration and lymph flow.

Antifibrillatory efficacy of long-term tedisamil administration in a postinfarcted canine model of ischemic ventricular fibrillation.

The electrophysiologic and antifibrillatory properties of tedisamil (KC-8857) were studied in vivo in a conscious canine model of sudden cardiac death. Male mongrel dogs were anesthetized, and surgical anterior myocardial infarction was induced by a 2-h occlusion, with reperfusion of the left anterior descending coronary artery. Three to five days after infarction, dogs were subjected to programmed electrical stimulation (PES) to identify those at risk for ischemia-induced ventricular fibrillation. Previous studies documented that dogs with a significant anterior-wall infarction develop ventricular tachycardia in response to PES and are at an increased risk for sudden cardiac death on imposition of a transient ischemic event in a region remote from the infarct-related artery. PES-inducible animals were randomized to either oral placebo or oral tedisamil treatment (3 mg/kg, b.i.d for 4 days, Group 1, n = 8). Control animals received empty gelatin capsules (Group 2, n = 8). The effective refractory period and QTc interval were unchanged after 3 days of oral placebo or tedisamil dosing. Arrhythmic activity after drug administration was not observed in dogs treated with tedisamil. PES induction of ventricular tachycardia was reduced significantly in the tedisamil-treated group (100% inducible before drug vs. 9% inducible after drug; p < 0.05). In the sudden-cardiac-death protocol, tedisamil reduced the incidence of lethal ischemic arrhythmias developing in response to acute posterolateral myocardial ischemia. Tedisamil-treated animals exhibited a 100% compared with a 25% survival rate in the control group (p < 0.05). Anterior-wall infarct size, expressed as a percentage of the left ventricle, did not differ between groups: Group 1 = 20 +/- 1%; Group 2 = 22 +/- 1%. Our findings suggest that tedisamil might be useful in the prevention of malignant ventricular arrhythmias in myocardial ischemic injury.

Mechanism of protective effect of dalargin against ischemic arrhythmias

Acute tests on cats with altered sympathetic innervation of the heart show that the protective action exerted by dalargin against the development of ischemic ventricular fibrillation is due to a modulating influence of this leu-enkephalin analog on both the sympathetic and parasympathetic regulation of cardiac activity.

Antifibrillatory Effects of BRL-32872 in Anesthetized Yucatan Minipigs with Regional Myocardial Ischemia

The antifibrillatory potential of BRL-32872, a novel antiarrhythmic compound with K+ and Ca2+ channel blocking activities, was examined in a minipig model of ischemia-induced arrhythmia. The effects of intravenous (i.v.) BRL-32872 (0.3 and 1.0 mg/kg, n = 8), dofetilide (0.3 mg/kg, n = 8), and flecainide (2.0 mg/kg, n = 8), were investigated on the incidence of ventricular fibrillation (VF) during a 20-min occlusion of the left anterior descending coronary artery (LAD). Ischemia-induced VF occurred in 6 of 9 vehicle-treated pigs. BRL-32872 reduced the incidence of ischemic VF to 13% at 0.3 mg/kg (p < 0.05) and to 0% at 1.0 mg/kg (p < 0.01). Dofetilide also prevented the occurrence of VF (0%, p < 0.01) In contrast, flecainide did not reduce the incidence of VF (63%). Indeed, flecainide shortened the time to onset of VF from 17 +/- 1 min in the vehicle group to 10 +/- 1 min (p < 0.001). The antifibrillatory effects of BRL-32872 and dofetilide were associated with a prolongation of QT interval on ECG. Flecainide did not prolong repolarization, but slowed the ventricular conduction velocity, as shown by significant increases in PR and QRS intervals. During early reperfusion, 1 of 8 surviving pigs in each group treated with BRL-32872 and 4 of 8 in the dofetilide group developed VF. This study demonstrated an antifibrillatory effect of BRL-32872 associated with prolonged ventricular repolarization and showed enhanced efficacy over dofetilide on reperfusion arrhythmias which is most likely a consequence of its Ca2+ blocking activity.

Profibrillatory effects of lidocaine in the acutely ischemic porcine heart.

Because recent clinical studies have failed to show evidence of the benefit of lidocaine in the arrhythmias occurring in the early stage of myocardial infarction and have even shown an increased mortality in patients thus treated, we investigated the value of lidocaine as a protective agent against ventricular fibrillation related to myocardial ischemia in the in situ heart of anesthetized open-chest pigs subjected to transient total occlusion of the proximal left anterior descending coronary artery (LAD) under ventricular pacing at a constant high rate. Vulnerability to the fibrillatory process induced by coronary occlusion was assessed both by time to onset of ventricular fibrillation (TF) and by electrical ventricular fibrillation threshold (EFT) determined after coronary occlusions of increasing duration (30, 60, 120, 180 s). Monophasic action potential (MAP) was recorded concurrently in the nonischemic and ischemic areas. Lidocaine, even in relatively high doses (2-4 mg.kg-1), did not prolong TF, nor did it increase EFT. On the contrary, TF was significantly shortened and EFT was significantly decreased (15-30%) at the maximal concentrations of lidocaine, with return to control values in 40-60 min. Therefore, lidocaine tends to increase the risk of ischemic ventricular fibrillation (VF): It fails to control the extreme enhancement of excitability and worsens conduction disorders, even though it decreases normal conduction only slightly. Use of lidocaine against rhythm disorders in acute myocardial infarction (AMI), is at least debatable and probably contraindicated.

QRS prolongation as an indicator of risk of ischemia-related ventricular tachycardia and fibrillation induced by exercise

The majority of patients with serious ventricular arrhythmias induced by exercise have ischemic heart disease. These arrhythmias, however, develop only in a minority of the patients with coronary artery disease. The aim of this study was to investigate whether patients with ventricular tachycardia or fibrillation produced by exercise-induced ischemia exhibit any premonitory electrocardiographic indicators of arrhythmia propensity and whether arrhythmia suppression by myocardial revascularization abolished these changes. High-quality exercise electrocardiograms (50 mm/sec) from 30 case patients with ventricular tachycardia and fibrillation produced by exercise-induced ischemia were studied before and after surgical revascularization. These results were compared with those obtained from 30 control patients matched for age, sex, heart disease, and preoperative exercise capacity. The resting and peak exercise electrocardiograms were examined separately in a blinded manner with respect to QRS duration, ST-segment depression, and JT intervals. Patients with bundle branch block patterns were excluded. The QRS duration at rest was similar in case and control patients preoperatively and increased significantly with exercise in both groups. However, the QRS prolongation was larger in the group, in which it was 11 ± 3 msec compared with 4± 2 msec in the control group ( p = 0.043). QRS prolongation ≥15 msec predicted ischemia-related ventricular arrhythmias in 73% of the patients. After surgical revascularization, there was no QRS prolongation with exercise in either group. In both groups, the QRS prolongation was associated with significant ST-segment depression, which was larger in the case patients. After revascularization, the ST-segment depressios at peak xercise were smaller in both groups. The rate adaption of the JT-apex and JT-end intervals was similar in the case and control group both before and after surgery. The current findings confirm that QRS prolongation is a specific characteristic of ischemia. Furthermore, they indicate that the prolongation is greater in patients exhibiting ischemia-related ventricular tachycardia and fibrillation and that arrhythmia suppression by surgical revascularization is associated with a normalization of these changes. QRS prolongation ≥15 msec, in the absence of bundle branch block, may be a useful indicator of risk of ischemic ventricular tachycardia or fibrillation related to exercise.

In vitro effects of capsaicin: antiarrhythmic and antiischemic activity

The antiarrhythmic effects of vehicle (0.1% dimethyl sulfoxide: DMSO) or capsaicin were evaluated in isolated perfused rat and guinea pig heart preparations. In the rat, capsaicin reduced ischemic ventricular tachycardia from 100% in control to 0%, and ischemic ventricular fibrillation from 60% in control to 0% at 30 μM, and diltiazem reduced the incidence of ischemic ventricular tachycardia and ventricular fibrillation to 55% and 0%, respectively. Reperfusion ventricular fibrillation was reduced from 90% to 20% and 33% for capsaicin and diltiazem, respectively, at these concentrations. In isolated perfused globally ischemic rat hearts, antiischemic efficacy was assessed as a significant extension (36% and 50%) in time to contracture with 30 μM capsaicin and 1 μM diltiazem, respectively. Capsaicin reduced left ventricular developed pressure by 35% in non-ischemic rat hearts, and increased coronary flow by 40%. The increased time to contracture for either compound was not blocked by glyburide (0.1 μM) suggesting a lack of any involvement of ATP-sensitive K + channels. In isolated guinea pig hearts subjected to global ischemia, capsaicin and diltiazem reduced reperfusion ventricular fibrillation from 100% to 10% and 0% at 30 and 3 μM, respectively. Electrophysiologic evaluation in guinea pig papillary muscles using standard microelectrode techniques demonstrated significant ( P < 0.05) action potential durations at 90% repolarization shortening at 1 Hz by 9%, 28% and 39%, and 23%, 37% and 51% at 10, 30, and 100 μM of capsaicin or diltiazem, respectively. Unlike diltiazem, no changes in action potential duration were observed with capsaicin (up to 100 μM) at faster stimulation rates (5 Hz). In conclusion, capsaicin displays both antiarrhythmic and antiischemic efficacy. These data suggest that the effects of capsaicin are mediated primarily through block of Ca 2+ channels in these preparations.

Effect of potassium on the action of the KATP modulators cromakalim, pinacidil, or glibenclamide on arrhythmias in isolated perfused rat heart subjected to regional ischaemia

The ATP sensitive potassium channel openers cromakalim (n = 10) and pinacidil (n = 10), and a blocker of this channel, glibenclamide (n = 10), were studied in isolated perfused rat hearts subjected to regional ischaemia at varying concentrations (2 to 8 mM) of external potassium ([K+]o). Hearts were isolated and perfused on a Langendorff apparatus. Vehicle (0.1% DMSO), cromakalim (10 microM), pinacidil (10 microM), or glibenclamide (10 microM) were given 10 min before ischaemia. The left coronary artery was then occluded for 15 min and reperfused for 5 min. No agent caused more than a 10% change in heart rate. Both cromakalim and pinacidil increased (30%), and glibenclamide decreased (30%) coronary flow at 4 and 6 mM [K+]o. In the vehicle group, increases in [K+]o produced concentration dependent reductions in arrhythmia scores by decreasing ventricular fibrillation. No concentration dependent effects of [K+]o on ischaemic ventricular tachycardia was observed. Under ischaemic conditions, potassium channel openers and glibenclamide more markedly reduced ischaemic ventricular tachycardia and fibrillation relative to the effects of increased [K+]o. Ischaemic ventricular fibrillation was inversely related to changes in [K+]o, whereas effects on ventricular tachycardia were all-or-none. Neither potassium channel openers nor glibenclamide elicited significant proarrhythmic activity despite variations in [K+]o. These data suggest that both potassium channel openers and glibenclamide display potential antiarrhythmic activity through their ability to abolish two distinct arrhythmogenic mechanisms during ischaemia. It is also suggested that the underlying mechanisms of ventricular tachycardia and fibrillation are coupled during ischaemia in the rat.

Antiarrhythmic properties of specific inhibitors of sarcoplasmic reticulum calcium ATPase in the isolated perfused rat heart after coronary artery ligation

Objective. T. hypothesis tested was that sequestration of calcium by the sarcoplasmic reticulum and internal calcium oscillations may play a rote in the genesis of ischemic and reperfusion ventricular arrhythmias.Background. Previous data suggest that inhibition of the release of intracellular calcium from the sarcoplasmic reticulum by ryamodine may prevent ventricular fibrillation.Methods. The isolated Langendorff perfused rat heart was treated with two specific inhibitors of the calcium ATPase pump of the sarcoplasmic reticulum (thapsigargin [10−6mol/liter] or cyclopiazomic acid[10−7mol/liter]) for 5 min before left anterior descending coronary artery ligation was performed, One group of hearts was subject to 30 min of coronary artery ligation, and ischemic arrhythimias were monitored. In a second group, the incidence of reperfusion arrhythmias was measured after 10,15, 20, 25 and 30 min of coronary artery ligation.Results. Thapsigargin treatment during ischemia and reperfusion decreased the incidence of reperfusion ventricular fibrillation after 10 min of coronary artery ligation from 67% (n = 6) to 0% (n = 6) (p < 0.05), after 15 mm from 81% (n = 16) to 25% (n = 20) (p < 0.002) and after 20 mm of ischemia from 90% (n = 10) to 46% (n = 13) (p < 0.05). Thapsigargin treatment also decreased the incidence of ischemic ventricular fibrillation from 83% (a = 12) to 0% (n = 12) (p < 0.002). Cyclopiazonic acid treatment during ischemia and reperfusion likewise decreased the incidence of ischemic and reperfusion arrhythmias.Conclusions. The highly specific inhibitors of the calcium uptake pump of the sarcoplasmic reticulum—thapsigargin and cyclopiazonic acid—have antifibrilltory properties in the isolated perfused rat heart. They appear to act by restriction of calcium oscillations between the sarcoplasmic reticulum and the cytosol.

Attenuation of the ischaemia-induced fall of electrical ventricular fibrillation threshold by a calcium antagonist, diltiazem.

Calcium antagonists have been reported to decrease the incidence of sudden death in postinfarction management and vulnerability to fibrillation secondary to experimental coronary occlusion. In order to confirm such beneficial results regarding ischaemic ventricular fibrillation, the threshold intensity for fibrillation electrically induced with impulses of 100 ms and 180 beats.min-1 was measured during the course of ischaemias obtained by total occlusion of the left anterior descending coronary artery near its origin in open-chest pigs. The variations of electrical fibrillation threshold with ischaemia duration (30, 60, 120, 180, 240, 360 s) were compared under control conditions and after i.v. diltiazem (0.50 mg.kg-1 plus 0.02 mg.kg-1.min-1 over 25 min). Electrical fibrillation threshold was not influenced by diltiazem before, but raised during ischaemia, particularly from the 60th s (1.7 to 4.0 mA), with delay in the triggering of fibrillation which occurs when the fibrillation threshold falls down to the pacing threshold (0.2 to 0.3 mA). In 6 pigs out of 8, fibrillation was even avoided in the longest of the ischaemic periods considered (360 s), for fibrillation threshold ceased falling before reaching the critical level. These experimental results obtained with diltiazem are consistent with the clinical effectiveness of calcium antagonists recently observed in the prevention of postinfarction sudden death, provided that myocardial contractility is not too much adversely affected. But, left ventricular dP/dtmax was not reduced by more than 6.8% in the present experiments.

Individualised selection of antihypertensive therapy.

Theoretically, it should be possible to match the requirements of individual patients with the pharmacological and clinical properties of the large number of antihypertensive drugs now available. The concept of automatic sequential stepped-care therapy is now largely outdated, but therapy of clinically important hypertension must be initiated with one agent. Diuretics remain a first-line option in the elderly and in Black patients, as do calcium antagonists. Outcome trials are available only for the elderly, and in these the benefits of initial diuretic therapy are well documented. Nonetheless, diuretics may often need to be co-prescribed with a beta-blocker or an adrenergic modifier such as methyldopa. beta-Blockers are preferred in patients with ischaemic heart disease or enhanced adrenergic drive, while alpha-blockers are preferred in patients with blood lipid abnormalities or prostatic problems. Calcium antagonists or angiotensin converting enzyme (ACE) inhibitors are being increasingly used as initial therapy when quality of life is important and metabolic neutrality is required. Calcium antagonists are more likely to be effective first-line therapy than ACE inhibitors in patients with a high salt intake, in patients with Raynaud's disease, when angina pectoris is present, and in Black patients. ACE inhibitors are preferred for combination with diuretic agents, and in the presence of congestive heart failure or low salt intake. Experimentally, both calcium antagonists and ACE inhibitors can prevent ischaemic ventricular fibrillation and atheroma. Combination therapy between these 2 drug classes is gaining increasing acceptance because of these theoretical advantages.(ABSTRACT TRUNCATED AT 250 WORDS)

Protection against ischaemic ventricular fibrillation by blocking agents of myocardial cell calcium influx. Electrophysiological study in the pig in situ heart

Protection against ischaemic ventricular fibrillation by blocking agents of myocardial cell calcium influx. Electrophysiological study in the pig in situ heart

Polyunsaturated fatty acids and cardiac arrhythmia

lschacmic heart disease is a major cause of death in the western world. The manifestation of this disease can be chest pain, heart attack or sudden cardiac death. Coronary heart disease (CHD) mortality is positively related to dietary saturated fat [I] . Such diets are correspondingly low in polyunsaturated fatty acids, in particular linoleic acid [2]. There is now ample support from cross-sectional and longitudinal studies that diets low in polyunsaturated fatty acids, whether of plant or fish oil origin, i.e. n 6 or ti 3 , may predispose to CHD 131. Ventricular fibrillation, a chaotic disturbance of the normal rhythm of the heart, occurs during the early, and hence potentially reversible, phase of an acute heart attack and is the principal cause of sudden cardiac death. It is not possible t o predict those who are at risk of imminent sudden cardiac death, because of the nature of the disease. Most of our current knowledge of factors predisposing to ischaemic arrhythmias has been derived from animal models. Acute myocardial ischaemia is induced by ligation of a major coronary artery and the resultant early appearance of arrhythmias is similar to that in man (heart models are widely used t o test the efficacy of anti-arrhythmic treatment in vivo or in vitro). Detailed recommendations on the conduction of such experiments have been proposed to ensure adequate group sizes, uniform definition of serious arrhythmias and awareness o f the requirement to exclude the influence of confounding factors (i.e. ischaemic area, heart rate, etc.) 141. Early studies examined the effect of large dietary supplements of linoleic acid-rich oils. Linoleic acid-rich diets, fed over varying periods ( 12 weeks12 months), reduced ischaemic ventricular fibrillation in anaesthetized and conscious rats [ 5-71. The polyunsaturated to saturated fatty acid (I ' / .S) ratios were extremely high (/'/S 6) and bear little resemblance to the human diet ( / ' / .S= 0.3), and dietary vitamin and mineral intake are not always balanced. The mechanisms of the reduction in arrhythmias is assumed to be due t o increased availability of arachidonic acid in myocardial phospholipids for prostanoid synthesis [ 71.

Role of myelinated and nonmyelinated fibers of the vagus nerves in the development of ischemic ventricular fibrillation

Role of myelinated and nonmyelinated fibers of the vagus nerves in the development of ischemic ventricular fibrillation

Prevention of primary acute ischemic ventricular fibrillation by coronary sinus obstruction

Prevention of primary acute ischemic ventricular fibrillation by coronary sinus obstruction

Alinidine Reduces the Incidence of Ischemic Ventricular Fibrillation in a Conscious Canine Model, a Protective Effect Antagonized by Overdrive Atrial Pacing

The antiarrhythmic and antifibrillatory effects of the specific bradycardic agent alinidine were evaluated in a conscious canine model of myocardial infarction and sudden death, and by determination of ventricular fibrillation thresholds (VFT) in anesthetized dogs. Programmed electrical stimulation (PES) was performed in conscious animals, 3-5 days after a 2-h occlusion/reperfusion of the left anterior descending coronary artery (LAD). Dogs in which PES resulted in a reproducible nonsustained or sustained ventricular tachycardia (VT) were randomized to receive either intravenous alinidine (1 mg/kg, n = 11) or intravenous vehicle (n = 10). Programmed electrical stimulation and measurement of electrophysiologic parameters were repeated after 30 min, and the animals were entered into the sudden death protocol by introducing a 150 microA anodal current to the lumen of the left circumflex coronary artery (LCX) via a surgically implanted silver wire electrode. A second alinidine-treated group (n = 3) had heart rates controlled by atrial pacing during this period. Alinidine failed to prevent the programmed electrical induction of VT in 10 of 11 animals, but significantly reduced both sudden (less than 1 h ischemia) and 24-h mortality as compared to the ventricle group. Infarct sizes were similar in the two groups, but the ischemia-related increase in heart rate was attenuated (p less than 0.05) by alinidine and the onset of ischemia tended to be delayed. All of the atrial-paced animals died acutely. Heart rate decreased after alinidine (p less than 0.01), but apart from a single index of refractoriness, the drug was without electrocardiographic or electrophysiologic effects. Neither alinidine nor vehicle demonstrated any effect upon VFT in two groups of five animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of glibenclamide to protect against ischemic ventricular fibrillation in a canine model of myocardial infarction: Liguo Chi, Andrew C. G. Uprichard, Benedict R. Lucchesi. University of Michigan, Ann Arbor, MI. 48109

Failure of glibenclamide to protect against ischemic ventricular fibrillation in a canine model of myocardial infarction: Liguo Chi, Andrew C. G. Uprichard, Benedict R. Lucchesi. University of Michigan, Ann Arbor, MI. 48109