Ventricular Fibrillation Threshold Research Articles

Time course of fibrillation and defibrillation thresholds after an intravenous bolus of amiodarone--an experimental study.

Experimental studies have described an increase in ventricular fibrillation threshold (VFT) by intravenous amiodarone. The aim of this study was to examine the early time course of changes in VFT and defibrillation thresholds (DFT) after an intravenous bolus of amiodarone in an experimental pig model of transient myocardial ischemia. VFT and relative effective ventricular refractory period (ERP) were measured in 15 anaesthetized open-chest pigs after 3 min of regional coronary ischaemia before (time 0) and 2, 15, 30, 60, and 90 min after the intravenous injection of normal saline (group A, n = 5) or amiodarone, 5 mg/kg over 15 s (group B, n = 10). DFT was measured by increasing the strength of DC shocks until defibrillation was accomplished. Amiodarone caused an increase in VFT, starting at 2 min after the infusion (11.4 +/- 8.4 mA versus 9.2 +/- 4.6 mA, P = 0.03), became significant at 15 min (13.7 +/- 6.5 mA, P = 0.009), continued to rise at 30 min (34.2 +/- 28.7 mA, P = 0.03) and reached a plateau at 60 min (50.3 +/- 37.8 mA, P = 0.008). An increase was also observed in the ERP (204 +/- 25 ms at 2 min versus 197 +/- 26 ms at baseline, P = 0.074, 211 +/- 38 ms at 15 min, P = 0.084, 212 +/- 40 ms at 30 min, P = 0.037, 220 +/- 34 ms at 60 min, P = 0.002, and 227 +/- 32 ms at 90 min, P = 0.008). No change was observed in DFT after amiodarone administration. No significant change in VFT, ERP, or DFT occurred in the control group. In this porcine model, the intravenous administration of amiodarone increased VFT and ERP over 60 min after the injection, without effect on DFT.

LIPOSOME-ENCAPSULATED HEMOGLOBIN SUPPRESSES VULNERABILITY AND IMPROVES REVERSIBILITY OF VENTRICULAR FIBRILLATION IN ISCHEMIC CANINE MYOCARDIUM

Background. Liposome-Encapsulated Hemoglobin (NRC, Terumo Co, Ltd) has been modified to have a high O2-affinity (P50=10 mmHg, hNRC) to increase O2, delivery to hypoxic tissues such as ischemic myocardium. We hypothesize that targeted O2 delivery by hNRC may suppress arrhythmogenicity and improve reversibility in caine myocardium under ischemia. Methods. Empty liposome or hNRC (0.5% of body weight) was infused 5 minutes after occlusion of the left anterior descending artery (LAD) in open chest dogs. Ten minutes after LAD occlusion, programmed electric stimuli on the left ventricle were started to titrate vulnerability for ventricular fibrillation (VF). Once VF is induced, LAD occlusion is released and defibrillated by direct current cardioversion using 1, 3, 5, 7 and 101. Ten minutes after reperfusion, the same VF inductionheversal study was repeated using the alternate solution, empty liposome or hNRC. Results. While hNRC increased VF threshold and decreased energy for defibrillation in each animal (n=3), empty liposome failed to change vulnerability or reversibility of VF in any of the animals (n=3) regardless of order of administration, empty liposome or hNRC. Conclusion. Liposome-Encapsulated Hemoglobin with a high O2-affinity appears to be effective to suppress vulnerability, and improve reversibility of VF in ischemic canine myocardium. Optimal dose, timing and O2-affinity need to he defined.

Frequency dependence of the cardiac threshold to alternating current between 10 Hz and 160 Hz.

It is still unclear what fundamental criteria influence the ability of alternating current (AC) to induce ventricular fibrillation (VF) in vivo. As the VF threshold has a bowl-shaped relationship with frequency (showing a minimum threshold at some frequency), similar to the nervous system, one proposed model has assumed that the mechanisms underlying AC stimulation of nerves are at work for VF induction. More recent work has suggested a second approach, whereby a simple RC-like model is sufficient to understand the cardiac AC stimulation threshold's frequency dependence, suggesting that some unarticulated mechanism is at work for VF. The paper directly tests these two models. In 12 intact dogs and 20 intact guinea pigs, DC pulses were used to stimulate AC square and AC sine waves at 10, 20, 40, 80 and 160 Hz. All electrodes were endocardial, with the return electrode being on a paw or thorax. It was found that, for square and sine wave stimulation in both dogs and guinea pigs, the stimulation threshold increased monotonically with frequency from 10 Hz up to 160 Hz (p < 0.01 for dogs and guinea pigs). Between 80 and 160 Hz, the AC stimulation threshold doubled, exactly as predicted by an RC model. It was concluded that the AC stimulation threshold is not bowl-shaped and is best understood with an RC model. As the VF threshold does exhibit a bowl-shape with frequency, as opposed to the stimulation threshold which does not, the VF induction frequency dependence must have different origins.

Activation of peripheral δ opioid receptors eliminates cardiac electrical instability in a rat model of post-infarction cardiosclerosis via mitochondrial ATP-dependent K + channels

The effects of the selective delta-1 (δ 1) opioid receptor agonist, DPDPE, and the selective δ 2 opioid receptor agonist, DSLET, have been studied on the ventricular fibrillation threshold (VFT) in rats with an experimental post-infarction cardiosclerosis (CS). It has been found that CS induced a significant decrease in VFT. This CS-induced decrease in VFT was significantly reversed by intravenous administration of DPDPE (0.1 mg/kg) 10 min before VFT measurement. On the contrary, intravenous injection of DSLET (0.5 mg/kg) exacerbated the CS-induced cardiac electrical instability. Pretreatment with the selective δ opioid receptor antagonist, ICI 174,864 (0.5 mg/kg), completely abolished the changes in VFT produced by both DPDPE and DSLET. Previous administration of a nonselective peripherally acting opioid receptor antagonist, naloxone methiodide (5 mg/kg) also completely reversed the antifibrillatory action of DPDPE. Naloxone methiodide and ICI 174,864 alone had no effect on VFT. Pretreatment with the nonselective K ATP channel blocker, glibenclamide (0.3 mg/kg), or with the mitochondrial selective K ATP channel blocker, 5-hydroxydecanoic acid (5-HD, 5 mg/kg), completely abolished the DPDPE-induced increase in cardiac electrical stability. Glibenclamide and 5-HD alone had no effect on VFT. These results demonstrate that the δ opioid receptor plays an important role in the regulation of electrical stability in rats with post-infarction cardiosclerosis. We propose that peripheral δ 1 opioid receptor stimulation reverses CS-induced electrical instability via mitochondrial K ATP channels. On the contrary, δ 2 opioid receptor stimulation may exacerbate the CS-induced decrease in VFT. Further studies are necessary to determine the δ opioid receptor subtype which mediates the antifibrillatory effect of DPDPE and pro-fibrillatory effect of DSLET.

Electrical heterogeneity and arrhythmogenesis: importance of conduction velocity dispersion.

An experimental model of conduction velocity (CV) and refractory period dispersion was established to determine which variable is a determinant of myocardial vulnerability. Anesthetized swine were instrumented with a left anterior descending coronary artery catheter for regional infusion of lidocaine (n = 6), low-dose d-sotalol (n = 4), high-dose d-sotalol (n = 6), or saline (n = 6), to create dispersion in CV (lidocaine), refractoriness (d-sotalol), or neither (saline). Ventricular fibrillation thresholds (VFTs) and refractory periods were determined at five sites (one drug perfused, four non-drug perfused). CV was determined in one drug-perfused area (left ventricular epicardial apex) and one non-drug perfused area (right ventricular epicardial base). Lidocaine and low- and high-dose d-sotalol increased VFT when stimuli were delivered in the drug-perfused area. However, lidocaine decreased VFT when stimuli were delivered at non-drug perfused areas by an average of 52%. Neither d-sotalol dose affected VFT when stimuli were delivered in non-drug perfused areas. Lidocaine increased CV dispersion by 18-26 cm/s but did not alter refractoriness. Both d-sotalol doses increased dispersion in refractoriness by 15-27 ms but did not alter CV. Saline did not affect either variable. Regional lidocaine had profibrillatory effects when stimuli were delivered in non-drug perfused areas, whereas regional d-sotalol did not. Hence, CV dispersion is a more likely determinant of myocardial vulnerability than refractoriness.

Myocardial ischemic preconditioning has no effect on the ventricular fibrillation and defibrillation threshold: Experiment study

Myocardial ischemic preconditioning has no effect on the ventricular fibrillation and defibrillation threshold: Experiment study

The Acute Effects of Cigarette Smoking on the Heterogeneity of Ventricular Repolarization in Healthy Subjects

Background and Objectives:Although cigarette smoking is a known risk factor of sudden cardiac death, little is known about the effects of smoking on the heart. QT interval and QT dispersion prolongation have been associated with a lowered ventricular fibrillation threshold and the occurrence of sudden cardiac death. The aim of this study was to clarify the acute effects of cigarette smoking on the QT interval and dispersion. Subjects and Methods:The study population consist of 30 young male cigarette smokers, (with a mean age, and body mass index of 26±2 years;and 22.3±2.1 kg/m) respectively. Standard 12-lead surface electrocardiograms were recorded, at immediately before, during, and 5 minutes after, smoking 3 cigarettes. The RR interval, maximum and minimum QT intervals, QT dispersion (QT maximum-QT minimum), and the ratecorrected QT dispersion were all evaluated. Results:The RR interval was significantly reduced after 1 cigarette smoking (885±200 vs. 730±110 ms, p<0.01). The maximal QTBc interval was significantly longer after smoking 1 cigarette (415±21 vs. 442±21 ms, p<0.01), but the minimum QTBc interval showed no significant changes (369±23 vs. 376±22 ms, p=0.11). The QTBc dispersion (40±14 vs. 52±12 ms, p<0.01) and QTFc dispersion (42±14 vs. 58±14 ms, p<0.01) were significantly increased after smoking. Conclusion:In young males, smoking acutely increases the maximum QT interval and QT dispersion. These changes may explain the higher risk of sudden cardiac death. (Korean Circulation J 2003;33(1):58-62)

Impact of myocardial ischemia and reperfusion on ventricular defibrillation patterns, energy requirements, and detection of recovery.

Shocks that have defibrillated spontaneous ventricular fibrillation (VF) during acute ischemia or reperfusion may seem to have failed if VF recurs before the ECG amplifier recovers after shock. This could explain why the defibrillation threshold (DFT) for spontaneous VF appears markedly higher than for electrically induced VF. The DFT for electrically induced VF (E-DFT) was determined in 15 pigs before ischemia, followed by left anterior ascending or left circumflex artery occlusion. VF was electrically induced 20 minutes after occlusion, followed 5 minutes later by reperfusion. Whether spontaneous or electrically induced, VF during occlusion or reperfusion was treated with up to 3 shocks at 1.5xE-DFT. If all 3 shocks failed, shock strength was increased. Thirty minutes after reperfusion, the other artery was occluded and the protocol was repeated. Defibrillation was considered successful if postshock sinus/idioventricular rhythm was present for > or = 30 seconds. VF recurring within 30 seconds after the shock was considered immediate or delayed if the first postshock activation complex in a rapidly restored ECG recording was VF or sinus/idioventricular rhythm, respectively. Defibrillation efficacy at 1.5xE-DFT was significantly higher for electrically induced ischemic VF (76%) than for spontaneous VF (31%). The incidence of delayed recurrence after electrically induced nonischemic (3%) or ischemic (20%) VF was significantly lower than after spontaneous VF (75%). Mean VF recurrence time after spontaneous VF was 4.6+/-5.3 seconds. Spontaneous VF can be halted by a shock but then quickly restart before a standard ECG amplifier has recovered from postshock saturation, making it appear that the shock failed.

Intravenous bolus amiodarone administration exhibits an immediate and gradual increase in ventricular fibrillation threshold: experimental study

Intravenous bolus amiodarone administration exhibits an immediate and gradual increase in ventricular fibrillation threshold: experimental study

The renin-angiotensin system does not contribute to the endothelial dysfunction and increased infarct size in rats exposed to second hand smoke.

Both second hand smoke (SHS) and the renin-angiotensin system (RAS) contribute to endothelial dysfunction and increased infarct size in a rat ischaemia-reperfusion model. However, the potential interaction between SHS and the RAS is unknown. Eighty-four rats were randomised into four groups: group C was a normal control; L was given 40 mg/kg/day of losartan in drinking water; SC and SL were exposed to SHS (smoking chamber) and given regular water or 40 mg/kg/day of losartan in drinking water, respectively. After six weeks of pre-treatment, rats were subjected to 17 minutes of left coronary artery occlusion and 2 hours of reperfusion with haemodynamic and ECG monitoring. Haemodynamics were not significantly different among the four groups. Losartan increased the threshold for ventricular fibrillation (p=0.0001) and reduced spontaneous ventricular arrhythmias (p=0.002) during ischaemia-reperfusion, while SHS did not (p=0.713, 0.110), and there was no interaction between losartan and SHS. The maximal endothelium-dependent vasorelaxation induced by a calcium ionophore (A23187) was increased by losartan (p=0.007). Myocardial infarct size was smaller in the losartan groups (p=0.032), larger in the SHS groups (p=0.0001), and there was no significant interaction. In conclusion, losartan decreased infarct size and increased endothelium-dependent vasorelaxation. SHS exposure impaired endothelial function and increased infarct size. The effects of losartan and SHS were consistently independent of each other. These results suggest that the RAS does not contribute to the adverse effects of SHS.

Defibrillation energy requirements and electrical heterogeneity during total body hypothermia.

Determine the effects of hypothermia on defibrillation energy requirements and cardiac electrophysiology. Prospective randomized acute intervention trial. Medical center animal laboratory. Fifteen domestic farm swine. Swine were randomized to a hypothermia group (n = 8) or a control group (n = 7). All animals were instrumented with a transvenous defibrillation system connected to a defibrillator that delivers a biphasic-truncated waveform. Values for defibrillation energy requirements were measured at baseline (normothermia, 38-40 degrees C) and during treatment with total body hypothermia (30 degrees C) or no temperature change (sham). Hypothermia was induced by circulating ice-water through anterior and posterior surgical thermal blankets. Defibrillation energy requirement values at 20%, 50%, and 80% were determined by using an up/down method. In the hypothermia group, defibrillation energy requirement values at baseline did not significantly change during hypothermia (defibrillation energy requirements 50% = 14 +/- 2 J vs. 15 +/- 2 J, respectively). Similarly, the defibrillation energy requirement values in the control group did not change from baseline to sham phase (defibrillation energy requirements 50% = 12 +/- 1 J vs. 13 +/- 1 J, respectively). Hypothermia profoundly affected cardiac electrophysiology, decreasing ventricular fibrillation threshold by 72%, conduction velocity by 25% (p < .01), and tissue excitability, while it prolonged ventricular repolarization and refractoriness by 7.5% to 15%, respectively (p < .05). Total body cooling to 30 degrees C was highly arrhythmogenic, although this unstable electrophysiological state did not alter ventricular defibrillation energy requirements. These data suggest that hypothermia may be used to slow metabolic processes without concern over the ability to successfully defibrillate and treat hypothermia-induced arrhythmias.

Restoration of normal ventricular electrophysiology in renovascular hypertensive rabbits after treatment with losartan.

Left ventricular hypertrophy (LVH) is associated with abnormal ventricular electrophysiology. We have shown complete regression of LVH and normalization of ventricular electrophysiology in renovascular hypertensive rabbits treated with captopril. To determine if angiotensin II type 1 receptor (AT1) blockade produces the same benefit, we treated hypertensive rabbits with losartan for 3 months. LVH was evaluated by heart-to-body weight ratio (HW/BW). Vulnerability to ventricular arrhythmia was assessed by ventricular fibrillation threshold (VFT) and dispersion of effective refractory period (ERP). The electrical properties of single left ventricular myocytes were characterized by action potential duration at 90% repolarization (APD90) and inward rectifier K+ current (I(K1)) density. Hypertensive rabbits treated with vehicle (LVH/Vehicle) had higher mean arterial pressure (MAP, 81+/-2 vs. 60+/-2 mm Hg) and HW/BW (2.71+/-0.07 vs. 1.97+/-0.04 g/kg), lower VFT (20+/-1 vs. 39+/-2 mA), larger dispersion of ERP (34+/-3 vs. 14+/-3 ms), longer APD90 (187+/-6 vs. 162+/-6 ms) and lower I(K1) density compared with control rabbits. Hypertensive rabbits treated with losartan (LVH/Losartan) had HW/BW (2.36+/-0.06 g/kg) between those of LVH/Vehicle and control rabbits, whereas MAP (65+/-2 mm Hg), VFT (34+/-2 mA), dispersion of ERP (19+/-1 ms), APD90 (160+/-6 ms), and I(K1) density were significantly different from LVH/Vehicle but similar to control. We conclude that AT1 blockade in renovascular hypertensive rabbits normalizes ventricular electrophysiology.

Optimal pH strategy for hypothermic circulatory arrest

I t was several years after the beginning of open heart surgery before hypothermia was introduced as a component of cardiopulmonary bypass (CPB). At about this time in the late 1950s, blood gas analysis became more readily available and revealed a surprising fact: when blood is cooled by the heat exchanger in the circuit, pH changes in an alkaline direction. The usual response in the 1960s and 1970s was to compensate for this alkaline shift by adding carbon dioxide, a technique that has come to be known as the pH-stat strategy. This also had what was perceived to be an important advantage in that carbon dioxide is a potent cerebral vasodilator. It was believed that adding carbon dioxide would increase the safety margin for cerebral oxygen supply and reduce the risk of major neurologic injury, which was all too common in the early years of CPB. In the late 1970s and early 1980s, a number of reports appeared that questioned whether the pH-stat strategy was indeed the correct response to the alkaline shift with hypothermia. It was found that cold-blooded vertebrates simply allow their blood pH to drift in an alkaline direction. It appeared that this alpha-stat strategy optimized intracellular enzyme function. Studies in dogs showed that the threshold for ventricular fibrillation was lower with the more acidotic pH-stat strategy. It also became increasingly apparent that the most common cause of neurologic injury in adults was embolic stroke rather than the global hypoxic insults that had been more common in the early years of bypass. Even if there was not a definite stroke, psychologists could measure important deficits in cognitive function in a remarkably high percentage of adult patients after heart surgery. Microembolization of atherosclerotic debris, fat, and air was probably the cause. It followed that if cerebral blood flow was increased to excessive, “luxuriant” levels by adding carbon dioxide, then injury would be increased. Randomized trials of neuropsychometric outcome have confirmed just this. Three of four trials demonstrated an improved cognitive outcome in adults undergoing continuous mildly or moderately hypothermic CPB with the alpha-stat strategy relative to the pH-stat strategy. The shift in pH strategy from pH-stat to alpha-stat was applied just as enthusiastically to children as adults in the early 1980s, although there was little evidence to support macroembolization or microembolization as important mechanisms of injury in this population. Apart from their lack of atherosclerotic vessels and calcified valves, in contrast to adults, children have intracardiac problems that require exposure through small incisions. Blood returning to the heart impairs exposure and can result in less accurate repair. This collateral return is almost always increased in patients who have cyanotic conditions and steals an important proportion of blood from the systemic circulation. A common response of surgical teams is to reduce flow and temperature or to apply deep hypothermic circulatory arrest (DHCA). Is a pH strategy that reduces cerebral blood flow the appropriate one under such circumstances? The article by Priestley and associates1 in this issue of the Journal is further evidence that the alpha-stat strategy results in a greater degree of cerebral injury when DHCA is used. Priestley and colleagues1 subjected 5to 10-day-old piglets to 90 minutes of DHCA at a brain temperature of 20°C. Animals were hemodiluted to a hematocrit value of 20% to 25% and were cooled at a flow rate of 100 mL kg 1 min . After being rewarmed, the animals were taken off CPB and were allowed to survive for the next 48 hours. They were assessed for neurologic injury by means of a graded scoring system by a blinded observer. Brain histologic features were also From Children’s Hospital (Cardiovascular Surgeon-in-Chief) and Harvard Medical School (William E. Ladd Professor of Surgery), Boston, Mass.

A placebo controlled evaluation of the antifibrillatory effects of carvedilol

This article evaluates the antifibrillatory effects of carvedilol 5 mg/kg and vehicle (dimethyl-formamide) over time. Sprague-Dawley rats were anesthetized and intubated. They underwent baseline ventricular fibrillation threshold (VFT) determination and then received 1 of the 2 treatments (n = 10/group) over 8 minutes. VFT and determinations were performed at 2, 7, 15, 30, 45, and 60 minutes postinfusion. Carvedilol significantly increased the VFT at 2, 7, 15, 30 minutes versus baseline and the vehicle control group. Carvedilol significantly reduced the heart rate and the mean arterial pressure at every evaluable time point versus baseline and vehicle control. Carvedilol showed significant antifibrillatory effects versus baseline and vehicle for the first 30 minutes but not thereafter, even though the heart rate and mean arterial pressure remain significantly reduced.

Effects of EGIS-7229 (S 21407), a novel class III antiarrhythmic drug, on myocardial refractoriness to electrical stimulation in vivo and in vitro.

The I(Kr) blocker EGIS-7229 (S-21407), displays class Ib and class IV effects that may alter its pharmacologic profile compared with those of pure I(Kr) blockers. Therefore, the concentration- and frequency-dependent effects of EGIS-7229, and of the I(Kr) blockers d,l-sotalol and dofetilide, on the effective refractory period (ERP) were measured in isolated right ventricular papillary muscle of the rabbit in vitro. The effects of these drugs on right ventricular fibrillation threshold (RVFT) at increasing intravenous doses were also determined in anesthetized cats. Dofetilide and d,l-sotalol increased ERP in a concentration-dependent manner (dofetilide: 3-100 nM; d,l-sotalol: 3-100 microM) with strong reverse frequency dependence at high concentrations. EGIS-7229 concentration dependently lengthened ERP at 1-30 microM. Its effect on ERP was clearly reverse frequency dependent at 3 microM, but this feature of the drug diminished at 10 microM and was not apparent at 30 microM. The effect of EGIS-7229 (30 microM) on ERP was devoid of reverse frequency dependence as it was more effective (31%) than dofetilide (16 %) at high-pacing rate (3 Hz), whereas it was less effective (50%) than dofetilide (70%) at slow-pacing rate (1 Hz). Reverse frequency-dependent ERP effect of dofetilide (100 nM) was similarly abolished by the addition of lidocaine (30 microM). EGIS-7229 (1-8 mg/kg iv), d,l-sotalol (1-8 mg/kg iv), and dofetilide (10-80 microg/kg iv) caused a dose-dependent increase in RVFT. The minimum effective dose of d,l-sotalol and EGIS-7229 was 1 and 2 mg/kg, respectively, whereas that of dofetilide was 10 microg/kg. EGIS-7229 induced a smaller peak effect in RVFT than sotalol or dofetilide. In conclusion, EGIS-7229 markedly increased refractoriness to electrical stimulation in vitro and in vivo. Compared with pure I(Kr) blockers, the benefits of EGIS-7229 seem to be a greater lengthening of effective refractory period at rapid stimulation rates, suggesting a strong antiarrhythmic action, and a smaller effect at slow stimulation rates, suggesting low potential to induce early afterdepolarizations.

P HYSICIAN I NTERPRETATION AND Q UANTITATIVE M EASURES OF E LECTROCARDIOGRAPHIC V ENTRICULAR F IBRILLATION W AVEFORM

Objectives. The characteristics of the ventricular fibrillation (VF) waveform may influence treatment decisions and the likelihood of therapeutic success. However, assessment of VF as being fine or coarse and the distinction between fine VF and asystole are largely subjective. The authors sought to determine the level of agreement among physicians for interpretation of varying VF waveforms, and to compare these subjective interpretations with quantitative measures. Methods. Six-second segments of waveform from LIFEPAK 300 units were collected. Fifty segments, including 45 VF and five ventricular tachycardia (VT) distracters, were graphed to simulate rhythm strips. These waveforms were quantitatively described using scaling exponent, root-mean-squared amplitude, and centroid frequency. Thirty-two emergency medicine residents were asked to interpret the arrhythmias as VT, “coarse” VF, “fine” VF, or asystole. Their responses were compared with the qantitative measures. Interphysician agreement was assessed with the kappa statistic. Results. One thousand four hundred forty interpretations were analyzed. There was fair agreement between physicians about the classification of arrhythmias (κ = 0.39). Mean values associated with coarse VF, fine VF, and asystole differed in all three quantitative measure categories. The decision whether to defibrillate was highly correlated with the distinction between VF and asystole (Pearson chi-square = 1,170.40, df = 1, p[two-sided] < 0.001). Conclusions. With only fair agreement on the threshold of fine VF and asystole, defibrillation decisions are largely subjective and caregiver-specific. These data suggest that quantitative measures of the VF waveform could augment the current standard of subjective classification of VF by emergency care providers.

Differential modulation of electrocardiographic indices of ventricular repolarization dispersion depending on the site of pacing during premature stimulation.

Dispersion of ventricular repolarization has been shown to increase with premature stimulation. Moreover, a straight correlation between the amount of dispersion of repolarization and the vulnerability to ventricular fibrillation was reported. On the other hand, differences between right ventricular (RV) and left ventricular (LV) fibrillation threshold have been reported. However, no data exist regarding the influence of the site of stimulation on modulation of dispersion of repolarization. In the present study, several ECG indices of dispersion of repolarization, as a function of the coupling interval and the site of stimulation, were evaluated in a modified Langendorff-perfused rabbit heart (n = 12), with a 5 x 8 array of a simulated body surface unipolar lead system. As the coupling interval was shortened, a biphasic modulation of dispersion of repolarization was found when stimuli were elicited at the LV. In contrast, when the heart was paced from the RV, the dispersion increased monotonically as coupling interval was shortened. A differential behavior of the modulation of dispersion of repolarization was found as a function of the site of stimulation.

Ventricular fibrillation threshold and local dispersion of refractoriness in isolated rabbit hearts with left ventricular dysfunction.

Patients with congestive heart failure or left ventricular dysfunction (LVD) have a high incidence of ventricular tachyarrhythmias and sudden cardiac death. In addition to structural, metabolic and neuroendocrine changes, mechanoelectrical feedback may play a role in arrhythmogenesis in heart failure. Three groups of rabbits (n = 10 for each) were studied: chronic coronary ligation with ejection fraction (EF) > or = 0.45 or < 0.45, and sham-operated controls. Ventricular fibrillation (VF) thresholds were measured at LV pressures of 0 and 40 mm Hg during modified Langendorff perfusion. Intervals between local activations during VF (VFI) were used as an index of refractoriness. Global dispersion was expressed as coefficient of variation of VFI; local dispersion by maximum difference in VFI between adjacent sites. Median VF threshold was lower at 0 mm Hg in the lower EF group compared to controls (30 vs. 67.5 mA, P<0.05). VF threshold in control hearts was lower at 40 mm Hg than at 0 mm Hg (P<0.01), but there was no further reduction in threshold in LVD hearts at 40 mm Hg. Global dispersion of VFI did not differ significantly between groups. Local dispersion of VFI in the lower EF group was greater than in controls at 0 mm Hg in the infarct border zone (P<0.05). At 40 mm Hg, local dispersion of VFI in zones bordering and remote from the infarct were greater in both LVD groups than in controls (P<0.05). Local inhomogeneity of refractoriness is more marked in the infarct border zone, but latent abnormalities are evident in normal myocardium of rabbits with left ventricular dysfunction and are revealed by left ventricular distension.

Effects of ICI 118.551, a selective beta-2 adrenergic blocking agent on the guinea pig cardiac excitability and ventricular fibrillation threshold.

In isolated guinea pig perfused hearts ICI 118.551, a selective beta 2 adrenoceptor antagonist, induced transient ventricular extrasystoles. Following the termination of the perfusion, a very significant increase of both the ventricular fibrillation threshold and the refractory periods were measured. In guanethidine pretreated hearts, ICI 118.551 failed to induce premature beats. At the same time the fibrillation threshold and refractory periods exhibited a very significant decrease. The perfusion of equimolecular concentration of metoprolol, a beta-1-adrenoceptor antagonist, and (+) propranolol, a quinidine-like compound, induced, in most experimental settings, similar results as ICI 118.551. Thus, besides its beta-2-adrenoceptor antagonist properties, ICI 118.551 presented other pharmacological actions.

Nonplatelet effects of aspirin during acute coronary occlusion: electrophysiologic and cation alterations in ischemic myocardium.

Mortality after acute myocardial ischemia has been reduced by aspirin (ASA) but mechanisms other than the antiplatelet effect have not been established. This article evaluates an antiarrhythmic action during sympathetic stimulation in the intact anesthetized dog with and without ischemia. The ventricular fibrillation threshold (VFT) was examined before and after epinephrine (E) in normals (group I). A VFT reduction during E was normalized after 1 week of ASA (P<.01). Regional myocardial ischemia for 1 hour resulted in similar hypoperfusion in controls of group II and after ASA. Action potential responses in isolated superfused ischemic tissue showed prolonged repolarization (APD90) in response to E, which was normalized after ASA (P<.01). To assess the antiarrhythmic role of the anion in group III, Na salicylate was given. During 1 hour of ischemia, the VF incidence was reduced and cation abnormalities diminished in ischemic myocardium compared with untreated ischemia. ASA antagonizes the reduction of the VFT induced by catecholamine in normals as well as the repolarization abnormality elicited by E during acute ischemia. The salicylate anion appears to be the active component in view of the efficacy in preventing VF during the early ischemic period.