Larry S. Green

Comparative effects of beta-adrenergic blocking drugs on experimental ventricular fibrillation threshold

Abstract Recent clinical studies suggest that certain betaadrenergic blocking drugs, such as timolol, may reduce sudden death in patients with ischemic heart disease, but the mechanism has not been established. To assess and compare antifibrillatory effects of beta-blocking drugs as a potential mechanism of sudden death prevention, the ventricular fibrillation (VF) threshold was measured in anesthetized, open-chest dogs before and after 3 minutes of coronary ischemia during intravenous administration of saline solution or 3-fold serial increments (0.003 to 1.0 mg/kg) of 5 beta-blocking drugs with various accessory properties. Ventricular fibrillation occurred in control studies after delivery of a current train of 11.7 ± 7.6 mA in the nonischemic state and 7.0 ± 7.4 mA during ischemia (n = 46). All 5 betablocking drugs but not saline solution caused substantial (average 6-fold) increases (p

The sequence of normal ventricular recovery

Abstract Functional refractory periods (FRPs) were measured at epicardial, intramural, and septal sites in pentobarbital anesthetized dogs. The sinus node was crushed and the atria were driven at a fixed rate. Activation times at the test sites were measured from electrograms recorded from closely spaced bipolar electrodes. The test stimuli were cathodal “make” stimuli delivered to one pole of the pairs of electrodes. FRPs at the base of the free wall of the left ventricle and of the septum were shorter than FRPs at the apex. FRPs on the epicardium were shorter than those on the endocardium, and FRPs on the right side of the septum were shorter than those on the left side of the septum. The findings indicate that normal ventricular recovery properties are systematically distributed and inversely related to activation sequence. Areas of the ventricle activated early have the longest FRPs, and areas activated late have the shortest FRPs. This distribution of recovery properties tends to make all portions of the ventricles complete recovery at about the same time, and may play a protective role in the prevention of reentrant arrhythmias. This distribution of recovery properties is also applicable to an explanation of the configuration of normal T waves.

QT interval dispersion: dispersion of ventricular repolarization or dispersion of QT interval?

The QT interval (QTI) has long been useful as a clinical index of the duration of ventricular repolarization, particularly as a marker of prolonged repolarization and its well-established association with arrhythmogenic cardiac states. Likewise, inhomogeneity (dispersion) of repolarization has been linked definitively to increased susceptibility to reentrant arrhythmias. Recent studies have reported the use of QTI dispersion as a meaningful clinical index to identify patients at risk, but the interpretation of the measurement has been controversial. A Langendorff-perfused, isolated canine heart suspended in a torso-shaped, electrolytic tank filled with NaCl-sucrose solution was used to investigate the relationship between body surface QTIs and ventricular repolarization measured directly from the cardiac surface by using activation-recovery intervals, which have been documented to reflect the duration of local action potentials as well as local refractory periods. The data showed poor correlation between cardiac surface activation-recovery intervals and QTIs, as well as the insensitivity of QTIs to regional repolarization shortening in the presence of prolonged repolarization elsewhere. Furthermore, the data confirmed that torso tank QTI dispersion does not reflect directly the full range of measured ventricular repolarization inhomogeneity. It is concluded that body surface QTI dispersion is not a reliable index of repolarization dispersion.

Epicardial potential mapping. Effects of conducting media on isopotential and isochrone distributions.

BackgroundEpicardial excitation sequences, recovery sequences, and potential distributions are recorded from patients during surgery and from animals in the research laboratory for a variety of purposes. During such recordings, a portion of the cardiac surface is exposed to air, and the remainder of the epicardial surface variably is in contact with conductive tissue. No systematic studies document the degree to which these different conditions affect measured excitation times, potential distributions, and/or the configuration of epicardial electrograms. Methods and ResultsEpicardial potential distribution was recorded from five isolated, perfused hearts using a 64-unipolar-lead sock. Data were recorded first with the heart suspended in air and then with the heart immersed in a heated tank filled sequentially to full and half-full levels with conductive Tyrodes solution and then NaCI-sucrose solution. These solutions had resistivity less than and more than that of blood, respectively, and air was assumed to have infinite resistivity. Epicardial potentials were recorded from two hearts before removal from the chest, both with and without a latex sheet insulating the heart from the pericardial cradle. Amplitude of recorded potentials from both intact and isolated hearts was markedly higher when the heart was surrounded by an insulating medium, but locations of positive and negative regions were less affected by surrounding medium. Isochrone activation maps calculated using the minimum derivative of the QRS (intrinsic deflection) were not affected by the conductivity of media surrounding the heart. ConclusionsThe present study provides evidence that isochrone maps recorded at surgery are not distorted by exposure of the cardiac surface to insulating air. Results suggest that epicardial isochrones recorded during cardiac surgery could be used in patients to assess the accuracy of “inverse” procedures that noninvasively compute epicardial electrograms and isochrones from body surface potentials.

A prospective study of myocardial damage in electrical injuries.

A prospective study was undertaken to determine the incidence of possible myocardial damage following electrical injury. Sixteen patients with non-flash electrical injuries were assessed utilizing serial electrocardiograms (ECG), creatine kinase (CK) and MB creatinine kinase (MB-CK) determinations, technetium 99m stannous pyrophosphate scans, and 24-hour Holter monitors. Results showed that five patients (31%) had abnormal ECG, nine patients (56%) had elevations of the MB-CK isoenzyme, and one patient had a transiently abnormal Holter monitoring. No patient had an abnormal technetium pyrophosphate cardiac scan. Of the nine patients with elevated MB-CK levels, only two had abnormal ECG. None of the patients had clinical evidence of cardiac dysfunction. These results indicate a poor correlation of elevated MB-CK levels with ECG abnormalities, and demonstrate a relatively low incidence of myocardial damage in association with electrical injuries.

The QRST deflection area of electrograms duringglobal alterations of ventricular repolarization

Changes of refractory period and QRST deflection area in cardiac electrograms due to localized myocardial warming and altered cycle length were determined. Localized myocardial warming consistently resulted in increased QRST deflection area which was highly correlated with reduction of refractory period. Similar reductions of refractory period by decreased cycle length were associated with insignificant changes of small QRST areas and significant reductions of larger QRST areas. The different effect of local thermal alteration of repolarization and global alteration due to cycle length changes is experimental evidence that QRST deflection area depends on differences in duration of ventricular repolarization properties. The finding of decreased deflection area with decreased cycle length is also evidence of decreased disparity of repolarization properties of normal myocardium at rapid heart rates.

Estimates of repolarization and its dispersion from electrocardiographic measurements: Direct epicardial assessment in the canine heart

This study investigates a technique to estimate dispersion based on the root mean square (RMS) signal of multiple electrocardiographic leads. Activation and recovery times were measured from 64 sites on the epicardium of canine hearts using acute in situ or Langendorff perfused isolated heart preparations. Repolarization and its dispersion were altered by varying cycle length, myocardial temperature, or ventricular pacing site. Mean and dispersion of activation and recovery times, and activation-recovery interval (ARI) were calculated for each beat. The waveform was then calculated from all leads. Estimates of mean and dispersion of activation and recovery times and mean ARI were derived using only inflection points from the RMS waveform. QT intervals were also measured and QT dispersion was determined. Estimates determined from the RMS waveform provided accurate estimates of repolarization and were, in particular, a better measure of repolarization dispersion than QT dispersion.

Resolution of pace mapping stimulus site separation using body surface potentials.

Several studies have related 12-lead ECG waveform during ventricular tachycardia to ECG waveform during ventricular pacing to identify ablation sites for therapy of ventricular tachycardia. QRS isopotential maps and QRS isointegral maps derived from body surface isopotential maps have also been correlated with left ventricular pacing sites with the same objective. The comparison process used is subjective and only semiquantitative. Improved accuracy of catheter placement may improve success rates of ablation therapy. Methods and ResultsThis animal study was performed to determine the spatial resolution with which left ventricular pacing sites could be distinguished by body surface isopotential mapping. Potentials were recorded from 64 evenly spaced thoracic leads. Hexapolar or octapolar pacing catheters with 2-mm interelectrode spacing were placed percutaneously in the left ventricle in each of six dogs, and bipolar endocardial pacing was performed using each pair of adjacent electrodes. QRS isopotential maps of each pacing site for each catheter placement were cross-correlated by computer. Difference maps for each pair of pacing sites were calculated lead by lead and time instant by time instant, and root-mean-square voltage differences were calculated. Results indicated that correlation coefficients and root-mean-square error of voltage differences monotonically decrease and increase, respectively, with stimulus site separation. Both measures were significantly different (P < .05) for separations of 4 mm or more. ConclusionsA method of quantitative comparison of body surface potential maps can be used in normal hearts to localize ventricular pacing sites within a 4-mm range. The method may have utility in determining potential ablation sites for therapy of ventricular tachycardia or preexcitation syndromes.

Time course of vulnerability to fibrillation after experimental coronary occlusion

Abstract The early time course of vulnerability of the ventricles to fibrillation after coronary artery occlusion was measured in 6 dogs. The duration of a train of 60 Hz stimuli with currents of 2 to 3 times the diastolic threshold was used as the measure of vulnerability to fibrillation. Within 2 minutes of coronary occlusion the duration of the train of 60 Hz stimuli inducing fibrillation fell by an average of 25 percent of control values. Five minutes after coronary occlusion the duration of the train was an average of 34 percent shorter than control values. In all animals, the duration of the train required to produce fibrillation began to increase 30 minutes after coronary occlusion and approached control values. The relation of these findings to the time course of arrhythmias in experimental infarction and the early high mortality rate in cases of infarction in man is discussed.

Assessment of spatial and temporal characteristics of ventricular repolarization

Measurement of dynamics and spatial characteristics of ventricular repolarization is of interest in assessing patients with ischemic heart disease, particularly in relation to the detection and characterization of ischemic events, identification of patients at risk of ventricular arrhythmias, or determination of the efficacy of drugs intended to alter repolarization. The QT interval (QTI) has been the index of choice for assessing repolarization abnormalities. It is a general measure of repolarization duration but lacks the power to assess the spatial aspects of repolarization and the ability to detect localized shortening in the setting of global prolongation. For direct cardiac surface measurement, QRST integrals and activation recovery intervals (ARIs) were used to assess repolarization and its disparity. The use of similar measurements from the body surface was proposed to provide better characterization of repolarization, its disparity, and its dynamics than is possible using the QTI. In one open-chest experiment using an intact canine heart and two experiments using isolated canine hearts suspended in a torso-shaped electrolytic tank, 64 epicardial electrograms and 192 torso surface electrocardiograms were measured simultaneously. Ventricular repolarization was globally altered by varying pacing cycle lengths or tank temperature. Atrial and ventricular pacing were used to assess sensitivity of repolarization indices to activation sequence. At the cardiac surface, (1) QTI tracks global repolarization changes but is affected by activation sequence and insensitive to localized shortening of repolarization; (2) distribution of QRST integrals reflects disparity of repolarization and is largely independent of activation sequence; and (3) ARI measures local repolarization duration and is only weakly affected by activation sequence.(ABSTRACT TRUNCATED AT 250 WORDS)