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Bull Vet Inst Pulawy 52, 305-311, 2008
PRELIMINARY OBSERVATIONS
OF THE EFFECT OF SHORT TIME EXPERIMENTAL
VENTRICULAR TACHYCARDIA
ON GLUCOSE AND INSULIN LEVELS IN PIGS.
A PRELIMINARY COMMUNICATION
AGNIESZKA NOSZCZYK-NOWAK, PIOTR SKRZYPCZAK1, JACEK GAJEK2,
URSZULA PASŁAWSKA, DOROTA ZYŚKO3, AND JÓZEF NICPOŃ
Department of Internal and Parasitic Diseases with Clinic for Horses, Dogs and Cats,
1Department and Clinic of Veterinary Surgery,
Wrocław University of Environmental and Life Sciences, 50-366 Wrocław, Poland
2Department of Cardiology, 3Departament of First-aid Service,
Medical University of Wroclaw, 50-367 Wrocław, Poland
agnieszkann@poczta.onet.pl
Received for publication February 22, 2008
Abstract
The aim of the research was to determine whether
short-time heart muscle ischemia caused by fast ventricular
pacing rate (ventricular tachycardia) provokes insulin and
glucose blood level alterations and if so, how long those
changes last after return to the physiological heart rate and
restoration of proper heart muscle perfusion as well. It was
stated that short-lasting tachycardia provoked by fast, forced
ventricle rate, with no damage on the cardiac muscle resulted
in significant fall of the glucose and insulin blood levels. The
glucose returned to its initial level several minutes after heart
rate normalisation; however, the insulin drop maintained for
more than 10 min.
Key words: pig, tachycardia, glucose, insulin.
Heart failure is the most common disease in
men above 45 years of age, often diagnosed in animals
as well, especially in dogs (1, 11, 12) with a 10%
prevalence. The first adaptive mechanism of heart
failure is an increase in heart rate (tachycardia) (3). A
common finding in many clinical trials is a negative
correlation between the heart rate and life time duration,
with no regard to the kind of heart disease (9, 10).
Increasing heart rate shortens the time of
diastole and reduces the coronary flow, which impairs
cardiomyocyte oxygen supply causing metabolic
alterations in the heart tissue. Under condition of
physiological heart muscle blood supply, 95% of ATP is
derived from oxygenic phosphorylation; meanwhile the
remaining 5% of ATP comes from anaerobic glycolysis.
The free fatty acids, lactic acid, and products of
incomplete fatty metabolism, like ketones, are the main
energy source under regular condition of the heart
muscle’s oxygen supply. It is because of their high-
energy value and oxygen abundance in the healthy heart,
which need large quantities of oxygen for further
metabolism of those substances. It has been proved, that
an increase in glycolysis is accompanied by a decrease
in oxygenic pathways during ischaemia (4, 14).
Afterwards, the intensification of glucose uptake occurs
followed by its displacement into the cardiomyocyte
with help of the GLUT 4 glucose transporter. Glucose
uptake is stimulated by insulin, which also inhibits
lipolysis and reduces the level of β-oxidation substrates
as well. It redirects the heart muscle’s metabolism to
anaerobic routes possessing energy for systole. High
insulin concentration was observed in patients with
severe heart failure where the anaerobic processes
become the long-term energy source for cardiomyocytes
(15, 17). In this state however, the insulinaemia can be
connected to the sign of insulin resistance, related to
sympathetic activation and systolic output failure.
There are no studies on the effect of short-time
ischaemia caused by tachycardia on the glucose and
insulin concentration and metabolism alterations in
cardiomyocyte and possible reversion of the mentioned
process.
The aim of the study was an evaluation into
whether the fast ventricle pacing rate (ventricle
tachycardia equivalent), which may induce cardiac
ischaemia, can change insulin and glucose levels in the
peripheral blood, and if so, how long can those changes
remain after the normal rhythm restoration and a proper
heart muscle perfusion as well.
306
Material and Methods
The research was conducted on 5 pigs of a
Polish Large White breed. Insulin and glucose levels
were evaluated before beginning of ventricle pacing
after 24 h of starvation diet (deprive of feed), and then 1,
5, 10, and 15 min after the onset of pacing with 150 bpm
rate, and 5, 10, 15, 30, and 60 min after the end of the
stimulation (Figs 1 and 2, Table 1). The heart pacing
was conducted under ketamine and pentobarbital
intravenous anaesthesia proceeded by azaperone
premedication, at the dosage of 10 mg/kg, 8-10 mg/kg,
and 2 mg/kg, respectively, continued by supporting
dosage of pentobarbital according to the effect. The
stimulation was driven with use of J&J 4 pole
intracardiac electrode with constant distance between
electrode rings and equal bend connected to the external
Biotronik UHS 20 pacemaker. The electrode was placed
by the use of a modified Seldinger’s method in the right
ventricle through a catheter located in the vena cava
( 10). The electrode was positioned by the use of X-ray
imaging (Fig. 2). In all the pigs, insulin and glucose
levels were evaluated during physiological heart rate 60-
80 bpm (before ventricle pacing). Blood was collected
every 5 min from the femoral vein. Glucose level was
evaluated by using a glucometer in the laboratory of the
Department of Internal and Parasitic Diseases, and
insulin concentration was measured on Abbot Axe
analyser in the Analytical Laboratory of Cardiology
Clinic, Medical University of Wrocław. Right
parasternal long- and short-axis two dimensional
echocardiography was performed to determine left
atrium and ventricle diameters during the stimulation.
Blood pressure was measured by using a cuff
manometer placed on the radial artery.
The results were statistically analysed by using
variable dependent ANOVA calculation. The statistical
significance level was accepted for P≤0.05.
Results
Decreased glucose level was affirmed as early
as during the first minute of pacing at a rate of 150 bpm,
and after 10 min of stimulation, the level was
significantly lower compared to the values before the
procedure (Fig. 3). Already 5 min after the stimulation
ended, glucose concentration did not differ significantly
from the values measured before pacing (Fig. 4). The
lowest glucose concentration was observed at the 15th
min of the stimulation and furthermore in 2 pigs the
level dropped below reference values (16).
Insulin level decreased significantly after 5 min
of ventricular pacing (Fig. 5) reaching the lowest level at
the 5th min after the stimulation ended (Fig. 6).
Significantly lower concentration of insulin maintained
for 30 min after ventricular stimulation, until the end of
observation in another words (Fig. 1). Short-time
tachycardia did not cause atrial enlargement and
hypertension in the investigated pigs.
Table 1
Glucose and insulin levels before pacing with 150 bpm rate, then after 1, 5, 10, and 15 min
after onset of heart stimulation and 5, 10, 15, and 30 min after pacing
No. Before
pacing
1 min of
pacing
5 min of
pacing
10 min of
pacing
15 min of
pacing
5 min after
pacing
10 min
after
pacing
15 min
after
pacing
30 min
after
pacing
1 4.4 3.6 3.5 2.6 2.7 4.0 4.4 5.2 4.5
2 3.1 2.9 2.8 2.1 1.7 4.8 6.7 5.6 5.7
3 5.6 3.8 2.8 1.6 1.9 1.6 1.2 2.2 3.4
4 5.2 4.3 4.6 3.7 2.8 3.6 3.8 4.0 4.2
Glucose
mmol/l
5 3.8 4.1 4.3 3.6 4.6 5.8 5.2 9.2 5.3
Mean±SD 4.425±1.17 3.75±0.62 3.6±0.99 2.7250±1.1 2.7±1.32 3.9±1.82 4.275±2.41 5.25±2.97 4.625±1.06
1 18.8 14.9 14.1 12.8 12.4 7.3 8.6 7.8 8.6
2 8.3 5.2 3.5 3.2 4.4 4.2 4.4 5.6 6.8
3 21.9 17.2 9.2 5.7 2.2 3.1 4.3 4.8 8.1
4 6.2 7.9 5.7 5.7 2.8 4.3 3.7 6.1 6.3
Insulin
mUI/l
5 12.5 9.5 8.1 6.6 5.4 5.9 5.2 6.0 7.4
Mean ±SD 13.55±8.05 10.95±5.98 8.1±4.93 6.825±4.14 5.45±4.72 4.975±2.28 5.25±2.25 6.07±1.26 7.45±1.64
* statistically significant values
307
Glucose level
0
1
2
3
4
5
6
123456789
mmol/l
control after pacing 150 bmp
Fig. 1. Glucose level measurement during control and 150 bpm pacing rate.
Insuline le vel
0
2
4
6
8
10
12
14
16
123456789
mUI/l
control after pacing 150 bmp
Fig. 2. Insulin level measurement during control and 150 bpm pacing rate.
308
P=0.02
mean
mean±S.M.
mean±S.D.
41
0
1
2
3
4
5
6
7
4 – glucose level 10 min after 150 bpm pacing
1 – glucose level before pacing
Fig. 3. Glucose level differences before and 10 min after 150 bpm pacing.
P=n.s.
mean
mean±S.M.
mean±S.D.
61
0
1
2
3
4
5
6
7
8
6 – glucose level 5 min after the end of heart stimulation
1 – glucose level before pacing
Fig. 4. Glucose level differences before stimulation and 5 min after the end of 150 bpm pacing.
309
P=0.05
mean
mean±S.M.
mean±S.D.
31
4
6
8
10
12
14
16
18
20
22
1 – insulin level before pacing
3 – insulin level 5 min after heart stimulation with 150 bpm
Fig. 5. Insulin level differences before stimulation and 5 min after 150 bpm pacing
P=0.04
mean
mean±S.M.
mean±S.D.
61
2
4
6
8
10
12
14
16
18
20
22
1 – insulin level before pacing
6 – insulin level 5 min after the end of heart stimulation
Fig. 6. Insulin level differences before stimulation and 5 min after the end of 150 bpm pacing.
310
Discussion
The obtained results may argue that there is an
increase in glucose uptake by the heart muscle cells
during tachycardia, which may lead to a significant
hypoglycaemia, especially in persistent arrhythmias. The
increase in glucose uptake is correlated with the insulin-
dependent dislocation of glucose transporter GLUT-4
into the sarcolemma. A similar mechanism was
observed in rats’ heart during stress and ischaemia ( 18).
Our experimental model presumed that anaesthesia
resulting in metabolism reduction will significantly
eliminate muscle and liver influence as two fundamental
factors in glucose metabolism.
The adrenergic activation is the most common
reason for tachycardia occurrence under physiological
conditions. Based on the present study, it may be
ascertained that doubling of a normal heart rate causes a
considerable increase in energy consumption leading to
significant glucose reduction. Insulin level decline was
stated simultaneously, which may affirm that the
accelerated heart rate alone is not an insulin resistance
releasing factor. The source of high insulin levels are
probably metabolic disorders, which are in turn induced
by tissue hypoperfusion and adrenergic activity. As it
results from the experiment, a short-time tachycardia is
not correlated with insulin level increase, and is
probably not related to the effect of insulin resistance.
Even if there is intensified insulin release under
catecholamine influence in healthy animals, this
substance is rapidly metabolised in the liver so that the
blood level of the insulin remains constant (7). It seems
however, that the most probable explanation of any
insulin level increase is a short duration of ischaemia
and lack of significant haemodynamic alterations.
Insulin is considered as an important component of a
complex compensatory mechanism, having to support
hypertension maintenance and to counteract hypotensive
influence of ANP (13). Short-time tachycardia did not
cause atrial enlargement and hypertension in the
investigated pigs. However, these phenomena are
responsible for the ANP release. The results of earlier
studies suggest that cytokines (like TNF-α) take part in
the development of insulin resistance but their level
increases significantly only after longer lasting heart
failure (6).
Glucose concentration already 5 min after the
stimulation ended did not differ significantly from the
concentration before pacing; this means that elimination
of the arrhythmia not only improves patient’s condition
through a circulation and the normalisation of the
brain’s oxygen supply, but also restores
normoglycaemia. Marked hypoglycaemia is seen in
healthy animals with paroxysmal tachycardia events, but
it recovers shortly after regular rhythm restoration.
Reduced insulin level maintained to the end of
observation. It seems therefore that the phenomenon of
insulin level increase and insulin resistance is the
expression of advanced but particularly chronic heart
diseases. In paroxysmal tachyarrhythmia in animals
without organic heart disease and serious metabolic
disorders the complicating factor is only a marked fall of
the glucose blood concentration.
A potential mechanism responsible for the
described glucose and insulin alterations in the presented
experiment is a lack of the possibility of cardiac output
adaptation and a flow distribution as a result. Cardiac
output is precisely regulated by the organism’s
metabolic demand, mainly resulting from the influence
of the autonomic nervous system and resistance
alterations in arterioles sensitive to metabolic changes
(acidosis) ( 3, 8, 16). In case of cardiac output increase
(in our experiment only by ventricular pacing) by about
60-80% of the resting values, fast blood redistribution
must be considered. In relation to many adverse
consequences of inappropriate blood flow increase, the
most probable mechanism of blood overflow
management is an increase in the muscle and/or skin
flow. Muscle vessels are particularly voluminous, and,
with regard to the results of our experiment, they may be
responsible for the glucose and insulin level decrease as
well.
Short-lasting tachycardia provoked by fast,
forced ventricle rate, with no damage on the cardiac
muscle, results in a significant fall of the glucose and
insulin blood level. Glucose returns to its initial level
several minutes after heart rate normalisation; however,
insulin drop maintains for more than 10 min.
With regard to the small animal group, the
research is treated as a preliminary communication. We
do not know exactly an impact of the used anaesthesia
and possible activation of other metabolic pathways
involving substances resulting in similar to insulin cell
effect (which may lower the insulin level). The blood
redistribution in the condition of metabolically
unjustified cardiac output increase will be further
investigated.
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