Vasodilatory effect of pentoxifylline in isolated equine digital veins

Kabbesh, Nasr; Gogny, Marc; Chatagnon, G.; Noireaud, Jacques; Thorin, Chantal; Desfontis, Jean‐Claude; Mallem, Yassine

doi:10.1016/j.tvjl.2011.09.005

Cited by 21 publications

(13 citation statements)

References 29 publications

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“…Aside from its antiplatelet effects, cilostazol also acts as vasodilator (36). Thus, this drug may have useful rheologic effects in conditions other than EHV-1 infection, such as recurrent airway obstruction and laminitis (37, 38). …”

Section: Discussionmentioning

confidence: 99%

Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, Block Ex Vivo Equid Herpesvirus Type-1-Induced Platelet Activation

et al. 2016

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Equid herpes virus type-1 (EHV-1) is a major pathogen of horses, causing abortion storms and outbreaks of herpes virus myeloencephalopathy. These clinical syndromes are partly attributed to ischemic injury from thrombosis in placental and spinal vessels. The mechanism of thrombosis in affected horses is unknown. We have previously shown that EHV-1 activates platelets through virus-associated tissue factor-initiated thrombin generation. Activated platelets participate in thrombus formation by providing a surface to localize coagulation factor complexes that amplify and propagate thrombin generation. We hypothesized that coagulation inhibitors that suppress thrombin generation (heparins) or platelet inhibitors that impede post-receptor thrombin signaling [phosphodiesterase (PDE) antagonists] would inhibit EHV-1-induced platelet activation ex vivo. We exposed platelet-rich plasma (PRP) collected from healthy horses to the RacL11 abortigenic and Ab4 neuropathogenic strains of EHV-1 at 1 plaque-forming unit/cell in the presence or absence of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH) or the PDE inhibitors, 3-isobutyl-1methylxanthine (IBMX), and cilostazol. We assessed platelet activation status in flow cytometric assays by measuring P-selectin expression. We found that all of the inhibitors blocked EHV-1- and thrombin-induced platelet activation in a dose-dependent manner. Platelet activation in PRP was maximally inhibited at concentrations of 0.05 U/mL UFH and 2.5 μg/mL LMWH. These concentrations represented 0.1–0.2 U/mL anti-factor Xa activity measured in chromogenic assays. Both IBMX and cilostazol showed maximal inhibition of platelet activation at the highest tested concentration of 50 μM, but inhibition was lower than that seen with UFH and LMWH. Our results indicate that heparin anticoagulants and strong non-selective (IBMX) or isoenzyme-3 selective (cilostazol) PDE antagonists inhibit ex vivo EHV-1-induced platelet activation. These drugs have potential as adjunctive therapy to reduce the serious complications associated with EHV-1-induced thrombosis. Treatment trials are warranted to determine whether these drugs yield clinical benefit when administered to horses infected with EHV-1.

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Section: Discussionmentioning

confidence: 99%

Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, Block Ex Vivo Equid Herpesvirus Type-1-Induced Platelet Activation

et al. 2016

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“…As mentioned earlier, increased generation of superoxide anions along with generation of lipid peroxides from placenta, inactivation of EDRF and impairment of ROS/RNS balance are of major causes of the disease [54,55]. Pentoxifylline enhances EDRF production, equilibrates ROS/RNS balance, increases endothelial NO synthesis in placenta and improves placental perfusion [89,[93][94][95], which are all disturbed in preeclampsia [34,52,54,60].…”

Section: Placentationmentioning

confidence: 93%

Hypothesis: Pentoxifylline explores new horizons in treatment of preeclampsia

et al. 2015

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“…Vasodilatory agents have been described to be useful in the treatment of equine laminitis (Belknap, 2010). Recently, we demonstrated that pentoxifylline (PTX) and propentofylline (PPT) induced endothelium-dependent vasorelaxation in equine digital veins (EDV) (Mallem, 2009;Kabbesh, 2011) but there is still a need of further studies clarifying these effects under experimental pathological conditions. The present study was designed to evaluate the PTX and PPT-mediated vasorelaxation in endotoxin-treated EDV and to determine their effect on endotoxin-induced impairment of EDV endothelium-mediated relaxation.…”

Section: Introductionmentioning

confidence: 99%

Poster Session 3

2012

Vet Pharm & Therapeutics

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Vasodilatory effect of pentoxifylline in isolated equine digital veins

Cited by 21 publications

References 29 publications

Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, Block Ex Vivo Equid Herpesvirus Type-1-Induced Platelet Activation

Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, Block Ex Vivo Equid Herpesvirus Type-1-Induced Platelet Activation

Hypothesis: Pentoxifylline explores new horizons in treatment of preeclampsia

Poster Session 3

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