الفهرس 
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Abstract
The present study was designed to explore the effect of
erythropoietin on the cardiac intrinsic function both under basal
condition as well as following ischemia-reperfusion in rats with
experimentally induced uremic cardiomyopathy.
Rats in the present study were classified into
I. 6 week groups: Rats in this group were further
divided into:
a) 6 week sham-operated control group (n= 20)
b) 6 week uremic cardiomyopathy group (UCM)
(n= 25), subjected to 5/6 nephrectomy for
experimental induction of uremic cardiomyopathy
and were studied after 6 weeks.
c) 6 week uremic cardiomyopathy erythropoietintreated
group (UCM-Epo) (n=19), subjected to 5/6
nephrectomy, followed postoperatively by immediate
intraperitonial (i.p.) injection of erythropoietin, and
were studied after 6 weeks.
II. 12 week groups: Rats in this group were further
divided into:
a) 12 week sham-operated control group (n= 26)
b) 12 week uremic cardiomyopathy group (UCM)
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(n= 28), subjected to 5/6 nephrectomy and were
studied after 12 weeks.
c) 12 week uremic cardiomyopathy
erythropoietin-treated group (UCM-Epo)
(n=17), subjected to 5/6 nephrectomy, and
received i.p. injection of erythropoietin 6 weeks
after the operation that continued for 6 weeks.
Rats of this group were studied after 12 weeks.
At the end of the study period, rats were subjected to
measurement of body weight and arterial blood pressure, ECG
recording, as well as heart isolation on Langendorff
preparation for assessment of the basal cardiac activities and
cardiac responses to 30 minutes of reperfusion following 30
minutes of total global ischemia. Plasma was assessed for
creatinine and urea for confirmation of renal failure as well as
oxidants/antioxidants markers, the total antioxidant capacity
and malondialdehyde. Hematocrite value and haemoglobin
concentration were determined. Cardiac muscle was also,
assessed for its content of the oxidative stress marker
malondialdehyde as well as the antioxidant glutathione
peroxidase enzyme activity.
Renal failure was confirmed by the significant elevation in
the plasma levels of creatinine and urea, that was significantly
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decreased upon Epo treatment, denoting better kidney
functions with Epo administration.
The results obtained revealed the final BMI showed
significant decrease in the 12 weeks UCM-Epo group
compared to the sham-operated group. Hematocrite value was
significantly decreased in 6 weeks UCM group and
significantly increased in 6 and 12 weeks UCM groups upon
Epo treatment. Plasma MDA increased significantly in 6 weeks
UCM group and decreased upon Epo treatment. Plasma TAC
decreased significantly in 12 weeks UCM group and increased
by Epo administration. Cardiac tissue GPx was increased in
both 6 and 12 weeks Epo treated groups.
ECG recordings showed significant bradycardia in the 6
weeks UCM group and significant increase in the QRS voltage
together with decrease in PR interval and QRS duration in both
6 weeks UCM and UCM- Epo groups. Q-To was increased in 6
weeks UCM and decreased upon Epo treatment. The SBP was
significantly elevated in UCM groups, whether 6 week or 12
weeks, treated or not treated. Also, the 12 weeks UCM showed
significantly higher DBP and MAP. Epo treatment resulted in a
significant decrease in SBP in the 6 week group and in all
arterial blood pressure values (SBP, DBP, MAP) in the 12
weeks group probably due to its antioxidant action as well as
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correction of volume overload through maintaining better
kidney functions.
Hearts isolated from both 6 and 12 weeks uremic
cardiomyopathy rats exhibited significantly reduced baseline
PT/LV denoting deterioration of inotropic activity. Epo treated
6 weeks group showed significant reduction of their HRT
denoting better diastolic function. In 12 weeks UCM-Epo
group, MFR was significantly reduced compared to 12 weeks
UCM and sham-operated groups but MFR/LV was
insignificantly different. Following 30 minutes of ischemiareperfusion,
hearts subjected to Epo treatment, showed
significantly higher PT and PT/LV in the 6 weeks group, and
significant increase in PT/LV at 30 min of reperfusion in the 12
weeks treated group, both findings highlight the favourable
effects of Epo on cardiac inotropy following
ischemia/reperfusion (I/R) injury.
The HRT was prolonged at 5 min of reperfusion in the 6
weeks UCM group and at all recorded periods of reperfusion in
12 weeks UCM group compared to baseline values but was
insignificantly changed at 15 and 30 min of reperfusion from
baseline in the 6 and 12 weeks UCM-Epo groups, denoting
preserved diastolic function upon Epo administration in these
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rats after I/R. The CT was also, insignificant from baseline
value in the 12 weeks UCM-Epo rats.
In 6 weeks and 12 weeks UCM groups, the MFR and
MFR/LV were significantly decreased at all recorded periods
of reperfusion from baseline values. Upon Epo treatment in
both groups, MFR and MFR/LV were insignificantly different
from baseline values after 5 min of reperfusion, this effect
reflects better perfusion with Epo treatment. On the other hand,
the MFR/LV was significantly reduced in the 12 weeks UCM
group at 15 and 30 min of reperfusion compared to their
respective 6 weeks UCM group, which denotes detrimental
effect in longer term renal failure, through its effect on
coronary vasculature. Also, MFR was significantly reduced in
12 weeks UCM-Epo group at 15 and 30 min compared to 12
weeks UCM and sham-operated groups.
6 and 12 weeks UCM groups demonstrated cardiac
hypertrophy shown by increased absolute weights of atria,
ventricles and whole heart as well as their cardiac indices
(AT/BW, LV/BW, WH/BW). Epo treatment significantly
decreased absolute cardiac weights and cardiac indices only in
the 12 weeks group compared to the UCM group, and their
respective 6 weeks UCM-Epo group as well, probably through
its effect on arterial blood pressure and kidney functions. Also,
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positive correlations were found between LV weight and
creatinine level and SBP as well
from the aforementioned data, it could be concluded that
Epo treatment ameliorated hypertension and cardiac
hypertrophy encountered in uremic cardiomyopathic state
possibly through its antioxidant effect. Also, Epo improved the
systolic and diastolic dysfunctions that uremic cardiomyopathic
rat hearts suffered in response to ischemia-reperfusion injury.
Moreover, early Epo treatment is more beneficial to hearts with
uremic cardiomyopathy subjected to ischemia-reperfusion
injury and has a preventive effect against the development of
hypertension, rather than amelioration upon late treatment.
Therefore, early Epo administration in uremic patients is
recommended.