Intestinal tachyarrhythmias during small bowel
ischemia
Scott A.
Seidel1,
Sanjay S.
Hegde1,
L. Alan
Bradshaw2,
J. K.
Ladipo1, and
William O.
Richards1,3
1 Department of Surgery,
Vanderbilt University School of Medicine,
3 Department of Surgery, Veterans
Affairs Medical Center, and
2 Living State Physics Group,
Department of Physics and Astronomy, Vanderbilt
University, Nashville, Tennessee 37232
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ABSTRACT |
The electrical control activity (ECA) of the
bowel is the omnipresent slow electrical wave of the intestinal tract.
Characterization of small bowel electrical activity during
ischemia may be used as a measure of intestinal viability. With
the use of an animal model of mesenteric ischemia, serosal
electrodes and a digital recording apparatus utilizing autoregressive
spectral analysis were used to monitor the ECA of 20 New Zealand White
rabbits during various lengths of ischemia. ECA frequency fell
from 18.2 ± 0.5 cycles per minute (cpm) at baseline to 12.2 ± 0.9 cpm (P < 0.05) after 30 min of
ischemia and was undetectable by 90 min of ischemia in
all animals. Tachyarrhythmias of the ECA were recorded in 55% of the
animals as early as 25 min after ischemia was induced and lasted from 1 to 48 min. Frequencies ranged from 25 to 50 cpm. These
tachyarrhythmias were seen only during ischemia, suggesting that they are pathognomonic for intestinal ischemia. The use of the detection of ECA changes during intestinal ischemia may
allow earlier diagnosis of mesenteric ischemia.
mesenteric ischemia; electrophysiology; gastrointestinal
motility; small intestine; electrical control activity; basic
electrical rhythm
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INTRODUCTION |
THE SEVERE MORBIDITY and mortality of mesenteric
ischemia is largely due to delayed diagnosis and, consequently,
the advanced stage of disease at laparotomy (21). The detection of
mesenteric ischemia is one of the most difficult and
challenging diagnoses for the clinician to make, often
requiring invasive diagnostic procedures such as angiography (with its
own inherent risks) or laparotomy. There are no noninvasive
lab tests with sufficient specificity or sensitivity that have proven
useful in the diagnosis of mesenteric ischemia (2, 5, 13,
21). To improve the prognosis in these patients, a more
effective means of detecting mesenteric ischemia must be found.
Ideally, such a test would be sensitive, specific, noninvasive, quick,
repeatable, and easily performed in critically ill patients.
Our lab has been involved in characterizing the effects of acute
mesenteric ischemia on the electrical control activity (ECA) of
the small intestine to enable the use of ECA (also known as the basic
electrical rhythm or BER) to predict bowel viability during
ischemia. The frequency and amplitude of small bowel ECA have
been previously shown to fall with arterial ischemia (7, 16,
18, 20) These changes have also been shown to occur before the onset of
pathological changes (11). Characterization of the electrical
properties of the ischemic ECA signal are important in identification
of the signature of ischemia. The studies reported here were
designed to prolong ischemia long enough for the ECA frequency
to fall to undetectable levels to enable the full characterization of
the relationship between mesenteric ischemia and ECA. During serosal electrode recordings of ECA, we recorded multiple intestinal tachyarrhythmias of various frequencies during ischemia. This is the first demonstration of intestinal tachyarrhythmias. Because these arrhythmias have been recorded only during acute
ischemia, they appear to be pathognomonic for small bowel ischemia.
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MATERIALS AND METHODS |
Twenty male New Zealand White rabbits weighing ~4 kg each were
divided into four study groups that were subjected to different lengths
of intestinal ischemia (90-210 min). General anesthesia was induced with acepromazine (0.5 mg/kg), xylazine (3 mg/kg), and
ketamine (40 mg/kg) intramuscularly, and an intravenous catheter was
placed for saline and intravenous ketamine to maintain
anesthesia. Temperature was kept constant (±5°F) with a
heating blanket and monitored with a rectal thermometer. A Silastic
four-channel electrode platform connected by shielded wires to a
Beckman amplifier (model R612) was sutured to a segment of proximal
jejunum after a laparotomy was performed. The bowel was returned to the
abdomen in a nonconducting latex glove (to prevent the recording of
ECA from adjacent loops of bowel). Data (ECA signals) were
sampled at a frequency of 20 Hz, with bandpass filters set from 0.016 Hz to 0.3 Hz. The amplifier was equipped with a 16-bit
analog-to-digital converter (model MP100, Biopac Systems) into an Apple
Powerbook (Apple Computer) utilizing Acqknowledge 3.1.2 software
(Biopac Systems). All experiments were performed in an electrically
shielded room to minimize background electrical interference.
Baseline ECA recordings were performed for 15-30 min, after which
we induced ischemia by transecting the segment of bowel
proximally and distally to prevent intramural blood flow and
by occluding the segmental artery and vein using a vascular
occluder. Complete ischemia was confirmed with a
Doppler flow probe (model ES-1000SPM, Koven Technology). The bowel
was then placed back into the abdomen in the latex glove. Varying lengths of complete ischemia were maintained (90, 120, 150, and 210 min for groups 1,
2, 3,
and 4, respectively) while
continuous recordings of ECA were made. At the end of the study each
animal was euthanized.
Autoregressive (AR) spectral analysis was used to determine ECA
frequency on a Power Macintosh (Apple Computer) running MATLAB software
(The Mathworks). Frequency is expressed as mean cycles per minute (cpm) ± SE. One-minute segments were analyzed continuously over the
duration of the entire study. The use of AR spectral analysis provides
an objective assessment of frequency, rather than simply counting peaks
over a known time period, which is subject to observer variability.
Another major advantage of AR spectral analysis is that it can be used
to examine short segments of recordings (1 min) rather than the longer
segments (5 min) required by other analysis methods [such as Fast
Fourier Transformation (FFT); Ref. 4]. Additionally, AR spectral
analysis can identify more than one frequency occurring within a single
recording. Tachyarrhythmias were defined as those frequencies greater
than two standard deviations higher than baseline ECA (18.2 + 4.6 = 22.8 cpm). Statistical analysis was performed using paired Student's
t-test with significance defined as
P < 0.05.
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RESULTS |
ECA recordings at baseline and at different time points during
ischemia from a single study are shown in Fig.
1. ECA frequency fell from 18.2 ± 0.5 cpm at baseline to 12.2 ± 0.9 cpm
(P < 0.05) after 30 min of
ischemia and was undetectable by 90 min of ischemia in
all animals. Tachyarrhythmias were recorded in at least one channel in
11 of 20 animals (55%) after various lengths of ischemia. These arrhythmias were noted to begin as early as 25 min after ischemia was induced (average time of onset 33.9 ± 1.9 min
into ischemia) and lasted from 1 to 48 min (mean duration 14.3 ± 4.0 min). Frequencies ranged from 25 to 50 cpm. However, these
tachyarrhythmias were not constant in frequency and could vary by as
much as 20 cpm in one animal during a single episode. The
characteristics of the tachyarrhythmias are shown in Table
1.

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Fig. 1.
Samples of electrical control activity (ECA) recordings from same
animal at different time points during study. Baseline recording is
shown in A. After 35 min (at 3,000 s
of study time) of ischemia
(B), frequency and amplitude of ECA
signal are decreased. After 60 min of ischemia (4,500 s of
study time), ECA signal is no longer detectable
(C).
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A typical tachyarrhythmia sequence is demonstrated in Fig.
2. The ECA during the baseline recording
period is ~17 cpm. Ischemia is induced at 1,600 s. The
frequency and amplitude decrease until after 3,600 s, at which time a
faster rhythm is noted. The tachyarrhythmia continues for 15 min, at
which time the ECA becomes undetectable. The running AR plot for the
data presented in Fig. 2 is shown in Fig.
3. The abrupt end of an arrhythmia with
reversion to a rhythm characteristic of ischemia is shown in
Fig. 4. Another important characteristic of
these tachyarrhythmias is that they were not always recorded in all
four electrodes simultaneously, indicating that discrete segments of
the ischemic loop of bowel were oscillating at different rates. Figure
5 demonstrates recordings obtained
simultaneously from separate channels (labeled
1 and 2). Tachyarrhythmias are seen in
both channels initially. However, the tachyarrhythmia in
channel 2 ends before the one in
channel 1 and reverts back to a rhythm
characteristic of ischemic bowel. Figure 6
shows another set of recordings taken simultaneously from different
channels. One segment of bowel experiences a tachyarrhythmia (channel 1), whereas another section
1 cm away appears to exhibit a bradyarrhythmia
(channel 2). Of the 11 studies in
which tachyarrhythmias were noted, 3 were seen in all channels, 3 were
seen in more than one, but not all channels, and 5 were seen in one
channel only. Even so, in all cases in which tachyarrhythmias were seen
in multiple channels, the tachyarrhythmia in each channel ended at
different times (such as Fig. 5), such that there were still times when a tachyarrhythmia was recorded with one electrode while a rhythm characteristic of ischemic ECA was seen in the others. Figure 7 demonstrates differential frequencies
during ischemic tachyarrhythmias. During the baseline period indicated,
all three consecutive channels (1,
2 and
3) demonstrate ECA cycling at the
same frequency, 18 cpm. During the period of
tachyarrhythmia, however, the three adjacent electrodes record
tachyarrhythmias of different frequencies by AR, indicating that the
sections of bowel are oscillating at different rates.

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Fig. 2.
Characteristic study progression of an animal exhibiting a
tachyarrhythmia. Sequential time segments (2 min each) are displayed,
and time points in seconds are shown for beginning and ending of each
segment. ECA during the baseline recording period is ~17 cpm.
Ischemia is induced at 1,600 s of study time (dashed line), and
frequency and amplitude decrease until after 3,600 s of study time, at
which time a faster rhythm is noted. Tachyarrhythmia continues for 15 min, after which the ECA becomes undetectable.
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Fig. 3.
Autoregressive (AR) spectral analysis. Corresponding AR graphs are
shown for time points in Fig. 2 with frequencies of 12-15 cpm
during baseline recording and 50 cpm during arrhythmia (seen after
3,600 s of study time).
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Fig. 5.
Tracings recorded simultaneously from separate channels.
Tachyarrhythmias are seen in both channels for some time, but
channel 2 tachyarrhythmia ends before
channel 1 tachyarrhythmia and reverts
back to a signal characteristic of ischemic bowel.
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Fig. 6.
Recordings obtained simultaneously from separate channels. In this
case, completely different arrhythmias are seen at same time points.
One segment of bowel experiences a tachyarrhythmia
(channel 1), and at same time
another adjacent section experiences a bradyarrhythmia
(channel 2).
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Fig. 7.
Differential frequencies during ischemic tachyarrhythmias. During
baseline period indicated (A), all 3 consecutive channels (1,
2, and
3) demonstrate ECA cycling at same
frequency, ~18 cpm. During period of tachyarrhythmia
(B), however, 3 adjacent electrodes
record tachyarrhythmias of different frequencies by AR, indicating that
sections of bowel are oscillating at different rates.
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DISCUSSION |
We have shown that acute intestinal ischemia induces
tachyarrhythmias that can be recorded using serosal electrodes.
Although there is a wide variation in frequency and duration (Table
1), the use of AR spectral analysis reveals that they are relatively common, occurring in 11 of 20 (55%) of the animals in the study.
Although the phenomenon of tachygastrias and gastric tachyarrhythmias
recorded with both serosal and cutaneous electrodes is quite common and
accepted, intestinal tachyarrhythmias have not been previously reported
(14). This is the first demonstration of small bowel electrical
tachyarrhythmias of any kind. Fich and colleagues (9, 10) reported late
postprandial rapid frequency (19-24 cpm) intraluminal pressure
waves in the canine ileum accompanied by a one-to-one ratio of spike
bursts and circular muscle layer contractions but noted that the ileal
slow wave, or ECA, persisted at the normal frequency of 13-15 cpm.
Another study (22) reported uncoordinated interdigestive myoelectric
complexes in the small intestine in a patient with chronic nausea and
vomiting but was unable to record ECA due to its small amplitude.
Within each segment of small bowel, the ECA is entrained by a proximal
pacemaker. These pacemaker cells pace a segment of smooth muscle cells
that are connected by gap junctions or nexi. The organization of these
syncytia of smooth muscle cells is such that there are segments of
bowel entrained by a pacemaker cell arranged in a series of plateaus.
The ECA frequency decreases in each successive (aboral) plateau, but
within the plateau the ECA frequency is constant and
determined by the proximal pacemaker (8). Although the exact mechanism
of this phenomenon is still debated, it is clear that this mechanism is
somehow disrupted in ischemic bowel, because the tachyarrhythmias
recorded do not originate from all segments of the ischemic
loop of bowel, as evidenced by the fact that they were not seen in all
four electrodes simultaneously (Figs. 5-7). In fact, in some
instances different arrhythmias were recorded simultaneously in
separate channels (Fig. 7). We hypothesize that this is due to a
"decoupling" of the smooth muscle cells. Ischemia has
been shown to decrease coupling in cardiac myocytes due to increased
deoxy stearic acids (6). Thus, in intestinal ischemia, separate
segments of the decoupled ischemic bowel may exhibit different rhythms
despite their close proximity. This phenomenon would most probably go
unnoticed without the aid of AR spectral analysis. In fact, the
occurrence of some of the tachyarrhythmias themselves would not be
identified without the use of AR spectral analysis. Other analysis
techniques, such as FFT spectral analysis, require at least 5 min of
stable rhythm to determine spectral frequency (4), whereas some of the
tachyarrhythmias last for only a short time interval. Thus the ability
of AR analysis to analyze short segments of data enables the
identification of more of these tachyarrhythmias than would be possible
with visual or FFT analysis.
After the induction of ischemia, the ECA decreases in amplitude
and frequency. This characteristic signal change is the first sign of
ischemia and always occurred before the tachyarrhythmias. Because the tachyarrhythmias were only seen after a period of ischemia (never during baseline recordings), we believe they
are pathognomonic for intestinal ischemia when they occur,
although not a frequent early sign. This study utilized serosal
electrodes to record the ECA signal and the intestinal arrhythmias.
Obviously, this is an invasive means of detection. However, we have
been able to utilize superconducting quantum interference devices
(SQUIDs) to noninvasively detect the frequency and amplitude changes in small bowel ECA during mesenteric ischemia in animal studies
(1, 2, 3, 12, 16). If intestinal tachyarrhythmias can be detected using
SQUID magnetometers, then we would have yet another signal marker
characteristic of ischemia to noninvasively identify mesenteric
ischemia. The specificity of such an indicator would be high,
because these tachyarrhythmias have been recorded only during episodes
of ischemia. The level of sensitivity remains to be seen, but
the fact that arrhythmias occurred in 55% of the animals in this study
is promising for noninvasive detection of mesenteric ischemia.
SQUIDs have also been used to record normal ECA in >40 human
volunteers (15, 17, 19). Currently, we are investigating whether
tachyarrhythmias can be recorded using the SQUID magnetometers. If
detecting tachyarrhythmias using SQUIDs is possible, then this method
of detecting mesenteric ischemia early in its course may lead
to a better prognosis in these critically ill patients.
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ACKNOWLEDGEMENTS |
This study was supported by the Deptartment of Veterans Affairs
Medical Research Service.
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FOOTNOTES |
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: W. O. Richards,
Rm. D-5203 MCN, Vanderbilt Univ. School of Medicine, Nashville, TN
37232-2577.
Received 22 October 1998; accepted in final form 5 August 1999.
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