Functional origin of rate-induced changes in atrioventricular nodal conduction time of premature beats in the rabbit

1987 ◽  
Vol 65 (11) ◽  
pp. 2329-2337 ◽  
Author(s):  
Jacques Billette ◽  
Marie St-Vincent
Keyword(s):  
Recovery Time ◽  
Rabbit Heart ◽  
Inhibitory Effect ◽  
Facilitatory Effect ◽  
Conduction Time ◽  
Recovery Times ◽  
Atrioventricular Nodal Conduction ◽  
Premature Beats ◽  
Induced Changes ◽  
Nodal Properties

The characteristics and origin of the rate-induced changes in atrioventricular nodal conduction time of premature beats (A2H2 intervals) were studied in isolated rabbit heart preparations. Increasing the basic driving rate during a periodic premature stimulation prolonged (a net inhibitory effect) and shortened (a net facilitatory effect) significantly (p < 0.01, n = 17) the A2H2 intervals associated with long and short recovery times (H1A2 intervals), respectively. The origin of these responses was sought for by analyzing interactions between facilitation and fatigue. When the fatigue developed at a fast basic rate was estimated from changes in conduction time of basic beats and subtracted from the corresponding A2H2 intervals, the calculated A2H2 intervals showed enhanced facilitation but no fatigue. When independently obtained fatigue and facilitation effects were added to the control A2H2 intervals for corresponding H1A2 intervals, resulting A2H2 intervals correlated strongly with the ones observed at the equivalent fast basic rate (r = 0.99, p < 0.001). Moreover, changes in the A2H2 intervals of premature beats tested with constant coupling intervals during 5-min fast rates were biphasic, confirming the overlapping and competition between facilitation and fatigue effects. Hence, rate-induced deviations of premature nodal conduction time from that predicted by changes in recovery time are consistent and result from the interaction between the overlapping effects produced by two independent, antagonist, and dynamically distinct nodal properties (facilitation and fatigue).

Beat-to-beat changes in AV nodal refractory and recovery properties during Wenckebach cycles

1992 ◽  
Vol 262 (6) ◽  
pp. H1899-H1907 ◽  
Author(s):  
J. Zhao ◽  
J. Billette
Keyword(s):  
Recovery Time ◽  
Atrioventricular Node ◽  
Rabbit Heart ◽  
Conduction Time ◽  
Refractory Periods ◽  
Isolated Rabbit Heart ◽  
Complementary Role ◽  
Recovery Times

The roles of changes in refractory and recovery properties of the atrioventricular node as affected by facilitation and fatigue in the genesis of Wenckebach periodicity were studied in isolated rabbit heart preparations. The contribution of nodal recovery time, facilitation, and fatigue to beat-to-beat changes in nodal conduction time (NCT) and effective (ERPN) and functional refractory periods of node (FRPN) occurring during stable 4:3 Wenckebach cycles was determined with premature stimulation protocols performed during these cycles. Fatigue prolonged, equally for each beat, NCT, ERPN, and FRPN, and therefore did not contribute to Wenckebach periodicity. Beat-to-beat increases in facilitation broadened the range of recovery times for which conduction was successful and decreased NCT, ERPN, and FRPN below the values expected from fatigue alone. However, ERPN and NCT increased overall from beat to beat because of NCT-induced (effects of NCT on ensuing refractoriness) increases in nodal refractoriness and consequent shortenings of the recovery time. These findings establish a complementary role for the recovery and refractory properties in generating the Wenckebach periodicity and demonstrate the modulating roles of facilitation and fatigue on this phenomenon.

Differential vagal effects on antegrade vs. retrograde atrioventricular conduction

1987 ◽  
Vol 253 (5) ◽  
pp. H1059-H1068 ◽  
Author(s):  
T. Mitsuoka ◽  
T. Mazgalev ◽  
L. S. Dreifus ◽  
E. L. Michelson
Keyword(s):  
Vagal Stimulation ◽  
Atrioventricular Node ◽  
Rabbit Heart ◽  
Heart Tissue ◽  
Atrioventricular Conduction ◽  
Conduction Time ◽  
Crista Terminalis ◽  
Time Optimal ◽  
Fixed Phase ◽  
Atrioventricular Nodal Conduction

The influence of postganglionic vagal stimulation (PGVS) on antegrade and retrograde atrioventricular nodal conduction was studied in 17 isolated rabbit heart tissue preparations by pacing at the crista terminalis or His bundle, respectively. The effect of short bursts of PGVS on prolongation of atrioventricular conduction was phase dependent with respect to the cardiac cycle. This phasic dependency was more pronounced during antegrade atrioventricular conduction. Although the control retrograde atrioventricular conduction time was longer than the antegrade (P less than 0.05) at or near the time in the cycle during which vagal stimulation caused maximal prolongation of conduction time (optimal phase), PGVS-induced maximal prolongation of the antegrade atrioventricular conduction time was significantly greater than that of the retrograde (P less than 0.02). Moreover, when PGVS was introduced at a fixed phase in the cycle, but with increasing amplitude, antegrade atrioventricular conduction time was progressively prolonged, and block was observed first in the antegrade direction, whereas retrograde atrioventricular conduction continued. Microelectrode recordings during these experiments showed consistently that PGVS-induced hyperpolarization in the N region of the atrioventricular node was greater during antegrade atrioventricular conduction. This suggests that vagal effects depended not only on the intensity and phase of stimulation, but also on electronic influences which apparently are different during antegrade and retrograde conduction.

Modulation of quinidine-induced arrhythmias by temperature in perfused rabbit heart

1998 ◽  
Vol 274 (3) ◽  
pp. H817-H828 ◽  
Author(s):  
Joseph F. Spear ◽  
E. Neil Moore
Keyword(s):  
Recovery Time ◽  
Rabbit Heart ◽  
Monophasic Action Potential ◽  
Triggered Activity ◽  
Recovery Times ◽  
Local Recovery ◽  
Ion Channel Kinetics ◽  
Kinetics Of ◽  
Electrophysiological Effects ◽  
Activation Sequence

We used low temperature to slow ion channel kinetics and studied the electrophysiological effects of quinidine at different pacing rates in isolated rabbit hearts. Fifteen epicardial electrograms together with an endocardial monophasic action potential were recorded. Epicardial activation and local recovery times were measured. Arrhythmias together with the characteristics of their mode of induction and rate were analyzed by epicardial activation sequence mapping. In the presence of quinidine, arrhythmias consistent with both triggered activity and reentry were observed. At baseline, triggered activity was not inducible, even though at 25°C the recovery time was greater than that in the presence of quinidine at 36°C. Also, with quinidine, the incidence of triggered activity decreased at 30 and 25°C. Therefore prolongation of the recovery time per se does not cause triggered activity. Quinidine’s use-dependent effects on conduction and reverse use-dependent effects on recovery time were amplified by low temperatures. These findings can be understood in terms of the known temperature sensitivities of the kinetics of the membrane ion channels responsible for activation and recovery. The results demonstrate that temperature can be used as a tool to elucidate mechanisms of drug action.

Mechanisms of conduction time hysteresis in rabbit atrioventricular node

1995 ◽  
Vol 269 (4) ◽  
pp. H1258-H1267 ◽  
Author(s):  
J. Billette ◽  
J. Zhao ◽  
A. Shrier
Keyword(s):  
Functional Properties ◽  
Cycle Length ◽  
Atrioventricular Node ◽  
Intrinsic Property ◽  
Rabbit Heart ◽  
Fatigue Properties ◽  
Conduction Time ◽  
Cycle Lengths ◽  
Respective Contribution ◽  
Nodal Properties

The functional origin of atrioventricular nodal hysteresis was studied in isolated rabbit heart preparations. This hysteresis is characterized by asymmetric changes in nodal conduction time (NCT) occurring for symmetric changes in cycle length. The respective contribution of the nodal properties of recovery, facilitation, and fatigue to the beat-to-beat changes in NCT observed during paired symmetric ramps of decreasing and increasing cycle length was determined with specifically design stimulation protocols. Nodal hysteresis was found to be entirely accounted for by variations in the contribution of nodal recovery and fatigue properties observed at corresponding cycle lengths. The study establishes how this contribution varies on a beat-to-beat basis as a result of cycle length history. This holds true for the numerous changes in hysteresis observed in response to changes in the sequence and slope of the ramps. Facilitation clearly affected NCT during these responses but did not contribute to the hysteresis. Moreover, the study demonstrates that there is no inherent change in the characteristics of nodal function with the direction of the ramp that could account for the hysteresis. Thus nodal hysteresis arises from nodal functional properties of recovery and fatigue but does not constitute a distinct independent intrinsic property of the node.

Quantitation of dynamic AV nodal properties and application to predict rate-dependent AV conduction

1991 ◽  
Vol 261 (2) ◽  
pp. H292-H300 ◽  
Author(s):  
M. Nayebpour ◽  
M. Talajic ◽  
S. Nattel
Keyword(s):  
Time Constant ◽  
Exponential Function ◽  
Conduction Time ◽  
Quantitative Characterization ◽  
First Order ◽  
Rate Dependent ◽  
Av Conduction ◽  
Coupling Interval ◽  
Premature Beats ◽  
Nodal Properties

A number of functional properties of the atrioventricular (AV) node have been described in response to changes in the atrial input rate. The purpose of this study was 1) to develop quantitative descriptors of these properties, and 2) to determine whether they can account for rate-dependent changes in AV nodal conduction. The delay in AV nodal conduction of single premature beats (recovery) was found to be an exponential function of coupling interval with a time constant of 66 +/- 2 (+/- SE) ms. A single abbreviated (facilitation) cycle did not alter the time constant of recovery or basal conduction for a subsequent beat but shifted its recovery curve to the left to an extent exponentially related to the facilitation cycle length. The induction of a tachycardia with HA interval fixed so as to control the recovery and facilitation variables resulted in a first-order onset of AV conduction slowing (fatigue). The fatigue process had a time constant in the range of 70 beats and a magnitude that was a decaying exponential function of HA interval. An equation incorporating quantitative descriptors of recovery, facilitation, and fatigue accurately predicted rate-dependent changes in AH interval. We conclude that 1) the AV nodal properties of recovery, facilitation, and fatigue are amenable to quantitative characterization, and 2) rate-dependent changes in AV nodal conduction time can be well described in terms of these underlying properties.

Neural network dysfunction in bipolar depression: clues from the efficacy of lamotrigine

2009 ◽  
Vol 37 (5) ◽  
pp. 1080-1084 ◽  
Author(s):  
Charles H. Large ◽  
Elena Di Daniel ◽  
Xingbao Li ◽  
Mark S. George
Keyword(s):  
Bipolar Disorder ◽  
Valproic Acid ◽  
Protein Kinase ◽  
Glycogen Synthase ◽  
Bipolar Depression ◽  
Inhibitory Effect ◽  
Mood Stabilizers ◽  
Mitogen Activated Protein Kinase ◽  
Facilitatory Effect

One strategy to understand bipolar disorder is to study the mechanism of action of mood-stabilizing drugs, such as valproic acid and lithium. This approach has implicated a number of intracellular signalling elements, such as GSK3β (glycogen synthase kinase 3β), ERK (extracellular-signal-regulated kinase)/MAPK (mitogen-activated protein kinase) or protein kinase C. However, lamotrigine does not seem to modulate any of these targets, which is intriguing given that its profile in the clinic differs from that of valproic acid or lithium, with greater efficacy to prevent episodes of depression than mania. The primary target of lamotrigine is the voltage-gated sodium channel, but it is unclear why inhibition of these channels might confer antidepressant efficacy. In healthy volunteers, we found that lamotrigine had a facilitatory effect on the BOLD (blood-oxygen-level-dependent) response to TMS (transcranial magnetic stimulation) of the prefrontal cortex. This effect was in contrast with an inhibitory effect of lamotrigine when TMS was applied over the motor cortex. In a follow-up study, a similar prefrontal specific facilitatory effect was observed in a larger cohort of healthy subjects, whereas valproic acid inhibited motor and prefrontal cortical TMS-induced BOLD response. In vitro, we found that lamotrigine (3–10 μM) enhanced the power of gamma frequency network oscillations induced by kainic acid in the rat hippocampus, an effect that was not observed with valproic acid (100 μM). These data suggest that lamotrigine has a positive effect on corticolimbic network function that may differentiate it from other mood stabilizers. The results are also consistent with the notion of corticolimbic network dysfunction in bipolar disorder.

Recovery of ectomycorrhizal fungi after exposure to subfreezing temperatures

1979 ◽  
Vol 57 (17) ◽  
pp. 1845-1848 ◽  
Author(s):  
R. C. France ◽  
M. L. Cline ◽  
C. P. P. Reid
Keyword(s):  
Growth Rate ◽  
Ectomycorrhizal Fungi ◽  
Recovery Time ◽  
Growth Form ◽  
Rapid Recovery ◽  
Active Growth ◽  
Growth Recovery ◽  
Recovery Times

Seventy-three isolates of eighteen ectomycorrhizal fungi were examined for their growth recovery after a 48-h exposure to −10 °C. Survival of all isolates was 97%. Recovery time to active growth varied between species and within species. Of surviving isolates, 72% initiated growth in less than 2 weeks after thawing. Growth rate was not affected for isolates exhibiting rapid recovery but was significantly lowered for isolates with recovery times of more than 5 weeks. Variation in growth form occurred with some species of Suillus and Xerocomus.

Modulation of release of [3H]acetylcholine in the major pelvic ganglion of the rat

1993 ◽  
Vol 264 (6) ◽  
pp. R1084-R1088
Author(s):  
G. T. Somogyi ◽  
W. C. de Groat
Keyword(s):  
Inhibitory Effect ◽  
Facilitatory Effect ◽  
K Channel ◽  
Muscarinic Agonist ◽  
Ach Release ◽  
Pelvic Ganglion ◽  
M1 Receptor ◽  
Major Pelvic Ganglion ◽  
Electrophysiological Findings ◽  
Frequency Of Stimulation

Cholinergic modulation of [3H]acetylcholine release evoked by electrical stimulation was studied in the rat major pelvic ganglion, which was prelabeled with [3H]choline. Acetylcholine (ACh) release was independent of the frequency of stimulation; 0.3 Hz produced the same volley output as 10 Hz. Tetrodotoxin (1 microM) or omission of Ca2+ from the medium abolished ACh release. The M1 receptor agonist (4-hydroxy-2-butynyl)-1-trimethylammonium m-chlorocarbanilate chloride (McN-A 343, 50 microM) increased release (by 136%), whereas the M2 muscarinic agonist oxotremorine (1 microM) decreased ACh release (by 22%). The muscarinic antagonists, atropine (1 microM) or pirenzepine (M1 selective, 1 microM), did not change ACh release. However, pirenzepine (1 microM) blocked the facilitatory effect of McN-A 343, and atropine (1 microM) blocked the inhibitory effect of oxotremorine. The cholinesterase inhibitor physostigmine (1-5 microM), the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP, 10 microM), and the nicotinic antagonist D-tubocurarine (50 microM) did not change ACh release. 4-Aminopyridine, a K+ channel blocker, significantly increased the release (by 146%). Seven days after decentralization of the major pelvic ganglion, the evoked release of ACh was abolished. It is concluded that release of ACh occurs from the preganglionic nerve terminals rather than from the cholinergic cell bodies and is not modulated by actions of endogenous ACh on either muscarinic or nicotinic autoreceptors. These data confirm and extend previous electrophysiological findings indicating that synapses in the major pelvic ganglion have primarily a relay function.

Corticofugal Modulation on Both on andoff Responses in the Nonlemniscal Auditory Thalamus of the Guinea Pig

2003 ◽  
Vol 89 (1) ◽  
pp. 367-381 ◽  
Author(s):  
Jufang He
Keyword(s):  
Auditory Cortex ◽  
Inhibitory Effect ◽  
Border Region ◽  
Cortical Activation ◽  
Facilitatory Effect ◽  
Auditory Signal ◽  
Inhibitory Input ◽  
Auditory Information ◽  
Medial Geniculate ◽  
Corticofugal Modulation

Corticofugal modulation on both on andoff responses in various nuclei in the medial geniculate body (MGB) was examined by locally activating the auditory cortex and looking for effects on the neuronal responses to acoustic stimuli. In contrast with a major corticofugal facilitatory effect on theon neurons in the lemniscal nucleus of the MGB of the guinea pigs, of 132 on neurons tested in three conditions with cortical activation through each of three implanted electrodes, the majority of the tested conditions (319/396) that were sampled from the nonlemniscal nuclei of the MGB received inhibitory modulation from the activated cortex. This inhibitory effect was >50% for 99 cases while the auditory cortex was activated. Most of the offand on-off MGB neurons (44/54) showed a facilitatory effect of 111.4 ± 99.9%, and three showed a small inhibitory effect of 25.7 ± 5.8% on their off responses. Thirty neurons in the border region between the lemniscal and nonlemniscal MGB showed mainly facilitatory corticofugal effects on both on andoff responses. Meanwhile, cortical stimulation induced almost exclusive inhibitory effects on the on response and facilitatory effects on the off response in the MGcm. It is suggested that the off response is produced as a disinhibition from the inhibitory input of the auditory stimulus. The present results provide a possible explanation for selective gating of the auditory information through the lemniscal MGB while switching off other unwanted sensory signals and the interference from the limbic system, leaving the other auditory cortex prepared to process only the auditory signal.

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