@article{landskroner_olson_jesmok_2005, title={Cross-species pharmacologic evaluation of plasmin as a direct-acting thrombolytic agent: Ex vivo evaluation for large animal model development}, volume={16}, ISSN={["1051-0443"]}, DOI={10.1097/01.RVI.0000148828.40438.D3}, abstractNote={PURPOSE
Human plasma-derived plasmin has been developed for the treatment of thrombosed hemodialysis arteriovenous grafts and vascular occlusive diseases. To further investigate this drug in large animal models and derive preliminary dosing estimates, the authors compared plasmin's relative lytic potential in four species, including man. The goal was to find which species' whole blood clots best compared to human clots in terms of lysis with plasmin. The results from these studies will serve to guide species selection for large animal experimentation.


MATERIALS AND METHODS
Clotted blood from human, pig, sheep, and bovine subjects were treated with saline solution control, plasmin, or tissue plasminogen activator. Electron microscopy (EM) techniques were used to investigate the effects of clot size and fragmentation on plasmin lysis, the effects of intrathrombic infusion by injection of plasmin directly into whole blood clots, and species fibrin structural differences.


RESULTS
Under static conditions, plasmin efficiently lysed clots from all species studied at an optimal dose of 4-5 mg per 4-5 g of clot. With fragmented human clots, plasmin (5 mg)-induced lysis was 80% +/- 2% at 60 minutes. Porcine clots were more resistant to plasmin lysis compared with human, ovine, and bovine clots. Percent lysis at 60 minutes with plasmin for ovine clots was 72% +/- 3% (4-mg dose), compared with 50% +/- 4% for porcine clots (5-mg dose; P < .05). EM of porcine clots showed a compact fibrin network that appeared more dense than that in human or sheep clots, which may account for the decreased lytic rate.


CONCLUSIONS
Human plasmin is an effective direct-acting thrombolytic agent that is capable of lysing fibrin from several species. Ex vivo lysis studies were used to investigate the most appropriate large animal model that best approximates plasmin lysis with human clots under certain conditions. It was determined that ovine clots treated with plasmin most closely resemble the lysis observed with human clots.}, number={3}, journal={JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY}, author={Landskroner, K and Olson, N and Jesmok, G}, year={2005}, month={Mar}, pages={369–377} }
 @article{landskroner_olson_jesmok_2005, title={Thromboelastography measurements of whole blood from factor VIII-deficient mice supplemented with rFVIII}, volume={11}, number={4}, journal={Haemophilia}, author={Landskroner, K. A. and Olson, N. C. and Jesmok, G. J.}, year={2005}, pages={346–352} }
 @misc{landskroner_olson_jesmok_2004, title={Enhanced factor VIII activity measurements using ROTEG and factor VIII-/- mice whole blood}, volume={2}, number={12}, journal={Journal of Thrombosis and Haemostasis}, author={Landskroner, K. A. and Olson, N. C. and Jesmok, G. J.}, year={2004}, pages={2274–2275} }
 @article{kruseelliott_whorton_olson_1998, title={Role of lipid-derived mediators in tumor necrosis factor-induced endothelin-1 release in vivo}, volume={9}, number={1}, journal={Shock (Augusta, Ga.)}, author={KruseElliott, K. T. and Whorton, A. R. and Olson, N. C.}, year={1998}, pages={40–45} }
 @article{dodam_adler_olson_1996, title={Effect of pertussis toxin and B-Oligomer on platelet-activating factor-induced generation of inositol phosphates in porcine alveolar macrophages.}, volume={57}, journal={American Journal of Veterinary Research}, author={Dodam, J. R. and Adler, K. B. and Olson, N. C.}, year={1996}, pages={574–579} }
 @misc{olson_hellyer_dodam_1995, title={MEDIATORS AND VASCULAR EFFECTS IN RESPONSE TO ENDOTOXIN}, volume={151}, ISSN={["0007-1935"]}, DOI={10.1016/S0007-1935(05)80023-5}, abstractNote={Recent experimental findings indicate that endotoxin (i.e. lipopolysaccharide) interacts with specific membrane receptors localized to mononuclear phagocytic cells and neutrophils. Binding of endotoxin to these cells, together with endotoxin-induced activation of host vascular endothelium, initiates a series of signal transduction events that culminate in release of numerous biochemical mediators. The latter include cytokines, platelet-activating factor, thromboxane A2, prostaglandins, leukotrienes, nitric oxide, proteases, toxic O2, radicals, and vasoactive amines. These mediators orchestrate complex biological interactions and amplification signals that lead to cardiopulmonary dysfunction and multi-organ failure within 4–6 h of experimental infusion of endotoxin into animals. The pathophysiological changes include decreased cardiac output, systemic hypotension, decreased blood flow and O2 delivery to tissues, intense pulmonary vasoconstriction and hypertension, bronchoconstriction, increased permeability, pulmonary oedema, ventilation-to-perfusion inequalities, hypoxaemia, and haemoconcentration. Metabolic alterations include increased blood lactate and pyruvate, metabolic acidosis, hyperkalaemia and hypoglycaemia. Potential therapeutic modalities for treatment of endotoxaemia/septicshock include specific antagonists directed against lipopolysaccharide, cytokine, and platelet-activating factor receptors, monoclonal antibodies directed against cytokines and lipid A/core polysaccharides of endotoxin, antiproteases, and agents that block release of toxic O2 and arachidonic acid metabolites.}, number={5}, journal={BRITISH VETERINARY JOURNAL}, author={OLSON, NC and HELLYER, PW and DODAM, JR}, year={1995}, pages={489–522} }
 @article{olson_dodam_kruse-elliott_1992, title={Endotoxemia and gram-negative bacteremia in swine: Chemical mediators and therapeutic considerations}, volume={200}, number={12}, journal={Journal of the American Veterinary Medical Association}, author={Olson, N. C. and Dodam, J. R. and Kruse-Elliott, K. T.}, year={1992}, pages={1884} }
 @article{olson_kruse-elliott_dodam_1992, title={Systemic and pulmonary reactions in swine with endotoxemia and gram-negative bacteremia}, volume={200}, number={12}, journal={Journal of the American Veterinary Medical Association}, author={Olson, N. C. and Kruse-Elliott, K. T. and Dodam, J. R.}, year={1992}, pages={1870} }
 @article{fleisher_ferrell_olson_mcgahan_1989, title={DIMETHYLTHIOUREA INHIBITS THE INFLAMMATORY RESPONSE TO INTRAVITREALLY-INJECTED ENDOTOXIN}, volume={48}, ISSN={["0014-4835"]}, DOI={10.1016/0014-4835(89)90038-9}, abstractNote={Dimethylthiourea, a potent scavenger of toxic oxygen metabolites such as the hydroxyl radical, hypochlorous acid, and hydrogen peroxide, was tested for its ability to inhibit an experimentally induced inflammatory response. Inflammation was induced in one eye of male New Zealand white rabbits by intravitreal injection of 10 ng Escherichia coli endotoxin; the contralateral eye received an equal volume of pyrogen-free saline vehicle. Dimethylthiourea was administered intraperitoneally to these animals at 0, 300, 450 and 600 mg kg−1. At 24 h post-endotoxin injection, all vehicle-injected eyes appeared normal with the exception of a small, but significant increase in aqueous humor protein concentration in the 600 mg kg−1 dimethylthiourea group. In endotoxin-injected eyes, treatment with dimethylthiourea, especially at the highest dose, significantly reduced iridal hyperemia, aqueous humor cell number and protein and prostaglandin-E concentrations, and the ex vivo release of prostaglandin-E from the lens. The ability of dimethylthiourea to significantly inhibit the inflammatory response to intravitreally-injected endotoxin suggests that toxic oxygen metabolites may play an important role in the initiation and/or propagation of this form of acute anterior uveitis. Furthermore, the data are consistent with an important interaction between toxic oxygen and arachidonic acid metabolites.}, number={4}, journal={EXPERIMENTAL EYE RESEARCH}, author={FLEISHER, LN and FERRELL, JB and OLSON, NC and MCGAHAN, MC}, year={1989}, month={Apr}, pages={561–567} }