Charles W. Haws

Correlation between in vivo transmembrane action potential durations and activation-recovery intervals from electrograms. Effects of interventions that alter repolarization time.

Classic cable theory was used to analyze the relation between the activation-recovery interval measured from unipolar electrograms and transmembrane action potential duration. Theoretic analysis demonstrated that the temporal derivative of the extracellular potential is proportional to a spatial weighting of the third temporal derivative of the transmembrane action potentials along a cable with uniform propagation in a homogeneous medium. Thus, the activation-recovery interval, measured as the interval between times of minimum derivative (Vmin) of the QRS and maximum derivative (Vmax) of the T wave, should be related to action potential duration, measured as the interval between times of Vmax of the upstroke and Vmin of the downstroke of the transmembrane action potential. This relation was examined experimentally in 12 anesthetized dogs. Unipolar electrograms and transmembrane action potentials were recorded simultaneously from sites within 2 mm of each other during control states, cardiac sympathetic nerve stimulation, localized epicardial warming, and graded reductions in myocardial perfusion. The heart was paced from several sites. There was close correlation between activation-recovery interval and action potential duration measurements taken during cardiac sympathetic nerve stimulation and local epicardial warming (r = 0.96 and 0.99 for cardiac sympathetic nerve stimulation and warming, respectively). In five animals in which coronary perfusion pressure was gradually lowered, the variables correlated closely over a range of values from 62 to 212 msec (r = 0.98). However, although the overall correlation was good and mean differences between activation-recovery interval and action potential duration were small, in individual cases there were differences up to 24 msec.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of bilateral and unilateral stellate stimulation on canine ventricular refractory periods at sites overlapping innervation.

The effects of unilateral right, unilateral left, and bilateral stellate stimulation on ventricular refractory periods at sites of overlapping cardiac sympathetic innervation were studied in 11 pentobarbital anesthetized dogs. The stellates were stimulated with 10 Hz pulses 4 msec in duration with intensities strong enough to produce T wave changes in a vertical ECG lead and just below the intensity at which control of drive of the ventricle at a 400-msec cycle length was lost. Refractory periods shortened more with left stellate stimulation, 17.8 ± 5.9 msec (mean ± SD) than with right stellate stimulation, 10.3 ± 5.1 msec, P < 0.001. During bilateral stimulation, shortening of refractory periods was no greater whether stimulation was applied first to the left and then right stimulation was added, 19.7 ± 6.9 msec, or the stimulation was applied first to the right and then left stimulation was added, 18.3 ± 6.5 msec. The shortening of refractory periods with bilateral stellate stimulation was not significantly different from that with left stellate stimulation alone. The results of this study suggest that ventricular recovery properties in areas of overlapping cardiac sympathetic innervation are less influenced by increases in tone of the right sympathetics than by increases in left sympathetic tone. In addition, the findings indicate that a bilateral increase in cardiac sympathetic tone has no greater effect on recovery properties than the effects of the left cardiac sympathetics alone.

Fine detail in body surface potential maps: Accuracy of maps using a limited lead array and spatial and temporal data representation

In order to evaluate the accuracy with which a limited lead array can be used to estimate fine details of the thoracic distribution of cardiac potentials, we compared 192-lead body surface maps and those constructed using a subset of 32 leads. We also evaluated preservation of detail in body surface maps reconstructed following spatial and temporal data representation, a method proposed for quantitative comparison of maps. Maps were analyzed with respect to four previously reported normal map features recorded with extensive lead arrays. The maps constructed from 32 leads accurately reproduced all map features with 92% or greater accuracy. Maps constructed after spatial and temporal data representation had a reproduction accuracy of 93% and 98% respectively for two map features more than 100 microV in amplitude but accuracy with respect to the two map features less than 100 microV in amplitude was 86% and 59% respectively. The study demonstrates that a selected limited lead array permits accurate estimation of the body surface distribution of cardiac potentials even when potentials are low level or occur in regions not directly sampled by a recording electrode. To represent potentials of less than 100 microV, more coefficients would be required to permit accurate spatial and temporal representation.

Effects of coronary occlusion on cardiac and body surface PQRST isoarea maps of dogs with abnormal activation simulating left bundle branch block.

The possibility of detecting myocardial infarction in the presence of left bundle branch block by analysis of cardiac and body surface PQRST isoarea maps was studied in nine open-chest and six closed-chest dogs. Recordings were taken during supraventricular drive or right atrial plus right ventricular pacing in control periods and at intervals for up to 10 hr after left anterior descending coronary artery occlusion. Right ventricular pacing was used to simulate left bundle branch block. Myocardial infarction was documented with triphenyl tetrazolium staining. The PQRST areas during supraventricular drive and right atrial plus right ventricular pacing were highly correlated to each other both before and after coronary occlusion. The PQRST isoarea maps after coronary occlusion showed a strong pole overlying the ischemic area on the cardiac surface in open-chest animals and over the left anterior thorax in closed-chest animals. The PQRST pole was positive during the first 1 to 2 hr of occlusion and became negative after several hours. The findings demonstrate that localized abnormalities due to ischemia and infarction are manifest in body and cardiac surface PQRST isoarea maps of both supraventricular complexes and right ventricular paced complexes. The findings suggest that PQRST isoarea maps may aid in identification and localization of ischemic or infarcted myocardium in the setting of abnormal activation such as left bundle branch block.

Effects of sympathetic stimulation on refractory periods of ischemic canine ventricular myocardium.

We studied the difference in effect of sympathetic stimulation on refractory periods of ischemic and non ischemic myocardium in eight dogs, and the effect of sympathetic stimulation on dispersion of refractory periods in ischemic myocardium in seven additional dogs. In the first group of dogs, refractory periods of ischemic sites averaged 164 +/- 2.2 msec (M +/- SEM) and those at non ischemic sites averaged 193 +/- 1.8 msec. Sympathetic stimulation shortened refractory periods at non ischemic sites to an average of 183 +/- 2.0 msec and prolonged refractory periods at ischemic sites to an average of 171 +/- 2.2 msec. As a result of the different effects of sympathetic stimulation on refractory periods of ischemic and non ischemic myocardium, refractory periods between ischemic and non ischemic areas were more uniform during sympathetic stimulation than during coronary occlusion alone. In the second group of dogs in which the effects of sympathetic stimulation on dispersion of refractory periods were studied, pooled variances in refractory periods were calculated. There was no statistically significant difference in the pooled variance of refractory periods during control periods and during sympathetic stimulation alone. Coronary occlusion alone significantly increased the variance in refractory periods, but there was no statistically significant difference in the variance of refractory periods during coronary occlusion alone and during coronary occlusion and sympathetic stimulation. Our findings suggest that at some times during the course of myocardial infarction the effects of high sympathetic tone may be partially protective with respect to arrhythmias by reducing inequalities of recovery between ischemic and non ischemic tissue.

Modulation of collision-induced changes in canine heart repolarization by cycle length

The possibility that cycle length modulates the electronic effect of activation sequence on repolarization was investigated in experiments using isolated canine cardiac Purkinje strands, in situ canine ventricular myocardium, and computer simulations. Action potential durations and refractory periods during one-way propagation were compared to those obtained during action potential collision. In both the computer simulations and the Purkinje strand experiments, collision decreased action potential duration more at long cycle lengths than at short cycle lengths. Comparably, collision of activation fronts in ventricular myocardium was associated with greater reductions in refractory period during pacing at long cycle lengths than at short cycle lengths. Theoretic considerations indicate that the magnitude of electrotonic effects of activation sequence on repolarization are directly related to action potential height and the square root of membrane resistance during repolarization and are inversely related to conduction velocity. In computer simulations and Purkinje strand experiments, changes in conduction velocity and action potential height elicited by decreasing cycle length could not fully account for the cycle length dependence of collision-induced changes in repolarization. Time-varying membrane resistance of a single cell was calculated in the simulations by briefly hyperpolarizing the membrane and determining the change in total ionic current. Membrane resistance during repolarization was less at short cycle lengths than at long cycle lengths. The results suggest the cycle length dependence of collision-induced changes in repolarization results largely from the effect of cycle length on membrane resistance during action potential repolarization, with changes in action potential height and conduction velocity playing a lesser role.