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

Abstract

BackgroundThe purpose of the present study was to quantify renal cell injury after ischemia and reperfusion in a pig model using 99mTc-lactadherin as a marker of apoptosis and 99mTc-sestamibi as a marker of mitochondrial dysfunction.MethodsThirty-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 51Cr-ethylenediaminetetraacetic acid, and apoptosis was quantified by immunohistochemical detection of caspase-3. After 240 min of reperfusion, intravenous 99mTc-lactadherin or 99mTc-sestamibi was injected simultaneously with 153Gd 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.ResultsIn 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 153Gd 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 99mTc-sestamibi in the ischemic kidney was significantly lower than the amount of 153Gd microspheres (40 ± 5 versus 51 ± 5 and 20 ± 11 versus 27 ± 17; p < 0.05).ConclusionsIn an established pig model with unilateral renal warm ischemia, we found significantly reduced 99mTc-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 99mTc-lactadherin in the post-ischemic kidneys despite increased number of caspase-3-positive cell profiles.Trial registrationThis study is approved by the Danish Inspectorate of Animal Experiments (2010/561-1837).

Corticomedullary shunting after ischaemia and reperfusion in the porcine kidney?

“…In both groups the renal weight was significantly higher than the weight of the contralateral non-ischaemic kidney ( p < 0.001). At baseline (60 min), we found a mean single kidney GFR value of 30.2 ± 8.8 ml/min with no significant difference between groups [ 11 ]. During reperfusion the regain in GFR was close to zero.…”

“…The methods are described in detail elsewhere [ 11 ]. In brief, 34 female Danish landrace/Yorkshire pigs with a mean weight of 38 ± 2 kg were exposed to unilateral warm ischaemia by clamping the renal artery for 2 h ( n = 18) or for 4 h ( n = 16) followed by 4 h of reperfusion.…”

Old tracer for a new purpose

“…Hurwitz et al [25] described 99m Tc-MIBI as behaving similarly to 99m Tc-DTPA. Of relevance in this context is the finding of Pedersen et al [26] that 99m Tc-MIBI parenchymal uptake is reduced more than perfusion in acute ischaemia-reperfusion injury, interpreted as mitochondrial injury. Its general diagnostic value in post-transplant applications awaits further experience.…”

Corticomedullary Shunting After Ischaemia and Reperfusion in The Porcine Kidney?

“…The methods are described in detail elsewhere [11]. In brief, 34 female crossbred slaughter pigs (Danish Landrace-Yorkshire-Duroc) weighing 35-45 kg were used.…”