Mid-Diastolic Potential is Related to the Reentrant Circuit in a Patient with Verapamil-Sensitive Idiopathic Left Ventricular Tachycardia

Mid-Diastolic Potential in Idiopathic VT. We report a case of verapamil-sensitive idiopathic ventricular tachycardia in which a mid-diastolic potential (MDP) 45 msec preceding the Purkinje potential ( P potential) was recorded. Pacing during the tachycardia caused concealed entrainment, and the stimulus–QRS interval was equal to the P potential–QRS interval. The interval between the last pacing stimulus and the next P potential (postpacing interval) was longer than the ventricular tachycardia cycle length, but the MDP was orthodromically activated. These findings suggest that the MDP was on the reentrant circuit and the P potential was not on the reentrant circuit, but a bystander.     

Melanopsin in the circadian timing system

In mammals, circadian rhythms are generated by a light-entrainable oscillator located in the hypothalamic suprachiasmatic nucleus (SCN). Light signals reach the SCN via a dedicated retinal pathway, the retinohypothalamic tract (RHT). One question that continues to elude scientists is whether the circadian system has its own dedicated photoreceptor or photoreceptors. It is well established that conventional photoreceptors, rods and cones, are not required for circadian photoreception, suggesting that the inner retinal layer might contribute to circadian photoreception. Melanopsin, a novel photo pigment expressed in retinal ganglion cells (RGCs), has been proposed recently as a candidate circadian photoreceptor. Melanopsin-containing RGCs are intrinsically photosensitive, form part of the RHT, and contain neurotransmitters known to play a critical role in the circadian response to light. Furthermore, melanopsin-containing RGCs do not depend on inputs from rods and cones to transmit light signals to the SCN. However, based on a review of the available information about melanopsin and on new data from our laboratory, we propose that melanopsin, in itself, is not necessary for circadian photoreception. In fact, it appears that of the known photoreceptor systems, none, in and of itself, is necessary for circadian photoreception. Instead, it appears that within the photoreceptive systems there is some degree of redundancy, each contributing in some way to photic entrainment.     

Flies and fish: birds of a feather

The identification of specific clock-containing structures has been a major endeavour of the circadian field for many years. This has lead to the identification of many key components of the circadian system, including the suprachiasmatic nucleus in mammals, and the eyes and pineal glands in lower vertebrates. However, the idea that these structures represent the only clocks in animals has been challenged by the discovery of peripheral pacemakers in most organs and tissues, and even a number of cell lines. In Drosophila, and vertebrates such as the zebrafish, these peripheral clocks appear to be highly autonomous, being set directly by the environmental light/dark cycle. However, a hierarchy of clocks may still exist in mammals. In this review, we examine some of the current views regarding peripheral clocks, their organization and how they are entrained.     

Developmental appearance of light-dark entrainment in the rat

Previous studies show that the developing circadian system is entrained by a maternal signal during the prenatal and early postnatal period. The present study investigated the developmental onset of retina-mediated, light-dark entrainment. Juvenile rats were exposed to phase-shifts in the light-dark cycle at different ages and the pineal N-acetyltransferase rhythm was monitored on postnatal day 10. The results show that retina-mediated, light-dark entrainment begins by postnatal day 6 and overrides maternal entrainment by postnatal day 8.     

The Upper Link of Human Common Atrial Flutter Circuit Definition by Multiple Endocardial Recordings during Entrainment

Common atrial flutter is due to a macroreentry circuit in the right atrium, but the cranial path of the circuit has not been defined. The objectives of this article are to determine the cranial turning point of flutter activation in relation to a hypothetic obstacle, the superior vena cava opening, by examining the changes in activation sequence produced by entrainment from different points. In 13 cases of common atrial flutter with typical counter-clockwise right atrial circuits confirmed by endocardial mapping the atrium was paced from the high posterior and mid-septal walls. Entrainment was confirmed by simultaneous recordings of 6–7 right atrial electrograms. Changes in sequence of electrograms from high septum and high anterolateral walls was sought. Electrogram sequence and morphology did not change with entrainment at the posterior wall with respect to the basal flutter or mid-septal wall entrainment. Pacing "below" the superior vena cava did not advance the anterior wall electrogram in relation to the septal electrogram. These findings suppport the concept that common Putter activation turned around (cranial and anterior to) the superior vena cava opening, and not around the free end of a line of block below the superior vena cava in the posterior wall. Common atrial flutter activation rotates cranial (and anterior) to the superior vena cava opening, through the "right atrial roof" The line of functional block should span from inferior to superior vena cava openings.     

Significance of Ventricular Pacing Site in Manifest Entrainment During Orthodromic Atrioventricular Reentrant Tachycardia with Left-Sided Accessory Pathway

We examined entrainment by ventricular pacing in six patients during orthodromic atrioventricular reentrant tachycardia (AVRT) utilizing a left-sided lateral accessory pathway. Constant fusion and progressive fusion were demonstrated in all patients by left ventricular pacing during tachycardia, but in none of the patients by right ventricular pacing. When left ventricular pacing was performed during AVRT, the antidromic wave front from the pacing impulse (n) collided with the orthodromic wave front of the previous pacing beat (n - 1) within the ventricle, therefore, constant fusion and progressive fusion were demonstrated in the surface electrocardiographic QRS complexes. On the other hand, when right ventricular pacing was performed during orthodromic AVRT, the antidromic wave front from the pacing impulse (n) collided with the orthodromic wave front of the previous paced beat (n - 1) within the normal atrioventricular pathway, and constant fusion and progressive fusion were therefore not demonstrated. These phenomena were explained by the relationship of the ventricular pacing site and the reentrant circuit. This study demonstrates the importance of the pacing site in manifest entrainment of orthodromic AVRT during ventricular pacing.     

The dorsomedial hypothalamic nucleus is not necessary for food-anticipatory circadian rhythms of behavior, temperature or clock gene expression in mice

Circadian rhythms in mammals are regulated by a light-entrainable circadian pacemaker in the hypothalamic suprachiasmatic nucleus and food-entrainable oscillators located elsewhere in the brain and body. The dorsomedial hypothalamic nucleus (DMH) has been proposed to be the site of oscillators driving food-anticipatory circadian rhythms, but this is controversial. To further evaluate this hypothesis, we measured clock gene, temperature and activity rhythms in intact and DMH-ablated mice. A single 4-h midday feeding after an overnight fast induced mPer1 and mPer2 mRNA expression in the DMH, arcuate nucleus, nucleus of the solitary tract and area postrema, and reset daily rhythms of mPer1 , mPer2 and mBMAL1 in the DMH, arcuate and neocortex. These rhythms persisted during 2 days of food deprivation after 12 days of scheduled daytime feeding. Acute induction of DMH mPer1 and mPer2 was N -methyl- d -aspartate (NMDA) receptor-dependent, whereas rhythmic expression after 6 days of restricted feeding was not. Thermal DMH lesions did not affect acute induction or rhythmic expression of clock genes in other brain regions in response to scheduled daytime feeding. DMH lesions attenuated mean daily activity levels and nocturnality but did not affect food-anticipatory rhythms of activity and body temperature in either light–dark or constant darkness. These results confirm that the DMH and other brain regions express circadian clock gene rhythms sensitive to daytime feeding schedules, but do not support the hypothesis that DMH oscillations drive food-anticipatory behavioral or temperature rhythms.     

Entrainment Onset in Atrioventricular Reciprocating Tachycardia: Value in Bypass Tract Localization and Relationship to the Preexcitation Index

The timing of entrainment onset has been shown to correlate with the conduction time to critical elements of a tachycardia circuit in a pacemaker model of reentrant ventricular tachycardia (VT). The utility of this method in evaluating clinical reentrant tachycardias was there/ore evaluated in 24 patients with symptomatic Wolff-Parkinson-White syndrome and single bypass tracts (left free wall in 17, posteroseptal in 5, anteroseptal in 1, and right free wall in 1). Right ventricular apex (RVA) pacing during orthodromic atrioventricular reentrant tachycardia (oAVRT) at 10–70 msec less than tachycardia cycle length demonstrated concealed entrainment of the tachycardia in all patients studied. An entrainment index (EI), defined as the minimal prematurity of the ventricular stimulus that first resulted in atrial reset, was calculated from multiple entrainments in each patient. The El was 121 ± 25, 83 ± 19, and 55 msec for left free wall, septal, and right free-wall bypass tracts, respectively (P = 0.004 for difference between left free wall and septal). A corrected EI, derived by subtracting the amount of atrial reset from the EI, gave values of 108 ± 22 and 71 ± 17 msec for left free wall and septal bypass tracts (P = 0.001). These values were compared to the preexcitation index (PI) by linear regression analysis in these patients. The PI correlated closely with both the EI and the corrected EI (r = 0.90 and 0.93, respectively), but the PI could only be derived in 12/17 (71%) left free-wall tachycardias versus the El in 17/17 (100%) (P < 0.05). Thus, the timing of entrainment onset can be used to calculate a relative conduction time to the tachycardia circuit in oAVRT, thus localizing the bypass tract. This may prove useful in localizing critical components of the reentrant circuit in other clinical tachycardias.     

Frequency Dependent Shortening of Conduction Time through the Reentrant Pathway during Transient Entrainment of Ventricular Tachycardia

In a patient with nonischemic ventricular tachycardia (VT), VT was entrained and the conduction time from the pacing site to the entrained local electrogram showed a rate dependent shortening and its degree affected by the pacing site. The QRS complex, which was entrained by the last pacing stimulus, was constant and identical to that of VT and no rate dependent facilitated conduction was observed when the heart was paced at similar paced cycle lengths during sinus rhythm. As the mechanism of the shortening of the conduction time through the reentrant circuit, a shift of the entrance seems most likely.