Role of heart mass in the developmental changes of ventricular fibrillation threshold and spontaneous defibrillation in young dogs.

In the course of studying developmental changes of induction and maintenance of ventricular fibrillation in canine pups, we have documented that at about the third week of age, hearts reach a critical point where ventricular fibrillation may become both inducible and sustainable, thus forming the basis for cardiac arrhythmic death. Since age-related variations of cardiac mass may account for these findings, this study was conducted to systematically investigate the role of changing heart mass on the induction and maintenance of ventricular fibrillation in the canine heart, during the early postnatal development. Repetitive determinations of ventricular fibrillation threshold and individual incidence of spontaneous defibrillation were obtained in 87 puppies 1-6 weeks old, from litters of varied body size breeds, studied at weekly intervals. Overall, ventricular fibrillation threshold correlated positively with ventricular weight (VFTmA = 3.30 + 1.27 Vwtg, r = 0.71). However the slopes were steeper and correlations were stronger for the first, second and sixth week and nonsignificant in the fourth and fifth weeks. The ventricular fibrillation to ventricular weight ratio also varied with age (P < 0.01). Spontaneous defibrillation occurred at least once in 68 of the puppies (78%). In general, spontaneous defibrillation was more likely to occur in hearts weighing less than 9 grams (P < 0.01), but the overall correlation of the decreasing defibrillation incidence to increasing weight was weak (SDF % = 48.6-0.90 Vwtg, r = 0.106). Spontaneous defibrillation was not observed at any age or weight in two litters, totaling 9 puppies.(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental changes of ventricular fibrillation threshold and spontaneous defibrillation in young dogs.

This study was conducted to systematically investigate whether induction and maintenance of ventricular fibrillation in the canine heart, change with age during the early postnatal development. Forty-eight mongrel puppies from seven litters, were randomly selected for size and studied at weekly intervals from 1-6 weeks for determination of ventricular fibrillation threshold and incidence of spontaneous defibrillation. Another fourteen mongrel puppies 8-11 weeks old and 10 adult dogs were similarly studied. Ventricular fibrillation threshold increased progressively with age up to the eighth week (VFTmA = 8.38 + 2.67 wk-0.134.wk2, r = 0.995) and thereafter reached a plateau, which was not significantly different from the ventricular fibrillation threshold of adult dogs (26.5 +/- 2.2 mA). In contrast, the high incidence of spontaneous defibrillation at early age decreased rapidly between second and fourth week and became rare thereafter, (%SDF = 281.e-0.60wk, r = 0.94. This rapid drop could not be explained by the increase in mean body weight, which did not change significantly during this early period (BWkg = 0.59.e0.23wk, r = 0.97). Our findings suggest first, that the vulnerability of the neonatal dog heart to electrical induction of ventricular fibrillation decreases progressively during early age. Second, that spontaneous defibrillation decreases precipitously between the second and fourth week of age, a change not sufficiently explained by the modest body weight gain during that time. Thus, it appears that about the third week of age ventricular vulnerability to fibrillation and ability to defibrillation reach a critical point, where lethal arrhythmias may become both inducible and sustainable, to result in death.

Correlation between refractory periods and activation-recovery intervals from electrograms: effects of rate and adrenergic interventions.

Unipolar electrograms from ventricular epicardium in dogs were analyzed for the timing of local excitation and repolarization with computer assistance. The most rapid decrease in voltage in the QRS (dV/dt min) was used to determine local excitation time, and the maximum rate of voltage increase (dV/dt max) near the peak of the T wave was used to time local repolarization. The difference between dV/dt min and dV/dt max, the activation-recovery interval, is theoretically related to the net effect of the durations of the action potentials at that site. Paired data for refractory periods and activation-recovery intervals obtained from the same electrodes during fixed activation orders were obtained before and during repolarization changes induced by changes in cycle length, infusion of norepinephrine, and cardiac sympathetic nerve stimulation. Correlation coefficients were close to 1.00 and standard errors were 2.0 to 4.3 msec for changes at individual sites. Pooling of data from multiple sites increased standard errors and reduced correlation coefficients. Results provide quantification of errors in the use of unipolar electrograms to time local repolarization changes induced by variations in rate and adrenergic tone. They should increase the practical usefulness of the unipolar electrogram as a tool for assessing the time course and spatial distribution of repolarization changes.

Changes in ventricular fibrillation threshold with stimulation of cardiac sympathetic nerves of the developing dog.

The effect of stimulation of the developing cardiac sympathetic nerves on the vulnerability to ventricular fibrillation was investigated in 50 puppies 1 to 6 weeks of age. Ventricular fibrillation thresholds were obtained before and during sympathetic nerve stimulation. Stimulation of either stellate ganglion increased ventricular fibrillation threshold, possibly due to diffuse functional innervation in pups. The effect of the left stellate increased progressively with age, whereas the effect of the right, although initially greater than that of the left, did not increase further with age. In contrast, stimulation of the left ventrolateral cardiac nerve, which is locally distributed, resulted in decreased ventricular fibrillation threshold. This decrease was progressively greater with age. The fact that activation of the left stellate ganglion and the left ventrolateral cardiac nerve affects ventricular fibrillation threshold in opposite directions suggests different sympathetically mediated changes on ventricular vulnerability in early life. The differing temporal patterns of maturation and the localized nature of the major distal branch distributions could provide a mechanism for promotion of arrhythmiogenesis under some conditions in early life.

Sympathetic neural effects on regional atrial recovery properties and cardiac rhythm.

The functional distribution of the cardiac sympathetic nerves to the atria and their arrhythmiogenic effects were determined in 16 open-chest pentobarbital-anesthetized dogs. Shortening of refractory periods at four right and two left atrial sites during stimulation of the nerves was taken as a criterion of their distribution. Stimulation of right stellate ganglion, craniovagal, and right stellate cardiac nerves produced localized shortening on the right atrium, particularly at the sinus node area, and invariably induced sinus tachycardia. The recurrent cardiac nerve produced little shortening at all sites and less arrhythmiogenic effect. The left stellate ganglion and ventrolateral cardiac nerve affected only left atrial sites and induced atrioventricular junctional rhythm. The ventromedial cardiac nerve affected all sites and had no consistent arrhythmiogenic effect. The innominate nerve had no substantial effect. We concluded that the functional distribution of the cardiac sympathetic nerves is localized, and that rate, rhythm, and refractory period changes induced by stimulation of these nerves are characteristic of the area of distribution.

Functional development of cardiac sympathetic nerves in newborn dogs: evidence for asymmetrical development.

The functional development of cardiac sympathetic nerves was investigated in 52 puppies, 1 to 6 weeks of age. The effect of nerve stimulation on refractory period shortening at eight epicardial sites was used as criterion. Zero or minimal effect was observed at the first week of life for all the nerves tested, then a sharp increase of effect was observed at the second week, while at the third week, an unexpected decrease was observed for all nerves. At the fourth week, the effect increased again and remained high for the subsequent weeks. Thus functional sympathetic innervation of the heart is not complete at birth, but continues to develop throughout the first 6 weeks of life, following an irregular pattern of progression. The nonuniform maturation of cardiac nerves coupled with the localised distribution of the nerves may provide a basis for regional sympathetic imbalance and subsequent arrhythmiogenesis in early life.