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Biomedical subjects

F X Witkowski

Publications and source records attributed to F X Witkowski.

At least 19 recordsLinked to original sources
PubMed2000

Voltage-sensitive dye mapping of activation and conduction in adult mouse hearts.

A custom-made apparatus based on a charge-coupled-device camera has been used to monitor changes in fluorescence from Langendorff-perfused adult mouse hearts stained with a voltage-sensitive dye, di-4-ANEPPS. With this approach it is possible to monitor activation of the ventricles at high temporal (375 micros/frame) and spatial resolution (72 x 78 pixels, 100 x 100 microm/pixel). In sinus rhythm, activation occurred with a complicated breakthrough pattern on both ventricles, and a total activation time of 3.51+/-0.16 ms (32 degrees C). A stimulus applied near the apex of the left ventricle resulted in a single activation wave front with a total activation time of 8.18+/-0.25 ms. Pacing from a site near the middle of the left ventricular epicardial surface revealed anisotropic conduction, indicating that conduction occurs preferentially in the direction of the predominant fiber orientation. The total activation time in this configuration was 5.44+/-0.24 ms. The difference in total activation time between sinus rhythm and epicardial stimulation suggests an important role for transmural conduction (the Purkinje system) in the mouse heart. These findings provide much of the necessary background needed for studying conduction abnormalities in genetically altered mice and suggest that the comparison of sinus rhythm and epicardial pacing can be used to reveal transmural conduction abnormalities.

Animals↗
PubMed1999

Electrophysiologic properties and ventricular fibrillation in normal and myopathic hearts.

This study tests the hypothesis that moderate myocardial dysfunction is associated with altered myocardial anisotropic properties and structurally altered ventricular fibrillation (VF). Mongrel dogs were randomized to either a control group or a group that was rapidly paced at 250 beats/min until the left ventricular ejection fraction was < or = 40%. Changes in anisotropic properties and the electrical characteristics of VF associated with the development of moderate myocardial dysfunction were assessed by microminiature epicardial mapping studies. In vivo conduction, refractory periods, and repolarization times were prolonged in both longitudinal and transverse directions in myopathic animals versus controls. VF was different in myopathic versus control animals. There were significantly more conducted deflections during VF in normal hearts compared with myopathic hearts. Propagated deflection-to-deflection intervals during VF were significantly longer in myopathic hearts compared with controls (125.5 +/- 49.06 versus 103.4 +/- 32.9 ms, p = 0.009). There were no abnormalities in cell size, cell shape, or the number of intercellular gap junctions and there was no detectable change in the expression of the gap junction proteins Cx43 and Cx45. Moderate myocardial dysfunction is associated with significant electrophysiological abnormalities in the absence of changes in myocardial cell morphology or intercellular connections, suggesting a functional abnormality in cell-to-cell communication.

Animals↗
PubMed1998

Spatiotemporal evolution of ventricular fibrillation.

Sudden cardiac death is the leading cause of death in the industrialized world, with the majority of such tragedies being due to ventricular fibrillation. Ventricular fibrillation is a frenzied and irregular disturbance of the heart rhythm that quickly renders the heart incapable of sustaining life. Rotors, electrophysiological structures that emit rotating spiral waves, occur in several systems that all share with the heart the functional properties of excitability and refractoriness. These re-entrant waves, seen in numerical solutions of simplified models of cardiac tissue, may occur during ventricular tachycardias. It has been difficult to detect such forms of re-entry in fibrillating mammalian ventricles. Here we show that, in isolated perfused dog hearts, high spatial and temporal resolution mapping of optical transmembrane potentials can easily detect transiently erupting rotors during the early phase of ventricular fibrillation. This activity is characterized by a relatively high spatiotemporal cross-correlation. During this early fibrillatory interval, frequent wavefront collisions and wavebreak generation are also dominant features. Interestingly, this spatiotemporal pattern undergoes an evolution to a less highly spatially correlated mechanism that lacks the epicardial manifestations of rotors despite continued myocardial perfusion.

Electric Stimulation↗
PubMed1997

Voltage-sensitive dye recordings of electrophysiological activation in a Langendorff-perfused mouse heart.

The pattern of electrophysiological activation of adult mouse ventricles was measured with the use of voltage-sensitive dye methods. Di-4-ANEPPS was used to monitor membrane potential as small changes in fluorescence, which were detected by a state of the art, cooled, charged coupled device camera/image intensifier system. The extremely rapid conduction velocity, coupled with the small size of this preparation, necessitated taking these measurements at room temperature (22 to 23 degrees C). Initial experiments demonstrate that ventricular activation can be identified and its conduction pattern can be monitored reproducibly and with high resolution for extended time periods (10 to 20 mins) during spontaneous activity.

Animals↗
PubMed1996

Order in disorder: effect of barium on ventricular fibrillation.

BACKGROUND: Drugs that prolong cardiac refractoriness can decrease defibrillation energy requirements. In particular, barium, a relatively selective blocker of cardiac Ik1 channels, produces marked decreases in defibrillation energy. The mechanism of this effect is unknown, and may relate to modulation of the effect of defibrillatory shocks, or an alteration of the pattern of ventricular fibrillation (VF) by the drug. METHODS AND RESULTS: Accordingly, the effect of barium chloride was examined, 1.1 mg/kg followed by 0.1 mg/kg/min intravenously, or saline control, on the pattern of unipolar electrograms using a 120 electrode array, during 73 episodes of VF (37 after saline, 36 after barium ). For each episode of VF, peak-dV/dt associated with local activations and mean activation-activation (ACT-ACT) intervals for the last 2 s of a 10 s episode of VF were measured for each electrode. 'Organization' in VF was measured by the variability in ACT-ACT intervals, their visually assessed pattern, and the relation between local activations on adjacent electrodes. Voltage gradients were measured at each of 40 epicardial sites for each defibrillation shock, delivered at voltages ranging from to 20% to 100% successful in defibrillation. At identical voltage shocks (400 V), mean voltage gradients before and after barium were similar: 18+/-9 and 19+/-1.2 V/cm, respectively. Mean peak -dV/dt for all activations was -8.7+/-0.5 V/s before and -7.7+/-2.8 V/s after barium, suggesting no apparent change in local conduction velocity. When the lowest voltage gradient at any site was less than 3.5 V/cm, defibrillation was successful 14% of the time (two of 14 ) during control, but 88% of the time (14 to 16) after barium infusion (P<0.01). Mean ACT-ACT intervals after barium for all episodes over all electrodes was 107.5+/-14.1 ms, significantly longer than 89.7 +/-3.9 ms after saline, indicating a 20% increase in the cycle length of fibrillation. During saline control, local epicardial electrogram patterns showed irregular, variable morphology electrograms and a mean lowest SD of ACT-ACT intervals over any electrode of 5.1+/-1.5 ms, compared with 1.2+/-0.7 ms after barium (P < 0.0001). Following barium, most unipolar epicardial electrograms showed regular, phasic activations that appear to reflect an organized, uniformly repetitive local activation pattern, suggesting spatially homogeneous and temporally regular activation wavefronts. CONCLUSIONS: During VF after barium, despite an apparently disorganized surface electrocardiographic pattern, epicardial electrogram patterns are altered and reflect a more ¿ordered', homogeneous and regular local activation. This increased order may be in part responsible for the decreased defibrillation energy requirements observed after barium.

Animals↗
PubMed1995

Epicardial cardiac source-field behavior.

The accurate determination of the spatial distribution of cardiac electrophysiological state is essential for the mechanistic assessment of cardiac arrhythmias in both clinical and experimental cardiac electrophysiological laboratories. This paper describes three fundamental cardiac source-field relationships: 1) activation fields, 2) electrotonic fields, and 3) volume conductor fields. The three cases are described analytically and illustrated with experimentally obtained canine cardiac recordings that capitalize on a recently formulated technique for in vivo cardiac transmembrane current estimation.

Heart↗
PubMed1995

Calculation of transmembrane current from extracellular potential recordings: a model study.

INTRODUCTION: A mathematical/computer model of cardiac tissue was used to study the estimation of transmembrane current (EIm) from extracellular potential recordings. METHODS AND RESULTS: The simulated EIm of transmembrane current was compared with the simulated transmembrane current (Im), and both simulated values were compared with experimentally derived EIm obtained during sinus rhythm and ventricular fibrillation in dogs. We found that although EIm measurements slightly overestimate the duration of the Im waveform, they provide a reasonable approximation of Im during normal conduction and during decremental conduction and conduction block. CONCLUSIONS: There is a very clear linear correlation between the time spent at or below 25% of the peak inward transmembrane current (Im25), its corresponding estimate (EIm25), the peak inward Im and EIm, and the peak ionic current, providing some evidence that EIm25 may be a suitable in vivo measure of peak ionic current.

Algorithms↗
PubMed1994

Barium decreases defibrillation energy requirements.

Certain antiarrhythmic drugs that inhibit myocardial repolarizing currents decrease defibrillation energy, but the effect of blocking particular currents on defibrillation is not well understood. We therefore investigated the effect of barium, a relatively selective blocker of inwardly rectifying potassium current (Ik1) on voltage and energy requirements for defibrillation in an open-chest dog model. Defibrillation energy and voltage requirements were assessed by delivering monophasic shocks through epicardial electrode patches at varying voltages to construct a dose-dependent curve of energy and voltage versus success in defibrillation. The energy and voltage for 50% success in defibrillation (E50 and V50, respectively) were determined by logistic regression. Monophasic action potential duration at 90% repolarization (MAPD90) was measured with a contact electrode, and ventricular refractory period (VERP) was measured. After baseline measurements were obtained of E50, V50, MAPD90, and VERP, saline (control) (n = 6) or barium (1.1 mg/kg/min for 5 min followed by 0.25 mg/kg/min) (n = 11) was administered. Defibrillation voltage and energy requirements and electrophysiologic measures were repeated after 30 and 120 min of barium or saline infusion. In control animals, there was no significant change with time in V50 (2.0 +/- 12.4 and -0.2 +/- 16.0% at 30 and 120 min, respectively), VERP (+3 +/- 5 and -2 +/- 3% at 30 and 120 min, respectively) or MAPD90 (+1 +/- 4 and -2 +/- 6, at 30 and 120 min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

Significance of inwardly directed transmembrane current in determination of local myocardial electrical activation during ventricular fibrillation.

Ventricular fibrillation (VF) is the principle cardiac rhythm disorder responsible for sudden cardiac death in humans. The accurate determination of local cardiac activation during VF is essential for its mechanistic elucidation. This has been hampered by the rapidly changing and markedly heterogeneous electrophysiological nature of VF. These difficulties are manifested when attempting to differentiate true propagating electrical activity from electrotonic signals and when identifying local activation from complex and possibly fractionated electrograms. The purpose of this investigation was to test the hypothesis that the presence of a balanced inwardly and outwardly directed transmembrane charge, obtained from the ratio of the inward to outward area under the cardiac transmembrane current curve (-/+ Im area), could reliably differentiate propagating from electrotonic deflections during VF. To test this hypothesis, we applied a recently described technique for the in vivo estimation of the transmembrane current (Im) during cardiac activation. A 17-element orthogonal epicardial electrode array was combined with an immediately adjacent optical fiber array to record electrical and optically coupled transmembrane potential signals during VF. Recordings were obtained during electrically induced VF in six dogs to determine the Im associated with activation and the time course of repolarization, as well as unipolar electrograms and bipolar electrograms recorded at multiple center-to-center interelectrode distances from 0.2 to 3 mm. Propagating local activations were associated with the presence of an easily identified inwardly directed Im, with a balanced inward and outward charge (-/+ Im area approximately 1.0). Electrotonic wave-forms lacked this inward Im (-/+ Im area approximately 0.0). Normal Na(+)-mediated inward currents were directly demonstrated to be responsible for some activations during VF.

Animals↗
PubMed1993

In vivo estimation of cardiac transmembrane current.

The ionic currents that cross the myocardial membrane during cardiac activation have a corresponding return path in the extracellular space. The transmembrane current (Im) during activation of cardiac cells in situ has previously been envisioned only in mathematical models. We have developed a remarkably simple in vivo technique that incorporates an electrode array with cellular dimensions to continuously estimate the extracellular counterparts of cardiac Ims. Mathematical modeling was performed for uniform plane wave propagation to clarify the biophysical basis and underlying assumptions inherent in this approach. Five-element electrode arrays incorporating 75-microns-diameter silver electrodes with center-to-center distances of 210 microns were experimentally verified to provide spatially sufficient samples for voltage gradient determinations of myocardial activation. Similar results were obtained with 25-microns-diameter electrodes at a center-to-center spacing of 65 microns. An estimate of Im was obtained from the derivative of the magnitude of the voltage gradient of the measured interstitial potentials. The inward component of Im generated by normal Na+ channel activation at 37 degrees C was measured in vivo to be less than 1 msec in duration, consistent with previously known voltage-clamp and simulation results. Intravenous KCl bolus injection was used to demonstrate the voltage-dependent depression of Na(+)-mediated Im in vivo, culminating in either severely depressed Na(+)-mediated or Ca(2+)-mediated activations. Normal Na(+)-, depressed Na(+)-, and possibly Ca(2+)-mediated currents can be recorded in vivo using this technique.

Animals↗
PubMed1991

One-dimensional model of cardiac defibrillation.

The response of a single strand of cardiac cells to a uniform defibrillatory shock assuming steady-state linear conditions is examined. It is argued that the effect of this current is quantitatively described by the induced transmembrane potential even under passive conditions. The characteristics of the single strand are those that would exist if the heart was a system of equivalent parallel pathways from apex to base. It is shown that essentially every cell is both hyperpolarized and depolarised from the shock by an amount proportional to the stimulus intensity and the intercellular junctional resistance. For physiological values of model parameters the evaluated depolarisations are consistent with levels necessary to affect electrophysiological behaviour.

Electric Countershock↗
PubMed1990

Epicardial activation times after defibrillation in open-chest dogs using unipolar DC-coupled activation recordings.

The widespread clinical application of implantable electrical defibrillation devices has engendered considerable interest into the mechanism of action of such devices. In addition, better means of rapid detection of postshock efficacy have been sought. The authors performed this study to test the following hypotheses: (1) postshock epicardial activation times may be used to differentiate successful from unsuccessful defibrillation attempts; and (2) successful defibrillation can be characterized by whether two or more activation wavefronts are simultaneously present on the epicardium after a defibrillation attempt. Unipolar Ag/AgCl sintered electrodes were directly coupled from 120 recording sites that covered both right and left ventricular surfaces. This technique was applied to 203 defibrillation attempts in 6 open-chest dogs during electrically induced ventricular fibrillation. There were 139 successful and 64 unsuccessful defibrillation attempts. The difference between the first and second post-shock activation times was significantly different between the successful and unsuccessful attempts. This difference was secondary to the activation time delay of the second post-shock activation cycle relative to the first post-shock activation cycle. When the first-to-second post-shock time delay was greater than 140 ms, the defibrillation attempt was found to be uniformly successful. In no case of successful defibrillation accompanied by total termination of ventricular fibrillation were more than two wavefronts simultaneously present on the heart after shock. In contrast, successful defibrillation accompanied by transient residual fibrillating activity or unsuccessful defibrillation attempts were observed to present with either two simultaneous activation wavefronts or an activation wavefront in temporal isolation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

An improved technique for his bundle recording and ablation in dogs.

Many physiological investigations of cardiac function require accurate control of heart rate. To examine heart rate effects at values lower than the intrinsic heart rate requires the ability to prevent an accelerated junctional rhythm from becoming dominant even after the sinus node is eliminated. A new method for the simple and reliable production of complete atrioventricular heart block in open-chest dogs is presented. It consists of two bonded parallel 22-gauge needles, one containing a bipolar recording electrode for localization at its tip and the other used for immediately adjacent formalin injection. The catheter is easily constructed, sterilizable, reusable, and durable, and can also provide a stable means of recording the His bundle electrical activity. Initial experiments performed in the first five dogs using this technique produced complete heart block with a stable ventricular escape rhythm in all five cases.

Animals↗
PubMed1990

Mechanism of cardiac defibrillation in open-chest dogs with unipolar DC-coupled simultaneous activation and shock potential recordings.

The automatic implantable cardioverter-defibrillator has been shown to dramatically improve survival. The future refinement of these devices requires a clear understanding of their mechanism of action. We performed the following study to test two hypotheses: 1) When defibrillation is successful, fibrillating activity must be annihilated in a critical mass of both ventricles; and 2) when defibrillation is unsuccessful, at least one area of the ventricular mass has been left fibrillating. Unipolar Ag/AgCl sintered electrodes were directly coupled from triangular arrays at 40 epicardial locations (total, 120 recording sites) that covered both right and left ventricular surfaces and were designed to measure the voltage gradient generated by the shock at each triangular array as well as the underlying myocardial electrical activity before and immediately after the shock. An algorithm was developed and tested that reliably scored whether a postshock activation was a continuation of the immediately previous fibrillating activity. This technique was applied to 203 defibrillation attempts in six open-chest dogs during electrically induced ventricular fibrillation. There were 139 successful defibrillation attempts and 64 unsuccessful attempts. Monophasic truncated exponential 10-msec defibrillation shocks (0.5-35 J) were delivered through an anodal patch on the right atrium and a cathodal patch on the left ventricular apex. In all cases of unsuccessful defibrillation, at least one ventricular site could be clearly identified that failed to be defibrillated. In cases of successful defibrillation two distinct patterns were observed: 1) complete annihilation of fibrillating activity at all sites or 2) nearly complete cessation of fibrillating activity with a single area of persistent fibrillation that subsequently self-extinguished within one to three activations. This single site in the second form of successful defibrillation was located in the region of minimum voltage gradient produced by the defibrillating waveform and was occasionally accompanied by dynamic encapsulation with refractory tissue as a result of a wavefront emanating from a region that had undergone successful defibrillation. These results support the hypothesis that a critical mass of myocardium must be affected for successful defibrillation and that unsuccessful defibrillation is always accompanied by residual fibrillating activity in at least one site. The results also demonstrate that the size of the critical mass required for successful defibrillation can be less than 100%.

Animals↗
PubMed1990

Exercise body surface potential mapping in single and multiple coronary artery disease.

Body surface ST integral maps were recorded in 36 coronary artery disease (CAD) patients at: rest; peak, angina-limited exercise; and, 1 and 5 min of recovery. They were compared to maps of 15 CAD patients who exercised to fatigue, without angina, and eight normal subjects. Peak exercise heart rates were similar (NS) in all groups. With exercise angina, patients with two and three vessel CAD had significantly (p less than 0.05) greater decrease in the body surface sum of ST integral values than patients with single vessel CAD. CAD patients with exercise fatigue, in the absence of angina, had decreased ST integrals similar (NS) to patients with single vessel CAD who manifested angina and the normal control subjects. There was, however, considerable overlap among individuals; some patients with single vessel CAD had as much exercise ST integral decrease as patients with three vessel CAD. All CAD patients had persistent ST integral decreases at 5 min of recovery and there was a direct correlation of the recovery and peak exercise ST changes. Exercise ST changes correlated, as well, with quantitative CAD angiographic scores, but not with thallium perfusion scores. These data suggest exercise ST integral body surface mapping allows quantitation of myocardium at ischemic risk in patients with CAD, irrespective of the presence or absence of ischemic symptoms during exercise. A major potential application of this technique is selection of CAD therapy guided by quantitative assessment of ischemic myocardial risk.

Adult↗