Biomedical subjects
Publications and source records attributed to J Schreieck.
Explore the source record for details and available documents.
We report a patient in whom mapping of the right atrium with multipolar catheters and electroanatomic mapping revealed the presence of three dissimilar rhythms: a reentrant atrial tachycardia in the antero-lateral wall of the right atrium and an atrioventricular nodal reentrant tachycardia (AVNRT) isolated from each other and a conduction disturbance at the interatrial septum resulting in a rate-related interatrial block and a slow left atrial rhythm. The AVNRT was stopped with intravenous adenosine (6 mg) and induced repeatedly by atrial extrastimuli associated with a critical atrioventricular delay and dual atrioventricular nodal pathways. Electroanatomic mapping disclosed extensive fibrosis isolating viable myocardium of the antero-lateral wall from the rest of the right atrium. The viable myocardium in the antero-lateral wall was activated by a reentrant rhythm circulating around an islet of fibrosis located in the middle of the viable tissue. The AVNRT was ablated by a standard approach and the reentrant atrial tachycardia by producing a linear lesion bridging the central islet of fibrosis with the anterior tricuspid annulus. This case highlights the complicated nature of some dissimilar atrial rhythms and the power of electroanatomic mapping tools to reveal the exact mechanism and guide radiofrequency ablation.
OBJECTIVES: The aim of this prospective study was to evaluate the role of programmed ventricular stimulation (PVS) after noninvasive risk stratification to identify a subgroup of acute myocardial infarction (AMI) survivors considered at risk for ventricular arrhythmias and whether these patients could benefit from internal cardioverter-defibrillators (ICDs). BACKGROUND: The predictive value of noninvasive and invasive risk stratifiers after AMI has been questioned. The question of whether the group of patients with inducible monomorphic ventricular tachycardia (VT) after AMI could profit from ICD implantation is unanswered. METHODS: A consecutive series of 1,436 AMI survivors was screened noninvasively by Holter monitoring, heart rate variability, ventricular late potentials, and ejection fraction. A subgroup of 248 patients (17.3%) were identified as high-risk patients and scheduled for PVS. Due to the study design, 54 patients >75 years were excluded; thus, 194 patients were eligible for PVS. Triple extrastimuli at two paced cycle lengths (600 ms and 400 ms) were applied. RESULTS: In a subgroup of 98 (51%) high-risk patients, PVS was performed; 21 patients had an abnormal response, and in 20 patients an ICD was implanted. During a mean follow-up of 607 days the arrhythmic event rate (sudden cardiac death, symptomatic VT, cardiac arrest) was 33% with a positive electrophysiological test versus 2.6% (p < 0.0001) with a negative electrophysiological test. A subgroup of 96 high-risk patients declined electrophysiological study. In this nonconsent group, cardiac mortality (combined sudden and nonsudden) was significantly higher (log-rank chi-square 9.38, p = 0.0022, relative risk 4.7, 1.6 to 13.9) compared to the group guided by electrophysiological testing and consecutive ICD implantation. CONCLUSIONS: After a two-step risk stratification, PVS is helpful in selecting a subgroup of AMI survivors without spontaneous ventricular arrhythmias who benefit from prophylactic ICD implantation.
It previously has been reported in ischemic rat hearts that local release of noradrenaline triggers ventricular fibrillation via alpha1A-adrenoceptor stimulation. In order to elucidate the intracellular pathway mediating ventricular fibrillation in this setting, we used inhibitors or activators of protein kinase C in the absence or presence of the alpha1A-adrenoceptor antagonist WB 4101. Regional ischemia was induced in isolated perfused rat heart byligature of the left coronary artery. Pharmacological interventions were tested by addition of drugs to the perfusate 10 min prior to ligature and throughout 30 min of ischemia while the epicardial electrocardiogram was continuously monitored. Blockade of protein kinase C by polymyxin B (1 micromol/l) significantly reduced ventricular fibrillation to 40% (from 87% in controls). Similar effects were seen with the protein kinase C inhibitors staurosporine 10 nmol/l (46% vs. 91%) and cremophor RH 40 100 micromol/l (33% vs. 77%). Activation of protein kinase C by 1,2-dioctanoyl-sn-glycerol (DOG, 10 micromol/l) or phorbol 12-myristate 13-acetate (PMA, 10 nmol/l) did not affect ventricular fibrillation. In the presence of the alpha1A-adrenoceptor antagonist WB 4101 (0.1 micromol/l), which per se suppressed ventricular fibrillation to 17%, both DOG and PMA increased the occurrence of ventricular fibrillation to 73% and 75%, respectively, whereas the inactive phorbol ester 4alpha-phorbol 12,13-didecanoate (4alpha-PDD, 10 nmol/l) revealed no proarrhythmic effect. In summary, during regional ischemia in the isolated perfused rat heart, alpha1A-adrenoceptor stimulation induces ventricular fibrillation mainly by activating protein kinase C.
OBJECTIVES: The aim of the study was to analyze the electrophysiologic characteristics of paroxysmal (PAF) and chronic (CAF) atrial fibrillation (AF) in the human right atrium (RA). BACKGROUND: Differences that exist between PAF and CAF and the mechanisms of self-sustenance of these arrhythmias are incompletely understood. METHODS: A total of 53 patients with PAF (25 patients, mean age 59 +/- 6.1 years, 3 women) and CAF (28 patients, mean age 59 +/- 13 years, 7 women) underwent multisite mapping of the RA during ongoing AF using a 64-electrode basket catheter. Quantitative evaluation and three-dimensional activation patterns were performed using a computerized system. RESULTS: Patients with PAF, as compared with patients with CAF, had significantly longer AF cycle length, shorter time intervals with type III AF throughout the RA and a smaller number of endocardial breakthroughs (mean 51 +/- 19 vs. 104 +/- 40, p < 0.001). The majority of endocardial breakthrough points (88% in PAF patients and 98% in CAF patients) were located in the septal region and coincided anatomically with major interatrial connection routes. Coexistence of re-entrant and apparently focal activation determined maintenance of AF in the RA in PAF, whereas random re-entry was documented more frequently in patients with CAF. In patients with CAF, the duration of arrhythmia (in years) correlated strongly with the percentage of time during which type III AF was observed in the lateral wall of the RA (r = 0.71). CONCLUSIONS: Clinical PAF and CAF, as recorded in the RA, have, at least quantitatively, distinct electrophysiologic features and different mechanisms of maintenance.
This report describes a patient with advanced heart failure, pronounced intraventricular conduction delay, and ventricular tachycardias who underwent implantation of a multisite pacing ICD. Pacing leads were placed in the right atrium, right ventricular apex, and to the left ventricular posterior wall via a coronary sinus vein. The system proved to have correct sensing and pacing function in an atrial synchronized biventricular pacing mode and an appropriate detection of ventricular fibrillation. However, 1 month after implantation the patient received an inappropriate shock delivery due to double detection of ventricular premature beats. The inherent detection problem of dual ventricular sensing is discussed.
Three-dimensional visualization of cardiac activation has become important in providing further insights into pathophysiological mechanisms of arrhythmias and to increase the efficacy of catheter ablation. The noncontact mapping enables a single beat analysis in a reconstructed geometry of the cardiac chamber. The aim of the study was to describe three-dimensional activation patterns and inferior vena caval-tricuspid annulus (IVC-TA) isthmus conduction characteristics in patients with atrial flutter and the noncontact guidance of the radiofrequency ablation of this arrhythmia. In 34 patients with atrial flutter, the noncontact probe was deployed in the RA. The global three-dimensional activation and the isthmus conduction (enhanced density mapping) were delineated during ongoing a trial flutter and paced rhythms. Ablation was performed nonfluoroscopically based on reconstructed anatomy and conduction patterns. Noncontact mapping was compared and validated with conventional multielectrode technique. IVC-TA isthmus ablation was completed successfully in 33 (97%) of 34 patients. In one patient a lower loop reentry around the inferior vena cava was depicted as a mechanism of atrial flutter. In another patient with positive flutter waves in inferior leads, an activation pattern typical of counterclockwise flutter was demonstrated in propagation maps. During a follow-up of 15.9 +/- 5.9 months, two atrial flutter recurrences occurred (5.8%). A gap of the resumed conduction through the IVC-TA isthmus was delineated as a mechanism of recurrence and ablated with one and three radiofrequency applications. Noncontact mapping allows construction of the global activation patterns in typical and atypical atrial flutter. It enables the nonfluoroscopic guidance of atrial flutter ablation and a comprehensive evaluation of the ablation results.
INTRODUCTION: Supraventricular tachyarrhythmias are the main cause of inappropriate therapies in patients with conventional single chamber implantable cardioverter defibrillators (VVI-ICD). It was anticipated that dual chamber cardioverter defibrillators (DDD-ICD), with their capacity to analyze atrial and ventricular rhythm, could substantially reduce inappropriate therapies. METHODS AND RESULTS: Our prospective study included 92 patients (87 men; mean age 61 +/- 12.7 years) who were randomly assigned to a VVI-ICD (45 patients) or a DDD-ICD (47 patients). Both groups were followed for 7.5 +/- 3.5 and 7.6 +/- 4.1 months, respectively. During the follow-up period, overall 725 ventricular tachycardia (VT)/ventricular fibrillation (VF) episodes were recorded in 45 (49%) of 92 patients. Of these episodes, 404 (56%) occurred in the VVI-ICD group and 321 (44%) episodes occurred in the DDD-ICD group. Twenty-three (51%) patients in the VVI-ICD group and 22 (47%) patients in the DDD-ICD group (P = 0.8) developed VT/VF. Overall, 73 (10%) of 725 treated episodes were inappropriate in 6 (13%) patients in the VVI group and in 10 (21%) patients in the DDD-ICD group (P = 0.2). There were 22 (31%) inappropriately treated episodes in the VVI-ICD group and 51 (69%) in the DDD-ICD group. Thirty-two of the 51 inappropriate episodes in the DDD-ICD patients resulted from intermittent atrial sensing problems that led to failure of the respective dual chamber algorithms. Nonfatal complications occurred in 6 (13%) patients in the VVI-ICD group and in 3 (6%) patients in the DDD-ICD group (P = 0.7). CONCLUSION: We conclude that the implanted DDD-ICD and conventional VVI-ICD are equally safe and effective for therapy of life-threatening ventricular tachyarrhythmias. Although DDD-ICDs allow better rhythm classification, the applied detection algorithms do not offer benefits in avoiding inappropriate therapies during supraventricular tachyarrhythmias.
INTRODUCTION: Coronary sinus (CS) recordings are routinely used during electrophysiologic studies for various supraventricular and ventricular arrhythmias with the understanding that they represent left atrial (LA) activity. However, the behavior of CS electrical activity during atrial arrhythmias has not drawn any special attention beyond standard considerations. METHODS AND RESULTS: The study population consisted of 9 patients (3 women; mean age 59 +/- 11 years) with atrial fibrillation (AF) and atrial flutter (AFL) who developed dissociation of conduction between the CS and posterior LA during spontaneous AF and AFL. In all patients, the LA and the CS were mapped using a 64-electrode basket catheter and a multipolar electrode catheter, respectively. The right atrium (RA) was mapped simultaneously using a 24-polar electrode catheter (7 patients) or a 64-electrode basket catheter (2 patients). Eight patients showed stable double potentials in CS recordings during AF (9 episodes) and AFL (3 episodes). During ongoing arrhythmias, the first row of potentials maintained a constant relationship with the RA activity, whereas the second row of potentials was discordant with the posterior wall of the LA in 7 patients and concordant in 2 patients. In 1 patient with counterclockwise AFL, CS activation was isolated from the posterior wall of the RA until it reached the distal portion of the CS, after which it entered the lateral region of the LA. In 1 patient, a macroreentrant LA tachycardia involving CS muscle was observed. Rapid atrial pacing from the proximal CS and extrastimuli produced longitudinal dissociation of CS activation in all patients. CONCLUSION: Conduction between the CS and posterior LA can be dissociated during spontaneous atrial arrhythmias and provocative proximal CS pacing.
AIMS: The purpose of the study was to compare the efficacy and safety of sotalol and bisoprolol in the maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation. METHODS: Patients (n=128) were randomized to sotalol (80 mg b.i.d.) or bisoprolol (5 mg x day(-1)). Patients with contraindications to beta-blockers, class III antiarrhythmic drugs or prior treatment with use of study medication for prevention of atrial fibrillation were excluded. Follow-up clinical evaluation was performed 1 day and 1 month after cardioversion and thereafter at 3-month intervals. RESULTS: There were no group differences in baseline clinical characteristics. After a follow-up of 12 months, 59% of all patients were still in sinus rhythm. The fraction remaining in sinus rhythm was calculated for the two groups by Kaplan--Meier analysis. During follow-up, 41% of patients on sotalol and 42% on bisoprolol developed atrial fibrillation (ns). In two patients (3.1%) on sotalol, life-threatening proarrhythmias (torsade de pointes tachycardias) occurred, whereas none were found in the bisoprolol group. Symptomatic bradycardias occurred in two patients on sotalol and three on bisoprolol. CONCLUSION: This study demonstrates that sotalol (160 mg x day(-1)) and bisoprolol (5 mg x day(-1)) are equally effective in maintaining sinus rhythm. Because of the side effects of sotalol, bisoprolol seems to be advantageous for maintenance of sinus rhythm after cardioversion of atrial fibrillation.
OBJECTIVES: The relationships that exist between endocardial and surface electrocardiogram (ECG) activity in patients with AFl have not been satisfactorily delineated. The aim of the study was to determine the relationships that exist between the atrial endocardial activity and the surface ECG in patients with atrial flutter (AFl). METHODS: In 40 patients with AFl, a 64-electrode basket catheter (BC) was deployed in the right atrium (RA). A decapolar catheter was inserted into the coronary sinus (CS) to record from the left atrium. The temporal relationship between endocardial and surface ECG activity was determined by means of electronic calipers. RESULTS: In counterclockwise AFl, the activation of the lateral wall of RA coincided with the positive deflections in lead I, V1 and V6 and the upstroke component in inferior leads. Plateau duration in lead III (121 +/- 27 ms) correlated strongly with isthmus conduction time (117 +/- 23 ms) (r = 0.91). Septal and left atrial conduction coincided with negative components in lead I, inferior leads and V6 and positive deflections in leads aVL and V1. In clockwise AFl, the F wave was notched in all ECG leads. The first component resulted from the activation of the septum and posterior wall of the RA. The second component was coincident with activity recorded in CS electrograms. The interval between the two deflections (60 +/- 18 ms) correlated strongly with interatrial conduction time (57 +/- 19 ms) (r = 0.84). Interatrial conduction interval was prolonged during AFl as compared to sinus rhythm (60 +/- 18 ms vs 43 +/- 13 ms, p = 0.04). Activation of the lateral wall of RA coincided with the negative components in lead I, inferior leads and V6. CONCLUSIONS: The electrical activity in surface ECG closely correlates with conduction in specific parts of the atria. Polarity of the F wave in an ECG lead is determined by a resultant of opposing activities from the lateral wall of the RA and the left atrium.
UNLABELLED: Linear lesions (LL) represent an option for curing of atrial fibrillation (AF) with ablation techniques. METHODS AND RESULTS: In 11 sheep (w. 72+/-16 kg), LL were created with radiofrequency ablation in the lateral, posterior and septal walls of the right atrium (RA). AF was induced before and after LL with burst pacing. Mapping of the AF was performed with a 64-electrode basket catheter deployed in the RA. Quantitative analysis was performed with a custom-made software program. LL were confirmed histologically 7 to 10 days after the procedure. LL were transmural in 78% of their length. Stimulation thresholds and right atrial activation times were increased after LL compared to preablation values. Effective refractory periods of the RA were prolonged significantly in 7 out of 12 regions after generation of LL. Conduction velocities in the RA segments between LL were reduced in lateral, posterior and septal walls. During paced rhythms double potentials were recorded in all animals. AF could be induced in all animals of this model despite the presence of LL in the RA. AF episodes were significantly more regular after LL throughout the RA due to a significant reduction of the number of the wave fronts in the RA. During AF episodes, in the presence of LL, the RA was driven by wave fronts of left atrial origin entering the right side of the septum through interatrial connections. CONCLUSIONS: 1) LL profoundly affect electrophysiologic parameters of RA. 2) In the presence of LL, AF manifest a higher degree of regularity as compared to preablation episodes. 3) Dissociation between wave fronts of left atrial origin entering the RA through the interatrial connections is an important mechanism of the antifibrillatory action of the septal LL.
Construction of three-dimensional activation maps and evaluation of ablation-created bidirectional block in the tricuspid valve-inferior vena caval (TV-IVC) isthmus in patients with atrial flutter (AF) are difficult with conventional mapping technique. In 36 patients with type I AF (25 men, 11 women; mean age 62 +/- 10.5 years) a multielectrode basket catheter (BC) was deployed in the right atrium (RA). Out of 64 BC electrodes, 56 bipolar electrograms were derived. Three-dimensional activation patterns were constructed with a software program. Stable electrograms of satisfactory quality were obtained in 49 +/- 2 electrode pairs. Capture was possible in 36 +/- 3 of bipoles. In counterclockwise AF (CCW-AF) and clockwise AF (CW-AF) episodes, cycle lengths and TV-IVC isthmus conduction times were 248 +/- 26 ms and 251 +/- 23 ms, (P = 0.74) and 105 +/- 28 ms and 106 +/- 33 ms (P = 0.92), respectively. Conduction velocity in the TV-IVC isthmus was lower than in the anterior or septal limbs of the circuit, in counterclockwise or clockwise episodes. Double potentials were recorded in 94% of patients. Three-dimensional activation patterns were delineated and displayed as isochronal maps. The reentry circuit involved the TV-IVC isthmus, septal, and anterior walls and a part of the RA roof anterior to superior vena cava. Postablation isthmus conduction was evaluated through the sequence criteria, local electrogram-based criteria, and the analysis of three-dimensional activation patterns of the paced rhythms. The complete isthmus block was associated with a significant increase of the low anterior low septal conduction interval (152 +/- 29 vs 104 +/- 32 ms, P = 0.001) and the low septal-low anterior conduction interval (150 +/- 31 vs 107 +/- 33 ms, P = 0.001). Radiofrequency ablation was successful in 32 (90%) of 36 patients. In conclusion, the current mapping system enables construction of three-dimensional activation patterns and facilitates evaluation of the postablation TV-IVC isthmus block in patients with AF.
We report two patients who had isolated atrial fibrillation in the left atrium and regular activation of the entire right atrium. Mapping of the arrhythmia was performed using a 64-electrode basket catheter that was inserted intravenously and deployed in the right and left atria. Both patients manifested a single, stable interatrial electrical connection conducting in a left-to-right direction, consistent with Bachmann's bundle location. The right and left sides of the interatrial septum were activated discordantly, each reflecting activation characteristics of the respective atria. A filtering effect at the level of interatrial septum was demonstrated by calculating the fibrillation intervals on both sides of the operative interatrial connection. It was concluded that differences in activation of the left and right surfaces of the interatrial septum and preferential use and the filtering effect of the interatrial connections play a significant role in explaining the differences in activation patterns of the left and right atria in patients with atrial fibrillation.
INTRODUCTION: Electrophysiologic remodeling is involved in the self-perpetuation of atrial fibrillation. To define whether differences in atrial electrophysiology already are present in patients with increased susceptibility for atrial fibrillation, we compared patients in sinus rhythm with and without heart failure. METHODS AND RESULTS: Atrial specimens were obtained from patients with reduced left ventricular ejection fraction (LVEF; n = 10) and normal LVEF (n = 16) who were undergoing aortocoronary bypass surgery and from donor hearts (n = 4). Enzymatically isolated atrial myocytes were investigated by whole cell, patch clamp techniques. Total outward current was significantly larger in myocytes of hearts with low LVEF than normal LVEF (19.4 +/- 1.3 vs 15.1 +/- 1.2 pA/pF at pulses to +60 mV, respectively). Analysis of inactivation time courses of different outward current components revealed that the observed current difference is due to the transient calcium-independent outward current I(to1) which is twice as large in the low LVEF group than in the normal LVEF group (9.4 +/- 0.9 vs 4.7 +/- 0.4 pA/pF at pulses to +60 mV, respectively). I(to1) recovery from inactivation was significantly more rapid in myocytes of hearts with low LVEF, and action potential plateau in these cells was significantly shorter. The results of I(to1) and action potential measurements in atrial myocytes of donor hearts were very similar to the results of patients with preserved heart function. CONCLUSION: I(to1) in human atrial myocytes of patients with reduced LVEF has an increased density and altered kinetics in sinus rhythm. These differences in outward current may explain the reduced plateau phase of action potentials.
We report the use of a novel noncontact mapping system used to perform left atrial mapping and to guide radiofrequency ablation in two patients, each with atrial fibrillation (AF) triggered by left atrial ectopy. A noncontact multielectrode probe and ablation catheter were advanced into the left atrium through a transseptal puncture or a patent foramen ovale. Isopotential mapping delineated the focal origin at the ostium of the right lower pulmonary vein in one patient and close to the ostium of the left upper pulmonary vein in the other patient. The ablation catheter was guided to the target sites using a locator signal. The foci were ablated successfully in both patients. No recurrences of AF were observed during follow-up at 4 and 6 months, respectively.
BACKGROUND: The complexity of atrial tachycardias (ATs) makes the electroanatomic characterization of the arrhythmogenic substrate difficult with conventional mapping techniques. The aim of our study was to evaluate possible advantages of a novel multielectrode basket catheter (MBC) in patients with AT. METHODS AND RESULTS: In 31 patients with AT, an MBC composed of 64 electrodes was deployed in the right atrium (RA). The possibility of deployment, spatial relations between MBC and RA, MBC recording and pacing capabilities, mapping performance, and MBC-guided ablation were assessed. MBC deployment was possible in all 31 patients. The MBC was left in the RA for 175+/-44 minutes. Stable bipolar electrograms were recorded in 88+/-4% of electrodes. Pacing from bipoles was possible in 64+/-5% of electrode pairs. The earliest activity intervals, in relation to P-wave onset, measured from the MBC and standard roving catheters were 41+/-9 and 46+/-6 ms, respectively (P=0.21). Radiofrequency ablation was successful in 15 (94%) of 16 patients in whom it was attempted, including 2 patients with polymorphic right atrial tachycardia (RAT), 2 with RAT-atrial flutter combination, 1 with macroreentrant AT, and 1 with focal origin of atrial fibrillation. CONCLUSIONS: These data demonstrate that MBC can be used safely in patients with right atrial arrhythmias. The simultaneous multielectrode mapping aids in the rapid identification of sites of origin of the AT and facilitates radiofrequency ablation procedures. The technique is especially effective for complex atrial arrhythmias.
The aim of this study was to determine whether endogenous adenosine has antiarrhythmic effects on ischemia-induced ventricular tachyarrhythmias. We therefore modulated the effect of endogenous adenosine in isolated rat hearts using four different approaches. First, interstitial adenosine was elevated by metabolic inhibition with either EHNA (erythro-9-(2-hydroxy-3-nonly)adenine) or acadesine [5-amino-1-beta-D-imidazole-4-carboxamide). Second, cardiac effects of A1 adenosine receptors were allosterically enhanced with PD81,723 (2-amino-4,5-dimethyl-3-thienyl)[3-(trifluoromethyl)phenyl]-methanone . Third, endogenous adenosine release was suppressed with NBMPR (S-(4-nitrobenzyl)-6-thioinosine), and fourth, adenosine receptor subtypes were blocked with antagonists of different selectivity. Regional ischemia, induced by coronary artery ligation, caused ventricular fibrillation of a reproducible kind in about 20% of untreated hearts with a low calcium concentration in the perfusion medium (0.80 mmol/l CaCl2) and in about 75% with high calcium (1.85 mmol/l) within an observation period of 30 min. At high calcium, EHNA (1 and 10 micromol/l) and acadesine (500 micromol/l) suppressed the occurrence of ventricular fibrillation from 68% (controls) to 47%, 33% and 38%, respectively. Conversely, PD81,723 (10 micromol/l) did not influence the occurrence of ventricular fibrillation. At low calcium, NBMPR (0.1 and 1 micromol/l) resulted in a concentration-dependent rise of ventricular fibrillation from 13% (controls) to 40% and 57%, respectively. The adenosine receptor antagonists theophylline (100 micromol/l), XAC (Xanthine Amine Congener; 1 micromol/l) and 8-PT (8-phenyltheophylline; 1 micromol/l) caused a rise in the occurrence of ventricular fibrillation from 25%, 15% and 18% (controls) to 57%, 39% and 44%, respectively, and the selective A2a receptors antagonist CSC (8-(3-chlorostyryl)caffeine; 5 micromol/l) from 20% to 56%. Conversely, the selective A1 receptor blocker DPCPX (8-cyclopentyl-1,3-dipropyl-xanthine; 1 micromol/l) was ineffective. NBMPR or EHNA concentration-dependent suppressed or increased ischemia-induced adenosine overflow, respectively, in a concentration-dependent manner, whereas the adenosine receptor antagonists did not influence adenosine overflow. We conclude that endogenous adenosine is an antiarrhythmic mediator accumulating in acute ischemic myocardium to a level which effectively decreases the occurrence of ventricular fibrillation by an A2 adenosine receptor activation in the isolated rat heart.