833

Unequal Atrial Stretch in Dogs Increases Dispersionof Refractoriness Conducive to Developing

Atrial Fibrillation

TADASHI SATOH, M.D., and DOUGLAS P. ZIPES, M.D.

From [he Kranncrt Institute of Cardiology. Indiana University, School itf Medicine, andRoudebush Veterans Affairs Medical Center, Indianapolis. Indiana

Atrial Stretch Precipitates Atrial Fibrillation. Introduction: We have shown previ-ously that acute atrial dilation prolonged atrial refractoriness. We hypothesized that this in-crease in refractoriness might be heterogeneous and could create an electrophysiologic sub-strate leading to atrial fibrillation. The purpose of the present study was to test that hypothesis.

Methods and Results: We studied 23 anesthetized open chest dogs. Bipolar plunge electrodeswere placed in the medial free wall of the right atrium (thin region) and in the lower crista ter-minalis of the right atrium (thick region). Two bipolar plunge electrodes were also placed inthe left ventricular apex to stimulate and record. Atrial ctTective refractory period (ERP) wasmeasured in a group of nine dogs using the atrial extrastimulus method (A1A2) in two ways:during atrial pacing (AP) and during simultaneous atrioventricular (AV) pacing that achievedan AV interval of 0 msec (AV = 0). One liter/liour of normal saline was infused intravenouslyto elevate right atrial pressure and produce right atrial stretch. Atrial ERPs were measuredbefore and after the normal saline infusion. To compare the extent of atrial stretch producedby volume overload, two pairs of sonomicrometer transducers were implanted in the thick andthin regions in a separate group of six dogs. The area encompassed by sonomicrometers wasmeasured before and after saline infusion. The inducibility of atrial fibrillation was comparedbefore and after saline infusion using rapid AP in another group of five dogs. Atrial pressureduring sinus rhythm increased from 5.1 ± 0.96 mniHg to 6.3 ± 0.93 nimHg after normal salineinfusion (P < 0.01). ERP increased in the thin free wall from 151 ± 14.3 to 172 ± 14.7 msec (AV= 0), and from 149 ± 12.0 to 170 ± 14.3 msec (AP). ERP increased in the thick crista terminalisfrom 134 ± 9.9 to 147 ± 10.2 msec (AV = 0), and from 133 ± 7.9 to 146 ± 9.8 msec (AP) (P <0.01). The increase in ERP in the thin free wall exceeded that in the thick crista terminalis (P <0.01), increasing the dispersion of atrial ERP. After 500-nil. saline infusion for 30 minutes, theincrease of area in the thin region was 12.8% ± 3.7%, and that in the thick was 3.5% ± 3.2%.The increase of the area in the thin region after 1000 mL for 1 hour was 18.8% ± 6.2%. andthat in the thick region was 6.3% ± 5.1% (P < 0.01). Atrial fibrillation was not induced in anydog before saline infusion, hut induced in all five dogs after saline infusion.

Conclusions: Atrial ERP in the thin right atrial free wall exceeds the ERP of the thick cristaterminalis, and an increase in atrial pressure produced by saline infusion exaggerates this ditter-ence by stretching thin segments of the atrial myocardium more than it stretches thick regions.Thus, atrial stretch, by increasing the dispersion of atrial ERP, may be conducive to the develop-ment of atrial fibrillation. (J Cardiuvasc Eleclrophysiol, Vol. 7, pp. 833-842, September 1996)

atrial refractoriness, thick region, thin region, regional atrial stretch, contraction-excitation feedback

This study was supponed in part by the Herman C. Krannerl Fund.Indianapolis. Indiana: and Grant HL-52323-Ol from the NationalHeart. Lung, and Blood Instilute. National Institutes of Health,Beihesda. Maryland.

Address for correspondence: Douglas P. Zipes. M.D., Krannert In-stitute of Cardiology. 11! I West 10th Street, Indianapolis. IN46202-4800. Fax: 317-274-7143.

Manuscript received 15 February 1996; Accepted for publication15 April 1996.

Introduction

Atrial fibrillation often occurs in patients whohave dilated atria caused by a variety of condi-tions.'^' We have shown previously that acute atrialdilation prolonged refractoriness,''^ and we hy-pothesized that this increase in refractoriness mightbe heterogeneous and could create an electro-physiologic substrate leading to atrial fibrillation.

834 Journal of Cardiovascular Electrophysiology Vol. 7. No. 9. Sepiemher 1996

This mechanism might be the cause of atrial fibril-lation in patients with atrioventricular (AV) andAV nodal (AVN) reciprocating tachycardias(RTs) whose atria dilate during tachycardia.**

The purpose of this present study was to test thehypotheses tliat: (I) acute volume overload stretchesthin regions of the right atrium, such as the freewall, more than it stretches thick regions, such asthe crista terminalis; (2) this difference in stretchcauses the effective refractory period (ERP) in thinregions to increase more than in thick regions; and(3) this increase in refractory period dispersion isconducive to developing atria! fibrillation.

Methods

Twenty-three mongrel dogs weighing 24 to 30kg were anesthetized with pentobarbital (25 mg/kgIV); additional doses were given as necessaiy tomaintain anesthesia. The dogs were intubaledand ventilated artiticially with room air using avolume-cycled respiralor (mtxlel 6()7. Hiirvaid Ap-paratus. South Natick, MA, USA). The chest wasopened through a median sternotomy, and the heartwas positioned in a periciirdial cradle. Dogs wereplaced on a heating pad. and the thoracotomy wascovered by plastic sheet. A table lamp was usedto maintain epicardial temperature at 36° to38^0. A fluid-filled catheter was placed in theleft femoral artery and connected to a transducer(Statham P23 Db. Gould, Cleveland, OH,USA) tomonitor arterial blood pressure. The left femoralvein was cannulated to infuse nonnai saline. An-other catheter was placed in the right femoral veinand passed retrogradely to the cavity of the rightatrium to monitor the right atrial blood pressure.The vagal and sympathetic nerves were left intactbecau.se we wished to maintain as nomial condi-tions as fwssible. We have shown previously thatautonomic denervation prolongs these ERPchanges.'

Electrode Placement

A bipolar. Teflon-coated, plunge wire electrodewas placed in the lower (to avoid tbe sinus nodearea) crista terminalis of the right atrium (tbickregion) for stimulation, wbile a second bipolarplunge electrode was placed nearby to record tbeatrial potential. Similarly, two bipoUir plunge elec-trodes were placed in the medial free wall of tberight atrium (thin region) to stimulate andrecord, and two bipolar plunge electrodes wereplaced in the left ventricular apex for stimulation

and recording. No data were obtained for 30 min-utes after placing tbe electrodes. Atrial and ven-tricular signals were filtered at a frequency rangeof 30 to 500 Hz. Surlace ECG lead II. local atrialand ventricular potentials, and rigbt atrial andfemoral arterial bUnxl pressures were recorded si-multaneously and stored on analog tape. After tbeexperiment, data were digitized by an analog-to-digital converter and displayed on a computer foranalysis.

Experimental Protocol

Atrial ERPs were measured in the thick regionsand thin regions of the right atrium before andafter the infusion of 1 L of nonnai .saline. ERPmeasurements took 15 to 20 minutes to obtain,during which a constant volume of saline infusionwas maintained to avoid volume redistribution thatmight occur after stopping the infusion prematurelyand alter the degree of atrial stretch. A total of1300 to 14(X) mL was infused in each dog. AtrialERPs were measured using the atrial extrastimu-lus method (Al A2) in two ways; during rigbt atrialpacing, and during simultaneous atrial and ven-tricular pacing at nn AV interval of 0 msec to repli-cate more closely the AV relationship during AVRTand AVNRT The basic cycle length (BCL) forail ERP determinations was 300 msec.

Measurement of Atrial ERP

Atrial ERP was measured at each pacing siteby tbe atrial extrastimulus method using a pro-grammable stimulator (Krannert Medical Engi-neering) that delivered a 2-msec constant current(Pulser 4i. Frederick Haer & Co.) rectangulai- stim-ulus at twice diastolic threshold. Diastolic ex-citability of the atrium was measured before eachdetermination of ERP The ventricular stimulus wasdelivered through a second constant current source(Pulser 6i, Frederick Haer & Co.) connected to tbestimulator. For eacb pacing metbod. a train of eigbtbasic atrial stimuli (SI) at a BCL of 3(K) m.sec wasfollowed by a late premature atrial extrastimulus(S2) tbat produced a propagated atrial response.The coupling interval {S1S2 interval) was short-ened in steps of 10 msec until S2 failed to pro-duce a propagated atrial response. Then the SIS2interval was increased by 10 msec and shortenedin steps of I msec decrementally until S2 failed toproduce a propagated atrial response. The ERPwas defined as ihe longest S1S2 interval at whichS2 failed to produce an atrial response. The

Satoh and Zipes Atrial Stretch Precipitates Atrial Fibrillation 835

ERPs were measured three times at each site andaveraged.

Measurement of Monophasic Action PotentialDuration

Monophasic action potentials (MAPs) wererecorded in the thick and thin regions using tbecontact electrode technique'' during constant atrialpacing at a pacing cycle length (PCL) of 300 msecin a separate group of dogs (n = 3). The record-ing was filtered at frequency range of 0 to 500 Hz.The thickness of the rigbt atrium in the thick andthin region also was measured in this group.

Measurement of Stretch in Thick and Thin Regionsof the Right Atrium

To compare the extent of stretch produced bynormal saline infusion, two pairs of sonomicrom-eter transducers (2.5 mm in diameter) (SL 5-2, Tri-ton Technology, San Diego, CA, USA) were im-planted in a long-axis direcfion (1.5 cm apart) andin a sbort-axis direction (1 cm apart) in botbtbick and thin regions of tbe right atrium in aseparate group of six dogs (Fig. 1). Sonomicrom-eter transducers were connected to a sonomi-crometer (Triton Technology), and signals weredisplayed on an oscilloscope and recorded by com-puter for later analysis. The area encompassed bytbe sonomicrometers was calculated by multiply-ing the distance of the long axis by the distanceof tbe sbort axis in botb thick and thin regions be-fore and after saline infusion. In Uiis fashion, we

were able to determine whether atrial stretch oc-curred after saline infusion and whether it occurredequally at botb sites. During measurements, sur-face ECG lead II, right atrial pressure, and femoralblood pressure were monitored. The area was mea-sured during ten consecutive A waves on the rigbtatrial pressure recording at control, after infusionof 500 mL of normal saline for 30 minutes, andafter infusion of 1000 mL of normal saline for Ihour. While it might be better to measure tbearea during diastole, the peak of tbe A wave couldbe used more accurately as a fiducial point, and itwas chosen to be able to compare all data.

Measurement of Thick and Thin Regions

At the conclusion of the experiment, the wholeheart was harvested, and the position of tbe elec-trodes and sonomicrometers in thick and thin re-gions was confirmed. Atrial wall thickness wasmeasured at eacb recording site in the group ofdogs in which stretch was measured (n = 6) andin the group of dogs that had MAP recordings(n = 3).

Induction of Atrial Fibrillation

To test whether the atrial vulnerability to de-veloping atrial fibrillation increased after acute vol-ume overload, we compared the effects of rapidrigbt atrial pacing before and after Infusing 1 Lof nonnai saline in another group of five dogs. Therigbt atrial appendage was paced at twice diastolicpacing threshold for 30 seconds, beginning at a

Superiorvena cava

Pulmonaryveins

atrialappendaqe

Rightcoronaryartery

Rightventricle

Inferiorvena c&va

Figure 1. Placement of two pairs of sonomicrometers in thick (lateral) and thin (medial) segments of right atrium.

836 Journal of Cardiovascular Electrophysiology Vol. 7. No. 9. September 1996

PCL of 250 msec. If atrial fibrillation did not oc-cur, the pacing interval was sbortened by 10 msecand pacing again performed for 30 seconds. Thisprocess was continued until a PCL of 100 msecwas reached.

Data Analysis

Data are expressed as mean value ± SD. Un-paired r-test was used to compare atrial ERPs be-tween the thick and thin regions. Paired /-testwas used to compare atrial ERPs obtiiined beforeand after normal saline infusion. The increase inarea between thick and thin regions measured bysonomicrometers was compared by unpaired /-test.Statistical significance was set at P < 0.05.

Results

Change in Right Atrial ERP and Atrial Pressure

Figure 2 shows an example of tbe electrogramrecordings and atrial pressures in an open chestdog, wbile pacing the rigbt atrium only (left) andwhile pacing the right atrium and the LV to achievean AV intei-val of 0 msec (right). A larger A wave

was observed at an AV interval of 0 msec thanduring right atrial pacing only.

Mean Right Atrial Pressure Before and After SalineInfusion

Mean right atrial pressure during sinus rhythmincreased from 5.1 ± 0.96 mmHg beftire saline in-fusion to 6.3 ± 0.93 mmHg (n = 9, P < 0.01) af-ter saline infusion (Table 1). Right atrial pressua- atan AV interval of 0 msec exceeded tbat during rightatrial pacing of the lower crista tenninalis and tliefree wall of the right atrium (n = 9) before (P <0.05) and alter (P < 0.01) saline infusion (Table I).

ERP in the Thick and Thin Regions of the RightAtrium Before and After Saline Infusion

Data are summarized in Table 2 and Figure 3.Atrial ERPs in the thin regions exceeded ERPs inthe thick regions before normal saline infusion (P< 0.01. n = 9). In tbe thick region, there was nodifference in atrial ERP among the two differentpacing methods, but in the thin region, atrialERP at an AV interval of 0 msec was longer thanduring right atrial pacing (P < 0.05).

AP AV=O

RA(lhin)

LV apex

15-

10-

I sec

JOLi1 I

0 mmHg

Figure 2, Analog tracings that show surface ECG lead It. right alrial electrogram in the thin region (RA), left ventiiculurapex electrogram (LV apex), and the right atrial pressure (RAP). The left panel shows the RAP at atrial pacing (AP) and theright panel shows RAP at an atrioventricular (AV) inten^al of 0 msec after high volume of normal saline iiifi4sion. Mean RAPat an A V inteiral of 0 msec was higher than RAP during airial pacing. There is a time delay in pressure tracings that wascaused by the hydraulic effect of the catheter.

Satoh and Zipes Atrial Stretch Precipitates Atrial Fibrillation 837

TABLK 1Mean Atrial Pressure in Control and During Pacing Bcfuri: and Afler Siiline Infusion

Atrial Presurc (miiiH({) Before Saline .\rtt'r Saline

ControlP value

5.1 ± 0.96

APAtrial Pacing SiteThick region

(lower crista terminaiis) 5.4 ± 1.02*P value P < 0.05

AV =

6.2 ± 1

0

.3*

P < O.OI

6 .8

AP

± 0.98**

6.3 ± 0.93

7

AV

.7 ±

= 0

1.14*

Thin region (free wall) 5.6 ± 0.971 6.1 ± 1.40+P<0.05

P < O.OI

6.« ± l.07tt 7.5 ±P< (I.OI

The righi atrial pressure is compared between AV = 0 and atriiil pacing before (*) and after (**) saline infusion in the thickregion, and before ( t ) and after ( I t ) saline infusion in the thin region.

After normal saline infusion, atrial ERPs pro-longed in both thick and thin regions of the rightutrium for each pacing method (P < 0.01) (Fig.4). In the thick region, there was no difference inatrial ERP between pacing tnethods. In the thin re-gion, atrial ERP at an AV intei-val of 0 msec pro-longed more than during right atrial pacing (P <O.OI). The increase in ERP in the thin region af-ter the saline infusion exceeded the increa.se in thethick region for each pacing methtxl (P < 0.01)(Table 2 and Fig. 5).

A V Interval at Normal Atrial Extrastimulus Method(A 1A2 Method)

During right atrial pacing at a PCL of 300 tnsec,AV intervals varied from dog to dog but they pro-longed after the saline infusion, possibly alsoinfluenced by atrial stretch. The mean AV intervalwas 118 ± 23.3 msec before and 137 ± 22.6msec after the saline infusion (P < 0.05).

Wall Thickness and MAP Duration in the Thin andThick Regions

The transmural thickness of the thin region {freewall in the right atrium) was 2.9 ±0.18 mm, andthat in the thick region (lower crista terminaiis)

was 4.1 ± 0.24 mm (P < O.OI. n = 9). MAP du-ration at 90% repolarization in the thin region (218± 8.0 msec) was longer than that in the thick re-gion (193 ± 13.3 msec) dtiring constant atrial pac-ing at a PCL of 300 msec in (P < 0.05, n = 3) incontrol.

Regional Atrial Stretch

Atrial stretch in the thin nsgion of the right atriumexceeded that in the thick region after rapid nor-mal saline infusion. After 500 mL of normal salineinfusion for 30 minutes, the increase of area in thethin region was 12.8% ± 3.7%, and that in the thickregion was 3.5% ± 3.2%. The increase of area inthe thin region after 1000 mL of normal saline in-fusion for 1 hour was 18.8% ± 6.2%, and that inthe thick region was 6.3% ± 5.1 % (P < O.OI. n =6) (Figs. 6 and 7).

Atrial Vulnerability

Before nonnal saline infusion, atrial fibrilla-tion was not induced by 30 seconds of burstatrial pacing at all PCLs msec in any dog. After1000 mL of nomial saline infusion, atrial fibrilla-tion lasting 90.6 ± 29.8 seconds (mean) was in-duced in all five dogs.

Mean ERP (msec)

Pacing MethodThick regionThin regionP value

AtrialTABLE 2

ERP Before and After Saline Infusion in !he TTiick and Thin

Before Saline

AP133 ± 7.9149 IP <

t 12.0O.OI

AV = 0134 ±9.9151 dP <

: 14.3O.OI

After Saline

AP AV146 ± 9.8 147 ±170 ± 14.3 172 ±P < O.OI P < 1

= 010.214.3

Regions

13.221.4

P<

Increase of ERP

AP AV = ()±5 .3 13.9 ±5.8± 7.0 21.1 ± 7.0

^O.Oi P < O.OI

P values are tor the comparison of airial ERP between the thick and thin regions, before and after saline infusion.

838 Journal of Cardiovascular Electrophysiology Vol. 7, No. 9. September 1996

Comparison of ERPs between thick and thin regions ol the right atrium prior to saline Inluslon

IBOn

170

^ ISO

AV=O

Pacing methodD thick region

• thin region

Figure 3. Comparison of the effective refractory period (ERF) recorded in the thin and thick regions of the right atrium he-fore high volume of normal saline infusion. Atrial ERP in the thin region exceeds the ERP in the thick region in both pacingmethods. AP = atrial pacing: AV = 0 indicates atrium and left ventricle are paced simultaneously at an AV interval of 0 msec.

Discussion

New Observations

This study demonstrated in open chest dogs thatatrial ERP and MAP duration at 90% repolariza-

tion in the free wall (thin region) of the right atriumwas longer than that in the lower crista terminaiis(thick region) in a control state, prior to saline in-fusion. Saline infusion that elevated right atrialpressure stretched atrial myocardium in the thin

ERP tn thick region before and after saline

p<0.01

AV=O

Pacing method • ERP belor©

• ERP after

ERP in thin region belore and alter saline

190-, p<O.Ol P<00'

170-

Pacing method D ERP belore

• ERP after

Figure 4. Comparison of the effective refractory period I ERP) before and after normal saline infttsion. The left panel showsthe ERPs in the thick region of the right atrium before and after saline infusion, and the right panel shows the ERPs in thethin region of the right atrium. The ERP after saline infusion increased compared with that before saline infusion in both re-gions in both pacing methods.

Satoh and Zipes Atrial Stretch Precipitates Atrial Fibrillation 839

Comparison of dlllerence in ERPs between thick and thin regions ol the right atrium

AV=O

Pacing method thick region

thin region

Figure 5, Comparison of difference in effective refractory period (A-ERP) between the thick and thin regions of the rightatrium. A-ERP is greater in the thin region than in the thick region in both pacing methods.

free wal! more than it did in the thick crista ter-minals and prolonged atrial ERP at both atrialsites, but the increase was greater in thin than inthick regions. Thus, the ERP difference betweenthick and thin regions increased during atrial stretch.Saline infusion also facilitated the induction ofatrial fibrillation by rapid atrial pacing, presumablyby stretch-induced increase in atrial dispersion ofrefractoriness that made reentry more likely.

Contraetion-Exeitation Feedback in the Atrium

In previous studies,̂ ** we have demonstrated inboth dogs and humans that tlie atrial ERP increasedas did the right atrial pressure during pacing al cer-tain AV intervals, and that., during AV sequentialpacing in dog model, mean right pressure variedas the AV interval changed, resulting in a sigmoidcurve. Tlie lowest atrial pressure occurred at AVintervals of 40 to 60 msec'"' and highest at 140 to180 msec.̂ While pacing at a cycle length of 300msec, in the present study, we tested the responseto atrial pacing at a normal AV interval and at anAV interval of 0 msec to produce a high atrial pres-sure, and closely replicate the AV relationship seenin AVRT and AVNRT. Atrial ERP prolonged asthe atrial pressure increased following the vol-ume overload produced by normal saline, andstretched thin regions of the atrium more than itstietched thick regions. Atrial ERP also increasedin thin regions, but not in thick regions, at an AV

interval of 0 compared with right atria! pacing, pre-sumably due to stretch of thin, but not thick, atrialmyocardium. These responses support the pres-ence of a contraction-^excitation feedback system"in the atrium that is influenced by dilation or stretch.

Previous Observations

Although there are many repoits about the acuteeffects of stretch or dilation on the cardiac actionpotential or refractory period, the results iire notconsistent and are influenced by animal species,tissue type, i.e.. atrium versus ventricle, and thedegree and duration of tbe stretch at the time theBRP was measured."-^ Results are also probablyinfluenced by how stretch was induced. We de-cided to test the effects of acute stretch induced byvolume expansion in vivo because this approachwould be least traumatic and most clinically rele-vant, compared with stretch that was induced byexpanding a balloon in a cardiac chamber, by me-chanically pulling on muscle, or by studies in vitroor in isolated hearts. Naturally, these other modelsmight permit increased control of many variablesbut potentially introduce artifacts that could con-found results.

Action potential duration has been reported tobe lengthened .several minutes after stretching thecat papillary muscle'- or dog ventricular mus-cle." In other in vitro studies using sheep Purkinjetiber'^ and cat papillary muscle,''̂ action potential

840 Journal of Cardiovascular Electrophysiulogy Vol. 7, No. 9, September 1996

II

RA presturt ^

Famoral BP

Signsi H In thin ,

Control 500 mt 1000 ml

Figure 6. An example of sonomicrometer measurements. A straight line iit/.v drawn at the top of the A v\ave. and the value oh-tained by the intersection of that line with the recording of signal I and .signal II indicates the distance for each region. SignalI in thick = signal in the thick region (short axis); signal IJ in thick = signal in the thick region (iong axis); signal I in thin =signal in the thin region (short axis}; signal II in thin = .signal in the thin region (long a.xis). RA = right atriat; BP = bloodpressure.

duration was not changed by stretch. Action po-tential duration was reported to be shortened in catpapillary muscle,'** frog ventricle,''' isolated canineheart,-" isolated rabbit,-' and isolated infarcted ca-nine heart.-- and as was refractory period in pa-tients undergoing balloon dilation of the pulmonaryvalve." Action potential duration was reported tobe unchanged in canine enlarged atria.-•̂ -'̂

In earlier studies we reported that action po-tentiiil dunititin prolonged after dilation of the atriumin dogs and in humans,̂ *̂ just as we have found inthe present experiments. One potential explanationfor why we found the atrial ERP to prolong whileothers have found shortening is as follows. If theaction potential of the stretched atrium shortenedearly in repolarization, e.g., 50% to 75% repolar-ization. but prolonged in the terminal portion, e.g.,90% to 100% repolarization, due to developmentof a terminal "foot." then a relatively weak stim-ulus, i.e., twice diastolic threshold (which we haveused) might uncover prolonged ERPs, while a .stim-ulus of higher intensity might find the ERP to beshortened. This possibility needs to be tested in fu-ture experiments. Regardless, these factors do not

invalidate our conclusions about the differential ef-fects of atrial stretch on thin and thick atrial seg-ments and the potential for developing stretch-in-duced atrial fibrillation.

Atrial Stretch Oceurs Unequally

In this study, tbe thin region (the free wall ofthe right atrium) had longer atrial ERP and MAPduration at 90% repolarization than the thick re-gion (the lower crista temiiniilis of the right atrium)in control. TTiis ERP difference was increased af-ter stretch of these regions prtxluced by saline in-fusion. The electrophysiologic basis for thesechanges in ERP is not known, nor is it known howheterogeneous the response can be at other atrialsites in view of the very complex and irregularatrial architecture. There inay be several differentdispersion responses following atrial stretcb. Amore complete atrial ERP map under the experi-mental conditions shown here would be desirablein tbe future to support our observations that atrialstretch occurs unequally, and that this response in-creased the dispersion of atrial refractoriness,-'*"^

Satoh and Zipes Atrial Stretch Precipitates Atrial Fibrillation 841

Comparison ol atrtal stretch between thtek and thin regions

peO.OI

Volunw ol saitna (ml)

D Ihieli raglon

• ttiln raglon

Figure 7. Comparison of the increase in area between thick and thin regions after saline infusion. The left side shows thecomparison after 500 ml of normal saline infusion. The right side shows the comparison after 1000 ml of saline infusion.

an event conducive to the development of reentryand tibrillation.

Limitations

Data were obtained in a model of acute vol-ume overload, and it is possible that changes pro-duced by chronic dilation might yield different re-sults. In addition, we only measured changes at twoatrial sites, and it is possible that different responsesoccurred at other atrial sites. Eurther, we did notmeasure other changes that might have been pro-duced by saline infusion, such as electrolyte shifts.Finally, we did not iiieasure ERP and atrial stretcbin the same dogs, because sewing in the sonomi-crometers sometimes caused minor local traumathat we were concerned might affect ERP mea-surements. Therefore, one could argue that salineinfusion produced atrial stretch in one group ofdogs. ERP prolongation in another group, and atrialfibrillation in a third, and that these responses wereunrelated. Naturally, this does not seem likely.

Clinical Implications

We conclude that the atrial ERP and MAP du-ration at 90% repolarization in the thin region (theright atrial free wall) exceeds the ERP and MAPduration of the thick region (the lower crista ter-minaiis of ibe right atrium) in control, and that thisdifference is exaggerated by the increase in atrialpressure produced by saline infusion, which

stretches thin segments of the atrial myocardiummore than it stretches thick regions. The increasein dispersion of atrial ERP facilitates the inductionof atrial fibrillation.

It is well established tbat atrial fibrillation oc-curs in some patients witb AVNRT and AVRT. Al-though tbe mechanism is unknown, the prevalenceof atrial fibrillation appears to decrease in thesepatients with elimination of tachycardia. Since atrialstretch occurs during AVRT and AVWRT** whenthe atria contract against closed AV values, it ispossible that atrial vulnerability to fibrillation is re-lated to the mechanism described in this study.While we have described one potential mecbanisiiiresponsible for tbe initiation of atrial fibrillation,other iTiechanisiTis could also be operative.''-^^

References

1. Cristal N, Peterburg I, Szwarchberg J: Atrial fibrilla-tion developing in the acute phase of myocardial in-farction: prognostic implications. Chest I976;7O:8-11.

2. Sung RJ. Caslellanos A. Mallon SM. et al: Mecha-nisms of spontaneous alternation between reciprocat-ing tachycardia and atrial llutter-tibrillation in theWolff-Parkinson-White syndrome. Circulation 1977;56:409-416.

3. Kannel WB, Abbott RD, Savage DD, et ai: Epidemio-logic features of chronic atrial librillation: The Fram-ingham study. N EngI J Med 1982;3O6:IOI8-1O22.

4. Meinertz T, Hofmann T, Kasper W. et al: Significanceof ventricular arrhythmias in Jdiopathic dilated car-diomyopathy. Am J Cardiol I y84;53:902-907.

842 Journal of Cardiovascular Electrophysiology Vol. 7, No. 9, September 1996

5. Unverferth DV, Magorien RD. Moeschberger ML, etal: Factors influencing the one-year mortality of dilatedcardiomyopalhy. Am J Cardiol 1984:54:147-152.

6. Mckenna WJ, Franklin RCG. Nihoyannopoulos P. etal: Arrhythmia and prognosis in infants, children andadolescents with hypertrophic cardiomyopathy. J AmColl Cardiol 1988:11:147-153.

7. Kaseda S, Zipes DP: Contraction-excitation feedbackin the atria: A cause of changes in refractoriness. J AmColl Cardiol 1988:11:1327-1336.

8. Klein LS, Miles WM. Zipes DP: Effect of atrioventdc-ular inlerval during pacing or reciprocating tachycardiaon airial size, pressure, and refractory period. Circula-tion 1990:82:60-68.

9. Franz MR: Bridging the gap between basic and clinicalelectrophysioiogy: What can be learned from mono-phasic action potential recording? J Cardiovasc Elec-trophysiol 1994:5:699-710.

10. Meisner JS. Mcqueen D. Ishida Y. et al: Effects of tim-ing of atrial syslole on LV filling and mitral valve do-sure: Computer and dog study. Am J Physiol 1985;249:H604-H619.

11. Lab MJ: Contraction-excitation feedback in myocar-dium: Physiological basis and clinical relevance. CircRes 1982:50:757-766.

12. Cronic CC, Tobler HG. Pritzker MC, et al: Electro-physiologic effects of papillary muscle traction in theintact heart. Circulation 1986:73:1013-1021.

13. Benditt DG. Kriett JM. Tobler HG. et al: Electrophysi-ological effects of transient aortic occlusion in intactcanine heart. Am J Physiol I985:249:H1017-Ht023.

14. Dominguez G, Fozzard HA: Effect of stretch on con-duction velocity and cable properties of cardiac Pur-kinje fibers. Am J Physiol I979:237:CI t9-CI24.

15. Penefsky ZJ, Hoffman BF: Effects of stretch on me-chanical and electrical properties of cardiac muscle.Am J Physiol 1963:2204:433-438.

16. Calkins H. E! Atassi R. Leon A. et al: Effect of theatrioventricular relationship on atrial refractoriness inhumans. PACE 1992:15:771-778.

17. Calkins H. Maughan WL. Kass DA. et al: Electrophys-iological effect of volume load in isolated caninehearts. Am J Physiol 1989:256:H 1697-H1706.

18. Lab MJ, Allen DG. Orchard CH: The effects of short-ening on myoplasmic calcium concentration and on theaction potential in mammalian ventricular muscle. CircRes 1984:55:825-829.

19. Lab MJ: Mechanically dependent changes in action po-tentials recorded from the intact frog ventricle. CircRes 1978:42:519-528.

20. Lerman BB. Burkhoff D. Yue DT, et al: Mechanoelec-

trical feedback: Independent role of preload and con-tractility in modulation of canine ventricular excitabil-ity. J Clin Invest 1985:76:1843-1850.

21. Reiter MJ. Synhorst DP. Mann DE: Electrophysiologi-cai effects of acute ventricular dilatation in the isolatedrabbit heart. Circ Res 1988:62:554-562.

22. Calkins H. Maughan WL. Weisman HF. et al: F.ffect ofacute volume load on refractoriness and arrhythmia de-velopment in isolated, chronically infarcted caninehearts. Circulation 1989:79:687-697.

23. Levine JH. Guarnieri T. White Rl. et al: Alterations ofrepolarization during valvuloplasty: Evidence for con-traction-excitation feed-back in humans. Circulation1988:77:70-77.

24. Boyden PA. HolTman BF: The effects on atrial electnvphysiology and structure of surgically induced right atrialenlargetiient in dogs. Circ Res 1981:49:1319-1331.

25. Boyden PA. Tilley LP. Pham TD. et al: Effects of leftatrial enlargement of atrial transmembrane potentialsand stnicture in dogs with mitral valve fibrosis. Am JCardiol 1982:49:1896-1908.

26. Hansen DE, Borganelli M. Stacy GP Jr. et al: Dose-de-pendent inhibition of stretch-induced arrhythmias bygadolinium in isolated canine ventricles. Circ Res1991:69:820-831.

27. Hansen DE. Craig CS, Hondeghem LM: Stretch-in-duced arrhythmias in the isolated canine ventricle: Evi-dence for the importance of mechanoelectrical feed-back. Circulation 1990:81:1094-1105.

28. Spach MS. Dolber PC. Anderson PAW: Multiple re-gional differences in cellular properties that regulaterepolarization and contraction in the right atrium ofadult and newborn dogs. Circ Res 1989:65:1594-1611.

29. Spach MS, Dolber PC, Heidlage JF: Interaction of in-homogeneities of repolarization with anisotropic prop-agation in dogs atria: A mechanism for both preventingand initiating reentry. Circ Res 1989:65:1612-1631,

30. Anzhen Q. Yeung-L-W JA. Xiao J, et al: Regional dif-ferences in rabbit atrial repolarization: Importance oftransient outward current. Am J Physiol 1994;266:H643-H649,

31. Wijffels MCEF. Kirchof CJHJ, Doriand R. et al: Atrialfibrillation begets atrial fibrillation. Circulation 1995;92:1954-1968.

32. Morillo CA. Klein GJ, Jones DL, et al: Chronic rapidatrial pacing. Structural, functional, and electrophysio-logical characteristics of a new model of sustainedatrial fibrillation. Circulation 1995:91:1588-1595.

33. Elvan A, Zipes DP: Pacing induced chronic atrialfibrillation impairs sinus node function in dogs. Circu-lation 1996: (In press).

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