Biomedical subjects

M R Franz

Publications and source records attributed to M R Franz.

At least 73 records · Page 4Linked to original sources

PubMed1992

Electrophysiological effects of myocardial stretch and mechanical determinants of stretch-activated arrhythmias.

BACKGROUND: Although the existence of myocardial mechanoelectrical feedback is well established, the mechanism of arrhythmia induction by ventricular dilatation or stretch remains insufficiently defined. In particular, controversy exists when comparing the arrhythmogenic potential of chronic versus acute myocardial stretch. Also, assessment of cellular electrophysiological effects of myocardial stretch has been incomplete. METHODS AND RESULTS: To evaluate the electrophysiological and arrhythmogenic effects of slow versus rapid ventricular wall stretch, we developed an isolated Langendorff-perfused rabbit heart model in which left ventricular (LV) volume can be changed by a computer-controlled servopump. Cellular electrophysiological effects and premature ventricular excitations (PVEs) and their origin produced by the volume increases were assessed by a multiple-site monophasic action potential (MAP) recording system and by volume-conducted ECGs obtained by immersing the entire preparation in a saline-filled tank. Volume was increased either gradually with slow volume ramps (0.1 ml/sec) or suddenly by volume pulses of varying pulse waveforms (three different amplitudes and five different rise velocities) applied randomly 250-350 times to each of eight hearts. Gradual LV volume loading caused gradual decreases in MAP resting and action potential amplitude, whereas rapid, transient volume pulses caused transient depolarizations. Despite similar membrane potential effects of stretch, gradual volume increases rarely (11%) produced PVEs, even with large volume loads, whereas rapid volume pulses of moderate amplitudes regularly triggered PVEs (45-100% of interventions). Logistic regression analysis showed that the probability of PVE occurrence increased independently with both the amplitude and the velocity of the volume increase, with the greatest sensitivity to stretch velocity exhibited at low and intermediate pulse amplitudes. Faster volume pulse rise velocities triggered PVEs at a lower instantaneous pulse amplitude than lower rise velocities, further corroborating the dependence of stretch-activated arrhythmias on the velocity of stretch. In contrast, an increase in the basic ventricular volume had no effect on the probability of PVE occurrence during the volume pulses. The MAP recordings demonstrated spatial variability in the extent of local depolarizations and site of PVE origin; transient depolarizations occurred, and PVEs originated most often in the posterolateral region of the left ventricle. CONCLUSIONS: Membrane depolarization is caused by both gradual and rapid ventricular stretch, but PVEs are more easily elicited by rapid stretch. Regions of greater myocardial compliance that experience greater relative stretch may act as "foci" for stretch-activated arrhythmias during dynamic ventricular loading. These whole-heart data corroborate the existence of stretch-activated membrane channels in ventricular myocardium and may help explain ventricular ectopy under conditions of differential ventricular loading, as in ventricular dyskinesia, or regional muscle traction, as in mitral valve prolapse syndrome.

Animals↗

PubMed1991

Response of relatively refractory canine myocardium to monophasic and biphasic shocks.

BACKGROUND: Certain biphasic waveforms defibrillate at lower energies than monophasic waveforms, although the mechanism is unknown. METHODS AND RESULTS: The relative ability of monophasic and biphasic shocks to stimulate partially refractory myocardium was compared because defibrillation is thought to involve stimulating relatively refractory myocardial tissue. Shocks of 25-125 V were given during regularly paced rhythm in 11 open-chest dogs. Computerized recordings of shock potentials, and of activations before and after the shocks, were made at 117 epicardial sites. To quantify the shock field strength, the shock potential gradients were calculated at the electrode sites. Monophasic action potential (MAP) electrode recordings, obtained in five dogs, confirmed direct myocardial excitation by the shock, that is, activations beginning during the shock. Tissue was directly excited up to 4 cm from the shocking electrode, and the area directly excited increased as the shock was made stronger or given less prematurely. In six dogs, strength-interval curves for direct excitation were determined from plots of potential gradient versus refractoriness at each electrode site. The biphasic curves were located to the right of the monophasic curves by 8 +/- 4 msec, indicating a lesser ability to excite refractory myocardium. When the gradient at the directly excited border was at least 3.8 +/- 1 V/cm, conduction failed to propagate away from the directly excited zone after the shock, and MAP recordings made near the border showed a shock-induced graded response. This graded response, which prolonged repolarization, may have been responsible for the failure of conduction from the directly excited zone. Although better for defibrillating, the biphasic waveform was thus less effective than the monophasic one in exciting relatively refractory myocardium. CONCLUSIONS: These results indicated that waveform selection for defibrillation should not be guided solely by the ability of the waveform to stimulate tissue, as these two properties can be discordant.

Action Potentials↗

PubMed1991

[Clinical value of monophasic action potentials].

The method of monophasic action potential (MAP) recording has experienced a significant surge in interest since the introduction of the contact electrode, which in contrast to the suction electrode, allows the safe and simple use of this technique in the clinical electrophysiology laboratory. MAP recording not only provide for a more precise determination of local activation, but most importantly, permit direct measurement of myocardial repolarization and action potential duration (APD), respectively. This had led to new insights into the cycle-length-dependence of the human APD, both in response to single extrastimuli and to steady-state heart rate changes. An advancement of the contact electrode catheter design now permits simultaneous pacing and MAP recording, and thereby, simultaneous determinations of APD and effective refractory periods (EPP) at the same endocardial site in the human heart. MAP recordings have demonstrated significant usefulness in the direct monitoring of antiarrhythmic drug effects, both in terms of dosage control and in the direct measurement of antiarrhythmic drug effects on the relationship between ERP and APD (ERP/ARD-ratio). Because MAP recordings reflect the local cellular electrophysiology, they also provide a more sensitive and precise index of myocardial ischemia than conventional ECG recordings. This can be utilized to assess the success of revascularizing procedures directly during or after the intervention. Recently, MAP recordings helped to discover early after-depolarizations in patients with "torsade de pointes", providing a possible explanation for the mechanism of polymorphous ventricular tachycardia in man.

Anti-Arrhythmia Agents↗

PubMed1990

Inefficacy and proarrhythmic effects of flecainide and encainide for sustained ventricular tachycardia and ventricular fibrillation.

OBJECTIVE: To assess the efficacy of encainide and flecainide in treating patients with sustained ventricular arrhythmias. DESIGN: Patients were treated with encainide or flecainide. Efficacy was assessed by comparing the results of programmed ventricular stimulation while patients received therapy with the results while they were drug free. SETTING: The electrophysiology laboratory of the University of California at San Francisco. PATIENTS: Forty-nine patients with spontaneous or inducible sustained ventricular tachycardia or ventricular fibrillation for whom treatment with at least one class IA antiarrhythmic agent had failed. INTERVENTIONS: Patients were treated with encainide, 35 to 50 mg three or four times daily, or flecainide, 100 to 200 mg twice daily. RESULTS: Arrhythmia worsened early in 5 of 16 patients receiving encainide and 3 of 33 patients receiving flecainide. Patients with poor left ventricular function were more likely to exhibit proarrhythmia (P = 0.02). Nine of eleven patients receiving encainide and 23 of 28 patients receiving flecainide who had repeat programmed ventricular stimulation while receiving drug therapy still had inducible, poorly tolerated ventricular tachycardia. CONCLUSION: Encainide and flecainide have a low efficacy rate and a high incidence of worsening of arrhythmia in patients with sustained ventricular arrhythmias, particularly when this condition is associated with poor left ventricular function.

Adult↗

PubMed1990

A new single catheter technique for simultaneous measurement of action potential duration and refractory period in vivo.

In vivo correlations of action potential duration measured by a monophasic action potential catheter and effective refractory period measured by a separate pacing catheter have been poor, probably because of the known variability of both action potential duration and effective refractory period between different ventricular sites. In this study, a new quadripolar contact electrode catheter designed for simultaneous pacing and monophasic action potential recording at closely adjacent sites (2 mm separation between recording electrodes and pacing electrodes) was tested in five closed chest dogs and four patients. Dog studies: Pacing thresholds were extremely low, ranging from 0.02 to 0.25 mA (mean +/- SD 0.099 +/- 0.051, n = 36) and were stable over time (less than 20% increase during 1 h of continuous pacing). Because of the close proximity of pacing and recording electrodes, the pacing artifact nearly coincided with the monophasic action potential upstroke. Because of the low pacing threshold, however, pacing artifacts were small (33 +/- 17% of the monophasic action potential amplitude at twice diastolic threshold strength) and did not affect the duration or configuration of the simultaneously recorded monophasic action potential. The short stimulus response time and the undisturbed monophasic action potential signal fidelity during pacing allowed precise simultaneous measurements of action potential duration and effective refractory period at the same endocardial site.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1990

Persistent functional atrioventricular block in two patients with prolonged QT intervals: elucidation of the mechanism of block.

This article describes two infants with prolonged QT interval and intermittent second-degree atrioventricular block. An asymptomatic 14-month-old child with persistent 2:1 atrioventricular conduction since birth underwent electrophysiology study including measurements with a contact monophasic action potential catheter. During 2:1 conduction, atrioventricular block occurred distal to the site of the His-bundle recording. Monophasic action potential duration was closely related to prior RR intervals. Single premature atrial or ventricular depolarizations during 1:1 conduction followed by a pause, lead to monophasic action potential prolongation and subsequent 2:1 atrioventricular conduction, which was perpetuated by the resulting long RR intervals. Paired premature ventricular contractions or short bursts of ventricular pacing elicited monophasic action potential shortening and subsequent 1:1 atrioventricular conduction that was perpetuated by the resulting short RR intervals. A second infant presented at birth with a prolonged QT interval, ventricular tachycardia, and episodes of second-degree atrioventricular block with persistent 2:1 atrioventricular conduction. The atrioventricular block was repeatedly elicited by single premature ventricular contractions and terminated by ventricular couplets. We conclude that the atrioventricular block in both patients is functional in nature and results from the interrelationships between ventricular rate, action potential duration, and His-Purkinje system refractoriness.

Action Potentials↗

PubMed1989

Sequential pulse internal defibrillation: is there an advantage to "switched" current pathways?

Sequential pulse internal defibrillation delivered via orthogonal current pathways has been postulated to improve defibrillation efficacy. The efficacy of twin truncated exponential sequential shocks was compared in four different defibrillation electrode configurations in six pentobarbital-anesthetized, open-chest dogs. Lead systems consisted of the conventional single current pathway spring-patch and patch-patch electrode configurations, as well as a multiple patch lead configuration, which utilized either a single (multiple patch-unswitched) or two different (multiple patch-switched) current pathways. Curves of percent successful defibrillation versus initial voltage and energy were constructed and the data were analyzed by logistic regression. The energy and initial voltage required for 50% successful defibrillation (E50 and V50, respectively) for each lead system were then compared. The E50 for the multiple patch-unswitched and switched lead systems (4.3 +/- 1.5 J and 4.6 +/- 1.7 J, respectively) were significantly lower than for the spring-patch (9.0 +/- 3.1 J; p less than .005) and patch-patch (6.6 +/- 1.2 J; p less than .005) lead systems. In addition, the V50 for the multiple patch-unswitched lead configuration (270.6 +/- 48.4 V) was significantly lower than that of all other lead systems (p less than .005). Therefore lead configurations utilizing multiple patch electrodes improve defibrillation efficacy over conventional lead systems, but there is no advantage to "switched" current pathways.

Animals↗

PubMed1989

Improved internal defibrillation efficacy with a biphasic waveform.

Clinically available automatic implantable defibrillators use a monophasic truncated exponential waveform shock; after delivery the charge remaining on the device's capacitors is "dumped" internally and wasted. The efficacy of a monophasic and biphasic truncated exponential defibrillation waveform produced by a single capacitor discharge was compared in seven closed-chest, pentobarbital-anesthetized dogs. Defibrillation leads consisted of a new deployable intrapericardial electrode system. The monophasic waveform was positive and 6 msec in duration. The biphasic waveform had a positive phase identical to that of the monophasic waveform and a negative phase of equal duration with its initial voltage equal to 50% of the final voltage of the positive phase. Defibrillation shocks of varying initial voltage were delivered to construct curves of the percentage of successful defibrillation versus initial voltage and delivered energy, and the voltage and energy required for 50% (V50 and E50, respectively) and 80% (V80 and E80, respectively) success were compared. The biphasic waveform had significantly lower initial voltage (V50: 194 +/- 48 volts vs 227 +/- 48 volts, p less than 0.001; V80: 217 +/- 55 volts vs 256 +/- 66 volts, p less than 0.02) and energy (E50: 2.7 +/- 1.3 joules vs 3.4 +/- 1.5 joules, p less than 0.01; E80: 3.4 +/- 1.6 joules vs 4.3 +/- 2.2 joules, p less than 0.05) requirements than the monophasic waveform. It is concluded that a biphasic waveform produced by a single discharge that uses the "free" energy remaining on the capacitors significantly reduces the initial voltage and energy requirements for successful defibrillation and may improve the efficacy of future automatic implantable defibrillators.

Animals↗

PubMed1989

Mechanically induced action potential changes and arrhythmia in isolated and in situ canine hearts.

Stretch of excised myocardial tissue causes electrophysiological and potentially arrhythmogenic changes in transmembrane action potentials but corresponding data of the intact mammalian heart are lacking. The effects of increases in ventricular volume and pressure on epicardial monophasic action potentials were therefore investigated in isolated, cross circulated and in situ canine hearts. In seven isolated hearts, increases in ventricular volume and pressure resulted in (1) a linearly related decrease in action potential amplitude (r = 0.988; slope = 0.41% amplitude.ml-1; volume intercept = 17.6 ml), mainly due to a decrease in maximum diastolic potential; (2) a decrease in action potential plateau duration (at 20% repolarisation) by 19 (SD 8)%; and (3) appearance of early afterdepolarizations, reaching up to 18% of total action potential amplitude. Afterdepolarizations occurred only when ventricular outflow was obstructed at end diastole but not at end systole. In eight in situ hearts, increase in left intraventricular pressure produced by transient occlusions of the ascending aorta was also accompanied by decrease in maximum diastolic potential and action potential plateau duration, and by appearance of early afterdepolarizations. In both isolated and in situ intact ventricles, the loading induced electrophysiological changes were associated with occurrence of ectopic ventricular beats. These data show that mechanical overload produces significant electrophysiological changes in the intact canine ventricle which may lead to arrhythmia.

Action Potentials↗

PubMed1989

Frequency-dependent effect of quinidine, mexiletine, and their combination on postrepolarization refractoriness in vivo.

Combination therapy with mexiletine and quinidine has been shown to enhance antiarrhythmic efficacy. To assess further the underlying electrophysiological mechanism, the effect of therapeutic concentrations of mexiletine and quinidine, and of their combination, on action potential duration (at the level of 90% repolarization, APD90), effective refractory (ERP), and the relationship between these two parameters (ERP-APD90) was determined in 21 in vivo canine hearts. The frequency dependence of these effects was assessed over a range of paced steady-state cycle lengths from 250-600 ms. A modified contact electrode technique allowed measurements of both APD90 and ERP simultaneously and at the same ventricular site. In the drug-free state, both APD90 and ERP shortened linearly with shorter cycle lengths, maintaining a constant relationship (ERP-APD90) difference = -9 +/- 2 ms) at all cycle lengths. Quinidine prolonged APD90 by a near constant amount of 11 +/- 1 ms over the entire range of cycle lengths, while mexiletine tended to shorten it. Both mexiletine and quinidine increased ERP and ERP-APD90 in a rate-dependent fashion, the effect increasing with shorter cycle lengths. When used in combination, mexiletine attenuated the lengthening effect of quinidine on APD90 but augmented the rate-dependent increase in ERP, thereby producing greater postrepolarization refractoriness than either drug alone. This effect may explain the clinically favorable antiarrhythmic efficacy of mexiletine and quinidine combination therapy.

Action Potentials↗

PubMed1989

Evaluation of a prototype DNA probe test for the noncultural diagnosis of gonorrhea.

A prototype, nonisotopic, chemiluminescent DNA probe test called the Gen-Probe PACE (Probe Assay-Chemiluminescence Enhanced) system for Neisseria gonorrhoeae (Gen-Probe, San Diego, Calif.) was compared with conventional Martin-Lewis culture medium in JEMBEC plates for the laboratory diagnosis of gonorrhea. This 2-h noncultural assay is based upon the use of an acridinium ester-labeled DNA probe. The rRNA-directed DNA probe hybridizes with the target rRNA, and the hybridized probe is separated from the unhybridized probe through the use of magnetic microparticles. The esterified acridinium is hydrolyzed from the hybridized probe by the addition of an alkaline hydrogen peroxide solution, resulting in the production of visible light which is measured in a luminometer. The amount of light generated is directly proportional to the amount of gonococcal target rRNA present in the sample. A total of 407 clinical specimens (203 urethral and 204 endocervical) were collected from high-risk walk-in patients attending a sexually transmitted disease clinic. Separate patient specimens were collected for culture on Martin-Lewis medium in JEMBEC plates and for DNA probe assay. Statistical analysis of the overall comparative results showed that the DNA probe assay had a sensitivity, specificity, and positive and negative predictive values of 93, 99, 97, and 99%, respectively, in a patient population with a gonococcal disease prevalence of 21%. The results of this comparative study showed that the prototype chemiluminescent DNA probe assay is a rapid and reliable noncultural alternative for the laboratory diagnosis of gonorrhea.

DNA Probes↗

PubMed1989

Slow and long-lasting modulation of myocardial repolarization produced by ectopic activation in isolated rabbit hearts. Evidence for cardiac "memory".

Prolonged ventricular pacing induces T wave polarity changes that persist long after cessation of pacing. To examine how ventricular repolarization is modulated by prolonged changes in activation sequence, we studied the effect of ectopic pacing on the distribution of action potential durations (APDs) in nine isolated Langendorff-perfused rabbit hearts. A contact electrode probe was used to map right and left ventricular-epicardial monophasic action potentials during three consecutive changes in stimulus site, that is, 1) during 45 minutes of right atrial pacing, 2) during 120 minutes of right ventricular pacing, and 3) again, during 60 minutes of right atrial pacing. During each of these phases, the effect of activation sequence on repolarization was examined by linear-regression analysis of APD on activation time (AT). Results averaged for all nine hearts showed that during the initial atrial-pacing phase, APD was inversely related to AT (slope [S] = -1.63; r = 0.76), indicating that sites with earlier activation repolarized later. With the onset of ventricular pacing, the inverse correlation between AT and APD disappeared (S = -0.19; r = 0.31). Continuing ventricular pacing, however, produced slow changes in APD that restored the inverse relation (S = -0.71; r = 0.68 at 120 minutes; p less than 0.0002 versus 5 minutes). Switching from ventricular to atrial pacing again perturbed the inverse correlation (S = 0.28; r = 0.35) but at 60 minutes of atrial pacing, a significant inverse correlation was reestablished (S = -1.25; r = 0.53; p less than 0.01 versus 5 minutes). An inverse correlation between AT and APD tends to synchronize repolarization time (RT, the sum of AT and APD).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1989

Frequency-dependent antiarrhythmic drug effects on postrepolarization refractoriness and ventricular conduction time in canine ventricular myocardium in vivo.

Both conduction time (CT) and effective refractory period (ERP), absolute and relative to action potential duration (APD), are major determinants of re-entry arrhythmia circuits. We compared the effects of 3 commonly used class I antiarrhythmic agents, lidocaine, mexiletine and quinidine, and of the combination of the latter 2, on APD, ERP, ERP/APD ratio and interventricular CT in 26 in vivo canine hearts. To assess also the frequency dependence of these effects, each measurement was made at multiple steady-state cycle lengths ranging from 600 to 250 msec. A modified contact electrode technique was used to measure both APD and ERP simultaneously and at the same left ventricular site. Interventricular CT was measured as the interval from the stimulus of right ventricular paced beats to the upstroke of the ensuing left ventricular action potential. Lidocaine did not change APD, ERP and ERP/APD ratio significantly at any basic cycle length. In contrast, both mexiletine and quinidine increased the ERP/APD ratio, with progressively greater effects toward shorter cycle lengths. The quinidine/mexiletine combination increased the ERP/APD ratio significantly more than either drug alone (cycle length 350 msec: 8.3 +/- 2.2% quinidine; 17.6 +/- 7.0% mexiletine; 35.3 +/- 9.6% mexiletine/quinidine combination, P less than .01 vs. quinidine, P less than .05 vs. mexiletine). CT increased only with quinidine but not with mexiletine or lidocaine. Combination of mexiletine and quinidine caused no further slowing of conduction as compared to quinidine alone. Thus, although both ERP/APD ratio and CT are related to sodium channel conductance, drug effect on one parameter does not necessarily imply quantitatively similar effects on the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1988

Immediate quantitation of antiarrhythmic drug effect by monophasic action potential recording in coronary artery disease.

A contact electrode catheter, which permits clinical recording of cardiac monophasic action potentials (MAPs), was used as a means of quantifying the electrophysiologic effect of 2 antiarrhythmic drugs, procainamide and quinidine. MAP recordings were made in continuous fashion from the right ventricle in 16 patients, before and after the intravenous administration of procainamide (11 patients) or quinidine (5). Increases in the MAP duration at 90% repolarization (MAPD90) were used as indexes of drug effect and related to plasma drug level. Surface electrocardiographic (QRS duration, corrected QT interval [QTC]) and electrophysiologic (ventricular effective refractory period) measurements, in addition to MAPD90, were made at the same time as blood sampling for plasma drug level determination. Dose response curves, plotting change in MAPD90 versus plasma drug level, showed strong linear correlation for both procainamide (p less than 0.0001) and quinidine (p less than 0.0001). The variance (error of estimation) of the predictive relation, change in MAPD90 versus plasma drug level, was significantly lower than that of change in QTC (p less than 0.001), QRS duration (p less than 0.0001) or ventricular effective refractory period (p less than 0.0001) versus plasma drug level for both procainamide and quinidine. Changes in MAP duration closely correlate with plasma drug level, and as such, may serve as an immediate, quantitative indicator of myocardial drug effect during the administration of antiarrhythmic agents.

Action Potentials↗

PubMed1988

In vitro studies of isolated supported human hearts.

We developed methods to revive human hearts, obtained at the time of cardiac transplantation, and study them in the physiology laboratory. The hearts were arrested with cardioplegic solution at the time of explanation and transported to the laboratory at 4 degrees C. The hearts were perfused with a human blood based solution whose flow rate, temperature, and ionic concentration were controlled. Six hearts with various endstage cardiomyopathies were revived in this manner. Once perfusion was started, the hearts maintained a steady contractile state for approximately 30 min during which time data could be collected. Within this time period we could measure end-systolic and end-diastolic pressure-volume relations, the time courses of contraction and relaxation, and the influence of heart rate and premature stimulation on contractile state. The results suggest that evidence of specific cellular abnormalities in human heart disease might be obtained from measurements of global ventricular performance. Furthermore, the type of abnormality identified, namely sarcoplasmic reticulum dysfunction, in several forms of cardiomyopathy was in concordance with results obtained in muscle bath studies of similarly diseased human and animal myocardium.

Cardiomyopathy, Dilated↗

PubMed1988

Mechanism of depolarization in the ischaemic dog heart: discrepancy between T-Q potentials and potassium accumulation.

1. To study the origin of ischaemic myocardial depolarization, the diastolic surface potential - T-Q depression-was correlated with subepicardial extracellular K+ accumulation during serial episodes of widespread ischaemia in open-chest dogs, and in isolated, blood-perfused canine hearts. Placement of the reference electrode on a small island of non-ischaemic myocardium simplified the interpretation of the T-Q potentials. 2. In some experiments, changes in resting potential in the ischaemic zone were recorded using a 'contact' monophasic action potential (MAP) electrode. The change in MAP resting potential was linearly related to T-Q depression for a wide range of experimental conditions (R greater than 0.98). T-Q depression is therefore a linear index of depolarization in superficial myocardial cells. 3. The validity of T-Q depression as a 'measure' of local cellular depolarization was further tested by infiltration of isotonic KCl into the superficial myocardium subjacent to the ischaemic zone electrode. Resulting T-Q depression was 2- to 3-fold larger than the maximum values obtained in ischaemia; and the ratio of T-Q depression to the amplitude of the accompanying monophasic potential was consistent with the assumption that KCl had fully depolarized the underlying myocardium (delta Vm = 89 mV). KCl prevented (i.e. occluded) further changes in the T-Q potential during ischaemia. KCl did not have these effects if it was introduced at sites more remote from the electrode (greater than 4 mm). 4. Ischaemic T-Q depression was drastically accelerated by increasing the heart rate from 90 to 180 beats/min and was further accelerated by arterial infusion of CaCl2. These effects were most striking during the first minute of ischaemia. 5. In contrast, the above manoeuvres produced little acceleration of subepicardial K+ accumulation. After CaCl2 infusion, large ischaemic potentials, severe conduction impairment, and arrhythmias could be observed when K+ activity was almost normal (aK = 4.0-4.5 mM). 6. T-Q depression was larger in vivo than in isolated hearts, both absolutely and relative to K+ accumulation. 7. Based on the reproducible amplitude of ischaemic epicardial potential-estimates of cellular depolarization (delta Vm) could be obtained, which were compared with the concurrent change in K+ electrode potential (delta EK) for each experimental condition. 8. Estimated depolarization was nearly identical to delta EK in isolated hearts under basal conditions. However, depolarization significantly exceeded delta EK during rapid pacing, CaCl2 infusion, or during paced occlusions performed in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1988

Frequency-dependent effects of quinidine on the relationship between action potential duration and refractoriness in the canine heart in situ.

To determine the normal relationship in vivo between action potential duration (APD) and effective refractory period (ERP) over a large range of steady-state cycle lengths (CLs) and to determine how a sodium channel-blocking agent, quinidine, affects this relationship, we developed a new contact electrode technique for simultaneous measurements of monophasic action potentials and refractoriness at a single site in the beating heart in situ. Recordings were made from left ventricular epicardium in open-chest dogs during steady-state pacing at CLs from 220 to 600 msec both before and after therapeutic intravenous administration of quinidine. During baseline both APD at 90% repolarization (APD90) and ERP were linearly correlated to CL with nearly identical slopes: y = 0.24x CL + 83.0 (r = 1.0; p less than .0001) for APD90 and y = 0.22x CL + 82.3 (r = 1.0; p less than .0001) for ERP. Expressed in percent repolarization, ERP coincided with a repolarization level of 79% to 83%, with no appreciable influence of CL on this relationship. Quinidine increased APD90 by a small but significant amount (8 to 12 msec), which was independent of CL. In contrast, the effect on ERP of quinidine exhibited marked frequency dependence (p less than .0002), producing progressively greater ERP increase at shorter CLs, as compared with both baseline ERP and concomitant APD90. The duration by which ERP exceeded APD90 reached 44 +/- 14 msec at a CL of 220 msec.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1988

Effect of ischemia on calcium-dependent fluorescence transients in rabbit hearts containing indo 1. Correlation with monophasic action potentials and contraction.

The effects of acute global ischemia on cytosolic calcium transients were studied in perfused rabbit hearts loaded with the fluorescent calcium indicator indo 1. Indo 1-loaded hearts were illuminated at 360 nm, and fluorescence was recorded simultaneously at 400 and 550 nm from the epicardial surface of the left ventricle. The F400/F550 ratio was calculated by an analog circuit, which allowed cancellation of optical motion artifact. Resulting calcium transients demonstrated a rapid upstroke and slow decay similar to those recorded in isolated ventricular myocytes. Global ischemia rapidly suppressed contraction, but it produced a concurrent increase in the systolic and diastolic levels of the calcium transients, together with an increase in the duration of the peak. The effects of ischemia were reversed by reperfusion, inhibited by verapamil, and mimicked by perfusion of nonischemic hearts with acidified (CO2-rich) solution. In addition to elevation of the calcium transients, ischemia caused a pattern of intracellular calcium alternans that was discernible after 2-3 minutes. The pattern of alternans was stable at a given epicardial site, but it could be out of phase at different sites. Similar nonuniformities were observed in contraction strength and in the duration of monophasic action potentials recorded immediately adjacent to the fiber-optic probe. Abnormalities in intracellular calcium may be a causal factor in the loss of electrical and mechanical synchrony in the acutely ischemic heart.

Action Potentials↗