Ventricular Fibrillation In Dogs Research Articles

Blood cardioplegia reduces intraoperative ventricular fibrillation and transfusion requirements compared to crystalloid cardioplegia in canine mitral valve repair.

Cardioplegic solutions are indispensable for open-heart surgeries, including mitral valve repair (MVR), a potentially curative treatment for myxomatous mitral valve disease in dogs. However, procedural methodologies are not fully established, and complications are yet to be comprehensively understood. Cardioplegic solutions contain various substances to protect the myocardium under temporal cardiac arrest. Nevertheless, ventricular fibrillation (VF) occurs as a common complication after releasing the crossclamp. Based on these backgrounds, the search for optimal cardioplegic solutions in dogs undergoing MVR is an urgent issue. This study aims to evaluate the occurrence of VF in dogs treated with blood cardioplegia (BCP) versus crystalloid cardioplegia (CCP) during MVR. A total of 251 client-owned dogs who underwent MVR from November 2015 to November 2017 were included. We retrospectively assessed the relationship between VF and type of cardioplegia (CCP or BCP) based on surgical records, including VF incidence, transfusion use, crossclamp time, and echocardiographic measurements. Logistic regression analysis showed that the CCP group was associated with the occurrence of VF (OR, 2.378; CI, 1.133-4.992; P = .022). In addition, the CCP group was associated with transfusion use (OR, 2.586; CI, 1.232-5.428, P = .022). There was no difference between the groups for the pre- and postoperative echocardiographic measurements. The BCP group had a lower incidence of VF and less transfusion use than the CCP group. This finding indicates that BCP may be a superior cardioplegic technique for MVR in dogs.

Cardiac remodeling accompanied by increased arrhythmia susceptibility in a dog model of chronic high-intensity endurance training

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by NKFIH grants (K-19992, K-135464) and GINOP-2.3.2-15-2016-00047. Background Despite the cardiovascular benefits of regular physical exercise, chronic high-level exercise can evoke malignant arrhythmias, including ventricular fibrillation and even sudden cardiac death, especially in young top athletes. In some cases the underlying mechanisms are unclear. Objectives The goal of this study was to assess mechanisms underlying cardiac structural-electrical changes and arrhythmia vulnerability by high-level vigorous exercise training in animal species that are electrophysiologically relevant to the human heart. Methods Beagle dogs were randomly assigned to matched sedentary (Sed) or intensive exercise-training (Ex) groups (n=12-12). Ex dogs underwent a 4-month-long intensive treadmill-running protocol (5 days a week, 6 hours a day at a speed of 14-21 km/h with an inclination from 5% to 12%). In vivo echocardiography and electrophysiological measurements were performed. Proarrhythmic sensitivity was tested and the autonomic alterations were examined. At study end, arrhythmia susceptibility was tested with high-frequency burst stimulation in open-chest anaesthetized dogs. This was followed by cardiac excision and cardiomyocyte isolation, formalin preservation for histology, snap-freezing in liquid nitrogen for molecular biology. Results The vigorous endurance training was resulted in increased left ventricular end-diastolic diameter, increased septal wall thickness and greater left ventricular mass index (Ex vs. Sed: 98±12 vs. 136±7 g/m2, p<0.05). Some degree of enhanced fibrosis was observed. Endurance training decreased heart rate both in whole animal and in vitro dog experiments. ECG recordings presented enhanced heart rate variability parameters, prolonged PQ (Ex vs. Sed: 98.3±2.9 vs. 116.7±3.6 ms, p<0.05), QRS (Ex vs. Sed : 60.5±2.4 vs 70.8±1.6 ms, p<0.05), QTc (Ex vs. Sed: 213.6±2.8 vs. 237.1±3.4 ms, p<0.05), Tp-Te (Ex vs. Sed: 27.9±2.5 vs.36.5±1.7 ms, p<0.05) intervals associated with significantly enhanced QT interval variability (eg. Ex vs. Sed: QT-STV, 2.5±0.2 vs. 3.6±0.4 ms, p<0.05), reflecting elevated level of repolarization dispersion. Ectopic activity was also enhanced in the exercised dog ventricle. Atropine treatment resulted in moderate heart rate increase in the Ex animals. Chronic endurance exercise elevated the proarrhythmic risk and consequent ventricular fibrillation in dogs subjected to burst electrical stimulation. Conclusion We developed a new animal model that shares similarities with the human endurance-trained athlete’s heart. The model represents increased arrhythmia susceptibility, an important clinical paradigm, and explores potential underlying mechanisms, including vagal enhancement, increased repolarization dispersion and enhanced fibrotic changes. Increased arrhythmia susceptibility is supported by the enhanced arrhythmia incidence in the exercised group. Similar changes may be present in young human top athletes, however further investigations are required.

The development of ventricular fibrillation as a complication of pericardiectomy in 16 dogs

To describe the clinical characteristics, perioperative protocols, and outcomes in dogs diagnosed with ventricular fibrillation (VF) while undergoing pericardiectomy. Retrospective, multi-institutional study. Sixteen client-owned dogs. Cases were accrued through a listserve request posted to 3 subspecialty veterinary societies. Dogs were included if they developed VF during a pericardiectomy performed through an open or thoracoscopic approach. Data collected included signalment, history and physical examination, surgical approach, histopathology, treatment, and outcome. Indications for pericardiectomy included idiopathic chylothorax (n=7), neoplasia (4), idiopathic pericardial effusion (4), and foreign body granuloma (1). Surgical approaches included thoracoscopy (12), intercostal thoracotomy (3) and median sternotomy (1). Electrosurgical devices were used to complete at least part of the pericardiectomy in 15 of 16 dogs. Ventricular fibrillation appeared to be initiated during electrosurgical use in 8/15 dogs. However, in 5/15 dogs it was not obviously associated with electrosurgical use. In 3/16 dogs the timing of initiation of VF was unclear. In 7/16 dogs, cardiac arrhythmias were noted prior to the development of VF. Fourteen of 16 dogs died from intraoperative VF. In most dogs ventricular fibrillation was a fatal complication of pericardiectomy. Ventricular fibrillation might be associated with the use of electrosurgical devices and cardiac manipulation during pericardiectomy although a causal link could not be established from the data in this study. Surgeons must be aware of the risk of VF during pericardial surgery. Electrosurgery might need to be used judiciously during pericardiectomy, particularly in dogs exhibiting cardiac arrythmias.

Dominant and Non-Dominant Frequency Structure of Evoked Ventricular Fibrillation in Dogs with Myocardial Ischemia.

The first 10 min of electrically provoked ventricular fibrillation in dogs with ischemic heart disease were characterized by organized myocardial activity evidenced by the dominant ECG frequency structure. During the first 2 min of ventricular fibrillation, low-frequency oscillations (4-7 Hz) dominated, while on min 3 to 10 after the onset of fibrillation, the dominant frequencies were low and medium (4-12 Hz). After 10-min fibrillation, the oscillations became non-dominant. Thus, ischemic myocardium maintains the organized structure of ventricular fibrillation for the first 10 min, which is important for the development of automatic diagnostics of abnormal cardiac activity in humans.

Effects of a novel amiodarone-like compound SAR114646A on the pig atrium and susceptibility to ventricular fibrillation in dogs and pigs

Amiodarone is one of the most effective antiarrhythmic drugs. However, poor solubility of this compound has limited its intravenous application. SAR11464A is a water-soluble amiodarone-like drug that lacks iodine and inhibits multiple cardiac ion channels in vitro. This study evaluated the antiarrhythmic efficacy of this drug in vivo. In porcine studies, atrial effective refractory period (AERP) was measured in pentobarbital-anesthetized thoracotomized pigs and atrial fibrillation (AF) was induced by a premature beat. Ventricular fibrillation (VF) was induced via either burst pacing or programmed electrical stimulation (a series of progressively shorter beats, S1-S5). In canine studies, VF was induced by a 2-min occlusion of the left circumflex coronary artery during the last minute of exercise in dogs with healed myocardial infarctions (n = 8). One week later, this test was repeated after pretreatment with SAR114646A (3.0 mg/kg, i.v., slow bolus). SAR114646A produced a significant dose-dependent prolongation of AERP, inhibited AF induced by a premature stimulus, and electrically induced VF in anesthetized pigs. At 1.0 and 3.0 mg/kg, i.v., it was superior to amiodarone, dofetilide, and flecainide. In dogs, SAR114646A did not alter any ECG parameter including QTc (control, 236.9 ± 8.5ms vs. SAR, 237.2 ± 3.5ms) but significantly reduced the incidence of VF, protecting six of eight animals (Fisher's exact test, P = 0.01). SAR114646A was effective against both atrial and ventricular arrhythmias without altering ventricular repolarization. These data suggest that the amiodarone-like drug SAR114646A may be an effective antiarrhythmic intervention that does not adversely prolong ventricular repolarization.

Activation becomes highly organized during long-duration ventricular fibrillation in canine hearts

Little is known about the three-dimensional (3-D) intramural activation sequences during long-duration ventricular fibrillation (VF), including the role of the subendocardium and its Purkinje fibers (PFs) in long-duration VF maintenance. Our aim was to explore the mechanism of long-duration VF maintenance with 3-D electrical mapping. We recorded 10 min of electrically induced VF in the left ventricular anterior free wall of six 10-kg, open-chest dogs using a 3-D transmural unipolar electrode matrix (9 x 9 x 6, 2-mm spacing) that allowed us to map intramural activation sequences. At 2.5 + or - 1.8 min of VF, although the body surface ECG continued to exhibit a disorganized VF pattern, intramurally a more organized, synchronous activation pattern was first observed [locally synchronized VF (LSVF)]. This pattern occurred one or more times in all dogs and was present 33.4 + or - 31.4% of the time during 5-10 min of VF. As opposed to the preceding changing complex activation sequences of VF, during LSVF, wavefronts were large and highly repeatable near the endocardium, first exciting the endocardium almost simultaneously and then rapidly spreading toward the epicardium with different levels of conduction block en route. During LSVF, PF activations always preceded working myocardium activations near the endocardium. In conclusion, long-duration VF in dogs frequently becomes highly organized in the subendocardium, with activation fronts arising in this region and passing intramurally toward the epicardium, even though the surface ECG continues to exhibit a disorganized pattern. PFs appear to play an important role during this stage of VF.

Dynamic Mechanism for Initiation of Ventricular Fibrillation In Vivo

Dynamically induced heterogeneities of repolarization may lead to wave-front destabilizations and initiation of ventricular fibrillation (VF). In a computer modeling study, we demonstrated that specific sequences of premature stimuli maximized dynamically induced spatial dispersion of refractoriness and predisposed the heart to the development of conduction block. The purpose of this study was to determine whether the computer model results pertained to the initiation of VF in dogs in vivo. Monophasic action potentials were recorded from right and left ventricular endocardium in anesthetized beagle dogs (n=11) in vivo. Restitution of action potential duration and conduction time and the effective refractory period after delivery of the basic stimulus (S(1)) and each of 3 premature stimuli (S(2), S(3), S(4)) were determined at baseline and during verapamil infusion. The effective refractory period data were used to determine the interstimulus intervals for a sequence of 4 premature stimuli (S(2)S(3)S(4)S(5)=CL(VF)) for which the computer model predicted maximal spatial dispersion of refractoriness. Delivery of CL(VF) was associated with discordant action potential duration alternans and induction of VF in all dogs. Verapamil decreased spatial dispersion of refractoriness by reducing action potential duration and conduction time restitution in a dose-dependent fashion, effects that were associated with reduced inducibility of VF with CL(VF). Maximizing dynamically induced spatial dispersion of repolarization appears to be an effective method for inducing VF. Reducing spatial dispersion of refractoriness by modulating restitution parameters can have an antifibrillatory effect in vivo.

Chemical ablation of the Purkinje system causes early termination and activation rate slowing of long-duration ventricular fibrillation in dogs

Endocardial mapping has suggested that Purkinje fibers may play a role in the maintenance of long-duration ventricular fibrillation (LDVF). To determine the influence of Purkinje fibers on LDVF, we chemically ablated the Purkinje system with Lugol solution and recorded endocardial and transmural activation during LDVF. Dog hearts were isolated and perfused, and the ventricular endocardium was exposed and treated with Lugol solution (n = 6) or normal Tyrode solution as a control (n = 6). The left anterior papillary muscle endocardium was mapped with a 504-electrode (21 x 24) plaque with electrodes spaced 1 mm apart. Transmural activation was recorded with a six-electrode plunge needle on each side of the plaque. Ventricular fibrillation (VF) was induced, and perfusion was halted. LDVF spontaneously terminated sooner in Lugol-ablated hearts than in control hearts (4.9 +/- 1.5 vs. 9.2 +/- 3.2 min, P = 0.01). After termination of VF, both the control and Lugol hearts were typically excitable, but only short episodes of VF could be reinduced. Endocardial activation rates were similar during the first 2 min of LDVF for Lugol-ablated and control hearts but were significantly slower in Lugol hearts by 3 min. In control hearts, the endocardium activated more rapidly than the epicardium after 4 min of LDVF with wave fronts propagating most often from the endocardium to epicardium. No difference in transmural activation rate or wave front direction was observed in Lugol hearts. Ablation of the subendocardium hastens VF spontaneous termination and alters VF activation sequences, suggesting that Purkinje fibers are important in the maintenance of LDVF.

The Long and the Short of Long and Short Duration Ventricular Fibrillation

See related article, pages 1256–1264 The mechanisms behind the complex activation sequences during ventricular fibrillation (VF) have been the topic of intense research over many years. Experimental studies in animal models of VF, as well as clinical studies of human VF,1–8 have provided a wealth of data on the nature of electric activity in the fibrillating heart. Supplemented by computer simulations and a theoretical framework of wave propagation in excitable media,9,10 our community has amassed significant insights into the mechanisms that lead to the degradation of electric activity into VF and of VF maintenance. However, the majority of these studies have been devoted to VF mechanisms in the short time period after VF onset (short-duration VF, lasting less than 1 minute). In an episode of cardiac arrest outside of the hospital, the median time to delivery of the first defibrillation shock is 4.4 minutes,11 with VF episodes often lasting as long as 10 minutes (long-duration VF); over this period, the heart becomes ischemic while being subjected to excessively high excitation rates. Changes in the electrophysiological properties of the myocardium take place over these long-duration VF episodes. This is reflected in the altered outcome of a defibrillation shock, with survival rates decreasing rapidly with the increase in minutes spent in VF.12 Similarly, the guidelines for optimal resuscitation therapy differ depending on VF duration: immediate defibrillation is prescribed if time from VF onset is less than 4 or …

Adenosine concentration in great cardiac vein is increased in non-ventricular fibrillation dogs

This study was conducted to clarify the relationship between myocardial endogenous adenosine concentration in the great cardiac vein during ischemia and reperfusion-induced ventricular fibrillation (VF) and the occurrence rate of ischemia and reperfusion-induced VF. Sixty anesthetized mongrel dogs were subjected to 10-min left anterior descending artery occlusion and reperfusion. Blood from the great cardiac vein was sampled for the determination of adenosine and catecholamine concentrations. Hemodynamic parameters (blood pressure, lift ventricular dp/dt, left ventricular end-diastolic pressure, and cardiac output) were monitored throughout the experimental period. During coronary occlusion and reperfusion, VF occurred in 25 dogs (VF group). Ventricular fibrillation did not occur in 35 other dogs (non-VF group). Adenosine concentration in the great cardiac vein before the coronary occlusion did not differ between the two groups. However, the adenosine concentration in the great cardiac vein of the non-VF group significantly increased compared with that of the VF group (2,343 vs 65 pmol/ml, P = 0.026) during coronary occlusion and reperfusion. In contrast, hemodynamic parameters did not differ between the two groups. The study results demonstrated that adenosine concentration in the great cardiac vein was higher in the non-VF group than in the VF group, suggesting that myocardial endogenous adenosine may have a role in the suppression of ischemia and reperfusion-induced VF in dogs.

Runaway Pacemakers in Ventricular Fibrillation

Arunaway pacemaker is a malfunctioning pacemaker that paces the heart at rapid rates. A report from Australia 30 years ago1 described a patient with runaway pacemaker that paced the ventricles at 280 bpm. The patient survived only because one of the coauthors alertly cut the pacemaker wires to disconnect the high-frequency focal source from the myocardium. In this issue of Circulation , Thomas et al2 report that they occasionally detected sustained high-frequency sources during ventricular fibrillation (VF) in sheep with myocardial infarction (MI). Specifically, in 3 of 12 hearts, they detected periodic high-frequency activations at 1.3% of the intramural electrodes sampled. The authors propose that these findings support the hypothesis3 that a relatively stable periodic source (“mother rotor”), with fibrillatory conduction block occurring in the remainder of the ventricle, may be the mechanism of VF in this model. This mother rotor mechanism of fibrillation contrasts with the multiple wavelet mechanism, in which all rotors are unstable and wavebreak is the engine driving fibrillation. Both mechanisms of fibrillation have been documented in various settings,4 but controversy exists over which is the most common in and clinically relevant to diseased human hearts. This issue has therapeutic implications because it has been suggested that ablation of the mother rotor may be a strategy to abolish VF. At the same time, ablation of the mother rotor may just allow the next-fastest daughter rotor to take its place because fibrillatory wavebreaks act as niduses for new rotors. In any case, however, to even test this intriguing therapeutic strategy, it is first necessary to identify the location of the mother rotor, which has been elusive to date, especially in large animals.5 The findings of the present study, in a large-animal diseased heart model, are therefore significant. They also raise important questions. …

Evolution of activation patterns during long-duration ventricular fibrillation in dogs.

Although resuscitation for sudden cardiac arrest attempts are frequently not instituted for several minutes after the onset of ventricular fibrillation (VF), previous mapping studies have examined only the first 40 s of VF or have involved isolated perfused hearts that did not become ischemic during VF. We applied quantitative pattern analysis to mapping data throughout the first 10 min of VF acquired from a 21 x 24 unipolar electrode array located on the ventricular epicardium of six open-chest dogs. The following twelve descriptors were continuously quantified: 1) number of wavefronts, 2) incidence of reentry, 3) wavefront propagation velocity, 4) incidence of breakthrough/focus, 5) incidence of block, 6) mean area activated by the wavefronts, 7) wavefront fractionations, 8) wavefront collisions, 9) multiplicity index, 10) repeatability, 11) negative peak rate of voltage change, and 12) peak frequency of activation. Cluster analysis of these descriptors divided VF into five stages (stages i-v). The values of most descriptors (except block and breakthrough incidence) increased during stage i (1-11 s after VF induction) and maintained high values with rapid dynamic fluctuations during stage ii (12-62 s). Descriptors changed quickly to values indicating greater organization during stage iii (63-86 s), decreased steadily during stage iv (87-310 s), and approached zero during stage v (311-600 s). There was a high incidence of reentry just before, during, and after stage iii. In conclusion, during the first 10 min, VF can be divided into five stages according to the evolution of electrophysiological characteristics. All of the parameters show a rapid deterioration during VF, except for a temporary reversal approximately 1 min after induction when activation briefly became more organized. Thus a quantitative description of activation does not uniformly decrease as VF progresses, but undergo rapid changes and exhibit a brief interval of increased organization after approximately 1 min of VF. Further studies are warranted to determine whether these changes, particularly the increased organization of stage iii, have clinical consequences, such as an alteration in defibrillation efficacy.

The effects of acute and chronic amiodarone on activation patterns and defibrillation threshold during ventricular fibrillation in dogs.

The goal of this study was to evaluate the effects of acute and chronic amiodarone on activation patterns during ventricular fibrillation (VF), ventricular effective refractory period (VERP) and defibrillation threshold (DFT). Acute and chronic amiodarone may act through different mechanisms. The VERP, VF activation patterns and DFT were determined in 24 dogs. Twelve dogs received acute intravenous amiodarone (10 mg/kg, n = 6) or saline (n = 6), and 12 dogs received chronic oral amiodarone (20 mg/kg/day, n = 6) or placebo (n = 6). Epicardial VF activation patterns were recorded with 504 electrodes. Quantitative descriptors of VF were calculated. The DFT was unchanged by acute or chronic amiodarone. Although chronic amiodarone significantly extended the VERP, acute amiodarone did not. In the mapped region, acute and chronic amiodarone decreased the number of VF wavefronts by 42% and 60%. Acute amiodarone decreased conduction block by 22%, while chronic amiodarone increased block by 41% but decreased wave fractionation by 50%. Both chronic and acute amiodarone increased the size of the core of re-entrant circuits and decreased the incidence of re-entry by 44% and 57%; however, chronic amiodarone increased wavelength, while acute amiodarone did not. Neither acute nor chronic amiodarone change the DFT. While both acute and chronic amiodarone decrease the number of wavefronts, decrease the incidence of re-entry and increase the size of re-entrant cores in the mapped region during VF, they achieve these antiarrhythmic effects through different electrophysiologic mechanisms. Chronic amiodarone prolonged the VF cycle length and slowed conduction velocity, indicating it increased the wavelength and/or the excitable gap.

Effect of IV amiodarone on CPR haemodynamics and outcome: experimental study in dogs

Amiodarone has been shown to be superior to placebo in improving admission to hospital for victims of out-of-hospital ventricular fibrillation. There is no data about haemodynamics induced by amiodarone alone or associated with epinephrine. This study compared outcome and haemodynamics of amiodarone alone, epinephrine alone, and the association of these two drugs in a model of resistant ventricular fibrillation in dogs (30 dogs were randomized; 10 to the epinephrine group, 10 to the amiodarone group and 10 to the association group). There were no differences among the groups in baseline variables. Compared to the association, epinephrine produced a better rate of ROSC, resuscitation, and 1-hour survival. There were no differences in outcome between amiodarone and epinephrine or amiodarone and association. Aortic systolic and diastolic, and coronary perfusion pressures were lower in the amiodarone than in the other two groups. Associated to epinephrine, amiodarone produced pressures similar to epinephrine alone. Amiodarone may be used during cardiac arrest, if associated with a vasoconstrictor like epinephrine.

Effects of hypothyroidism on the vulnerability to ventricular fibrillation in dogs: a comparative study with amiodarone.

It has been shown that thyroid hormone has a significant effect on the heart and that suppression of thyroid function may contribute to the antiarrhythmic effect of amiodarone. The study was aimed at investigating the effects of hypothyroidism, compared with those of amiodarone, on vulnerability to ventricular fibrillation in dogs. In this study, 25 adult dogs were randomly divided into three groups: a hypothyroid group following total thyroidectomy (n = 9), an amiodarone group (n = 8, 400 mg per day, 4 weeks), and a control group (n = 8). Both amiodarone and control groups were subjected to sham surgery. Five to 8 weeks after surgery, ventricular fibrillation threshold and other electrophysiological parameters were determined. Right ventricular effective refractory period, monophasic action potential duration, and ventricular fibrillation threshold were significantly increased in both the thyroidectomized and amiodarone-treated animals. There was no significant change in monophasic action potential duration dispersion. The incidence of ventricular fibrillation during ischemia and reperfusion was significantly reduced in both treated groups compared with the sham-operated euthyroid controls. These observations suggest that hypothyroidism has a significant antifibrillatory effect in dogs. Homogeneous prolongation of repolarization and refractoriness may contribute to the antifibrillatory action of hypothyroidism.

Reentrant wave fronts in Wiggers' stage II ventricular fibrillation. Characteristics and mechanisms of termination and spontaneous regeneration.

The mechanisms of Wiggers' stage II ventricular fibrillation (VF) are poorly understood. Using computerized mapping techniques, we studied the patterns of activation during Wiggers' stage II VF in 13 open-chest dogs. In 7 of the 13 dogs, the right ventricular Purkinje fibers and adjacent subendocardial myocytes were ablated with Lugol solution. VF was induced electrically, and 3 to 5 seconds of data were obtained beginning approximately 2.5 seconds after the onset of VF. Dynamic displays of the activation patterns and isochronal maps revealed the presence of reentrant wave fronts in 17 of 33 runs of VF in ablated ventricles and in 12 of 45 runs of VF in intact ventricles. The incidence of reentry was not different between the subendocardium-ablated group versus the nonablated group (1.7 +/- 1.6 versus 1.2 +/- 1.6 rotations per episode of VF, P = .19). There were no differences in the core size (25 +/- 19 versus 29 +/- 18 mm2), life span (3.4 +/- 1.1 versus 3.2 +/- 1.2 rotations), or cycle length (111 +/- 12 versus 107 +/- 8 ms) in ablated ventricles versus intact ventricles, respectively. The core was unstable as it meandered within the mapped area displacing the entire reentrant wave front. In all episodes, the reentrant wave fronts were spontaneously initiated by an interaction between two propagating wave fronts roughly perpendicular to each other. The second wave front met the tail of the first wave front 69 +/- 11 ms (range, 40 to 90 ms) after its latest activation, indicating that the interaction occurred during a vulnerable period. The reentrant wave fronts terminated spontaneously (n = 7), as the result of interference by an invading wave front (n = 19 or meandered off the mapped region (n = 3). We conclude the following: (1) Reentrant activities with short life spans and meandering cores are present during Wiggers' stage II VF in dogs. (2) New reentrant wave fronts are generated when one wave front interacts with another wave front during its vulnerable period. (3) The reentrant wave fronts terminate spontaneously or as the result of interference. (4) Chemical subendocardial ablation does not affect the incidence, life span, cycle length, or core size of the reentrant wave fronts.

K+ Channel Blockade in the Prevention of Ventricular Fibrillation in Dogs with Acute Ischemia and Enhanced Sympathetic Activity

The value of K+ channel blockade in preventing lethal arrhythmias, and specifically those triggered by acute myocardial ischemia and sympathetic hyperactivity, remains unproven. To address this issue, we tested the antifibrillatory effect of d-sotalol, and Ikr blocker, d,l-sotalol, its racemic compound which blocks Ikr, and beta-adrenoreceptors, and propranolol. Ten dogs with a healed anterior myocardial infarction (MI) had ventricular fibrillation (VF) during a 2-min occlusion of the circumflex coronary artery performed toward the end of a submaximal exercise stress test. In successive trials in the same animals, d-sotalol (three injections of 8 mg/kg, one every 12 h), d,l-sotalol (8 mg/kg), and propranolol (1 mg/kg) were tested. All three interventions significantly reduced heart rate (HR) response to exercise, but only d,l-sotalol and propranolol also blunted the reflex HR increase during acute myocardial ischemia. With d-sotalol, HR at 30 s of coronary occlusion was similar (253 +/- 28 beats/min) to that observed in the control tests (259 +/- 35 beats/min). d-Sotalol prevented recurrence of VF in only 1 of 10 dogs tested. One dog was lost to the continuation of the study after occurrence of VF with d-sotalol. Six of 9 dogs (67%) tested with d,l-sotalol and 5 (56%) of the same 9 dogs tested with propranolol were protected from VF. d-Sotalol does not reduce risk of VF during acute myocardial ischemia associated with sympathetic hyperactivity, and lethal events can be prevented by antiadrenergic interventions.

Calculation of transmembrane current from extracellular potential recordings: a model study.

A mathematical/computer model of cardiac tissue was used to study the estimation of transmembrane current (EIm) from extracellular potential recordings. The simulated EIm of transmembrane current was compared with the simulated transmembrane current (Im), and both simulated values were compared with experimentally derived EIm obtained during sinus rhythm and ventricular fibrillation in dogs. We found that although EIm measurements slightly overestimate the duration of the Im waveform, they provide a reasonable approximation of Im during normal conduction and during decremental conduction and conduction block. There is a very clear linear correlation between the time spent at or below 25% of the peak inward transmembrane current (Im25), its corresponding estimate (EIm25), the peak inward Im and EIm, and the peak ionic current, providing some evidence that EIm25 may be a suitable in vivo measure of peak ionic current.

808-3 Reentrant Wavefronts During Wiggers’ Stage II Ventricular Fibrillation in Dogs

The mechanisms of ventricular fibrillation (VF) are unknown. Reentrant wavefronts have been shown to underlie the onset (Wiggers’ stage I) of electrically induced VF in intact canine ventricles. These reentrant wavefronts, however, have a limited lifespan (1–2 s) while VF persists. Using computerized mapping techniques, we studied the mechanism by which VF is maintained beyond the initial few seconds (Wiggers’ stage II), both in normal and subendocardium-ablated canine ventricles. Eleven open-chest dogs were studied. In 6 of the dogs, the RV subendocardium was ablated with lugol's solution. A plaque electrode array with 317–509 bipolar recording electrodes was sutured on the RV epicardium. VF was induced by a strong premature stimulus (S 2 ). Starting 2.5 s after the onset of VF, 2–5 s of data were analyzed. The activation patterns were visualized via dynamic display. Conventional isochronal maps were also constructed. Of the 15 runs of VF in dogs with intact ventricles, 3 episodes of reentrant wavefronts were detected. The mean lifespan was 4.5 ± 2.1 rotations. The mean cycle length was 102.5 ± 5.5 msec. The incidence of reentry was 0.018 ± 0.048 rotations/sec-cm 2 . Of the 18 runs of VF in dogs with ablated ventricles, 8 episodes of reentry were detected. The mean lifespan was 3.6 ± 1.1 rotations (p = 0.39 compared with intact ventricles). The mean cycle length was 107.2 ± 9.6 msec (p = 0.16). The incidence of reentry was 0.075 ± 0.097 rotations/sec-cm 2 (p = 0.048). In both groups of dogs, dynamic displays of the activation patterns demonstrate that the reentrant wavefronts spiral rather than follow a simple circular pathway. (a) reentrant wavefronts are consistently present during Wiggers’ stage II VF, (b) ablation of the subendocardium and Purkinje fibers results in an increased incidence of reentrant wavefronts on the epicardium, and (c) the reentrant wavefronts are compatible with spiral waves of excitation.

O65 Sodium bicarbonate increases in efficacy with increasing cardiac arrest interval in resuscitation from ventricular fibrillation in dogs

O65 Sodium bicarbonate increases in efficacy with increasing cardiac arrest interval in resuscitation from ventricular fibrillation in dogs