Abstract
For endovascular research pigs are an established animal model. However, experiences regarding analyses of platelet inhibition in pigs using the Multiplate® Analyzer are limited. The aims of the present study were to investigate if (1) the Multiplate® Analyzer is a suitable method for examination of porcine platelet function using manufacturers’ recommendations for human blood, and (2) platelet inhibition can be induced with acetylsalicylic acid (ASA) and clopidogrel in pigs reliably, and if (3) non-responders to one of the drug can be detected. Additionally we examined differences in (4) the effectiveness of ASA between oral administration and intravenous application, and (5) between domestic pigs (German Landrace; GL) and miniature pigs (MP). We investigated platelet function of 36 unmedicated pigs (GL n = 28; MP n = 8). In addition, 32 blood samples taken from medicated pigs (GL n = 15; MP n = 17) were analysed. Platelet inhibition was induced in four different ways: (1) 500 mg ASA intravenously (n = 11), (2) 500 mg ASA intravenously and 450 mg clopidogrel orally (n = 5), (3) 250 mg ASA orally (n = 11), (4) 250 mg ASA orally and 75 mg clopidogrel orally (n = 5). Results of the ASPI and ADP test of the Multiplate® Analyzer subtests in unmedicated and medicated pigs were in a comparable range to results known from humans. Application of ASA decreased the mean values of the ASPI test significantly regardless of the application method. Joined administration of ASA and clopidogrel also decreased the mean values of the ADP test significantly. Both, oral and intravenous administrations of ASA as well as oral administration of clopidogrel effectively inhibited platelet function in pigs. One pig did not respond to clopidogrel. We found no differences between domestic and miniature pigs regarding reference values in unmedicated pigs and the effectiveness of ASA and clopidogrel.
Highlights
In humans, dual platelet inhibition with acetylsalicylic acid (ASA) and clopidogrel are essential points of secondary stroke prevention and after implantation of neurointerventional and coronary devices [1,2,3]
Dual platelet inhibition using ASA and clopidogrel has been shown to effectively reduce complications resulting from intravascularly implanted materials in humans [7,8,9]
Platelet inhibition was induced in four different ways: (1) 500mg ASA (Aspirin1, Bayer, Leverkusen, Germany) intravenously, (2) 500mg ASA intravenously and 450mg clopidogrel (Iscover1, Orifarm, Leverkusen, Germany) orally, (3) 250mg ASA orally, (4) 250mg ASA orally and 75mg clopidogrel orally
Summary
Dual platelet inhibition with acetylsalicylic acid (ASA) and clopidogrel are essential points of secondary stroke prevention and after implantation of neurointerventional and coronary devices [1,2,3] Because of their synergistic effect the combination of both drugs induces efficient platelet inhibition and the risk of adverse events like recurrent vessel occlusion and in-stent-stenosis is minimized [4]. In clinical studies prevalence rates for ASA resistance have been reported between 5% and 60% [16,17,18,19,20] This may be attributable to the reliability of tablet intake by patients, but to some extent to specific tablet formulations (i.e., coated versus uncoated tablets). Based on these results medication doses can be modified or other platelet inhibitors can be used
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