Publikationsserver der RWTH Aachen University
Zur Übertragbarkeit tierexperimenteller endovaskulärer Studien : Unterschiede der Gerinnungs- und Fibrinolyse-Systeme bei häufig verwendeten Tierspezies im Vergleich zum Menschen
Abstract
dc:descriptionFor the development and improvement of endovascular interventional therapy-methods the use of test-animals unavoidable. Criterions for the selection of a particular animal kind are quite often the vessel-size and thereof resulting the applicatibility of different implants (Catheters, Coils, Stents), law-reasons, society-ethical reasons, subject- and experiment-specific use of a particular animal model as well as costs. Less known and less attention is paid to coagulation-physiologic and -pathologic aspects, especially in comparison to man. The most frequently used laboratory animals for endovascular studies are pigs, dogs and rabbits; less used are sheep and very seldom used are primates. An extensive literature-research shows that every particular species is used in a broad experimental spectrum but there is only little information on coagulation-parameters of those species. Besides a number of publifications about coagulation- and fibrinolysis systems are contradictous in terms which makes the extrapolation of those results to man more difficult or even impossible. More information about this topic is spread through pharmacologic and pharmacodynamic publications than experimental interventional studies. In most cases of interventional literature pig and dog are claimed to be the most suitable test animals without any experimental validation. In our study we faced that problem and tried with own systematic experiments and extensive literature-research to recommend an animal model which is most suitable concerning the coagulation and fibrinolysis system. We tested the coagulation systems of those species who are mostly used in interventional studies: pig, dog, rabbit and sheep. The blood of ten animals of each species was examined and all the relevant coagulation parameters were measured. The results were compared to the human standard values and the ones in between species. Because a direct quantitative comparison of the parameters was often impossible due to the complexity of the systems (intrinsic and extrinsic coagulation, influence of fibrinolysis, etc) or would have distorted the results, we tried to create a qualitative ratio by analyzing the parameters of the particular subsystems, assembling them and creating a ranking order. Human parameters counted as baseline and the results of different species were graded as increased or decreased in comparison. We wanted to rate the antagonistic coagulation and fibrinolysis activity as whole. A limitation occurred in the rating of plasminogen activity. Our tests showed (confirmed through other publications) that Plasminogen of all analyzed species was insufficiently activated by Streptokinasis. Another limitation appeared in the results of aPTT. An activation of the intrinsic coagulation with Ellag-acid resulted in massive prolongation of rabbit-aPTT and a moderate prolongation of dog- and pig-aPTT compared to an activation with Kaolin as described in other publications. Also one has to recognize a species specifity of Thromboplastine especially when transferring the results of sheep and dog to the human coagulation system. In consideration of all systems sheep are closest to human coagulation and fibrinolysis. According to our results the sheep is well suitable with ist coagulation system. The rabbit takes second place in ranking. Coagulation and fibrinolysis are more active compared to human which is yet compensated by a more active contra-coagulation (AT III, Protein C) and increased fibrinolysis. Third place in ranking is held by the dog whose coagulation system is distinguished with a remarkably active extrinsic coagulation. The pig appears to be last in ranking. Its coagulation system is very increased compared to human and cannot be quite compensated by its fibrinolysis activity. Compared to the other species the contra-regulation of coagulation is decreased. Besides primates sheep and rabbit seem to be well suitable for endovascular experimental operations and the development of therapy methods. A little less suitable is the dog, least suitable is the pig. A suitable animal model without limitation for different experiments does not exist. Rather in consideration of literature one has to make a careful selection. It is important that existing differences between animal species and human are demonstrated and, if necessary, limitations of a particular test animal are recognized. Correcting factors can simplify the extrapolation. Because of lacking standardization of many experimental arrangements in numerous cases a comparison of publications is quite difficult. It is necessary that more standardized tests concerning coagulation and fibrinolysis of frequently in interventional studies used animal kinds are carried out for improvement of extrapolation of those studies to man.
Degree
thesis:*- Grantor dc:publisher
- Publikationsserver der RWTH Aachen University
- Year dc:date
- 2000
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Höhle, Philip
- Contributors dc:contributor
-
- Reul, Jürgen
Subjects
dc:subject × 2Rights
dc:rights- Statement dc:rights
-
- info:eu-repo/semantics/openAccess
- Language dc:language
- ger