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Cell injury after ischemia and reperfusion in the porcine kidney evaluated by radiolabelled microspheres, sestamibi, and lactadherin.

Pedersen SS, Keller AK, Nielsen MK, Jespersen B, Falborg L, Rasmussen JT, Heegaard CW, Rehling M - EJNMMI Res (2013)

Bottom Line: In WI240, the uptake of microspheres was severely reduced in both groups (17% ± 11% and 27% ± 17%).GFR was severely reduced in the post ischemic kidney in both groups.In both groups, the uptake of lactadherin was reduced (41% ± 8%, 17% ± 13%) but not different from the uptake of (153)Gd microspheres.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark ; Department of Clinical Physiology and Nuclear Medicine, Aarhus University Hospital, Skejby, Denmark.

ABSTRACT

Background: The purpose of the present study was to quantify renal cell injury after ischemia and reperfusion in a pig model using (99m)Tc-lactadherin as a marker of apoptosis and (99m)Tc-sestamibi as a marker of mitochondrial dysfunction.

Methods: Thirty-four pigs were randomized into unilateral renal warm ischemia of 120 (WI120) or 240 min (WI240). The glomerular filtration rate (GFR) was calculated by renal clearance of (51)Cr-ethylenediaminetetraacetic acid, and apoptosis was quantified by immunohistochemical detection of caspase-3. After 240 min of reperfusion, intravenous (99m)Tc-lactadherin or (99m)Tc-sestamibi was injected simultaneously with (153)Gd microspheres into the aorta. Ex-vivo static planar images of the kidneys were acquired for determination of the differential renal function of tracer distribution using a gamma camera.

Results: In WI120, there was no significant difference in the uptake of microspheres in the ischemic and contralateral normal kidney indicating adequate perfusion (uptake in ischemic kidney relative to the sum of uptake in both kidneys; 46% ± 12% and 51% ± 5%). In WI240, the uptake of microspheres was severely reduced in both groups (17% ± 11% and 27% ± 17%). GFR was severely reduced in the post ischemic kidney in both groups. In both groups, the uptake of lactadherin was reduced (41% ± 8%, 17% ± 13%) but not different from the uptake of (153)Gd microspheres. Caspase-3-positive cell profiles were increased in the post-ischemic kidneys (p < 0.001) and increased as the length of ischemia increased (p = 0.003). In both WI120 and WI240, the amount of (99m)Tc-sestamibi in the ischemic kidney was significantly lower than the amount of (153)Gd microspheres (40 ± 5 versus 51 ± 5 and 20 ± 11 versus 27 ± 17; p < 0.05).

Conclusions: In an established pig model with unilateral renal warm ischemia, we found significantly reduced (99m)Tc-sestamibi uptake relative to perfusion in the kidneys exposed to ischemia indicating a potential ability to detect renal ischemic and reperfusion injuries. However, apoptosis was not detected using (99m)Tc-lactadherin in the post-ischemic kidneys despite increased number of caspase-3-positive cell profiles.

Trial registration: This study is approved by the Danish Inspectorate of Animal Experiments (2010/561-1837).

No MeSH data available.


Related in: MedlinePlus

Diuresis for groups with warm ischemia (WI) of 120 (left) and 240 (right) min. Data are presented as median (range). Capped line indicates ischemic period. IK, ischemic kidney; CK, control kidney.
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Figure 3: Diuresis for groups with warm ischemia (WI) of 120 (left) and 240 (right) min. Data are presented as median (range). Capped line indicates ischemic period. IK, ischemic kidney; CK, control kidney.

Mentions: At baseline (t60), we found a mean single kidney GFR value of 30.2 ± 8.8 ml/min with no significant difference between WI120 and WI240 or between the ischemic and the control kidney (p > 0.1). Immediately after initiating unilateral ischemia, the GFR dropped to values near zero in the ischemic kidneys as no urine was produced. During reperfusion, some urine production was established, but GFR stayed close to zero. Figure 3 shows the diuresis during WI120 and WI240 from the ischemic as well as the control kidneys. In the control kidneys, we found an increase in GFR during the ischemic period which was significant compared to baseline in all but two measurements in each group (WI120; t240 32.6 ± 6.4 ml/min (p = 0.1), t480 32.1 ± 8.1 ml/min (p = 0.3), WI240; t180 36.8 ± 7.7 ml/min (p = 0.2), t600 37.1 ± 12.5 ml/min (p = 0.3)). Compared to baseline (WI120 15 (8,80) ml, WI240 38 (16,121) ml), an increased urine production was observed in the control kidneys during the study period. This was significant in most measurements; however, a few were non-significant, (WI120 t240, t300; WI240 t180, t240, t360, t420 (p > 0.05).


Cell injury after ischemia and reperfusion in the porcine kidney evaluated by radiolabelled microspheres, sestamibi, and lactadherin.

Pedersen SS, Keller AK, Nielsen MK, Jespersen B, Falborg L, Rasmussen JT, Heegaard CW, Rehling M - EJNMMI Res (2013)

Diuresis for groups with warm ischemia (WI) of 120 (left) and 240 (right) min. Data are presented as median (range). Capped line indicates ischemic period. IK, ischemic kidney; CK, control kidney.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750402&req=5

Figure 3: Diuresis for groups with warm ischemia (WI) of 120 (left) and 240 (right) min. Data are presented as median (range). Capped line indicates ischemic period. IK, ischemic kidney; CK, control kidney.
Mentions: At baseline (t60), we found a mean single kidney GFR value of 30.2 ± 8.8 ml/min with no significant difference between WI120 and WI240 or between the ischemic and the control kidney (p > 0.1). Immediately after initiating unilateral ischemia, the GFR dropped to values near zero in the ischemic kidneys as no urine was produced. During reperfusion, some urine production was established, but GFR stayed close to zero. Figure 3 shows the diuresis during WI120 and WI240 from the ischemic as well as the control kidneys. In the control kidneys, we found an increase in GFR during the ischemic period which was significant compared to baseline in all but two measurements in each group (WI120; t240 32.6 ± 6.4 ml/min (p = 0.1), t480 32.1 ± 8.1 ml/min (p = 0.3), WI240; t180 36.8 ± 7.7 ml/min (p = 0.2), t600 37.1 ± 12.5 ml/min (p = 0.3)). Compared to baseline (WI120 15 (8,80) ml, WI240 38 (16,121) ml), an increased urine production was observed in the control kidneys during the study period. This was significant in most measurements; however, a few were non-significant, (WI120 t240, t300; WI240 t180, t240, t360, t420 (p > 0.05).

Bottom Line: In WI240, the uptake of microspheres was severely reduced in both groups (17% ± 11% and 27% ± 17%).GFR was severely reduced in the post ischemic kidney in both groups.In both groups, the uptake of lactadherin was reduced (41% ± 8%, 17% ± 13%) but not different from the uptake of (153)Gd microspheres.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark ; Department of Clinical Physiology and Nuclear Medicine, Aarhus University Hospital, Skejby, Denmark.

ABSTRACT

Background: The purpose of the present study was to quantify renal cell injury after ischemia and reperfusion in a pig model using (99m)Tc-lactadherin as a marker of apoptosis and (99m)Tc-sestamibi as a marker of mitochondrial dysfunction.

Methods: Thirty-four pigs were randomized into unilateral renal warm ischemia of 120 (WI120) or 240 min (WI240). The glomerular filtration rate (GFR) was calculated by renal clearance of (51)Cr-ethylenediaminetetraacetic acid, and apoptosis was quantified by immunohistochemical detection of caspase-3. After 240 min of reperfusion, intravenous (99m)Tc-lactadherin or (99m)Tc-sestamibi was injected simultaneously with (153)Gd microspheres into the aorta. Ex-vivo static planar images of the kidneys were acquired for determination of the differential renal function of tracer distribution using a gamma camera.

Results: In WI120, there was no significant difference in the uptake of microspheres in the ischemic and contralateral normal kidney indicating adequate perfusion (uptake in ischemic kidney relative to the sum of uptake in both kidneys; 46% ± 12% and 51% ± 5%). In WI240, the uptake of microspheres was severely reduced in both groups (17% ± 11% and 27% ± 17%). GFR was severely reduced in the post ischemic kidney in both groups. In both groups, the uptake of lactadherin was reduced (41% ± 8%, 17% ± 13%) but not different from the uptake of (153)Gd microspheres. Caspase-3-positive cell profiles were increased in the post-ischemic kidneys (p < 0.001) and increased as the length of ischemia increased (p = 0.003). In both WI120 and WI240, the amount of (99m)Tc-sestamibi in the ischemic kidney was significantly lower than the amount of (153)Gd microspheres (40 ± 5 versus 51 ± 5 and 20 ± 11 versus 27 ± 17; p < 0.05).

Conclusions: In an established pig model with unilateral renal warm ischemia, we found significantly reduced (99m)Tc-sestamibi uptake relative to perfusion in the kidneys exposed to ischemia indicating a potential ability to detect renal ischemic and reperfusion injuries. However, apoptosis was not detected using (99m)Tc-lactadherin in the post-ischemic kidneys despite increased number of caspase-3-positive cell profiles.

Trial registration: This study is approved by the Danish Inspectorate of Animal Experiments (2010/561-1837).

No MeSH data available.


Related in: MedlinePlus