The effect of lidocaine and bretylium on the defibrillation threshold during cardiac arrest and cardiopulmonary resuscitation

The effect of intravenous lidocaine, 2 mg/kg, and bretylium, 5 mg/kg, on defibrillation threshold (DFT) was investigated in alpha-chloralose anesthetized dogs undergoing conventional closed chest cardiopulmonary resuscitation (CPR) following induced ventricular fibrillation. Ventricular fibrillation was induced electrically and CPR was performed by a pneumatic device set to compress the chest 60 times and inflate the lung 12 times a minute. Defibrillation was achieved using underdamped sinusoidal current shocks from a special defibrillator which allowed determination of delivered energy. The DFT was defined as the peak current which defibrillated, but no more than 20% higher than a current which did not defibrillate. All DFTs were obtained within 5 min of CPR. The mean +/- SD current and energy thresholds required for defibrillation during lidocaine-CPR (seven dogs) were 17.0 +/- 8.9 A and 53.0 +/- 40.7 J as compared to 12.5 +/- 6.2 A and 34.3 +/- 30.7 J, respectively during control-CPR (P less than 0.05). The mean +/- SD current and energy thresholds during bretylium-CPR were 11.0 +/- 3.4 A and 24.1 +/- 1.3 J as compared to 11.8 +/- 1.7 A and 29.4 +/- 9.6 J, respectively, during control-CPR (NS). These results show that lidocaine acutely elevated defibrillation threshold whereas bretylium did not produce such an effect. The effect on DFT along with other pharmacologic properties should be considered when lidocaine or bretylium is used in the setting of cardiac arrest and CPR.     

Transitions among atrial fibrillation, atrial flutter, and sinus rhythm during procainamide infusion and vagal stimulation in dogs with sterile pericarditis

The mechanism of atrial flutter and fibrillation induced by rapid pacing in 22 dogs with 3-day-old sterile pericarditis was investigated by computerized epicardial mapping of atrial activation before and after administration of agents known to modify atrial electrophysiologic properties: procainamide, isoproterenol, and electrical stimulation of the vagosympathetic trunks. Before the administration of any of these agents, a total of 30 episodes of sustained atrial flutter (greater than 1 min duration, monomorphic; regular cycle length, 127 +/- 12 ms, mean +/- SD) was induced in 15 out of 22 dogs and 9 episodes of unstable atrial flutter (duration, less than 1 min; cycle length, 129 +/- 34 ms; monomorphic, alternating with fibrillation) were induced in the remaining 7 preparations. In the latter, administration of procainamide transformed unstable atrial flutter and atrial fibrillation to sustained atrial flutter (cycle length, 142 +/- 33 ms; n = 9 episodes). During control atrial flutter, atrial maps displayed circus movement of excitation in the right atrial free wall with faster conduction parallel to the orientation of intra-atrial myocardial bundles. Vagal stimulation changed atrial flutter to atrial fibrillation in 32 of 73 trials; this was associated with acceleration of conduction in the lower right atrium, leading to fragmentation of the major wave front. Isoproterenol produced a 6-25% increase of the atrial rate in 6 out of 14 trials of atrial flutter and induced atrial fibrillation in 4. After procainamide, the reentrant pathway was lengthened and conduction was slowed further in the right atrium. Maps obtained during unstable atrial flutter showed incomplete circuits involving the right atrium. Following procainamide infusion, the area of functional dissociation or block was enlarged and a stable circus movement pattern, which was similar to the pattern seen in control atrial flutter, was established in the right atrium. We conclude that (1) the transitions among atrial fibrillation, atrial flutter, and sinus rhythm occur between different functional states of the same circus movement substratum primarily located in the lower right atrial free wall, and (2) the anisotropic conduction properties of the right atrium may contribute to these reentrant arrhythmias and may be potentiated by acute pericarditis.     

Left ventricular geometry immediately following defibrillation: shock-induced relaxation

A previous two-dimensional (2D) ultrasound study suggested that there is relaxation of the myocardium after defibrillation. The 2D study could not measure activity occurring within the first 33 ms after the shock, a period that may be critical for discriminating between shock- and excitation-induced relaxation. The objective of our study was to determine the left ventricular (LV) geometry during the first 33 ms after defibrillation. Biphasic defibrillation shocks were delivered 5-50 s after the induction of ventricular fibrillation in each of the seven dogs. One-dimensional, short-axis ultrasound images of the LV cavity were acquired at a rate of 250 samples/s. The LV cavity diameter was computed from 32 ms before to 32 ms after the shock. Preshock and postshock percent changes in LV diameter were analyzed as a function of time with the use of regression analysis. The normalized mean pre- and postshock slopes (0.2 +/- 2.2 and 3.3 +/- 7.9% per 10 ms) were significantly different (P < 0.01). The postshock slope was positive (P < 0.005). Our results confirm that the bulk of the myocardium is relaxing immediately after defibrillation.     

Developmental changes of ventricular fibrillation threshold and spontaneous defibrillation in young dogs.

This study was conducted to systematically investigate whether induction and maintenance of ventricular fibrillation in the canine heart, change with age during the early postnatal development. Forty-eight mongrel puppies from seven litters, were randomly selected for size and studied at weekly intervals from 1-6 weeks for determination of ventricular fibrillation threshold and incidence of spontaneous defibrillation. Another fourteen mongrel puppies 8-11 weeks old and 10 adult dogs were similarly studied. Ventricular fibrillation threshold increased progressively with age up to the eighth week (VFTmA = 8.38 + 2.67 wk-0.134.wk2, r = 0.995) and thereafter reached a plateau, which was not significantly different from the ventricular fibrillation threshold of adult dogs (26.5 +/- 2.2 mA). In contrast, the high incidence of spontaneous defibrillation at early age decreased rapidly between second and fourth week and became rare thereafter, (%SDF = 281.e-0.60wk, r = 0.94. This rapid drop could not be explained by the increase in mean body weight, which did not change significantly during this early period (BWkg = 0.59.e0.23wk, r = 0.97). Our findings suggest first, that the vulnerability of the neonatal dog heart to electrical induction of ventricular fibrillation decreases progressively during early age. Second, that spontaneous defibrillation decreases precipitously between the second and fourth week of age, a change not sufficiently explained by the modest body weight gain during that time. Thus, it appears that about the third week of age ventricular vulnerability to fibrillation and ability to defibrillation reach a critical point, where lethal arrhythmias may become both inducible and sustainable, to result in death.     

Effect of autonomic neurotransmitters on excitable gap composition in canine atrial flutter

Atrial arrhythmias are believed to be influenced by autonomic nervous system tone. We evaluated the effects of sympathetic and parasympathetic activation on atrial flutter (AF1) by determining the effects of norepinephrine (NE) and acetylcholine (ACh) on the composition of the excitable gap. A model of reentry around the tricuspid valve was produced in 17 chloralose anesthetized dogs using a Y-shaped lesion in the intercaval area that extended to the right atrial appendage. Excitable gap characteristics were determined during AF1 by scanning diastole with a single premature extrastimulus at progressively shorter coupling intervals to define the reset-response curve. Measurements were made during a constant infusion of NE (15 microg/min) into the right coronary artery and repeated during ACh infusion (2 microg/min) following a 15 min recovery period. The excitable gap (27 +/- 1 ms) was significantly (P < 0.001) increased by NE (34 +/- 1 ms) and ACh (50 +/- 2 ms). The fully excitable portion (7 +/- 1 ms) was also significantly (P < 0.001) increased by NE (17 +/- 1 ms) and ACh (43 +/- 2 ms). We conclude that both neurotransmitters increase the safety margin of full excitability ahead of the wavefront, demonstrating that parasympathetic and sympathetic activation can facilitate the persistence of this refractory atrial arrhythmia.     

Nonreentrant focal activations in pulmonary veins in canine model of sustained atrial fibrillation

Repetitive rapid activities are present in the pulmonary veins (PVs) in dogs with pacing-induced sustained atrial fibrillation (AF). The mechanisms are unclear. We induced sustained (>48 h) AF by rapidly pacing the left atrium (LA) in six dogs. High-density computerized mapping was done in the PVs and atria. Results show repetitive focal activations in all dogs and in 12 of 18 mapped PVs. Activation originated from the middle of the PV and then propagated to the LA and distal PV with conduction blocks. The right atrium (RA) was usually activated by a single large wavefront. Mean AF cycle length in the PVs (left superior, 82 +/- 6 ms; left inferior, 83 +/- 6 ms; right inferior, 83 +/- 4 ms) and LA posterior wall (87 +/- 5 ms) were significantly (P < 0.05) shorter than those in the LA anterior wall (92 +/- 4 ms) and RA (107 +/- 5 ms). PVs in normal dogs did not have focal activations during induced AF. No reentrant wavefronts were demonstrated in the PVs. We conclude that nonreentrant focal activations are present in the PVs in a canine model of pacing-induced sustained AF.     

Thoracic vein ablation terminates chronic atrial fibrillation in dogs

The thoracic vein hypothesis of chronic atrial fibrillation (AF) posits that rapid, repetitive activations from muscle sleeves within thoracic veins underlie the mechanism of sustained AF. If this is so, thoracic vein ablation should terminate sustained AF and prevent its reinduction. Six female mongrel dogs underwent chronic pulmonary vein (PV) pacing at 20 Hz to induce sustained (>48 h) AF. Bipolar electrodes were used to record from the atria and thoracic veins, including the vein of Marshall, four PVs, and the superior vena cava. Radio frequency (RF) application was applied around the PVs and superior vena cava and along the vein of Marshall until electrical activity was eliminated. Computerized mapping (1,792 electrodes, 1 mm resolution) was also performed. Sustained AF was induced in 30.6 +/- 6.5 days, and ablation was done 17.3 +/- 8.5 days afterward. Before ablation, the PVs had shorter activation cycle lengths than the atria, and rapid, repetitive activations were observed in the PVs. All dogs converted to sinus rhythm during (n = 4 dogs) or within 90 min of completion of RF ablation. Rapid atrial pacing afterward induced only nonsustained (<60 s) AF in all dogs. Average AF cycle lengths after reinduction were significantly (P = 0.01) longer (183 +/- 31.5 ms) than baseline (106 +/- 16.2 ms). There were no activation cycle length gradients after RF application. We conclude that thoracic vein ablation converts canine sustained AF into sinus rhythm and prevents the reinduction of sustained AF. These findings suggest that thoracic veins are important in the maintenance of AF in dogs.     

Characterization of fibrillatory rhythms by ensemble vector directional analysis

Recent studies have demonstrated that fibrillatory rhythms are not random phenomena but have definable patterns. However, standard mapping techniques may have limitations in their ability to identify the organization of fibrillation. The purpose of this study was to develop and apply a method, "ensemble vector mapping," for characterizing the spatiotemporal organization of fibrillation. Ventricular fibrillation was induced by burst pacing in normal mongrel dogs. In a separate protocol, atrial fibrillation was induced by epicardial aconitine application. Epicardial electrograms were recorded from a 112-electrode plaque array using a computerized mapping system. Vectors were created by summing orthogonal bipolar electrograms. The magnitude of the vectors was transformed using a logarithmic function, integrated over time, and normalized for local electrogram amplitude to produce an "ensemble vector" index whose magnitude is high when beat-to-beat activation direction is consistent and low when activation direction is variable. The mean index was 137 +/- 36 mV/s during ventricular pacing at a cycle length of 300 ms but only 39 +/- 23 mV/s during ventricular fibrillation (P < 0.001). The ensemble vector index was also lower during atrial fibrillation (60 +/- 54 mV/s) than during atrial pacing (115 +/- 27 mV/s, P < 0.01 vs. atrial fibrillation) but not as low as during ventricular fibrillation (P < 0.05, atrial vs. ventricular fibrillation). The index was also capable of distinguishing atrial tachycardia from atrial fibrillation. Ensemble vector mapping produces an objective assessment of the consistency of myocardial activation during fibrillation. The consistency of activation direction differs in different models of fibrillation and is higher during atrial than ventricular fibrillation. This technique has the potential to rapidly characterize repetitive activation patterns in fibrillatory rhythms and may help distinguish among different characteristics of fibrillatory rhythms.     

Is there a correlation between ventricular fibrillation cycle length and electrophysiological and anatomic properties of the canine left ventricle?

We hypothesized that myocardial infarction-related alterations in ventricular fibrillation (VF) cycle length (VFCL) would correlate with changes in local cardiac electrophysiological and anatomic properties. An electrophysiological study was performed in normal, subacute, and chronic infarction mongrel dogs. VF was induced by programmed electrical stimulation and mean and minimum early and late VFCL was determined and correlated with local electrophysiological and anatomic properties. Effective refractory period (ERP), activation recovery time (ART), ERP/ART ratio, threshold, and ERP and ART dispersion were determined at 112 sites on the anterior left ventricle. Wave front progression was analyzed over a 2-s period. The extent of local tissue necrosis and of myocardial fiber disarray was also evaluated. The early mean VFCL was significantly longer in the subacute infarction (149 +/- 35 ms) and chronic infarction dogs (129 +/- 18 ms) compared with control dogs (102 +/- 15 ms; P < 0.0001 for both comparisons) as was the early minimum VFCL with similar trends seen during late VF. Complete epicardial reentrant circuits were significantly more common in normal dogs (4.3 +/- 2.4, 22.4% of cycles) than in subacute (0.75 +/- 0.96, 5.3% of cycles, P < 0.05 vs. normal) and chronic infarction dogs (1.3 +/- 1.3, 7.5% of cycles, P < 0.05 vs. normal). There was a poor correlation between the mean and minimum early and late VFCL and local electrophysiological and anatomic properties (R(2) < 0.2 for all comparisons) with a much better correlation between average mean and minimum VFCL (over the entire plaque) and global ERP and ART dispersion during early and late VF. In conclusion, VFCL in normal and infarcted myocardium shows a poor correlation with local ventricular electrophysiological and anatomic properties measured in sinus rhythm. However, there was a much better correlation between the average VFCL with global dispersion of repolarization. The lack of correlation between local VFCL and refractoriness and the infrequent occurrence of epicardial reentry suggests that intramural reentry may be the primary mechanism of VF in this model.     

Effects of electroporation on optically recorded transmembrane potential responses to high-intensity electrical shocks

The outcome of defibrillation shocks is determined by the nonlinear transmembrane potential (DeltaVm) response induced by a strong external electrical field in cardiac cells. We investigated the contribution of electroporation to DeltaVm transients during high-intensity shocks using optical mapping. Rectangular and ramp stimuli (10-20 ms) of different polarities and intensities were applied to the rabbit heart epicardium during the plateau phase of the action potential (AP). DeltaVm were optically recorded under a custom 6-mm-diameter electrode using a voltage-sensitive dye. A gradual increase of cathodal and well as anodal stimulus strength was associated with 1) saturation and subsequent reduction of DeltaVm; 2) postshock diastolic resting potential (RP) elevation; and 3) postshock AP amplitude (APA) reduction. Weak stimuli induced a monotonic DeltaVm response and did not affect the RP level. Strong shocks produced a nonmonotonic DeltaVm response and caused RP elevation and a reduction of postshock APA. The maximum positive and maximum negative DeltaVm were recorded at 170 +/- 20 mA/cm2 for cathodal stimuli and at 240 +/- 30 mA/cm2 for anodal stimuli, respectively (means +/- SE, n = 8, P = 0.003). RP elevation reached 10% of APA at a stimulus strength of 320 +/- 40 mA/cm2 for both polarities. Strong ramp stimuli (20 ms, 600 mA/cm2) induced a nonmonotonic DeltaVm response, reaching the same largest positive and negative values as for rectangular shocks. The transition from monotonic to nonmonotonic morphology correlates with RP elevation and APA reduction, which is consistent with cell membrane electroporation. Strong shocks resulted in propidium iodide uptake, suggesting sarcolemma electroporation. In conclusion, electroporation is a likely explanation of the saturation and nonmonotonic nature of cellular responses reported for strong electric stimuli.     

Effects of endurance exercise training on heart rate variability and susceptibility to sudden cardiac death: protection is not due to enhanced cardiac vagal regulation.

Low heart rate variability (HRV) is associated with an increased susceptibility to ventricular fibrillation (VF). Exercise training can increase HRV (an index of cardiac vagal regulation) and could, thereby, decrease the risk for VF. To test this hypothesis, a 2-min coronary occlusion was made during the last min of a 18-min submaximal exercise test in dogs with healed myocardial infarctions; 20 had VF (susceptible), and 13 did not (resistant). The dogs then received either a 10-wk exercise program (susceptible, n=9; resistant, n=8) or an equivalent sedentary period (susceptible, n=11; resistant, n=5). HRV was evaluated at rest, during exercise, and during a 2-min occlusion at rest and before and after the 10-wk period. Pretraining, the occlusion provoked significantly (P<0.01) greater increases in HR (susceptible, 54.9+/-8.3 vs. resistant, 25.0+/-6.1 beats/min) and greater reductions in HRV (susceptible, -6.3+/-0.3 vs. resistant, -2.8+/-0.8 ln ms2) in the susceptible dogs compared with the resistant animals. Similar response differences between susceptible and resistant dogs were noted during submaximal exercise. Training significantly reduced the HR and HRV responses to the occlusion (HR, 17.9+/-11.5 beats/min; HRV, -1.2+/-0.8, ln ms2) in the susceptible dogs; similar response reductions were noted during exercise. In contrast, these variables were not altered in the sedentary susceptible dogs. Posttraining, VF could no longer be induced in the susceptible dogs, whereas four sedentary susceptible dogs died during the 10-wk control period, and the remaining seven animals still had VF when tested. Atropine decreased HRV but only induced VF in one of eight trained susceptible dogs. Thus exercise training increased cardiac vagal activity, which was not solely responsible for the training-induced VF protection.     

Elimination of disorders of electric stability of the heart during post-infarct cardiosclerosis using adaptation to short-term stress and the antioxidant ionol

The experiments were carried out on male Wistar rats (300-400 g) subject to open chest surgery under nembutal anesthesia. One group of rats with postinfarction cardiosclerosis (PC) was exposed to short-term immobilization stress for 15 days one month after the occlusion of the descending branch of the left coronary artery. The other group of rats with PC was administered synthetic antioxidant ionol (BHT) (60 mg/kg, per os) 3 days prior to the experiments. The electrical stability of the heart was evaluated by assessing ventricular fibrillation threshold (VFT) determined by stimulation of the right ventricular apex by single premature impulses (10 ms) and by measuring the amount of ectopic beats developing during 30-sec stimulation of the right vagus (2 mA, 20 Hz). VFT in rats with PC was significantly lower, as compared to sham-operated rats (2.9 +/- 0.2 and 6.4 +/- 0.2 mA, respectively), with pronounced extrasystoles appearing during vagal bradycardia. In stress-adapted animals with PC VFT returned to the level of sham-operated rats and the amount of premature beats decreased 3-4-fold, as compared to unadapted rats with PC. Ionol (BHT) was shown to have the same effect.     

Opposite change with ischaemia in the antifibrillatory effects of class I and class IV antiarrhythmic drugs resulting from the alteration in ion transmembrane exchanges related to depolarization

It is known that class I antiarrhythmic drugs lose their antifibrillatory activity with severe ischaemia, whereas class IV antiarrhythmic drugs acquire such activity. Tachycardia, which is also a depolarizing factor, has recently been shown to give rise to an alteration of ion transmembrane exchanges which is particularly marked in the case of calcium. This leads one to wonder if the change in antifibrillatory activity of antiarrhythmic drugs caused by ischaemia depends on the same process. The change in antifibrillatory activity was studied in normal conditions ranging to those of severe ischaemia with a class I antiarrhythmic drug, flecainide (1.00 mg x kg(-1) plus 0.04 mg x kg(-1)x min(-1), a sodium channel blocker, and a class IV antiarrhythmic drug, verapamil (50 microg x kg(-1) plus 2 microg x kg(-1) x min(-1)), a calcium channel blocker. The experiments were performed in anaesthetized, open-chest pigs. The resulting blockade of each of these channels was assessed at the end of ischaemic periods of increasing duration (30, 60, 120, 180, 300, and 420 s) by determining the ventricular fibrillation threshold (VFT). VFT was determined by means of trains of diastolic stimuli of 100 ms duration delivered by a subepicardial electrode introduced into the myocardium (heart rate 180 beats per min). Ischaemia was induced by completely occluding the left anterior descending coronary artery. The monophasic action potential was recorded concurrently for the measurement of ventricular conduction time (VCT). The monophasic action potential duration (MAPD) varied with membrane polarization of the fibres. The blockade of sodium channels by flecainide, which normally raises VFT (7.0 +/- 0.4 to 13.8 +/- 0.8 mA, p < 0.001) and lengthens VCT (28 +/- 3 to 44 +/- 5 ms, p < 0.001), lost its effects in the course of ischaemia. This resulted in decreased counteraction of the ischaemia-induced fall of VFT and decreased aggravation of the ischaemia-induced lengthening of VCT. The blockade of calcium channels, which normally does not alter VFT (between 7.2 +/- 0.6 and 8.4 +/- 0.7 mA, n.s.) or VCT (between 30 +/- 2 and 34 +/- 3 ms, n.s.), slowed the ischaemia-induced fall of VFT. VFT required more time to reach 0 mA, thus delaying the onset of fibrillation. Membrane depolarization itself was opposed as the shortening of MAPD and the lengthening of VCT were also delayed. Consequently there is a progressive decrease in the role played by sodium channels during ischaemia in the rhythmic systolic depolarization of the ventricular fibres. This reduces or suppresses the ability of sodium channel blockers to act on excitability or conduction, and increases the role of calcium channel blockers in attenuating ischaemia-induced disorders.     

Effects of pituitary adenylate cyclase-activating polypeptide on canine atrial electrophysiology

We hypothesized that pituitary adenylate cyclase-activating polypeptide (PACAP) activates intracardiac postganglionic parasympathetic nerves and has a different effect than cervical vagal stimulation. We measured effective refractory period (ERP) and conduction velocity at four atrial sites [high right atrium (HRA), low right atrium (LRA), high left atrium (HLA), and low left atrium (LLA)] and minimum atrial fibrillation (AF) cycle length at 12 atrial sites during cervical vagal stimulation and after PACAP in 26 autonomically decentralized, open-chest, anesthetized dogs. PACAP shortened ERP to a similar extent at all four sites (HRA, 58 +/- 2.0 ms; LRA, 60 +/- 6.3 ms; HLA, 68 +/- 11.5 ms; and LLA, 60 +/- 8.3 ms). Low- and high-intensity vagal stimulation shortened ERP at the HRA, but not in the other atrial sites (low-intensity stimulation: HRA, 64 +/- 4.0 ms; LRA, 126 +/- 5.1 ms; HLA, 110 +/- 9.5 ms; and LLA, 102 +/- 11.5 ms; high-intensity stimulation: HRA, 58 +/- 4.2 ms; and HLA, 101 +/- 4.0 ms). Conduction velocity was not altered by any intervention. Minimum AF cycle length after PACAP was similar in both atria but was shorter in the right atrium than in the left atrium during vagal stimulation. After atropine administration, no interventions changed ERP. These results suggest that PACAP shortens atrial refractoriness uniformly in both atria through activation of intrinsic cardiac nerves, not all of which are activated by cervical vagal stimulation.     

Comparison of Ca2+-handling properties of canine pulmonary vein and left atrial cardiomyocytes

Cardiac tissue in the pulmonary vein sleeves plays an important role in clinical atrial fibrillation. Mechanisms leading to pulmonary vein activity in atrial fibrillation remain unclear. Indirect experimental evidence points to pulmonary vein Ca(2+) handling as a potential culprit, but there are no direct studies of pulmonary vein cardiomyocyte Ca(2+) handling in the literature. We used the Ca(2+)-sensitive dye indo-1 AM to study Ca(2+) handling in isolated canine pulmonary vein and left atrial myocytes. Results were obtained at 35 degrees C and room temperature in cells from control dogs and in cardiomyocytes from dogs subjected to 7-day rapid atrial pacing. We found that basic Ca(2+)-transient properties (amplitude: 186 +/- 28 vs. 216 +/- 25 nM; stimulus to half-decay time: 192 +/- 9 vs. 192 +/- 9 ms; atria vs. pulmonary vein, respectively, at 1 Hz), beat-to-beat regularity, propensity to alternans, beta-adrenergic response (amplitude increase at 0.4 Hz: 96 +/- 52 vs. 129 +/- 61%), number of spontaneous Ca(2+)-transient events after Ca(2+) loading (in normal Tyrode: 0.9 +/- 0.2 vs. 1.3 +/- 0.2; with 1 microM isoproterenol: 7.6 +/- 0.3 vs. 5.1 +/- 1.8 events/min), and caffeine-induced Ca(2+)-transient amplitudes were not significantly different between atrial and pulmonary vein cardiomyocytes. In an arrhythmia-promoting model (dogs subjected to 7-day atrial tachypacing), Ca(2+)-transient amplitude and kinetics were the same in cells from both pulmonary veins and atrium. In conclusion, the similar Ca(2+)-handling properties of canine pulmonary vein and left atrial cardiomyocytes that we observed do not support the hypothesis that intrinsic Ca(2+)-handling differences account for the role of pulmonary veins in atrial fibrillation.     

High-density mapping of pulmonary veins and left atrium during ibutilide administration in a canine model of sustained atrial fibrillation

Ibutilide can prolong refractory period and terminate reentry. Whether ibutilide has the same effects on pulmonary vein (PV) focal discharge (FD) is unclear. We induced sustained atrial fibrillation (AF) in seven dogs by rapid left atrial (LA) pacing for 74 +/- 46 days. Ibutilide was repeatedly infused until it terminated AF (0.02 +/- 0.01 mg/kg) or when a cumulative dose was reached (0.04 mg/kg). High-resolution computerized epicardial mapping was performed. We found intermittent FD at the PVs and reentry at the PV-LA junction during AF. Ibutilide increased the cycle length of consecutive reentry from 97 +/- 13 to 112 +/- 18 ms and increased FD from 96 +/- 7 to 113 +/- 9 ms. In four dogs with both FD and reentry at the PVs, the incidence of reentry decreased from 3.5 +/- 1.9/s at baseline to 2.2 +/- 1.8/s after ibutilide administration. However, the incidence of FD remained unchanged. The conducted wave fronts between PV and LA were significantly reduced by ibutilide (10.4 +/- 2.0/s vs. 8.0 +/- 1.6/s). The ibutilide dose needed to terminate AF correlated negatively with the baseline effective refractory period of PV and LA. We conclude that ibutilide reduces reentrant wave fronts but not PV FD in a canine model of pacing-induced sustained AF. These findings suggest that the PV FD during AF is due to nonreentrant mechanisms. High doses of ibutilide may completely terminate all reentrant activity, converting AF to PV tachycardia before the resumption of sinus rhythm.     

Chronic nicotine in hearts with healed ventricular myocardial infarction promotes atrial flutter that resembles typical human atrial flutter

The potential of chronic nicotine exposure for atrial fibrillation (AF) and atrial flutter (AFL) in hearts with and without chronic myocardial infarction (MI) remains poorly explored. MI was created in dogs by permanent occlusion of the left anterior descending coronary artery, and dogs were administered nicotine (5 mg.kg(-1).day(-1) sc) for 1 mo using osmotic minipumps. High-resolution epicardial (1,792 bipolar electrodes) and endocardial Halo catheters were used to map activation during induced atrial rhythms. Nicotine promoted inducible sustained AFL at a mean cycle length of 134 +/- 10 ms in all MI dogs (n = 6) requiring pacing and electrical shocks for termination. No AFL could be induced in MI dogs (n = 6), control (non-MI) dogs (n = 3) not exposed to nicotine, and dogs with no MI and exposed to nicotine (n = 3). Activation maps during AFL showed a single reentrant wavefront in the right atrium that rotated either clockwise (60%) or counterclockwise (40%) around the crista terminalis and through the isthmus. Ablation of the isthmus prevented the induction of AFL. Nicotine caused a significant (P < 0.01) but highly heterogeneous increase in atrial interstitial fibrosis (2- to 10-fold increase in left and right atria, respectively) in the MI group but only a 2-fold increase in the right atrium in the non-MI group. Nicotine also flattened (P < 0.05) the slope of the epicardial monophasic action potential duration (electrical restitution) curve of both atria in the MI but not in non-MI dogs. Two-dimensional simulation in an excitable matrix containing an isthmus and nicotine's restitutional and reduced gap junctional coupling (fibrosis) parameters replicated the experiments. Chronic nicotine in hearts with MI promotes AFL that closely resembles typical human AFL. Increased atrial interstitial fibrosis and flattened electrical restitution are important substrates for the AFL.     

Anti-arrhythmic activity of the beta2-adrenoblockader alpheprol]

Experiments were conducted on dogs, cats and rats in which various disturbances of the cardiac rhythm were induced. Beta2-adrenoblocker alpheprol proved to produce a marked antiarrhythmic action. The preparation arrested the auricular arrhythmias caused by electric stimulation of the auricles or by aconitine application, eliminated the auricular arrhythmias resulting from occlusion of a branch of the coronary artery or oubaine intoxication, prevented lethal auricular fibrillation in rats after the calcium chloride intoxication. It is supposed that along with the beta-adrenoreceptor block the antiarrhythmic effect of alpheprol was also caused by quinidine-like action of the preparation.     

Effects of taurine and dipeptide Tyr-Tyr on ventricular defibrillation]

Results of the study of taurine and dipeptide Tyr-Tyr effect on the threshold values of functional lesions of the myocardium and heart defibrillation are reported. The experiments were carried out on 27 narcotized mongrel dogs weighing 12-30 kg. Defibrillation was performed using Lifepak-7 defibrillator (USA). Lesion threshold (LT), defibrillation threshold (DT) and electrotherapeutic index (ETI) as a LT:DT ratio were determined. In 14 experiments (control group) these parameters were evaluated during 3 h. In group 1 (6 experiments) taurine (100 mg/kg) was infused intravenously by the end of the 1st hour, in group 2--Tyr-Tyr (25 mg/kg). It was shown that infusion of taurine did not have a noticeable effect of the LT, DT and ETI values. Infusion of Tyr-Tyr resulted in an increase in LT and DT. The possibility to use dipeptide Tyr-Tyr in the complex of measures aimed at ceasing ventricular fibrillation is discussed.     

Conduction left-to-right and right-to-left across the crista terminalis

A line of block between the vena cava and the crista terminalis (CT) region is important for atrial flutter (AFL), but whether it is fixed or functional is controversial. To test the hypothesis that conduction across the CT normally occurs, but when block occurs in this region it is functional, we analyzed atrial activation during right and left atrial pacing (cycle lengths of 500--130 ms), AFL, and atrial fibrillation in 15 dogs with sterile pericarditis and 7 normal dogs. Electrograms from 396 right, left, and septal atrial sites were simultaneously recorded. Activation across the CT occurred during atrial pacing, AFL, and atrial fibrillation. Activation wave fronts from the right to the left atrium and vice versa traveled over several routes, including Bachmann's bundle and inferior to the inferior vena cava, as well as across the CT. In these models, there is no fixed conduction block across the CT, and when block in the CT region occurs, as during AFL, it is functional.