Biomedical subjects

R Cardinal

Publications and source records attributed to R Cardinal.

At least 19 recordsLinked to original sources

PubMed1996

Cycle length dynamics and spatial stability at the onset of postinfarction monomorphic ventricular tachycardias induced in patients and canine preparations.

BACKGROUND: The aim of this study was to determine whether cycle length (CL) variations at the onset of monomorphic ventricular tachycardias follow distinctive patterns. METHODS AND RESULTS: We retrospectively analyzed 59 monomorphic ventricular tachycardias induced in 40 patients in whom intraoperative mapping was performed with 63 epicardial and 64 endocardial electrograms recorded simultaneously. Activation times and CL were determined at each electrode site over several beats (36+/-10 beats, mean+/-SD) starting with the first after programmed stimulation. In the majority of the tachycardias, CL variations were accounted for by fitting to an exponential function: CL=CLs+Ae-b/tau, where CLs is the stable CL, b is beat number, tau is the time constant (in beat number), and A is the magnitude of CL relaxation. A decelerating trend (with reference to rate) (negative A) accounted for 21 tachycardias, an accelerating trend in rate (positive A) accounted for 12 tachycardias, and 4 others displayed a double dynamic behavior, with an initial acceleration followed by a decelerating trend in rate. Among the ventricular tachycardias that were not fitted to exponential models, 12 showed a constant trend and 10 others showed irregular CL fluctuations. The monomorphic character of the tachycardias was established by principal-component analysis, which also indicated that CL dynamics associated with the accelerating and decelerating trends may be related to shortening and prolongation of activation times, respectively, occurring in equal proportion at all recording sites. In canine preparations in which reentry circuits could be mapped with high resolution, CL showed an accelerating trend in rate when circus movement of excitation occurred around a transmural scar in muscle generating unipolar electrograms with relatively high -dV/dtmax, and a decelerating trend in rate occurred when functional reentry occurred in muscle generating unipolar electrograms with depressed -dV/dtmax. CONCLUSIONS: Beat-to-beat CL variations may occur at the onset of sustained monomorphic ventricular tachycardia as a result of uniform acceleration or deceleration of activation times while the overall activation pattern remains constant. The associated initial trends in the rate of sustained monomorphic ventricular tachycardia follow typical patterns that might provide "signatures" corresponding to reentry substrates with distinctive functional properties.

Adult↗

PubMed1996

Mapping of septal ventricular tachycardia: clinical and experimental correlations.

In patients with chronic myocardial infarction, ventricular tachycardia originating in the interventricular septum may account for a significant number of arrhythmia recurrences after direct ablative operations. We used total computer-assisted cardiac mapping (epicardial sock, left and right ventricular endocardial balloon electrode arrays) to assess whether tachycardia originating in deep or right-sided layers of the interventricular septum is associated with a specific pattern of epicardial activation sequence. We performed these studies during operations in 18 patients and during experiments in 12 dogs in which a septal myocardial infarction was produced by ligating the anterior septal coronary artery. Intraseptal needle electrodes were plunged into the septum of all animal preparations to generate pace-mapping data and to obtain intraseptal recordings (six preparations) during reentrant ventricular tachycardia induced by programmed stimulation. In addition, pace-mapping data of infarcted canine heart preparations were compared with those of nine healthy heart preparations. In the clinical study, 31 ventricular tachycardias with a septal site of origin were analyzed. Twenty tachycardias displayed an epicardial breakthrough in the area of the interventricular groove, whereas 11 had an epicardial breakthrough in the right ventricular free wall. Biventricular endocardial mapping revealed that left septal endocardial activation preceded right septal activation in the former and that right septal activation occurred earlier in the latter. In the experimental study, 14 ventricular tachycardias (cycle length 146 +/- 34 msec) were induced by programmed stimulation in 11 infarcted heart preparations. Eight tachycardias displaying an epicardial breakthrough on the right ventricle were found to originate in the right ventricular septal subendocardial layers, whereas six tachycardias in which the epicardial breakthrough occurred on the anterior interventricular groove originated in the left ventricular septal subendocardial layers. The epicardial breakthrough preceded the left ventricular endocardial breakthrough in six tachycardias (85.7%) originating in intermediate or right ventricular septal layers, but in only one of five tachycardias originating in the left ventricular septal layers. In the pace-mapping study, the epicardial breakthrough shifted progressively from the right ventricular free wall toward the interventricular groove area in response to pacing from the right, intermediate, and left ventricular thirds of the basal septum. This relationship was similar for infarcted and noninfarcted hearts, although transseptal conduction time was prolonged in infarcted hearts (45 +/- 10 msec vs 33 +/- 7 msec, p < 0.01). Therefore the information integrated from the localization of the epicardial breakthrough and the relative timing between the epicardial and the left ventricular endocardial breakthroughs can be used to estimate the depth of the site of origin of septal ventricular tachycardias. This study confirms that a three-dimensional view of the substratum of ventricular tachycardia can be derived from simultaneous epicardial and left ventricular endocardial mapping and can provide a superior basis for therapeutic interventions.

Animals↗

PubMed1996

Kinin-induced prolongation of action-potential duration in right ventricular muscle from rat: involvement of B1 and B2 receptors.

Previous work has shown that, in rat ventricular muscle, bradykinin (BK) causes a dose-dependent increase in action potential duration (APD), an action that may be responsible for APD prolongation by captopril (kininase II). To determine which kinin receptor might be involved in APD prolongation, we studied the effects of B1- and B2-receptor agonists, as well as those of antagonists and mergepta (a kininase I inhibitor) added during BK superfusion. Action potentials were recorded by using the standard glass microelectrode technique in rat ventricular muscle preparations. Action-potential characteristics were compared between preparations superfused with peptide/drug-free Tyrode's solution (control group) and preparations superfused with peptide/drug-containing solution. APD was significantly longer in preparations superfused with BK (10(-8) M) than in the control group. The APD prolongation induced by BK, a known B2-receptor agonist, was significantly reduced by Hoe 140 (a B2 antagonist) and also by Lys[Leu8]des-Arg9-BK (a B1 antagonist), an action presumably related to inhibition of B1 receptor stimulation by the BK metabolite des-Arg9-BK. When mergepta was added in the presence of BK, APD prolongation by BK was significantly reduced, an effect that could have been related to reduced B1-receptor stimulation after inhibition of the endogenous generation of des-Arg9-BK by kininase I. Sar4-[d-Phe8]des-Arg9-BK, a B1-receptor agonist that is not degraded by kininase II, also prolonged APD. We conclude that both B1 and B2 receptors may be involved in APD prolongation induced in rat ventricular muscle preparations.

3-Mercaptopropionic Acid↗

PubMed1996

Direct chronotropic effects of atrial and C-type natriuretic peptides in anaesthetized dogs.

1. The chronotropic effects of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) were investigated using injections (50 micrograms in 1 ml of Tyrode solution as bolus over 1 min) directly into the sinus node artery of 21 anaesthetized and vagotomized dogs which had been pretreated with a beta-adrenoceptor antagonist. The injections were also repeated following: (a) alpha-adrenoceptor antagonism (prazosin) and muscarinic receptor antagonism (atropine); (b) inhibition of prostaglandin synthesis (indomethacin); (c) angiotensin II AT1 receptor antagonism (losartan); (d) histamine H1 (mepyramine) and H2 (cimetidine) receptor antagonism. 2. The results obtained indicate that ANP had no significant effect on the basal sinus rate, whereas CNP produced a slight but significant increase of 12 +/- 2 beats min-1. The effect of CNP was long-lasting (return to pre-injection levels after maximum effect in 17 +/- 3 min) and was not influenced by the various antagonists mentioned above. 3. During in vitro experiments on spontaneously beating right atria isolated from 6 dogs, the injection of CNP (50 micrograms in 1 ml of Tyrode solution) into the sinus node artery produced an increase in atrial rate of 14 +/- 1 beats min-1. 4. The results of this work indicate that CNP exerts a significant and prolonged positive chronotropic effect both in vivo and in vitro. Other studies are required to elucidate the mechanism of action of CNP on the heart conduction system, to ascertain the presence of natriuretic peptide receptor B in the region of the sinoatrial node and to determine the role of CNP in the control of heart rate.

Adrenergic beta-Antagonists↗

PubMed1996

Ventricular, but not atrial, M2-muscarinic receptors increase in the canine pacing-overdrive model of heart failure.

OBJECTIVE: To investigate the effects of heart failure induced by chronic rapid ventricular pacing (six weeks) on canine atrial and ventricular muscarinic receptors. DESIGN: Dogs (n = 4) were fitted with a bipolar pacing electrode connected to a Medtronic pacemaker set at 240 stimuli/min. Pacing was maintained for six weeks. Tissue samples obtained from the left atrium and ventral wall of the left ventricle were frozen at -70 degrees C. Control tissue was obtained from normal dogs (n = 6) following anesthesia and thoracotomy. M2-muscarinic receptors were characterized and quantified in tissue micropunches using the hydrophilic ligand [3H] N-methyl-scopolamine (NMS). MAIN RESULTS: Cardiac tissue bound [3H] NMS with the specificity of an M2 subtype. Tachycardia-induced heart failure did not affect atrial muscarinic receptors but signify left ventricular myocytes (control 160.0 +/- 10.0 fmol/mg protein versus heart failure 245.0 +/- 25.0 fmol/mg protein; P < 0.01). CONCLUSIONS: Canine ventricular muscarinic receptors display a specificity for the M2 subtype. In contrast to previous work, tachycardia-induced heart failure was accompanied by an increase (+ 53%) in ventricular, but not atrial, M2 receptors compared with normal dogs.

Animals↗

PubMed1996

Class III antiarrhythmic effects of ceruloplasmin on rat heart.

Recently it has been shown that ceruloplasmin presents a protective action against reperfusion-induced arrhythmias in the isolated perfused rat heart, an effect that is lost when the protein is denaturated by heat. The present study was carried out to see whether ceruloplasmin can alter electrophysiological properties such as ventricular effective refractory periods, conduction time, and action potential duration calculated at 50, 75, and 90% levels of repolarization (APD50, APD75, APD90). To check the specificity of the electrophysiological effects of ceruloplasmin, we have also compared them with those of heat-denatured ceruloplasmin, superoxide dismutase, catalase, deferoxamine, and albumin. In isolated rat hearts, ceruloplasmin (0.25-3 microM) (n = 8 for each concentration) was shown to increase the effective refractory period in a concentration-dependent manner by 26 to 89%. Conduction time was not significantly altered. Heat-denatured ceruloplasmin (0.50-3 microM) (n = 8 for each concentration) increased the effective refractory period by 33 to 70% and did not affect the conduction time. In contrast, superoxide dismutase (1-4 microM), catalase (1-2 microM), deferoxamine (500 microM-1 mM), and albumin (1-4 microM) (n = 8 for each substance and for each concentration) had no significant effect on effective refractory period and conduction time at any dose, suggesting that the ceruloplasmin effect might be specific. In rat ventricular preparations, ceruloplasmin (1 microM) also induced a constant prolongation of APD50 (52%), APD75 (64%), and APD90 (41%) after 15 min of infusion (n = 6). The prolongation of effective refractory period and of action potential duration, by native and heat-denatured ceruloplasmin, suggests that this substance has specific class III effects, although this cannot entirely account for its antifibrillatory action at reperfusion in isolated rat hearts.

Action Potentials↗

PubMed1996

Reduced capacity of cardiac efferent sympathetic neurons to release noradrenaline and modify cardiac function in tachycardia-induced canine heart failure.

To investigate the capacity of efferent sympathetic neurons to modulate the failing heart, stellate ganglion stimulation was performed in dogs with biventricular heart failure induced by rapid ventricular pacing (240 beats/min) for 4-6 weeks. Less noradrenaline was released from cardiac myoneural junctions into coronary sinus blood in response to left stellate ganglion stimulation in anesthetized failing heart preparations (582 pg/mL, lower and upper 95% confidence intervals of 288 and 1174 pg/mL, n = 19) compared with healthy heart preparations (6391 pg/mL, 95% confidence intervals of 4180 and 9770 pg/mL, n = 14; p < 0.001). There was substantial adrenaline extraction by failing hearts (49 +/- 6%), although it was slightly lower than in healthy heart preparations (65 +/- 9%, p = 0.055). In contrast with healthy heart preparations, no net release of adrenaline occurred during stellate ganglion stimulation in any of the failing heart preparations, and ventricular tissue levels of adrenaline fell below the sensitivity limit of the HPLC technique. In failing heart preparations, maximal electrical stimulation of right or left stellate ganglia resulted in minimal augmentation of left ventricular intramyocardial (17%) and chamber (12%) systolic pressures. These indices were augmented by 145 and 97%, respectively, following exogenous noradrenaline administration. Thus, the cardiac efferent sympathetic neurons' reduced capacity to release noradrenaline and modify cardiac function can contribute to reduction of sympathetic support to the failing heart.

Animals↗

PubMed1996

[A study of autonomic innervation of the atrial septum by iso-integral mapping in dogs].

Although neuronal cell bodies have been identified in the upper part of the atrial septum, the functional anatomy of its autonomic innervation remains unknown. To study parasympathetic inputs to the atrial septum, we performed isointegral distribution mapping using a 64-electrode balloon array inserted in the right atrium under cardiopulmonary bypass in 9 anesthetized mongrel dogs. Unipolar electrograms were recorded during stimulation of either the right or left vagus nerve or right atrialpulmonary vein ganglionated plexus before and after surgical ablation of tissues along the superior vena cava, of the right atrial-pulmonary vein ganglionated plexus, the aorto-pulmonary tissues and the inferior vena cava fat pad. Local neural effects were estimated from integral changes of each electrogram which were plotted on a septal grid to generate isointegral distribution maps. Changes were considered significant whenever integral differences exceeded twice the standard deviation of control values. Stimulation of the right and left vagi induced significant effects in the high atrial septum in 5 preparations and in the low septum in 6. These effects were suppressed by the dissection of tissues around the superior vena cava and ablation of the right atrial-pulmonary vein ganglionated plexus, but not by that of the inferior vena cava or the aorto-pulmonary tissues. Direct stimulation of the right atrial-pulmonary vein ganglionated plexus produced effects in the high and low septum in 8 and 4 preparations, respectively, which persisted after dissection around the superior vena cava, suggesting the existence of local circuit neural elements. We conclude that the canine atrial septum is innervated by axons from both vagi which course near the superior vena cava and converge through the right atrial-pulmonary vein ganglionated plexus and also by intrinsic neural elements independent of central parasympathetic efferents.

Animals↗

PubMed1995

Body surface potential distributions during idiopathic ventricular tachycardia.

BACKGROUND: The purpose of this report is to describe the body surface potential maps (BSPMs) during idiopathic ventricular tachycardia (VT) and to determine what differences exist between different idiopathic VT morphologies. METHODS AND RESULTS: We performed BSPMs during VT on 12 consecutive patients (3 women and 9 men; mean age, 42 +/- 13 years) presenting symptomatic idiopathic VT referred to our institution for electrophysiological study. Basal ECG, chest radiograph, and echocardiogram were normal in all patients. Clinical tachycardia showed left bundle branch block pattern (LBBB) in 9 patients, with sustained VT in 5 and nonsustained VT in 4, and right bundle branch block pattern (RBBB) in 3 with sustained VT. We found a unique pattern of BSPMs in each of the 9 patients during idiopathic LBBB VT configuration, whether sustained or nonsustained VT. This pattern appeared at the onset of the QRS and remained stable during the whole QRS complex. The area of minimal potential located in the upper anterior part of the torso was compatible with an origin of VT in the right ventricular outflow tract, as confirmed in 5 patients by successful radiofrequency ablation. We found an evolving pattern with two phases in each of the three RBBB VTs. The electrical axis during the initial part of the QRS could correspond to an endocardial-epicardial vector. The second phase, with a high voltage and area of minimal potential located in the inferior and anterior part of the torso, was compatible with a left ventricular apical origin that was confirmed by epicardial and endocardial mapping during cryosurgery in 1 patient. For all the VTs, the QRS isoarea maps showed the same pattern as the second phase of the QRS. CONCLUSIONS: Two different BSPM patterns were found. All LBBB VTs had the same stable pattern corresponding to an infundibular origin. All RBBB VTs had an evolving pattern that stabilized in the second part of the QRS complex corresponding to an apical origin.

Adult↗

PubMed1995

Three distinct patterns of ventricular activation in infarcted human hearts. An intraoperative cardiac mapping study during sinus rhythm.

BACKGROUND: Comprehensive data based on single-beat analysis of the ventricular activation sequence during sinus rhythm in infarcted hearts are currently not available. It was the aim of our study (1) to measure and analyze these activation sequences on the epicardial surface of the right and left ventricles and on the left ventricular endocardial surface, and (2) to correlate specific activation patterns with the surface ECG. METHODS AND RESULTS: Isochronal maps were computed from 127 endocardial and epicardial unipolar electrograms recorded simultaneously during sinus rhythm in 45 post-myocardial infarction patients operated on for recurrent ventricular tachycardia (age, 57 +/- 10 years [mean +/- SD], left ventricular ejection fraction, 29 +/- 9%). Patients with bundle-branch block, but not with intraventricular conduction defects, were excluded. Data such as the timing of initial and terminal activation, the number of breakthroughs, the total activation time, and the number of ventricular segments without activation were measured and analyzed according to location of the myocardial infarction. The global epicardial activation was characterized in all patients by a widespread initial breakthrough on the anterior right ventricle (16 +/- 8 milliseconds after QRS onset), which was followed by one or two other breakthroughs in 65% of patients. Subsequently, three characteristic epicardial patterns of the activation spread were found: (1) radial, from the right to the left ventricle, found in all patients with inferoposterior myocardial infarction; (2) counterclockwise rotation, in which posteroseptal crossing preceded the anteroseptal crossing, found in 38% of patients with anterior myocardial infarction; and (3) pincerlike encirclement, in which both septal crossings and/or breakthroughs occurred nearly simultaneously and merged at the left ventricular free wall (typical for apical involvement in anterior and combined myocardial infarction). The simultaneous presence of multiple major activation wave fronts typically found in patients with the pincerlike activation pattern was reflected on the surface ECG by multiphasic, notched QRS complexes. Activation delay was observed in 89% of patients, and terminal activation was topographically related to myocardial infarction in 94% of patients. Delayed activation exceeding the surface QRS was observed in 11% and 31% of cases on the endocardium and epicardium, respectively. CONCLUSIONS: These results offer a solid basis for a more precise interpretation of a wide range of electrophysiological data and provide a framework for future investigations of surface ECG reflections of endocardial and epicardial activation patterns recorded in patients with chronic myocardial infarction.

Electrocardiography↗

PubMed1995

Differential effects of lignocaine and hypercalcaemia on anisotropic conduction and reentry in the ischaemically damaged canine ventricle.

OBJECTIVE: Anisotropic conduction characteristics, which may be expressed as the ratio of conduction velocities in the longitudinal (Vlong) and transverse (Vtrans) fibre directions, have been shown to stabilise reentry and favour the induction of sustained, uniform ventricular tachycardia. The aim of this study was to investigate whether interventions affecting either excitability (lignocaine) or both excitability and cell coupling (hypercalcaemia) might produce differential effects on the Vlong/Vtrans ratio, and whether an intervention reducing this ratio might prevent the induction of sustained reentrant ventricular tachycardia. METHODS: The effects of hypercalcaemia [8.2(SD 3.8) mmol.litre-1] and lignocaine infusion [to 24.4(19) and 42.3(29) mumol.litre-1] on Vlong and Vtrans were determined from 127 electrograms recorded with a plaque electrode on the anterior left ventricular wall of healthy dogs or 3 d after occlusion of the left anterior descending coronary artery. Vlong and Vtrans were computed from isochronal maps displaying ellipsoid patterns with a long axis corresponding to longitudinal conduction and a short axis corresponding to transverse conduction, as determined during basic (S1) and premature (S2) stimulation from the centre of the plaque electrode. Infarcted heart preparations were subjected to programmed stimulation for induction of reentrant ventricular tachycardias. RESULTS: Hypercalcaemia reduced both Vlong and Vtrans (P < 0.05) but did not modify either the Vlong/Vtrans ratio or the induction and patterns of ventricular tachycardias. Lignocaine reduced Vlong and the Vlong/Vtrans ratio during premature stimulation (S2) of infarcted heart preparations (P < 0.05) and stabilised reentrant ventricular tachycardias in preparations in which only nonsustained, multiform ventricular tachycardias were induced under control conditions. CONCLUSIONS: Conduction velocities in the longitudinal and transverse directions can be differentially affected by selected pharmacological interventions, but the Vlong/Vtrans ratio is not a representative index of the facilitating influence of tissue anisotropy on reentry. Therefore, the role of anisotropy in this model of reentry is not confined to establishing disparity of a functional character between conduction velocities in the longitudinal and transverse directions.

Animals↗

PubMed1995

Clinical applications of BSM.

Body surface mapping (BSM) has now become a feasible clinical technique, providing useful information applicable to the diagnosis of cardiac arrhythmias and their treatment by surgical and endocardial catheter ablation. In WPW patients, validation of preexcitation patterns has been obtained by computer simulation and by direct epicardial mapping at surgery. BSM pacemapping has subsequently been developed to be used during radiofrequency catheter ablation. This method has been evaluated prospectively and its predictive accuracy assessed. The recognition of two distinct BSM patterns in idiopathic ventricular tachycardia, has led to the application of successful pacemapping for radiofrequency catheter ablation. The use of a realistic tri-dimensional heart-torso computer model has shown that specific sites of endocardial stimulation are related to distinct thoracic map patterns.

Body Surface Potential Mapping↗

PubMed1995

Regional distribution of atrial electrical changes induced by stimulation of extracardiac and intracardiac neural elements.

UNLABELLED: Autonomic nerves and intrinsic cardiac neural elements are known to influence the electrophysiologic and dynamic properties of the heart. This study describes the regional distribution in the canine atria of electrophysiologic effects induced by stimulation of the right and left cervical vagosympathetic complexes, the right atrial ganglionated plexus, and the right and left stellate ganglia. Local atrial effects were determined from changes in QRST area of unipolar electrograms recorded from multiple sites with plaque electrodes sewn onto the atria in 16 anesthetized dogs. RESULTS: (1) Although being very consistent in any given preparation, atrial changes varied between animals when similar neural structures were stimulated. (2) Among the common features identified between preparations, consistent effects were induced by neural stimulation in the region of the sinus node, indicating that this atrial region is the most richly innervated. (3) All other regions of the atria could be affected by stimulation of either right-sided or left-sided efferent nerves. (4) Responses to right atrial ganglionated plexus stimulation after atropine administration indicated that the corresponding fat pad contains both sympathetic and parasympathetic neural elements. CONCLUSION: This study demonstrates that there is considerable overlapping of atrial innervation affecting all regions of the atria, as well as the sinus node region.

Animals↗

PubMed1995

Electrode polarity does not alter the initial ventricular activation sequence during pacing with extracardiac electrodes.

Ventricular epicardial mapping was performed in six closed-chest anesthetized dogs to investigate the cardiac electrical response to external pacing. A right thoracotomy was performed, complete AV block was produced by formaldehyde injected into the AV node and a sock electrode array, comprised of 127 unipolar electrodes, was placed over the ventricles. Isopotential and isochronal epicardial maps were generated by computer from the unipolar electrograms. Unipolar stimulation pulses were applied between pairs of different types of cutaneous (metal, carbon) and esophageal (metal) electrodes, and recordings were performed at maximum lung inflation. Isopotential maps recorded during the stimulation artifacts showed that the epicardial electrical field was little affected by the type of electrode but depended mostly on electrode position. A reproducible and relatively uniform apex-to-base potential gradient was regularly produced with anteroposterior and anteroesophageal electrode configurations. This uniform potential gradient induced ventricular activation sequences that showed interindividual differences. Thus, for each dog, the areas of initial activation observed on the isochronal maps during pacing tended to remain the same (i.e., apical, lateral, and anterior) despite changes in the stimulation protocol. Inverting the polarity of the electrodes did not appreciably change the site of origin of activation (81% remained the same) and activation never originated from the area showing the most negative potential during the stimulation artifact. In conclusion, since electrode polarity does not seem to alter the ventricular activation sequence during cardiac pacing with extracardiac electrodes, the standard nomenclature for cutaneous patches, which defines the negative electrode as the "active" electrode, may have to be revised.

Animals↗

PubMed1995

Hypoxia-induced release of prostaglandins: mechanisms and sources of production in coronary resistance vessels of the isolated rabbit heart.

The mechanism of hypoxia-induced prostacyclin (PGI2) release was studied in isolated, modified Krebs-Henseleit buffer perfused rabbit hearts under constant-flow conditions. The contribution of vascular endothelium and the role of catecholamines and calcium influx through L-type calcium (Ca2+) channels in hypoxic release of PGI2 were investigated. Reduction in the perfusion solution PO2 (from 476 +/- 13 to 127 +/- 24 mmHg; 1 mmHg = 133.3 Pa) in the presence of glucose (5 mM) and pyruvate (2 mM) caused a significant release of 6-keto-PGF1 alpha, the stable metabolite of PGI2 (from 3.0 +/- 0.4 to 7.3 +/- 2.0 pmol.min-1.g-1, p < 0.05, n = 12), whereas no variation in washout of catecholamines in the perfusate was observed. Electrolysis of the perfusion buffer solution was used to destroy the endothelium. Endothelium impairment by electrolysis almost completely abolished the vasodilation induced by serotonin (5HT) and acetylcholine (ACh), without affecting that caused by papaverine. The basal release of 6-keto-PGF1 alpha was significantly enhanced after electrolysis. However, its release during hypoxia was completely abolished. In a separate group of normal hearts, verapamil (10(-7) M) completely blocked the release of 6-keto-PGF1 alpha during hypoxia. Similar results were obtained in 15 mM KCl arrested hearts challenged with hypoxia. Under normoxic conditions, isoproterenol (10(-7) M) induced a significant release of 6-keto-PGF1 alpha (from 2.9 +/- 0.5 to 5.3 +/- 0.8 pmol.min-1.g-1, p < 0.05, n = 9). To stimulate endogenous catecholamine release, hearts perfused with glucose-free buffer (pyruvate 14.8 mM) were submitted to hypoxia. Under these conditions, hypoxia was accompanied by an enhanced release of noradrenaline (from 1.3 +/- 0.5 to 19.7 +/- 7.8 pmol.min-1.g-1). Despite the increased noradrenaline washout in effluent, the hypoxia-induced release of 6-keto-PGF1 alpha in glucose-free perfused hearts was not enhanced. Our results suggest that endothelial cells are the major site of PGI2 synthesis during hypoxia and that myocardial contractility is a prime factor involved in this process. Verapamil reduction of PGI2 release is most probably through its negative inotropic effect. Although exogenous beta-adrenergic stimulation can induce PGI2 release, endogenous catecholamines do not appear to contribute to the hypoxia-induced release of PGI2.

Animals↗

PubMed1995

[Identification of deep septal ventricular tachycardia substrates from epicardial breakthrough characteristics].

This study aimed to elucidate the relationship between the epicardial activation pattern and the site of origin of the ventricular tachycardia (VT) occurring from the interventricular septum, and to find epicardial breakthrough characteristics identifying VT substrates. Seven patients undergoing intraoperative mapping including right ventricular endocardial mapping were studied. Thirteen septal VTs, which were defined as VTs in which both right and left ventricular endocardial breakthroughs were on the septal aspect, were induced. The VT site of origin was identified from the site and timing of right and left septal endocardial breakthroughs. All VTs were classified into three groups according to the site of epicardial breakthrough: type A, epicardial breakthrough in the anterior interventricular area; type F, epicardial breakthrough in the right ventricular free wall; type P, epicardial breakthrough in the posterior interventricular area. All type F VTs had a right ventricular endocardial breakthrough in the anterior septum and preceded the left ventricular endocardial breakthrough, thereby indicating right anterior septal origin. In the types A and P, both the right and left endocardial breakthroughs were localized in consistent (anterior and posterior, respectively) halves of the septum, but their relative timing was inconstant. This result suggests that epicardial mapping, and even noninvasive methods like body surface mapping, can identify the site of origin of the septal VTs, especially when the epicardial breakthrough occurs in the right ventricular free wall.

Aged↗

PubMed1995

[Comparison of the infusion of acetylcholine into the artery of the sinoatrial node with the electric stimulation of cardiac parasympathetic nerves].

Atrial fibrillation occurring after open heart surgery largely depends on heterogeneous dispersion of refractoriness. To investigate the contribution of the autonomic nervous system in this phenomenon, we studied the regional distribution of neurally induced atrial electrophysiological events. Electrical stimulation of the right atrial fat pad, acetylcholine injection into the sinus node artery, and stimulation of the right and left vagosympathetic trunks were compared with respect to detailed atrial mapping. Unipolar electrograms were recorded from 127 atrial sites before and after neural stimulation or acetylcholine injection (10(-7) mol) in 8 anesthetized dogs. Regional changes in atrial repolarization were estimated by epicardial isointegral maps generated from computed values of the area under each electrogram and plotted on an atrial grid. The anatomical distribution of the sinus node artery was assessed by intra-arterial injection of microspheres. The effects of right and left vagal and right atrial fat pad stimulation extended contralaterally. Acetylcholine injected into the sinus node artery affected the lower left atrium whereas no microspheres could be found in this region upon microscopic examination. Therefore, this effect was possibly related to cholinergic activation of neuronal cell bodies located in the right atrial wall and projecting to the lower left atrium, supporting the hypothesis that local circuit neurons were involved in the activation of the intrinsic nervous system of the heart.

Acetylcholine↗

PubMed1994

Markedly different effects on ventricular remodeling result in a decrease in inducibility of ventricular arrhythmias.

OBJECTIVES: The purpose of this study was to determine whether the type and extent of ventricular remodeling after infarction influence inducibility of ventricular arrhythmias after infarction. BACKGROUND: Although serious ventricular arrhythmias after infarction are related to ventricular dysfunction, the relation between inducibility of ventricular arrhythmias and ventricular remodeling remains incompletely understood. METHODS: Rats that survived ligation of the left anterior descending coronary artery (n = 218) were randomized to receive placebo (saline solution) or captopril or propranolol therapy and were followed up for 5 weeks. Hemodynamic and neurohumoral blood measurements were obtained, and therapy was stopped. Two days later, susceptibility to ventricular arrhythmias was assessed by programmed electrical stimulation, and hearts were prepared for pathologic studies. RESULTS: Placebo-treated rats with a large myocardial infarction had ventricular dysfunction, marked neurohumoral activation, ventricular enlargement (endocardial circumference 16 +/- 3 [mean +/- SD] to 20 +/- 4 mm, p < 0.05) and increased cardiac fibrosis (volume density of collagen 2.3 +/- 0.8% to 5.6 +/- 2.4%, p < 0.05). In many rats this resulted in easily inducible ventricular arrhythmias (inducibility quotient 4.9 +/- 2.2). Captopril attenuated the development of ventricular dysfunction, neurohumoral activation, ventricular hypertrophy and dilation (endocardial circumference 18 +/- 3 mm) and cardiac fibrosis (3.1 +/- 0.8%, p < 0.05). These modifications were accompanied by decreased inducibility of ventricular arrhythmias (inducibility quotient 1.1 +/- 2.0, p < 0.05). Propranolol did not prevent ventricular dysfunction, had variable effects on neurohumoral activation and led to increased ventricular dilation (endocardial circumference 25 +/- 4 mm, p < 0.05) and cardiac fibrosis (7.7 +/- 1.2%, p < 0.05). Nevertheless, these morphologic changes led to decreased inducibility of ventricular arrhythmias (inducibility quotient 2.2 +/- 2.5%, p < 0.05). CONCLUSIONS: This study indicates that the inducibility of ventricular arrhythmias can be reduced as a result of markedly different effects on ventricular remodeling, indicating that the relation between ventricular remodeling, arrhythmias and survival is more complex than previously thought.

Animals↗