Modifications of mechanoelectric feedback induced by 2,3-butanedione monoxime and Blebbistatin in Langendorff-perfused rabbit hearts.

AIM: Myocardial stretching is an arrhythmogenic factor. Optical techniques and mechanical uncouplers are used to study the mechanoelectric feedback. The aim of this study is to determine whether the mechanical uncouplers 2,3-butanedione monoxime and Blebbistatin hinder or modify the electrophysiological effects of acute mechanical stretch. METHODS: The ventricular fibrillation (VF) modifications induced by acute mechanical stretch were studied in 27 Langendorff-perfused rabbit hearts using epicardial multiple electrodes and mapping techniques under control conditions (n = 9) and during the perfusion of 2,3-butanedione monoxime (15 mM) (n = 9) or Blebbistatin (10 µm) (n = 9). RESULTS: In the control series, myocardial stretch increased the complexity of the activation maps and the dominant frequency (DF) of VF from 13.1 ± 2.0 Hz to 19.1 ± 3.1 Hz (P < 0.001, 46% increment). At baseline, the activation maps showed less complexity in both the 2,3-butanedione monoxime and Blebbistatin series, and the DF was lower in the 2,3-butanedione monoxime series (11.4 ± 1.2 Hz; P < 0.05). The accelerating effect of mechanical stretch was abolished under 2,3-butanedione monoxime (maximum DF = 11.7 ± 2.4 Hz, 5% increment, ns vs baseline, P < 0.0001 vs. control series) and reduced under Blebbistatin (maximum DF = 12.9 ± 0.7 Hz, 8% increment, P < 0.01 vs. baseline, P < 0.0001 vs. control series). The variations in complexity of the activation maps under stretch were not significant in the 2,3-butanedione monoxime series and were significantly attenuated under Blebbistatin. CONCLUSION: The accelerating effect and increased complexity of myocardial activation during VF induced by acute mechanical stretch are abolished under the action of 2,3-butanedione monoxime and reduced under the action of Blebbistatin.

The training-induced changes on automatism, conduction and myocardial refractoriness are not mediated by parasympathetic postganglionic neurons activity.

The purpose of this study is to test the role that parasympathetic postganglionic neurons could play on the adaptive electrophysiological changes produced by physical training on intrinsic myocardial automatism, conduction and refractoriness. Trained rabbits were submitted to a physical training protocol on treadmill during 6 weeks. The electrophysiological study was performed in an isolated heart preparation. The investigated myocardial properties were: (a) sinus automatism, (b) atrioventricular and ventriculoatrial conduction, (c) atrial, conduction system and ventricular refractoriness. The parameters to study the refractoriness were obtained by means of extrastimulus test at four different pacing cycle lengths (10% shorter than spontaneous sinus cycle length, 250, 200 and 150 ms) and (d) mean dominant frequency (DF) of the induced ventricular fibrillation (VF), using a spectral method. The electrophysiological protocol was performed before and during continuous atropine administration (1 µM), in order to block cholinergic receptors. Cholinergic receptor blockade did not modify either the increase in sinus cycle length, atrioventricular conduction and refractoriness (left ventricular and atrioventricular conduction system functional refractory periods) or the decrease of DF of VF. These findings reveal that the myocardial electrophysiological modifications produced by physical training are not mediated by intrinsic cardiac parasympathetic activity.

Effects of chronic exercise on myocardial refractoriness: a study on isolated rabbit heart.

AIM: To determine whether chronic physical training increases atrial and ventricular refractoriness in isolated rabbit heart. METHODS: Trained rabbits were submitted to a protocol of treadmill running. The electrophysiological parameters of refractoriness investigated in an isolated heart preparation were: (1) atrial effective refractory period (AERP) and atrial functional refractory period and ventricular effective and functional refractory periods (VERP and VFRP) using the extrastimulus technique at four different pacing cycle lengths; (2) the dominant frequency (DF) of ventricular fibrillation (VF). A multi-electrode plaque containing 256 electrodes and a spectral method were used to obtain the mean, maximum and minimum DF of VF. Sinus cycle length of the isolated hearts was determined as an electrophysiological parameter of training. In vivo heart rate, myocardial heat shock proteins (HSP60) and inducible nitric oxide synthase were also determined in some animals as electrophysiological and biochemical markers of training respectively. RESULTS: VERP and VFRP were longer in the trained group than in the control group. The mean DF of VF was lower in the trained group than in the control group. Despite the fact that training did not significantly modify the AERP, it tended to be longer in the trained group (P = 0.09). CONCLUSION: Training seems to increase the electrical stability of ventricular myocardium. As the electrophysiological modifications were exhibited in hearts not submitted to extrinsic nervous system or humoral influences, they are, at least in part, intrinsic modifications. These electrophysiological data also suggest that training could protect against reentrant ventricular arrhythmias.

A halocin acting on Na+/H+ exchanger of Haloarchaea as a new type of inhibitor in NHE of mammals

The capability of halocin H6 (a bacteriocin-like protein produced by haloarchaeaHaloferax gibbonsii) to inhibit Na+/H+ exchange (NHE) in mammalian cells and its cardio-protective efficacy on the ischemic and reperfused myocardium were evaluated in the present study. H6 inhibits NHE activity (measured by a flow cytometry method) in a dose-dependent form of cell lines of mammalian origin (HEK293, NIH3T3, Jurkat and HL-1) as well as in primary cell culture from human skeletal muscle (myocytes and fibroblasts).In vivo, an ischemia-reperfusion model in dogs by coronary arterial occlusion was used (two hours of regional ischemia and three hours of reperfusion). In animals treated with halocin H6 there was a significant reduction of premature ventricular ectopic beats and infarct size, whereas blood pressure and heart rate remained unchanged. Up to date, halocin H6 is the only described biological molecule that exerts a, specific inhibitory activity in NHE of eukaryotic cells (AU)

En el presente trabajo se evalúa la capacidad de la halocina H6 (una proteína tipo bacteriocina producida por la haloarchaeaHaloferax gibbonsii) para inhibir el intercambiador Na+/H+ (NHE) de céludas de mamífero y su posible eficacia cardioprotectora frente a los daños causados por isquemia-reperfusión del miocardio. En experimentosin vitro H6 inhibe la actividad de NHE (determinada por citometría de flujo) de forma dosis-dependiente tanto en líneas celulares de mamíferos (HEK293, NIH3T3, Jurkat y HL-1) como en cultivos primarios de miocitos y fibroblastos aislados de músculo esquelético humano. En experimentosin vivo se utilizó un modelo de isquemia-reperfusión en perros por oclusión de la arteria coronaria (dos horas de isquemia y tres de reperfusión). En animales tratados con halocina H6 se produjo una disminución significativa a nivel estadístico, tanto del número de latidos ectópicos ventriculares como del tamaño del infarto, mientras que no se produjeron cambios tanto en la presión sanguínea como en el ritmo cardíaco. Hasta la fecha la halocina H6 es la única molécula biológica descrita que ejerce una actividad inhibidora específica sobre el NHE de células eucariotas (AU)

A halocin acting on Na+/H+ exchanger of haloarchaea as a new type of inhibitor in NHE of mammals.

The capability of halocin H6 (a bacteriocin-like protein produced by haloarchaea Haloferax gibbonsii) to inhibit Na+/H+ exchanger (NHE) in mammalian cells and its cardio-protective efficacy on the ischemic and reperfused myocardium were evaluated in the present study. H6 inhibits NHE activity (measured by a flow cytometry method) in a dose-dependent form of cell lines of mammalian origin (HEK293, NIH3T3, Jurkat and HL-1) as well as in primary cell culture from human skeletal muscle (myocytes and fibroblasts). In vivo, an ischemia-reperfusion model in dogs by coronary arterial occlusion was used (two hours of regional ischemia and three hours of reperfusion). In animals treated with halocin H6 there was a significant reduction of premature ventricular ectopic beats and infarct size, whereas blood pressure and heart rate remained unchanged. Up to date, halocin H6 is the only described biological molecule that exerts a specific inhibitory activity in NHE of eukaryotic cells.

Intrinsic changes on automatism, conduction, and refractoriness by exercise in isolated rabbit heart.

We have studied the intrinsic modifications on myocardial automatism, conduction, and refractoriness produced by chronic exercise. Experiments were performed on isolated rabbit hearts. Trained animals were submitted to exercise on a treadmill. The parameters investigated were 1) R-R interval, noncorrected and corrected sinus node recovery time (SNRT) as automatism index; 2) sinoatrial conduction time; 3) Wenckebach cycle length (WCL) and retrograde WCL, as atrioventricular (A-V) and ventriculoatrial conduction index; and 4) effective and functional refractory periods of left ventricle, A-V node, and ventriculoatrial retrograde conduction system. Measurements were also performed on coronary flow, weight of the hearts, and thiobarbituric acid reagent substances and glutathione in myocardium, quadriceps femoris muscle, liver, and kidney, to analyze whether these substances related to oxidative stress were modified by training. The following parameters were larger (P < 0.05) in trained vs. untrained animals: R-R interval (365 +/- 49 vs. 286 +/- 60 ms), WCL (177 +/- 20 vs. 146 +/- 32 ms), and functional refractory period of the left ventricle (172 +/- 27 vs. 141 +/- 5 ms). Corrected SNRT was not different between groups despite the larger noncorrected SNRT obtained in trained animals. Thus training depresses sinus chronotropism, A-V nodal conduction, and increases ventricular refractoriness by intrinsic mechanisms, which do not involve changes in myocardial mass and/or coronary flow.

Mapping of atrial activation patterns after inducing contiguous radiofrequency lesions: an experimental study.

High resolution mapping techniques are used to analyze the changes in atrial activation patterns produced by contiguous RF induced lesions. In 12 Langendorff-perfused rabbit hearts, left atrial activation maps were obtained before and after RF induction of epicardial lesions following a triple-phase sequential protocol: (phase 1) three separate lesions positioned vertically in the central zone of the left atrial wall; (phase 2) the addition of two lesions located between the central lesion and the upper and lower lesions; and (phase 3) the placement of four additional lesions between those induced in the previous phases. In six additional experiments a pathological analysis of the individual RF lesions was performed. In phase 1 (lesion diameter = 2.8+/-0.2 mm, gap between lesions = 3+/-0.8 mm), the activation process bordered the lesions line in two (250-ms cycles) and four experiments (100-ms cycles). In phase 2, activation bordered the lesions line in eight (250-ms cycles, P < 0.01 vs control) and nine experiments (100-ms cycles, P < 0.001), and in phase 3 this occurred in all experiments except one (both cycles, P < 0.001 vs control). In the experiments with conduction block, the increment of the interval between activation times proximal and distal to the lesions showed a significant correlation to the length of the lesions (r = 0.68, P < 0.05, 100-ms cycle). In two (17%) experiments, sustained regular tachycardias were induced with reentrant activation patterns around the lesions line. In conclusion, in this acute model, atrial RF lesions with intact tissue gaps of 3 mm between them interrupt conduction occasionally, and conduction block may be frequency dependent. Lesion overlap is required to achieve complete conduction block lines. Tachycardias with reentrant activation patterns around a lesions line may be induced.

[Epicardial mapping of reentrant activation during ventricular fibrillation. An experimental study]. / Cartografía epicárdica de la activación reentrante durante la fibrilación ventricular. Estudio experimental.

INTRODUCTION AND OBJECTIVES: High-resolution epicardial mapping was used in an experimental model to analyze reentrant activation during ventricular fibrillation. METHODS: In 30 isolated Langendorff-perfused rabbit hearts, recordings were made of ventricular fibrillation activity using an epicardial multiple electrode. In the activation maps with reentrant activation patterns, determinations were made of the number of consecutive rotations, the maximum length of the central core, the area encompassed by the core and two electrodes surrounding it, and the cycle defined by reentrant activation. RESULTS: Most of the activation maps analyzed showed complex patterns with two or more wave fronts that either collided or remained separated by functional block lines (514 maps, 86%). In 112 maps (19%) activation patterns compatible with epicardial breakthrough of the depolarization process were observed. Reentrant activity was recorded in 42 maps (7%) - the maximum number of consecutive rotations being 3 (mean = 1.3 +/- 0.5). The maximum length of the central core ranged from 3 to 7 mm (mean = 5 +/- 1 mm), while the area encompassed by the central core plus two electrodes surrounding it ranged from 35 to 55 mm2 (mean = 45 +/- 6 mm2). The reentrant cycle length (mean = 47 +/- 8 ms) showed a linear relation to the maximum length of the central core reentry (cycle = 4.52 x length + 24.6; r = 0.7; p < 0.0001). CONCLUSIONS: a) Epicardial mapping allowed the identification of reentrant activation patterns during ventricular fibrillation in the experimental model used; b) the reentrant activity detected is infrequent and unstable, and c) a linear relation exists between the duration of the cycles defined by reentrant activity and the maximum length of central core reentry.

Alteration of ventricular fibrillation by flecainide, verapamil, and sotalol: an experimental study.

BACKGROUND: The purpose of this study was to determine whether the myocardial electrophysiological properties are useful for predicting changes in the ventricular fibrillatory pattern. METHODS AND RESULTS: Thirty-two Langendorff-perfused rabbit hearts were used to record ventricular fibrillatory activity with an epicardial multiple electrode. Under control conditions and after flecainide, verapamil, or d,l-sotalol, the dominant frequency (FrD), type of activation maps, conduction velocity, functional refractory period, and wavelength (WL) of excitation were determined during ventricular fibrillation (VF). Flecainide (1.9+/-0.3 versus 2.4+/-0.6 cm, P<0. 05) and sotalol (2.1+/-0.3 versus 2.5+/-0.5 cm, P<0.05) prolonged WL and diminished FrD during VF, whereas verapamil (2.0+/-0.2 versus 1. 7+/-0.2 cm, P<0.001) shortened WL and increased FrD. Simple linear regression revealed an inverse relation between FrD and the functional refractory period (r=0.66, P<0.0001), a direct relation with respect to conduction velocity (r=0.33, P<0.01), and an inverse relation with respect to WL estimated during VF (r=0.49, P<0.0001). By stepwise multiple regression, the functional refractory periods were the only predictors of FrD. Flecainide and sotalol increased the circuit size of the reentrant activations, whereas verapamil decreased it. The 3 drugs significantly reduced the percentages of more complex activation maps during VF. CONCLUSIONS: The activation frequency is inversely related to WL during VF, although a closer relation is observed with the functional refractory period. Despite the diverging effects of verapamil versus flecainide and sotalol on the activation frequency, WL, and size of the reentrant circuits, all 3 drugs reduce activation pattern complexity during VF.

[Characteristics of atrial electrograms recorded in radiofrequency induced block lines in an experimental model]. / Características de los electrogramas auriculares registrados en las líneas de bloqueo producidas con radiofrecuencia en un modelo experimental.

AIM: To analyze and quantify atrial electrogram modifications following the induction of linear lesions in the atrial wall using radiofrequency ablation procedures. METHODS: An epicardial multiple electrode (221 unipolar electrodes) was used in 12 Langendorff perfused rabbit hearts to analyze atrial activation before and after radiofrequency induction of a linear lesion in the left atrial wall. After confirming the existence of conduction blockade in the lesion zone by epicardial mapping and propagation vector analysis, six electrodes each were selected in the lesioned and non-lesioned zones in all experiments, comparing the amplitude, maximum negative slope and morphology of the electrograms in both zones, before (control) and after radiofrequency delivery. RESULTS: Analysis of the reproducibility of the measurements in two consecutive cycles showed a variation of 1 +/- 5% for amplitude (NS) and 1 +/- 9% for maximum negative slope (NS). In the non-damaged zone, amplitude (105 +/- 22%) and slope (92 +/- 16%) (values normalized with respect to those recorded before radiofrequency) did not vary significantly following radiofrequency, and simple electrograms were the most frequent recordings (82 vs 83% in control; NS). Amplitude (19 +/- 7%, p < 0.001) and slope (24 +/- 11%; p < 0.001) decreased significantly in the lesion zone, as did the percentage of simple electrograms (6 vs 86% in control; p < 0,001). In this same zone the morphology could not be determined in 12% of the recordings, while multiple electrograms were obtained in 15% (vs 2% in control; p < 0.01), and the most frequent type corresponded to double electrograms (67 vs 12% in control, p < 0.001), with both components coinciding in time with atrial activation in the zones proximal and distal to the lesion line. CONCLUSIONS: Electrograms recorded directly in radiofrequency induce block lines show a significant decrease in amplitude and maximum negative slope. Double electrograms predominate in these recordings, both components of which represent activation on either side of the lesion. In a small proportion of cases simple and multiple electrograms can also be recorded in the block line.

Opposite effects of myocardial stretch and verapamil on the complexity of the ventricular fibrillatory pattern: an experimental study.

An experimental model is used to analyze the effects of ventricular stretching and verapamil on the activation patterns during VF. Ten Langendorff-perfused rabbit hearts were used to record VF activity with an epicardial multiple electrode before, during, and after stretching with an intraventricular balloon, under both control conditions and during verapamil (Vp) infusion (0.4-0.8 mumol). The analyzed parameters were dominant frequency (FrD) spectral analysis, the median (MN) of the VF intervals, and the type of activation maps during VF (I = one wavelet without block lines, II = two simultaneous wavelets with block lines, III = three or more wavelets with block lines). Stretch accelerates VF (FrD: 22.8 +/- 6.4 vs 15.2 +/- 1.0 Hz, P < 0.01; MN: 48 +/- 13 vs 68 +/- 6 ms, P < 0.01). On fitting the FrD time changes to an exponential model after applying and suppressing stretch, the time constants (stretch: 101.2 +/- 19.6 s; stretch suppression: 97.8 +/- 33.2 s) do not differ significantly. Stretching induces a significant variation in the complexity of the VF activation maps with type III increments and type I and II decrements (control: I = 17.5%, II = 50.5%, III = 32%; stretch: I = 7%, II = 36.5%, III = 56.5%, P < 0.001). Vp accelerates VF (FrD: 20.9 +/- 1.9 Hz, P < 0.001 vs control; MN: 50 +/- 5 ms, P < 0.001 vs control) and diminishes activation maps complexity (I = 25.5%, II = 60.5%, III = 14%, P < 0.001 vs control). On applying stretch during Vp perfusion, the fibrillatory process is not accelerated to any greater degree. However, type I and II map decrements and type III increments are recorded, though reaching percentages similar to control (I = 16.5%, II = 53%, III = 30.5%, NS vs control). The following conclusions were found: (1) myocardial stretching accelerates VF and increases the complexity of the VF activation pattern; (2) time changes in the FrD of VF during and upon suppressing stretch fit an exponential model with similar time constants; and (3) although stretching and verapamil accelerate the VF process, they exert opposite effects upon the complexity of the fibrillatory pattern.

Intravenous BQ-123 and phosphoramidon reduce ventricular ectopic beats and myocardial infarct size in dogs submitted to coronary occlusion and reperfusion.

The aim of this work was to investigate the influence of endothelin on myocardial ischemia and reperfusion in anaesthetized dogs. Animals were submitted to left thoracotomy and 120 min of left anterior descending coronary occlusion, followed by 180 min of reperfusion. Arterial blood pressure and electrocardiogram (ECG) were recorded in order to analyze heart rate (HR)-pressure product and production of ectopic beats. Infarcted areas were identified by a macroscopic staining method and infarct size was expressed as percentage of risk zone. To inhibit the effects of endothelin in a group of animals, we administered intravenously an endothelin synthesis inhibitor (phosphoramidon) and in another group, an endothelin-1 A receptor blocker (BQ-123). Phosphoramidon decreased the HR-pressure product during reperfusion period, and both, phosphoramidon and BQ-123 decreased infarct size by 40% and the number of ventricular ectopic beats by 88% and 68%, respectively, as compared to the saline treated dogs. In conclusion, endothelin seems to play a deleterious role on the myocardium submitted to ischemia and reperfusion.

Flow cytometric analysis of peroxidative activity in granulocytes from coronary and peripheral blood in acute myocardial ischemia and reperfusion in dogs: protective effect of methionine.

BACKGROUND: Methionine has shown protective effects in experimental models of myocardial infarction and is highly reactive to oxidative compounds produced by polymorphonuclear leukocytes (PMN), which in turn have been associated with myocardial damage. We have investigated the effect of methionine administration on spontaneous leukocyte peroxidative activity in myocardial ischemia and reperfusion. METHODS: In anesthetized dogs, with coronary occlusion (90 min) and reperfusion (90 min), PMN activation was measured by flow cytometric determination of H(2)O(2) with dihydrorhodamine 123, and correlated to hemodynamic parameters and infarct presence. To assess a possible direct effect of methionine, H(2)O(2) and superoxide were measured by flow cytometry in dog leukocyte suspensions following in vitro stimulation with f-MLP. RESULTS: PMN peroxidative activity in saline-treated dogs increased significantly after coronary occlusion and after reperfusion. These changes were greater in coronary venous blood than in femoral blood. Methionine administration (150 mg/kg, i.v.) before occlusion totally suppressed PMN activation, both after occlusion and reperfusion. CONCLUSIONS: PMN are promptly activated in myocardial ischemia, and methionine administration prevents such activation. However, methionine has no direct effect on spontaneous peroxidative activity, and f-MLP induced peroxidative activity. These in vivo effects of methionine, may additionally contribute to explain its protective role in experimental -788-877-7QQ8-8-7-88-8-8778--8Q78-----8--8-Q-7-Q7----- --------------8888 888888-7777777777777777777777777777777----------------888888888888888888 8877777--87--------8-----------------7-8888-887-----------8----8-8-87777 7777777------------------------------------------------------T7OW

[The activation patterns during atrial fibrillation in an experimental model]. / Patrones de activación durante la fibrilación auricular en un modelo experimental.

INTRODUCTION AND OBJECTIVES: In atrial fibrillation, along with the mechanisms of complete reentry and random activation focal activation patterns have been described which have been attributed both to propagation from the endocardium and to the existence of zones with automatic activity. The objectives of present study are to analyze and quantify the atrial activation patterns in an experimental model of atrial fibrillation. MATERIAL AND METHODS: In 11 Langendorff-perfused rabbit hearts atrial fibrillation was induced by atrial burst pacing after right atrial dilatation with an intra-atrial balloon. A multiple electrode consisting of 121 electrodes and positioned in the right atrial free wall was used to construct the activation maps corresponding to 10 segments of 100 ms in 11 different episodes of sustained atrial fibrillation (one per experiment). RESULTS: Of the 110 segments analyzed, 44 (40%) corresponded to random activation patterns. Fifteen segments (14%) corresponded to complete reentry, and in these cases the number of consecutive rotations ranged from 1 to 2.25 (mean 1.4 +/- 0.4). In 49 segments (44%) a single activation front was seen to pass through the recording area without block; alternatively, two simultaneous fronts were recorded that did not re-excite the zone activated by the other. In two segments (2%) there was a focal activation pattern without evidence of propagation from the epicardium surrounding the activated zone. CONCLUSIONS: a) in the experimental atrial fibrillation model used, random activation patterns are more frequent than complete reentry patterns; b) complete reentry can occur in areas smaller than 1 cm2, and c) focal activation during atrial fibrillation is rare.

Modulation of adrenergic contraction of dog pulmonary arteries by nitric oxide and prostacyclin.

The aim of this work was to investigate the influence of endothelium-derived nitric oxide and prostaglandins on the contractile responses of isolated dog pulmonary arteries to electrical field stimulation and noradrenaline. Electrical field stimulation (1-8 Hz, 20 v, 0.25 ms duration, for 30 s) produced frequency-dependent contractions that were abolished by tetrodotoxin, guanethidine and, prazosin (all at 10(-6) M). Noradrenaline induced concentration-dependent contractions with an EC50, of 1.85 x 10(-6) M. The increases in tension induced by electrical stimulation and noradrenaline were of greater magnitude in arteries denuded of endothelium. In segments with endothelium, N(G)-nitro-L-arginine methyl ester (10(-4) M) or indomethacin (10(-5) M) had no effects on the basal tone, but significantly enhanced the neurogenic and noradrenaline-induced contractions. The potentiation by N(G)-nitro-L-arginine methyl ester of electrical stimulation-induced contractile responses was partially reversed by L-arginine (10(-4) M). In the presence of N(G)-nitro-L-arginine methyl ester together with indomethacin the electrical stimulation-induced contractile responses were higher than those obtained when only N(G)-nitro-L-arginine methyl ester or indomethacin was used. N(G)-nitro-L-arginine methyl ester and indomethacin did not influence neurogenic-induced contractile responses of endothelium-denuded arteries. The results suggest that endothelial cells of isolated dog pulmonary arteries depress the contractile response to electrical field stimulation of intramural nerves and that endothelium-derived dilator prostaglandins and nitric oxide may interact to inhibit contractile effects of adrenergic stimulation.

Reduction of atrial fibrillation inducibility by radiofrequency ablation: an experimental study.

UNLABELLED: A study is made of the antifibrillatory effects of radiofrequency (RF)-induced atrial lesions using nine Langendorff-perfused rabbit hearts in which the atrial electrophysiological properties and atrial fibrillation (AF) inducibility were modified by atrial stretching. Using a multiple electrode consisting of 121 unipolar electrodes, determinations were made of the atrial refractory periods, conduction velocity, wavelength of the atrial activation process, and the inducibility of sustained AF episodes (duration over 30 s) by atrial burst pacing in four situations: (a) control; (b) following dilatation of the right atrium; (c) after adding an RF linear lesion at the cava-tricuspid annulus isthmus; and (d) after adding two RF linear lesions rounding the base of the right atrial appendage and extending from the inferior zone of the sulcus terminalis to the anterior wall of the appendage. Under control conditions, AF was not induced in any of the experiments. The wavelengths were 10.5 +/- 1.2 cm for basic cycles of 250 ms and 6.6 +/- 0.5 cm for cycles of 100 ms. Following dilatation, a significant decrease was recorded in the atrial refractory periods, conduction velocity, and wavelength, which reached values of 6.1 +/- 0.7 cm (250-ms cycle, P < 0.01), and 3.9 +/- 0.3 cm (100-ms cycle, P < 0.01); AF was induced in five cases (P < 0.05). After producing the lesion at the cava-tricuspid isthmus, the electrophysiological modifications induced by atrial dilatation persisted (wavelength = 6.2 +/- 0.6 cm (250-ms cycle) and 4.3 +/- 0.3 cm (100-ms cycle); P < 0.01 vs the control) and AF was triggered in eight cases (P < 0.0001). In turn, on adding the two lesions at the right atrial free wall and appendage, AF was induced only in one experiment (P = NS vs control), and the dilatation-induced decrease in refractoriness and wavelength was attenuated. Nevertheless, differences remained significant with respect to the controls, with the exception of the functional refractory periods determined at cycles of 100 ms. In this phase, the wavelength was 6.6 +/- 0.7 cm (250-ms cycle, P < 0.01 vs control) and 4.9 +/- 0.5 cm (100-ms cycle; P < 0.05). Atrial conduction between the zones separated by the lesions was blocked at any frequency, or selectively at rapid atrial activation frequencies. IN CONCLUSION: (a) the production of three linear lesions in the right atrium (cava-tricuspid isthmus, atrial appendage, and inferior free wall) reduces AF inducibility in the experimental model used; (b) conduction block (either absolute or frequency dependent) through the lesions, reduction in tissue mass caused by lesion creation, and possibly the attenuation of the shortening of atrial refractoriness and wavelength in the zones not separated by the lesions are implicated in the reduction of AF inducibility; and (c) the single lesion in the cava-tricuspid isthmus does not impede AF inducibility.

[Acute changes in wavelength of the process of auricular activation induced by stretching. Experimental study]. / Modificaciones agudas de la longitud de onda del proceso de activación auricular inducidas por la dilatación. Estudio experimental.

OBJECTIVE: An evaluation is made of the acute modifications in the wavelength of the atrial excitation process induced by atrial stretching. MATERIAL AND METHODS: In 10 isolated Langendorff-perfused rabbit hearts and using a multiple electrode the wavelength of the atrial activation process (functional refractory period x conduction velocity) was determined in the right atrium. An analysis was also made of the inducibility of rapid repetitive atrial responses after 20 episodes of atrial burst pacing. Measurements were made under control conditions, after inducing two degrees of atrial wall stretch (D1 and D2), and following the suppression of atrial dilatation. RESULTS: Under control conditions the wavelength was 72.6 +/- 7.7 mm (250 ms cycle) and 54.0 +/- 5.1 mm (100 ms cycle). In D1 (mean longitudinal increase in atrial wall length = 24 +/- 3%) the wavelength shortened, with values of 59.8 +/- 6.6 mm (250 ms cycle; p < 0.01) and 44.9 +/- 5.1 mm (100 ms cycle; p < 0.01). In D2 (mean longitudinal increase in atrial wall length = 41 +/- 4%) the wavelength also shortened significantly, with values of 41.6 +/- 2.5 mm (250 ms cycle; p < 0.01 vs control) and 29.6 +/- 2.1 mm (100 ms cycle; p < 0.01 vs control). After suppressing atrial dilatation the wavelength was 65.7 +/- 8.0 mm (250 ms cycle, NS vs control) and 47.9 +/- 5.5 mm (100 ms cycle; NS vs control). The inducibility of rapid repetitive atrial responses increased during dilatation (22 episodes with over 30 consecutive repetitive responses in D1 [p < 0.01], 50 episodes in D2 [p < 0.001] vs 5 episodes under control conditions), and diminished after suppressing atrial dilatation (0 episodes with over 30 consecutive repetitive responses; p < 0.05). CONCLUSIONS: In the experimental model used, acute atrial dilatation produced a shortening in refractoriness and a decrease in conduction velocity. Both effects shortened the wavelength of the atrial activation process, facilitating the induction of atrial arrhythmias. The effects observed reverted upon suppressing atrial dilatation.

Acute effects of radiofrequency ablation upon atrial conduction in proximity to the lesion site.

The electrophysiological effects of RF ablation upon the areas in proximity to the lesioned zones have not yet been well characterized. An experimental model is used to investigate atrial conduction in the boundaries of RF damaged zones. In 11 isolated and perfused rabbit hearts, endocardial atrial electrograms were recorded using an 80-lead multiple electrode positioned in the left atrium. Both before and after the RF application (5 W, 8 s, 1-mm diameter unipolar epicardial electrode) in the mid-portion of the free left atrial wall, measurements were made of conduction time from the pacing zone (posterior wall of the left atrium) to three points between 7.5 and 7.9 mm distal to the damaged zone. Conduction velocity and the direction of the activation propagation vector were determined in ten groups of four electrodes positioned around the damaged zone, and at the left atrial appendage. The mean diameter (+/- SEM) of the transmural lesions produced by RF ablation and defined by macroscopic examination was 4.2 +/- 0.2 mm. The conduction times to the three points distal to the lesion site were significantly prolonged as a result of RF ablation; 7.6 +/- 0.4, 7.4 +/- 0.5, and 6.9 +/- 1.0 ms (control); and 11.3 +/- 1.0 (P < or = 0.01), 11.1 +/- 1.3 (P < 0.01), 10.6 +/- 1.4 ms (P < 0.05) (post-RF). The differences between the conduction velocities determined in the areas surrounding the lesion, before and after RF application, failed to reach statistical significance: 86.2 +/- 6.5 cm/s (control) versus 75.5 +/- 5.7 cm/s (post-RF) (NS). After RF, significant variations were only observed in the direction of impulse propagation in the proximal-inferior quadrant adjacent to the lesion site, the difference being -61 degrees +/- 18 degrees (P < 0.02). In 2 of 4 experiments in which the lesion size was increased by a second RF application (5 W, 16 s), tachycardias with activation sequence around the lesion could be induced, with cycle lengths of 56 and 50 ms, respectively. In the atrial wall, the conduction times to the regions distal to the RF lesion are significantly prolonged. No significant changes are observed in conduction velocity in the areas in proximity to the lesion. Prolonged conduction to the areas distal to the ablation site is due to the lengthened pathway traveled by the impulses in reaching these areas. Tachycardias with activation patterns that suggest reentry around the RF damaged zone may be induced.

Are double potentials markers of a specific zone of the atrioventricular junction in the isolated rabbit heart?

A study is made of the characteristics of the atrial potentials recorded in the Koch triangle and its proximity, their variations on modifying the site of cardiac pacing, and their usefulness as markers of a distinct zone of the AV junction. In 12 isolated and perfused rabbit heart preparations an analysis was made of the endocardial atrial electrograms recorded with a multiple electrode positioned in the AV junction. The electrograms were obtained during spontaneous rhythm and on pacing at the crista terminalis (CT), interatrial septum (IAS), left atrium, and right ventricle. Double potentials were frequently obtained. On pacing at the CT, high-low double potentials (DP [H-L]) were more frequent (P < 0.05) in the low CT (11% +/- 4% of the electrodes) and posterior zone of the Koch triangle (6% +/- 5%), than in the IAS (1% +/- 2%) and anterior zone of the Koch triangle (2% +/- 3%). A similar tendency was observed either on pacing at the left atrium or during spontaneous rhythm. During pacing at the IAS the percentages of low-high double potentials (DP (L-H]) were significantly higher (P < 0.05) in the low CT (7% +/- 6%). DP (H-L) were of low sensitivity in indicating a given zone; maximum sensitivity was 61% in the low CT when pacing at the CT. DP (L-H) proved even less sensitive in indicating a given zone, though their specificity was greater in the low CT (91%) during pacing at the IAS. The specific zones in which the highest percentages of DP (H-L) or DP (L-H) are obtained depend on the site of cardiac pacing. On pacing at the IAS, DP (L-H) are more specific of the low CT. During pacing at both the CT and at the IAS, DP (H-L) sensitivity in indicating a given zone is low.