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Biomedical subjects

L Such

Publications and source records attributed to L Such.

At least 37 records · Page 2Linked to original sources

Radiofrequency versus pharmacologic modification of the atrioventricular node.

Although transcatheter radiofrequency modification of the atrioventricular (AV) node has been proposed as curative treatment in AV nodal reentry tachycardias, its role for the control of the ventricular rate in atrial tachyarrhythmias remains unclear. The aim of this study was to analyze the acute effect of radiofrequency current on AV nodal conduction and refractoriness, and to compare it with the effects of two antiarrhythmic drugs such as amiodarone (class III) and flecainide (class I). Twenty-one dogs were studied: (1) radiofrequency group (5 W for less than 45 seconds; 2 to 12 discharges; seven dogs); (2) amiodarone group (5 mg/kg intravenously; seven dogs); and (3) flecainide group (2 mg/kg intravenously; seven dogs). The following parameters were measured under basal conditions and after each procedure: AH interval, AV nodal functional refractory period, Wenckebach cycle length, minimum R-R interval during atrial fibrillation, and fitting of AV nodal function curve to a hyperbolic equation using its linear transformation. The AV nodal effective refractory period could not be calculated in any dog in the basal study because it was shorter than the atrial functional refractory period.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗

Effect of site, summation and asynchronism of inputs on atrioventricular nodal conduction and refractoriness.

The impulses coming from the sinus node synchronically penetrate the AV node via the crista terminalis and inter-atrial septum. Studies in superfused rabbit AV preparations suggest that the crista terminalis is a more effective input than the inter-atrial septum, and that the summation of both inputs facilitates AV nodal conduction. The aim of this study was to verify the hypothesis in a more physiological model, such as the whole rabbit heart perfused by a Langendorff system. Fifteen rabbit hearts were studied in a Langendorff perfusion system with six bipolar extracellular electrodes: two for stimulating (crista terminalis and inter-atrial septum) and four for recording (crista terminalis, inter-atrial septum, His bundle electrogram and right ventricle). Seven hearts (Group I) were consecutively paced at the crista terminalis, inter-atrial septum and both sites simultaneously, to determine the AV nodal Wenckebach cycle length and effective refractory period under basal conditions and after acetylcholine (0.75 x 10(-6) M). In eight hearts under 0.75 x 10(-6) M acetylcholine (Group II), the crista terminalis and inter-atrial septum were simultaneously (delay = 0 ms) or sequentially (delay = 2, 4, 6, 8, 10, 12, 14, and 16 ms) stimulated to calculate the AV nodal effective refractory period and the AH interval at an atrial coupling interval 5 ms longer than the AV nodal effective refractory period, for each delay tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in canine ventricular fibrillation threshold induced by verapamil, flecainide and bretylium.

The changes produced by verapamil, bretylium and flecainide in both ventricular fibrillation threshold (VFT) and ventricular repetitive response threshold (VRRT) were studied in 20 closed-chest dogs anaesthetized with pentobarbital. Right ventricle endocardium thresholds were determined using bipolar electrode catheters. Increasing intensity stimulus trains (200 ms, 4 ms, 100 Hz, 1 mA steps) were delivered 50 ms after QRS; VRRT and VFT were calculated before and after drug administration. Three study groups were considered according to the drug assayed: (1) verapamil 0.15 mg.kg-1 n = 6; (2) flecainide 2.0 mg.kg-1 n = 7, and (3) bretylium 10.0 mg.kg-1 n = 7. Flecainide significantly increased VRRT (4.8 +/- 1.4 vs 9.4 +/- 1.5 mA, P < 0.05), but the latter failed to change in the other two groups. VFT remained unchanged with verapamil, increased slightly post-flecainide (10.3 +/- 4.6 vs 12.4 +/- 4.1, P < 0.05 mA) and markedly post-bretylium (10.3 +/- 4.6 vs 17.3 +/- 7.5, P < 0.05). VFT changes were significantly correlated (r = 0.77, P < 0.05) with the effective refractory period changes in the bretylium group. Thus, of the three drugs tested, bretylium induced the greatest VFT increases without modifying VRRT, whereas flecainide affected both parameters. Only in the bretylium series were ERP changes significantly correlated to the corresponding VFT changes. This suggests that ventricular fibrillation threshold increase is not a non-specific property of antiarrhythmic drugs. Changes in ventricular repetitive response threshold may provide additional information.

Animals↗

Effect of glutathione on canine myocardial ischaemia without reperfusion.

The present study was to evaluate the effect of exogenous glutathione on myocardial damage resulting from permanent (no reperfusion) coronary ligation (3 or 6 h) in anaesthetized dogs. Haemodynamics, infarct size and myocardial glutathione content were determined. Erythrocyte superoxide dismutase (SOD) activity was also determined in coronary venous blood samples. Glutathione was administered by the intraperitoneal route, 100 mg kg-1 as initial dose given 5 min before coronary ligation, and successive doses of 25 mg kg-1 every 40 min throughout the study period. Saline-treated dogs showed myocardial infarction, a decrease in myocardial glutathione content, and a transient increase in SOD activity. Three hours occlusion in glutathione-treated dogs resulted in a small reduction of infarct size, and no changes in myocardial glutathione content and SOD activity. By contrast, administration of glutathione failed to reduce infarct size and failed to prevent myocardial glutathione decrease in dogs subjected to 6 h occlusion. These results indicate that exogenous glutathione is of minor beneficial effect for myocardial damage resulting from permanent coronary occlusion and suggest that endogenous glutathione has a limited role in protecting against myocardial ischaemia without reperfusion.

Animals↗

[Transcatheter ablation with high-frequency currents as a method for creating useful experimental models in the study of cardiac conduction and automatism].

PURPOSE: analyze the utility of transcatheter ablation with high-frequency currents to create different experimental models of altered cardiac automatism and conduction. METHOD: the results were obtained in six anesthetized dogs subjected to electrophysiological study after selectively applying transcatheter radiofrequency ablation to different zones of the specific cardiac conduction system. Ablation was carried out using conventional bipolar 7F catheter-electrodes. High-frequency currents (0.7 MHz) were emitted through the distal electrode, with variable intensity and duration according to the aim of the experiment. Anatomic (fluoroscopic) and electrophysiological criteria were used to position the electrode within the ablation zone. RESULTS: selective radiofrequency application to the atrioventricular junction zone affords complete A-V blocks with escape rhythms located in the A-V node or His-Purkinje system, together with different degrees of infra- and intra-hisian and intranodal blocks. The modification of intranodal refractoriness and conduction without interrupting atrial pulse transmission may manifest atypical patterns with truncated nodal conduction curves. The abolition of sinus function through ablation in the zone of the sulcus terminalis makes it possible to obtain supraventricular subsidiary rhythms. The obtaining of intranodal complete blocks with supra-Hisian escape rhythms demonstrates phenomena such as the modulation of subsidiary automatism by non-transmitted atrial pulses, analyzed by constructing phase-response curves. CONCLUSION: transcatheter ablation using high-frequency currents is useful in demonstrating phenomena related to intranodal and His-Purkinje conduction, subsidiary pacemaker automatism or the modulation of automatism and conduction via non-transmitted pulses.

Animals↗

The effects of selective stellate ganglion manipulation on ventricular refractoriness and excitability.

The effects of selective stellate ganglion stimulation or stellectomy on ventricular excitability were studied in 30 open chest mongrel dogs anesthetized with alpha-chloralose. The effective refractory period (ERP) and strength interval curves (stimulus intensity [S2] = twice the diastolic threshold [ERP], and 2, 3, 5, 7, and 14 mA) were determined using bipolar epicardial electrodes placed in the mid-anterior wall of the right ventricle (RV) and the mid-posterolateral wall of the left ventricle (LV) during left stellate ganglion stimulation (LSGSt, n = 8) or right stellate ganglion stimulation (RSGSt, n = 8), or after left stellectomy (LSGEx, n = 7) or right stellectomy (RSGEx, n = 7). LSGEx prolonged ERP-LV (172 +/- 9 vs 167 +/- 8 msec, P < 0.05) and ERP-RV (163 +/- 10 vs 158 +/- 14 msec, P < 0.05). RSGEx prolonged ERP-LV (168 +/- 17 vs 162 +/- 15 msec, P < 0.01) and ERP-RV (166 +/- 14 vs 160 +/- 13 msec, P < 0.01), and the times of the strength interval curves obtained for each S2 intensity in both ventricles. LSGSt decreased ERP-LV (157 +/- 11 vs 163 +/- 12 msec, P < 0.01) and ERP-RV (147 +/- 18 vs 157 +/- 17 msec, P < 0.05), and the times of the strength interval curves obtained for each S2 intensity in both ventricles. RSGSt did not significantly decreased ERP-LV (152 +/- 11 vs 156 +/- 9 msec); however, it significantly shortened the times of the strength interval curves obtained for S2 intensities of 2 and 7 mA in the LV, and shortened ERP-RV (139 +/- 10 vs 145 +/- 7 msec, P < 0.01) and the times of the strength interval curve for S2 intensities of 2, 3, and 5 mA in the RV. A significant interaction (MANOVA test) was observed between the ventricle studied and the ganglion stimulated for S2 intensities of 2 and 3 mA, and between the effect of stimulation and the ganglion stimulated for S2 intensities of 3 and 14 mA. To conclude, selective stellectomy prolonged epicardial ventricular refractoriness in both the mid-anterior wall of the RV and the mid-posterolateral wall of the LV; the magnitude of the epicardial excitability variations in both areas was different during selective stellate ganglion stimulation.

Analysis of Variance↗

Protective effect of N-acetylcysteine on ischaemia-induced myocardial damage in canine heart.

The glutathione redox pathway is an important antioxidant system in the myocardium. N-Acetylcysteine is a low molecular weight glutathione precursor that has been used clinically to replenish glutathione stores. The present study was aimed at evaluating the protective effect of N-acetylcysteine on myocardial damage resulting from permanent coronary occlusion (without reperfusion) in anaesthetized dogs. N-Acetylcysteine (150 mg kg-1 i.v.) administered 2 min before occlusion reduced infarct size in dogs subjected to 24 h ischemia. The infarct size as a percentage of the area at risk was 86.8 +/- 3.6% (n = 11) in control (saline-treated) dogs and 68.2 +/- 2.4% (n = 7; P less than 0.05 vs control) in N-acetylcysteine-treated animals. Haemodynamic variables (heart rate, mean arterial pressure and rate-pressure product) were similar in the control and the treated group. Regional myocardial blood flow was determined with radioactive microspheres in ischaemic and non-ischaemic zones before occlusion and 3 h post-occlusion. N-Acetylcysteine did not influence the regional distribution of myocardial blood flow. The myocardial content of reduced glutathione was significantly (P less than 0.05) decreased 3 h post-occlusion (0.53 +/- 0.19 mumol/g-1; n = 5) compared to either pre-occlusion values (0.94 +/- 0.03 mumol/g-1; n = 8) or values 3 h post-occlusion in sham-operated animals (0.93 +/- 0.15 mumol/g-1; n = 5). Depletion of myocardial glutathione 3 h post-occlusion was not observed in dogs treated with N-acetylcysteine (0.87 +/- 0.11 mumol/g-1; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗

Effects of atrial impulse timing on AV concealed conduction in the rabbit heart.

The influence of the timing of a nontransmitted or transmitted atrial impulse on the atrioventricular (AV) conduction time of the subsequent impulse was studied in nine isolated rabbit hearts. AV conduction curves were determined by applying the atrial extrastimulus test. The extrastimulus was delivered preceded or not by an interposed atrial impulse whose coupling interval with respect to the last atrial beat of a basic train was kept constant at 100, 120, 140, 160, 175, 200, 225, 250, and 300 msec. In all experiments, there was a "concealment interval," i.e., the AV effective refractory period was longer than the atrial functional refractory period, and in seven experiments was comprised between 100 and 160 msec. For any given extrastimulus coupling interval in the presence of an interposed nontransmitted atrial impulse, AV conduction time was significantly greater than in its absence; the increase was greater than the longer the nontransmitted atrial impulse coupling interval, i.e., the shorter the subsequent transmitted impulse coupling interval with respect to the previous interposed nontransmitted impulse. The AV conduction curves relating the extrastimulus AV conduction time to its coupling interval with respect to the last atrial impulse of the basic train fitted to a hyperbolic model both in the absence of the interposed atrial impulse and in its presence (mean square residual 31 +/- 23 msec2), and the interposed atrial impulse modified the constants of the functions; the slope of the linear transformations was progressively more negative as the interposed atrial impulse was delayed. Furthermore, the effects of the interposed atrial impulse--transmitted or not--on AV conduction time of the subsequent impulse were qualitatively similar, their magnitude depending on the time elapsed were qualitatively similar, their magnitude depending on the time elapsed between the two.

Animals↗

Atrioventricular electrotonic interaction in complete atrioventricular block: an experimental model using radiofrequency energy in the rabbit heart.

UNLABELLED: Provided the conditions for electrotonic transmission exist, an automatic focus surrounded by a block zone may be externally modulated. The atrioventricular (AV) electrotonic interaction was studied in 16 perfused rabbit hearts with supra-Hisian complete AV block induced using low radiofrequency energy doses (2.5 watts; 10 seconds). In nine experiments the sinus node was preserved (group I), whereas in seven it was removed maintaining an AV nodal rhythm (group II). The V-V (ventricular cycle length) and V-A (coupling of the intervening atrial beat) in both groups, and also the A-A (atrial cycle length) and A-V (coupling of the intervening ventricular beat) intervals in group II, were measured beat by beat after current delivery. The phase response curves V-V versus V-A, and A-A versus A-V showed AV interaction in five experiments from group I, and in four from group II, as follows: (1) accelerating phase response curve, characterized by a pacemaker acceleration (V-V or A-A abbreviation) at a critical V-A or A-V coupling interval; maximum acceleration could be progressively (phase response curve without rapid cross-over) or briskly (phase response curve with rapid crossover) reached; from this point onwards acceleration decreased with a further increase in V-A or A-V coupling interval (acceleration slope). (2) Biphasic phase response curve, characterized by initial delaying and late accelerating phases. Maximum acceleration and the acceleration slope were both smaller in accelerating phase response curves without rapid cross-over. On reverting complete block in two experiments, a progressive increase in maximum acceleration and acceleration slope was observed. CONCLUSIONS: (1) AV interaction in complete AV block can be manifested as accelerating or biphasic phase response curves; (2) transition from electrotonic interaction to conduction seems to be a continuum.

Animals↗

Transcatheter ablation of the sinus node in dogs using high-frequency current.

Sinus node ablation by high-frequency current (HFC) (0.7 MHz. 5-10 W), delivered through the distal electrode of a conventional endocavitary catheter, was induced in seven thoracotomized dogs under autonomic blockade. The HFC was delivered for variable periods of time under ECG monitoring, while sinus tachycardia was produced or after attaining sinus arrest. The procedure was repeated until a stable non-sinus rhythm was obtained. Sinus rhythm was abolished in all seven dogs after a variable number (7-20) of discharges. The escape rhythm obtained after the last discharge, characterized by means of epicardial electrodes and analysis of P-wave morphology, length of PR interval and the rate, showed an atrial activation pattern different from sinus rhythm in all cases. The P-wave was retrograde in two cases, and in one case no atrial activity was detected after the last discharge; however, atrial activity recovered after 35 min, the activation pattern being different from the controls. After 2 h, sinus rhythm had not returned in any case. In no case was there perforation of the atrial wall. Acute histological findings showed coagulation necrosis of the endocardium, extending to the muscle fibres and affecting the sinus cells.

Animals↗

Closed chest radiofrequency ablation of the sinoatrial node in dogs.

UNLABELLED: Transcatheter ablation of the sinoatrial node with radiofrequency energy (0.6 MHZ, 2.5-5 watts) was performed in 10 dogs under fluoroscopic monitoring and autonomic blockade. Sinus function was previously studied in terms of cycle length, recovery time and atrial activation pattern by catheter mapping. Several discharges (8-22) were applied for variable periods of time (maximum 1 minute). Sinus tachycardia and/or sinus arrest during ablation confirmed correct catheter position. Sinus rhythm was abolished in eight dogs. The ectopic rhythm was atrial in six and AV nodal in two dogs. Ectopic atrial cycle length and recovery time were longer than the baseline sinus values: 724 +/- 321 versus 509 +/- 147, P less than 0.05; 1103 +/- 775 versus 618 +/- 151, P less than 0.05 (values in msec). The study was repeated 10-14 days later in six dogs; three maintained the same atrial rhythm, one persisted in sinus rhythm, and one dog changed from atrial to sinus rhythm, whereas another changed from sinus to atrial rhythm. Gross findings revealed transmural lesions in all dogs, without perforation. Histology in chronic dogs showed sinus cell necrosis and its replacement by granulation tissue. IN CONCLUSION: sinus function may be abolished by closed chest radiofrequency ablation.

Animals↗

Induction of complete AV block in dogs by transcatheter ablation using high-frequency current: an alternative to direct-current high energy shock.

The utility of high-frequency current applied through the distal electrode of a conventional electrode-catheter for altering atrio-ventricular conduction was studied in 18 anaesthetized dogs. Following adequate unipolar His bundle recording, current was applied over periods of 20-30 s, with an output power of 30 W. Complete AV block was achieved in all dogs (four dogs on the third attempt, five on the second, and nine on the first). Ten of the dogs were killed after four hours of continuous ECG monitoring (Group I); examination revealed circumscribed spheroidal myocardial lesions at the base of the right atrium over the posterior tricuspid valve; no thrombus formation was encountered. The remaining eight dogs (Group II) were kept alive for three months during which complete block persisted in all cases. The histologic study showed partial replacement of AV nodal and His bundle tissues and myocardium by fibrous tissue. In conclusion, electro-catheter ablation using high-frequency energy is effective for producing complete AV block. The resulting lesions are circumscribed. This method may prove to be an alternative to the transcatheter DC shock for ablation of the AV conduction system.

Animals↗

[Prediction of the tachycardia cycle based on auriculoventricular re-entry. Experimental study in dogs].

Seven anaesthesized mongrel dogs subject to thoracotomy were used in a electronic simile of A-V accessory pathway with retrograde conduction to generate reentrant tachycardias with different ventriculo-atrial delays. This was done both under control conditions and following amiodarone i.v. administration. The ability to predict tachycardia cycle length was studied, using a mathematical model of the circuit, in which the cycle length is obtained from the function of nodal conduction and the time of extranodal conduction of the circuit. An analysis was made of the repercussions in using four different mathematical functions describing nodal conduction: three were non-linear (exponential and hyperbolic A and B) and one linear. In the case of the first three, the consequences of using a direct non-linear data-fitting procedure or an indirect procedure by linear transformations of the functions were studied. The exponential and hyperbolic B functions provide a better prediction of tachycardia cycle length on being used in the model; in the case of these functions, a mean value of the squared differences between the real and estimated values of 19.1 +/- 31.0 ms2 and 19.1 +/- 26.7 ms2, respectively, was obtained.

Animals↗

Mathematical descriptions of AV nodal function curves in dogs.

Thirty-four anaestheized mongrel dogs subjected to thoracotomy were used to study AV node conduction during atrial pacing at increasing rates. Epicardial atrial electrodes were used, together with endocavitary recordings of His bundle electrogram. An analysis was made of the repercussions involved in using four different mathematical functions describing nodal conduction: three were nonlinear (exponential and hyperbolic A and B) and one linear. In the case of the first three, the consequences of using a direct nonlinear data-fitting procedure or an indirect procedure by linear transformations of the functions were studied. The exponential and hyperbolic B functions provided the least mean squared residual in quantifying nodal conduction (8.6 +/- 10.8 ms2 and 10.8 +/- 13.9 ms2, respectively). The use of nonlinear function transformation into a linear representation caused loss of precision in the fit to the data in the case of the exponential function (18.3 +/- 22.2 ms2 versus 8.6 +/- 10.8 ms2, p less than 0.01) and, to a lesser extent, in the case of the hyperbolic B function (12.5 +/- 16.4 ms2 versus 10.8 +/- 13.9 ms2, P less than 0.05).

Animals↗

Myocardial glutathione alterations in acute coronary occlusion in the dog.

Glutathione (GSH) decreases in dog myocardium upon acute coronary occlusion when compared with sham-operated dogs. Total glutathione content (GSHeq = GSH + 2GSSG) remains unchanged throughout the experiment (6 h after surgery) in both sham- and acute coronary occlusion-operated dogs. GSSG and GSH/GSSG ratio increases and decreases respectively in all animals but tends to reach the normal value after 6 h in sham-operated dogs. Both parameters (GSSG and GSH/GSSG ratio) remain altered in acute coronary occlusion-operated ones. This alteration of glutathione status in ischemic myocardium is discussed.

Animals↗

[Quantification of concealed conduction in the atrioventricular node].

Twenty-eight anaesthetized open-chest mongrel dogs were used. Programmed atrial pacing was used and Hisian electrograms recorded through endocavitary electro-catheters to study and quantify the concealed conduction of non-transmitted atrial impulses in the A-V node. An exponential model was used in three situations to quantify the nodal conduction during incremental atrial pacing: a) during 1:1 conduction, b) during 2:1 nodal block, and c) during pacing, coupling an atrial impulse delivered at fixed intervals and blocked in the A-V node to each transmitted impulse. The relation between intranodal conduction times was analyzed both with and without the presence of blocked impulses, and the quotient between the obtained functions in situations b, c and situation a was determined. In a subgroup of 13 dogs the study was repeated following pharmacological block of the autonomic nervous system. In dogs with autonomic block, this relation always tended to decrease when the atrial pacing rate increased. The variations in the group of dogs with intact autonomic nervous systems were not homogeneous. During pacing with coupled block impulses, the progressive removal of conduction curves obtained for each coupling interval with respect to those obtained during 1:1 transmission, expresses the interval with respect ot those obtained during 1:1 transmission, expresses the lesser influence of the blocked impulses on decreasing their coupling interval.

Animals↗