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M J Janse

Publications and source records attributed to M J Janse.

At least 55 records · Page 3Linked to original sources
PubMed1997

Electrical activity in Koch's triangle.

The authors have conducted several experimental studies of the cellular electrophysiology of the atrioventricular (AV) node employing the Langendorff-blood perfused heart of both dogs and pigs. Two types of experiments are described: experiments showing that cells with electrophysiological characteristics of typical nodal cells can be found outside Koch's triangle; and mapping experiments during the induction of ventricular echo beats in an attempt to delineate the reentrant circuit thought to underlie AV nodal reentry.

Animals↗
PubMed1996

Atrioventricular junctional tissue. Discrepancy between histological and electrophysiological characteristics.

BACKGROUND: Previous work has demonstrated that cells with AV nodal-type action potentials are not confined to Koch's triangle but may extend along the AV orifices. The aim of this study was to examine the histological and electrophysiological characteristics of this tissue. METHODS AND RESULTS: Studies were performed in isolated, blood-perfused dog and pig hearts. Microelectrode recordings revealed cells with nodal-type action potentials around the tricuspid and mitral valve rings. These cells were found within 1 to 2 mm of the valve annuli. A zone of cells with intermediate action potentials, approximately 1 cm wide, separated cells with nodal-type action potentials from cells with atrial-type action potentials in the body of the atria. In cells with nodal-type action potentials, adenosine caused a reduction in action potential amplitude (49 +/- 2 versus 33 +/- 2 mV, mean +/- SE; P < .001), upstroke velocity (2.5 +/- 0.2 versus 2.0 +/- 0.2 V/s, P < .05), and duration (150 +/- 4 versus 96 +/- 8 ms, P < .001). The light microscopic appearance of AV junctional cells was similar to that of myocytes in the body of the atrium. A polyclonal antibody raised against connexin-43 bound to atrial and ventricular tissue but not to the AV junctional tissue or AV nodal region. The absence of connexin-43 correlated with the sites of cells with nodal-like action potentials. With pacing techniques, the AV junctional tissue in the region of the posterior AV nodal approaches could be electrically dissociated from atrial, AV nodal, and ventricular tissue. AV nodal echoes were induced with ventricular pacing in three dog hearts. In each case, retrograde conduction was through the slow pathway, and anterograde conduction was through the fast pathway. During echoes, activation of AV junctional cells preceded atrial activation during retrograde slow pathway conduction, but these cells were not activated during anterograde fast pathway conduction. CONCLUSIONS: AV junctional cells around both annuli are histologically similar to atrial cells but resemble nodal cells in their cellular electrophysiology, response to adenosine, and lack of connexin-43. The light microscopic appearance of AV junctional cells is a poor guide to their action potential characteristics. The AV junctional cells in the posterior AV nodal approaches appear to participate in slow pathway conduction. These cells may be the substrate of the slow "AV nodal" pathway.

Action Potentials↗
PubMed1996

Electrophysiologic and extracellular ionic changes during acute ischemia in failing and normal rabbit myocardium.

The incidence of ventricular arrhythmias is higher in failing hearts than in control hearts, especially during acute ischemia. Electrophysiological and extracellular ionic changes during acute ischemia in normal and failing rabbit myocardium were assessed. Heart failure was induced in rabbits by combined volume and pressure overload. In perfused papillary muscles, the onset of electrical uncoupling and changes in action potential duration and conduction velocity during acute ischemia were determined. In Langendorff-perfused rabbit hearts the changes in extracellular potassium concentration ([K+]o) and pH during acute global ischemia were studied. In perfused papillary muscles, during the first 10 min of ischemia, action potential duration at 80% of repolarization decreased more in preparations from failing than from control hearts (from 174 to 104 ms and from 156 to 119 ms respectively (P < 0.001)). Conduction velocity was significantly lower in failing hearts during ischemia (P < 0.005). The onset of electrical uncoupling was similar in failing and control hearts (mean +/- S.E.M., 17 +/- 1 and 15 +/- 1 min respectively, n.s.). Langendorff-perfused hearts [K+]o, after 10 min of ischemia, was 11.0 +/- 0.4 mM in failing and 9.5 +/- 0.3 mM in control hearts (P < 0.01), while the change in pH was the same. After pretreatment with glibenclamide, an ATP sensitive K+ channel blocker, [K+]o reached lower values after 10 min of ischemia in both failing (8.8 +/- 0.5 mM) and control hearts (7.2 +/- 0.4 mM). During ischemia, action potential duration shortening is more pronounced and conduction velocity is lower in failing myocardium than in control myocardium. [K+]o reaches higher values during acute ischemia in failing compared with normal myocardium. These changes are not caused by an earlier activation of IK.ATP. Increased spatial dispersion in electrophysiological parameters and [K+]o over the ischemic border in failing hearts may explain the higher propensity for reentrant arrhythmias during acute regional ischemia in failing hearts.

Action Potentials↗
PubMed1996

Fractionated electrograms in dilated cardiomyopathy: origin and relation to abnormal conduction.

OBJECTIVES: We sought to investigate the origin of the fractionated electrogram and its relations to abnormal conduction in cardiomyopathic myocardium. BACKGROUND: Patients with dilated cardiomyopathy have a high incidence of ventricular tachycardias. Electrograms recorded in these patients are often fractionated. METHODS: High resolution mapping (200-microM interelectrode distance) of the electrical activity was carried out in 11 superfused papillary muscles and 6 trabeculae from 7 patients who underwent heart transplantation because of dilated cardiomyopathy. Similar measurements were taken in four papillary muscles from dog hearts in which electrical barriers had been artificially made. Ten human preparations were studied histologically. RESULTS: All preparations revealed sites with fractionated electrograms. In three human preparations, activation patterns showed a discernible line of activation block running parallel to the fiber direction. Fractionated electrograms were recorded at sites contiguous to the line of block. In five preparations, fractionated electrograms were recorded at sites where lines of block were not identified. In these preparations, electrical barriers consisted of short stretches of fibrous tissue. In the remaining nine preparations, fractionated electrograms were recorded, both from sites contiguous to distinct obstacles and sites without evidence of a barrier. CONCLUSIONS: Our observations showed that fractionated electrograms recorded in myocardium damaged by cardiomyopathy were due to both distinct, long strands and short stretches of fibrous tissue. Delayed conduction was caused by curvation of activation around the distinct lines of block and by the wavy course of activation between the short barriers. The latter reflects extreme nonuniform anisotropy.

Animals↗
PubMed1996

Intracellular Ca2+, intercellular electrical coupling, and mechanical activity in ischemic rabbit papillary muscle. Effects of preconditioning and metabolic blockade.

During myocardial ischemia, electrical uncoupling and contracture herald irreversible damage. In the present study, we tested the hypothesis that an increase of intracellular Ca2+ is an important factor initiating these events. Therefore, we simultaneously determined tissue resistance, mechanical activity, pH(0), and intracellular Ca2+ (with the fluorescent indicator indo 1, Molecular Probes, Inc) in arterially perfused rabbit papillary muscles. Sustained ischemia was induced in three experimental groups: (1) control, (2) preparations preconditioned with two 5-minute periods of ischemia followed by reperfusion, and (3) preparations pretreated with 1 mmol/L iodoacetate to block anaerobic metabolism and minimize acidification during ischemia. In a fourth experimental group, intracellular Ca2+ was increased under nonischemic conditions by perfusing with 0.1 mmol/L ionomycin and 0.1 mumol/L gramicidin. Ca2+ transients and contractions rapidly disappeared after the induction of ischemia. In the control group, diastolic Ca2+ began to rise after 12.6 +/- 1.3 minutes of ischemia; uncoupling, after 14.5 +/- 1.2 minutes of ischemia; and contracture, after 12.6 +/- 1.5 minutes of ischemia (mean +/- SEM). Preconditioning significantly postponed Ca2+ rise, uncoupling, and contracture (21.5 +/- 4.0, 24.0 +/- 4.1, and 23.0 +/- 5.3 minutes of ischemia, respectively). Pretreatment with iodoacetate significantly advanced these events (1.9 +/- 0.7, 3.6 +/- 0.9, and 1.9 +/- 0.2 minutes of ischemia, respectively). In all groups, the onset of uncoupling always followed the start of Ca2+ rise, whereas the start of contracture was not different from the rise in Ca2+. Perfusion with ionomycin and gramicidin permitted estimation of a threshold [Ca2+] for electrical uncoupling of 685 +/- 85 nmol/L. In conclusion, the rise in intracellular Ca2+ is the main trigger for cellular uncoupling during ischemia. Contracture is closely associated with the increase of intracellular Ca2+ during ischemia.

Animals↗
PubMed1996

Electrophysiology of the A-V node in relation to A-V nodal reentry.

During A-V nodal reentry the impulse is supposed to travel through two distinct pathways in the A-V nodal junction, called slow and fast pathways. Clinically, catheter ablation of these pathways has been very successful in abolishing A-V nodal reentrant tachycardias. So-called double potentials have been used as a marker for the slow pathway, and the occurrence of accelerated junctional rhythms (AJR) following ablation is an indicator of successful destruction of the slow pathway. In Langendorff, blood-perfused porcine and canine hearts, extensive mapping of extracellular potentials, combined with microelectrode recordings, was carried out to answer the following questions: 1) what is the origin of double extracellular potentials? 2) what causes post-ablation AJR? 3) what is the activation pattern of the AV junction during ventricular echoes? 1) Two types of double potentials were found: a low-frequency component followed by a high-frequency deflection, the LH potential was caused by asynchronous activation of the sinus septum above the coronary sinus and the region between the coronary sinus orifice and tricuspid annulus, where the L component is a far field potential. HL potentials (high-frequency deflection followed by a low frequency component) were caused by asynchronous activation of atrial cells and cells with AV nodal characteristics at the same location. These cells were present around the entire tricuspid annulus, and were not part of the compact node. The proximity of LH potentials to the slow pathway is probably serendipity, HL potentials could represent the slow pathway. 2) Two types of AJR could be initiated both by application of radiofrequency energy and by heat: a regular rhythm that progressively accelerated and an irregular rhythm. The discrete sites where heat application induced AJR did not correlate with areas showing double potentials, nor with exit regions during ventricular pacing. They were close to the compact node and the underlying mechanism was accelerated phase 4 depolarization in single or multiple foci, the latter accounting for irregular AJR. The association between presence of AJR and successful slow pathway ablation is probably also serendipity. 3) During ventricular pacing, two separate areas of earliest atrial activity were found. When ventricular echoes were induced by premature stimulation, the retrograde impulse activated both atrial exit sites and still returned in the ventricles as an echo. Thus, no evidence was found that atrial tissue forms part of the reentrant circuit.

Animals↗
PubMed1995

Heterogeneities in [K+]o and TQ potential and the inducibility of ventricular fibrillation during acute regional ischemia in the isolated perfused porcine heart.

BACKGROUND: The relation between the inducibility of ventricular fibrillation (VF) and heterogeneity of the extracellular potassium concentration ([K+]o) and of TQ potential is unknown. METHODS AND RESULTS: Data from 78 epicardial DC electrodes or from up to 32 intramural K+ electrodes were acquired simultaneously. Induction of VF was attempted with one or two ventricular premature beats induced in normal myocardium in isolated porcine hearts during (1) regional perfusion of the left anterior descending artery (LAD) with a normoxic, hyperkalemic solution ([K+] 6 to 19.6 mmol/L), (2) simulated ischemia, ie, LAD perfusion with a glucose-free, hypoxic solution ([K+] 4 to 16 mmol/L, PO2 < 5 mm Hg, pH 6.98), and (3) regional ischemia produced by stopping LAD flow. During normoxic, hyperkalemic LAD perfusion, no VF could be induced (12 interventions, 7 hearts). During simulated ischemia (27 interventions), VF could be induced only when [K+]o was between 8 and 13.5 mmol/L. After 5 minutes of true regional ischemia, more sites with [K+]o between 8 and 13.5 mmol/L were present than after 10 minutes. VF could be induced with 1 ventricular premature beat in 11 of 17 interventions after 5 minutes and in 0 of 14 interventions after 10 minutes of ischemia (P < .001). Regional simulated ischemia presents a relatively homogeneous condition compared with 5 minutes of regional ischemia (SD +/- SEM of TQ potential in LAD tissue, 0.9 +/- 0.05 versus 2.1 +/- 0.13 mV, respectively). True ischemia superimposed on regional simulated ischemia caused the rapid development of heterogeneities in [K+]o and TQ potential and caused VF after 45 +/- 7 seconds in all interventions. Activation maps of induction of VF suggest a different mechanism of unidirectional block during simulated ischemia from that in true ischemia. CONCLUSIONS: (1) In the presence of hypoxia and acidosis, [K+]o between 8 and 13.5 mmol/L provides the conditions necessary for the induction of VF; (2) after 5 minutes of ischemia, these conditions are present in a larger area and inducibility of VF is higher than after 10 minutes of ischemia; and (3) small heterogeneities within the intermediate K(+)-concentration domain (8 to 13.5 mmol/L) are associated with high inducibility of VF.

Animals↗
PubMed1995

Dispersion of 'refractoriness' in noninfarcted myocardium of patients with ventricular tachycardia or ventricular fibrillation after myocardial infarction.

BACKGROUND: Postinfarction ventricular tachycardias (VTs) may degenerate into ventricular fibrillation (VF), but this does not happen in all patients. The underlying mechanism is not exactly known, but dispersion of refractory periods is considered a major factor in both induction and persistence of reentrant arrhythmias in general. Hypertrophied, noninfarcted myocardium has altered electrophysiological characteristics. We hypothesized that noninfarcted ventricular tissue may provide the heterogeneities that cause the transition from VT into VF. Local fibrillation intervals, ie, the average interval between local activations during VF, have previously been shown to correlate well with local refractoriness in human and canine atrium and in porcine and canine ventricle and may therefore be used as an index of local refractoriness. This technique permits simultaneous assessment of refractoriness at multiple sites. METHODS AND RESULTS: We measured local fibrillation intervals at 32 to 64 sites in the noninfarcted part of the left ventricle in patients undergoing antiarrhythmic surgery for symptomatic, drug-refractory, postinfarction ventricular tachyarrhythmias. The grid of electrodes (interelectrode distance, 7 mm) was attached to the epicardium of the left ventricle remote from the infarcted tissue. Group 1 consisted of 7 patients with hemodynamically tolerable sustained VT (VT group). Group 2 consisted of 7 patients with cardiac arrest and documented VF (VF group). With the patients on cardiopulmonary bypass, VF was induced by multiple premature stimulation. The VF interval was not significantly different in the two study groups (VT group, 136 +/- 5.5 ms; VF group, 129 +/- 3.4 ms, mean +/- SEM). However, spatial dispersion of the VF intervals (remote from the infarcted area) expressed as the coefficient of variation of VF intervals (SD x 100/mean VF interval in each heart) was significantly larger in the VF group. It was 3.63 +/- 0.56 in the VF group and 1.55 +/- 0.40 in the VT group (mean +/- SEM; P < .01). Differences between the shortest and longest VF intervals in one and the same heart and the largest difference between two adjacent sites were also larger in the VF group (P < .02 and P < .05, respectively). CONCLUSIONS: This study shows larger dispersion in VF intervals and therefore suggests larger dispersion of refractory periods in parts of the myocardium remote from the infarction in patients with postinfarction VF than in patients with postinfarction VT.

Aged↗
PubMed1995

Thrombolysis and reocclusion in experimental jugular vein and coronary artery thrombosis. Effects of a plasminogen activator inhibitor type 1-neutralizing monoclonal antibody.

BACKGROUND: Thrombolytic therapy for acute myocardial infarction is often complicated by reocclusion of the initially reperfused artery. Platelets have been shown to play an important role in this process. We determined the contribution of plasminogen activator inhibitor type 1 (PAI-1), stored in the alpha-granules of platelets, to thrombolysis resistance and to reocclusion. METHODS AND RESULTS: In a rabbit jugular vein thrombosis model, the effect of a PAI-1-neutralizing monoclonal antibody (CLB-2C8) on thrombolysis and thrombus growth was assessed. The effect on reperfusion, reocclusion, and duration of vessel patency was studied in a canine model of coronary artery thrombosis superimposed on a high-grade stenosis and endothelial damage. In the rabbit jugular vein model, the intravenous administration of 1 mg/kg anti-PAI-1 antibody significantly enhanced the endogenous thrombolysis from 5.5 +/- 1.3% in the animals treated with a nonspecific monoclonal antibody (control) to 13.7 +/- 2.6% in the animals treated with the anti-PAI-1 antibody. Thrombus growth was reduced significantly, from 41.3 +/- 2.6% in the control animals to 22.8 +/- 2.8% in the animals treated with the anti-PAI-1 antibody. In combination with a single bolus injection of recombinant tissue-type plasminogen activator (rTPA; 0.25 mg/kg), the anti-PAI-1 antibody reduced thrombus growth significantly, from 21.5 +/- 2.7% in the animals treated with rTPA alone to 12.2 +/- 2.6% in the animals treated with rTPA and the antibody. No additional effect of the anti-PAI-1 antibody was observed on rTPA-induced thrombolysis. In the canine coronary artery thrombosis model, the administration of a suboptimal dose of rTPA (0.45 mg/kg) induced reperfusion in 7 of the 8 dogs after 19.5 +/- 8.2 minutes. Reperfusion was followed by reocclusion in all animals after 3.3 +/- 2.6 minutes. Administration of the anti-PAI-1 antibody in combination with rTPA significantly reduced time to reperfusion (8.1 +/- 5.2 minutes) and delayed the occurrence of reocclusion to 11.6 +/- 12.5 minutes. CONCLUSIONS: Administration of the anti-PAI-1 antibody (CLB-2C8) results in increased endogenous thrombolysis and inhibition of thrombus growth in a venous thrombosis model in rabbits and facilitated reperfusion and reduction of reocclusion in a canine model of coronary artery thrombosis.

Animals↗
PubMed1995

The relation between extracellular potassium concentration and pH in the border zone during regional ischemia in isolated porcine hearts.

During regional ischemia gradients of extracellular potassium concentration ([K+]o) and extracellular pH (pHo) exist. In globally ischemic papillary muscles increased PCO2 causes a rise in [K+]o. We studied whether pHo and [K+]o are causally related during acute regional ischemia in the isolated blood-perfused pig heart. Multiple pH- or K(+)-sensitive electrodes were inserted in the left ventricular midmyocardium. Local electrograms and ionic data were simultaneously acquired. Regional ischemia was produced by interrupting left anterior descending (LAD) artery flow (10 min). Up to 5 mm from the electrophysiological border the pH-K relation deviated from that in the central ischemic zone. Respiratory acidosis (pH about 7.10) of the perfusate in the presence of LAD-ischemia caused acidification of the ischemic border zone without a local change in [K+]o. We conclude that pHo changes are not related to changes of intramural [K+]o in the lateral border zone during regional ischemia.

Animals↗
PubMed1995

Future prospects of antiarrhythmic treatment based on experimental studies.

Based on recent experimental studies, a number of speculations about future developments are made regarding the treatment of atrial fibrillation, the problem of proarrhythmia in patients with heart failure, and the treatment of ventricular tachycardia developing during the first 6 weeks following the onset of myocardial infarction. Rapid atrial pacing, or atrial fibrillation, leads to a shortening of the atrial refractory period which persists for a long time following cardioversion. This 'cardiac memory', which also exists on the ventricular level, favours re-induction of atrial fibrillation because the wavelength for re-entry is reduced. Future development of drugs that would prolong the atrial action potential after prolonged periods of atrial fibrillation would increase the success of cardioversion. Although atrial fibrillation is probably most often caused by multiple wavelet re-entry, recent studies show that in some instances a small stable re-entrant circuit is responsible for the arrhythmia. If catheter mapping could reliably localize such a circuit, catheter ablation may be a new therapeutic option. Drug treatment for atrial fibrillation carries a high risk for mortality in patients with heart failure. The arrhythmogenic mechanisms in heart failure are poorly understood, even though there are indications for an increased likelihood of triggered arrhythmias based on delayed afterdepolarizations. Further research in this area is required, particularly where it concerns the response of the (prolonged) action potential in failing hearts to K(+) channel blocking agents. Mortality in patients developing their first attack of ventricular tachycardia within 6 weeks after the onset of myocardial infarction is almost twice that of patients who have their first tachycardia later. Action potential characteristics of ventricular cells overlying an infarct are abnormal during the first weeks of infarct healing, and return to normal after 2 months. It would be worthwhile to study the response to anti-arrhythmic drugs in such cells, in the hope of finding drugs that would increase their refractory periods. Eventually, this could lead to different forms of drug treatment in ventricular tachycardia during the first 6 to 8 weeks following infarction as compared to tachycardias in later stages.

Animals↗
PubMed1995

New insights on anatomical location of components of the reentrant circuit and ablation therapy for atrioventricular junctional reentrant tachycardia.

The success of radiofrequency catheter ablation in the treatment of atrioventricular junctional, or atrioventricular nodal, reentrant tachycardia has rekindled interest in the electrophysiological and anatomical characteristics of the reentrant circuit. We conclude that there is no evidence that within the atrioventricular nodal area, which contains both the compact node and transitional cells, there are anatomically delineated dual or multiple pathways. Rather, the two main atrial inputs into the atrioventricular nodal area (posterior and anterior) seem to be the anatomically relevant structures for "slow" and "fast" pathways. Two other inputs (sinus septum and left atrial) may be the cause for multiple pathways in some individuals. Nonuniform anisotropic properties of the zone of transitional cells may account for slow or fast conduction in the same area, depending on directional differences of wavefronts. We prefer the term atrioventricular junctional reentrant tachycardia rather than atrioventricular nodal reentrant tachycardia because of mounting evidence that perinodal tissue is involved in the reentrant circuit. Finally, the role and origin of double extracellular electrograms is discussed. Further research is required to establish whether an anatomical or an electrogram-guided approach for catheter ablation is preferred.

Atrioventricular Node↗
PubMed1995

Ventricular fibrillation is not always due to multiple wavelet reentry.

INTRODUCTION: It is not known whether ventricular fibrillation (VF) is always caused by multiple wavelet reentry, or if it could also be caused by a single wandering reentrant wavefront. Activation mapping of the entire ventricles during VF is practically impossible. METHODS AND RESULTS: We studied VF in a two-dimensional sheet of left ventricular subepicardial tissue of isolated, Langendorff-perfused pig hearts. Left and right endocardial cryoablation via probes filled with liquid nitrogen caused coagulation necrosis of the right ventricle, interventricular septum, and most of the left ventricular wall, leaving a thin subepicardial layer intact. Left ventricular epicardial activation patterns were constructed based on simultaneous recording of 128 unipolar extracellular electrograms. Regular pacing through a central electrode before and after freezing revealed that, following cryoablation, the activation pattern no longer showed evidence of involvement of the Purkinje system, and that it was compatible with propagation through a two-dimensional anisotropic tissue sheet. VF was induced by burst pacing. When the mass of surviving subepicardium was < 10 g, no VF could be induced; when it was between 10 and 20 g, VF was nonsustained; when it was > 20 g, VF was sustained. Unipolar extracellular electrograms during VF before and after cryablation could not be distinguished from each other; however, epicardial activation patterns were markedly different. In the intact left ventricle, up to six different wavefronts were simultaneously present during a 100-msec time window. In the "frozen heart," during a period of about 0.5 seconds, at most two wandering reentrant waves were simultaneously present; sometimes only one reentrant wave was seen in a 100-msec time window. CONCLUSION: The extracellular waveform during VF can be caused by different forms of reentry: multiple wavelet reentry (on the order of six different wavefronts), two independent wandering reentrant waves, and a single wandering reentrant wave.

Animals↗
PubMed1995

Activation delay in healed myocardial infarction: a comparison between model and experiment.

Conduction delay in healed myocardial infarction, facilitating reentry, is frequently based on an increased path length the activation has to travel in a matrix of merging and diverging bundles that survive in the infarcted area. Additional delay occurs at sites where bundles bifurcate. The purpose of this study was to investigate conduction delay at sites where bundles bifurcate. A computer model was developed to simulate spread of activation in a two-dimensional sheet of excitable elements. A structure consisting of two isolated bundles merging into a single one was modeled. Extracellular electrograms calculated in the model were comparable to electrograms obtained in a superfused infarcted papillary muscle model. A zone of crowded isochrones or local conduction delay was found at the site where an isolated bundle bifurcated. The position of the isochrones in this area depended on the way activation times were determined. Lines of activation delay were mainly perpendicular to the fiber direction. In conclusion, the results have enabled us to better understand extracellular electrograms at pivoting points and show that activation sequences at a microscopic level can best be constructed on the basis of Laplacian signals.

Computer Simulation↗
PubMed1994

Contribution of mechanical activity and electrical activity to cellular electrical uncoupling in ischemic rabbit papillary muscle.

We separated mechanical and electrical activity during ischemia and we assessed the contribution of each of these variables to ischemia induced cellular electrical uncoupling. In two groups of rabbit papillary muscles, mechanical and electrical activity at the onset of ischemia was abolished. We determined how this affected the time of onset of uncoupling. Also, action potential duration (APD80), conduction velocity and extracellular pH were recorded. In the first group, the BDM group, mechanical arrest was achieved with 10 mM BDM (2,3-butanedione monoxime). This had no effect on APD80 and conduction velocity. In the second group, the quiescent group, electrical as well as mechanical arrest was obtained by not stimulating the muscles. The effect of electrical arrest was estimated as the difference between this group and the BDM group. Mechanical arrest delayed uncoupling significantly (control: 14.6 +/- 0.9 (min), mean +/- S.E.M., n = 10; BDM: 19.3 +/- 1.1, n = 10; P < 0.025). Electrical arrest caused an even greater delay (quiescent: 41.6 +/- 4.6, n = 7; P < 0.001 v control and BDM). In the BDM group, these effects were not associated with a difference of APD80 during ischemia, but with a smaller decrease of conduction velocity. Delay of uncoupling correlated with delay of extracellular acidosis. We conclude: (1) mechanical and electrical activity both are significant determinants of ischemia induced uncoupling; (2) delay of uncoupling is associated with delay of extracellular acidosis, indicating a reduced rate of metabolism.

Action Potentials↗