Abstract 321: Prasugrel, a Platelet P2y 12 Receptor Antagonist, Improves Abnormal Gait in a Novel Murine Model of Thrombotic Hind Limb Ischaemia

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Kousaku Ohno ◽  
Atsuyuki Tomizawa ◽  
Makoto Mizuno ◽  
Joseph A Jakubowski ◽  
Atsuhiro Sugidachi

Background: The efficacy of P2Y 12 inhibition for the prevention of cardiovascular events in patients with peripheral arterial disease (PAD) has been established. However the therapeutic effects on ischaemic limb manifestations are less clear. Accordingly, we developed a novel murine model of thrombotic hind limb ischaemia to reflect that found in patients with PAD exhibiting ischaemic limb symptoms. We further investigated the effects of P2Y 12 inhibition by prasugrel in this model. Methods and Results: Thrombus formation induced by application of ferric chloride to the femoral artery resulted in a significant reduction in blood flow in the injured limb. In gait analysis of the ischaemic limb using the CatWalk system, maximum contact area and stance phase duration were reduced and swing phase duration increased in this model. Blood flow reduction and gait abnormalities gradually recovered over 21 days to levels present before arterial injury. Compared to wild-type (WT) mice, significant increases in blood flow and improvement in gait were observed in P2Y 12 -deficient mice. In addition, daily oral administration of prasugrel (3 mg/kg/day) to WT mice resulted in significant inhibition of blood flow reduction and gait abnormalities to levels found in P2Y 12 deficient mice. Conclusions: In conclusion, acute femoral artery thrombosis resulted in hind limb ischaemia and moderate gait abnormalities in mice. In addition, the present study suggests a therapeutic role for P2Y 12 antagonism in reducing the manifestations of limb ischaemia in PAD.

2005 ◽  
Vol 21 (s2) ◽  
pp. 55-59 ◽  
Author(s):  
J. Hata ◽  
T. Kamada ◽  
N. Manabe ◽  
H. Kusunoki ◽  
D. Kamino ◽  
...  

Author(s):  
Yusuke SHIMIZU ◽  
Susumu ISHIKAWA ◽  
Hideki MISHIMA ◽  
Yuki MATSUNAGA ◽  
Yuki NISHIHARA ◽  
...  

2011 ◽  
Vol 171 (2) ◽  
pp. 532-539 ◽  
Author(s):  
Ruy J. Cruz ◽  
Alejandra G. Garrido ◽  
Décio de Natale Caly ◽  
Mauricio Rocha-e-Silva

Neurology ◽  
2002 ◽  
Vol 59 (3) ◽  
pp. 321-326 ◽  
Author(s):  
M. O'Sullivan ◽  
D. J. Lythgoe ◽  
A. C. Pereira ◽  
P. E. Summers ◽  
J. M. Jarosz ◽  
...  

2019 ◽  
Vol 51 (2) ◽  
pp. 130-136
Author(s):  
Franca Tecchio ◽  
Federico Cecconi ◽  
Elisabetta Colamartino ◽  
Matteo Padalino ◽  
Luca Valci ◽  
...  

Somatosensory evoked potential (SEP) monitoring is a standard tool during clipping of aneurysms of the middle cerebral artery (MCA), and the parameter used to detect a state of cortical ischemia is amplitude. We think that the sensitivity of SEP can however be improved by using other parameters. Our study moves in this direction via SEP morphology. In this pilot preliminary study, involving a small sample without postoperative neurological deficit, we aimed at investigating the value of SEP morphology (in the 15- to 35-ms time frame), in comparison with SEP amplitude (N20 peak-to-peak), as a measure of sensitivity to blood flow reduction. The changes in the SEP morphology of 16 patients undergoing clipping of an unruptured MCA aneurysm was studied. We applied the Morph-Fréchet index for each recorded SEP (at 30-second intervals), quantifying the pattern shape change with regard to the average SEP recorded after dura opening (baseline). We also compared 3 measurements of the SEP morphology, without and with GARCH-derived filter. Filtered Morph-Fréchet never exceeded the individual’s “normality” range in baseline but did so in 81% of the risk phase on average across the 16 subjects, which is more than that for amplitude (36%, P = .002). This pilot study indicates that a measurement derived from the networking nature of the brain was sensitive to blood flow reduction. The SEP morphology approach promises to improve SEP monitoring sensitivity during clipping of unruptured MCA aneurysms. New and Noteworthy. The higher sensitivity to blood flow reduction of SEP morphology than amplitude promises to improve the effectiveness of intraoperative monitoring during MCA aneurysm clipping procedures.


1996 ◽  
Vol 270 (1) ◽  
pp. R246-R253 ◽  
Author(s):  
D. W. Boyle ◽  
S. Lecklitner ◽  
E. A. Liechty

The purpose of the present investigation was to study the effect of 7 days of uterine blood flow reduction on fetal growth. Reduction in uterine blood flow was accomplished by external occlusion of the terminal aorta in 20 pregnant sheep. Linear growth was monitored daily by means of a crown-rump length measuring device. The deliveries of oxygen, glucose, and lactate to the fetus, as well as their uptakes by the fetus, were determined before and after 7 days of uterine blood flow reduction and correlated with rates of fetal growth. Identical studies were conducted in nine control animals. Uterine blood flow reduction resulted in a significant decrease in fetal oxygen delivery and fetal arterial oxygen content. Linear growth rate decreased by 38% in the occluded animals during hypoxemia. In addition, there was a 20% reduction in daily weight gain in occluded animals compared with controls. There were no differences in the uptakes of oxygen, glucose, and lactate by the fetus. Positive correlations were found between linear growth rate and fetal arterial oxygen content (r2 = 0.25, P = 0.0001) and between linear growth rate and fetal oxygen delivery (r2 = 0.21, P = 0.0006). The correlations between linear growth rate and fetal oxygenation provide strong evidence of the central role of oxygen in the regulation of fetal growth.


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