Renal Artery Occlusion Model in Dogs for the Evaluation of Thrombolytic Agents

Abstract

The purpose of this study was to develop a model of renal artery occlusion and to investigate the effects of various thrombolytic agents on an acute occlusion of the renal artery with respect to ischemic tolerance of renal parenchyma. In order to do this, a thrombosis model in dogs (n = 36) was established and a total of 72 dorsal renal arteries occluded using autologous clot material. For the in vitro preparing of a clot, autologous blood (20 mL) was withdrawn and 100 U thrombin immediately added. Then 1 mL of the clot material was injected into the dorsal branch of the exposed renal artery. The dogs were divided into 8 groups (2 control groups, 6 therapy groups with local and systemic thrombolytic therapy). Thrombolysis was performed using urokinase, single-chain urokinase, and recombinant tissue-plasminogen activator. In all cases the clot preparation technique allowed complete and stable occlusion of the renal arteries. Local and systemic application of the thrombolytic agents, however, resulted in complete recanalization of the clot material in all study groups. Recombinant tissue-plasminogen activator turned out to be the most effective agent in terms of recanalization time. The technique described allowed effective and reproducible artery occlusion for in vivo experimental work to study comparatively thrombolytic agents with respect to fibrin specificity, lytic efficacy, and side effects.

Pulmonary thromboembolism

“…171 Urokinase was not associated with serious hemorrhage in that study. Urokinase has been used experimentally in dogs [172][173][174] and has been reported in 1 dog with PTE. 175 t-PA directly converts plasminogen to plasmin.…”

2022 Update of the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) Domain 6: Defining rational use of thrombolytics

“…Ten studies supported the PICO question (all LOE 3, 3 good quality, 56,75,99 6 fair, 16,17,32,53,74,77 Of the 10 supporting studies, 4 demonstrated that a thirdgeneration thrombolytic agent was superior to a second-generation thrombolytic. Specifically, 2 studies supported that monteplase was superior to rt-PA, 53,56 1 noted that intraarterial reteplase was superior to IV alteplase, 35 and 1 that noted that IV reteplase was supe-rior to IV alteplase.…”

“…11,12 Thirteen LOE 3 studies of fair quality supported the PICO question. [13][14][15][16][17][18][19][20][21][22][23][24][25] These studies included no thrombolytic control groups without randomization of group allocation. Zhang and colleagues injected a fibrin-rich embolus into the left anterior descending (LAD) coronary artery causing occlusion.…”

“…Nonetheless, kidney injury, as demonstrated by increased serum urea or creatinine and decreased glomerular filtration rate, remained during 8 weeks follow-up, despite successful thrombolysis. 17 Tomaru and colleagues reported the use of thrombolytics in a model of bilateral iliac artery thrombosis where contralateral arteries acted as controls. 19 In 5 dogs, saline placebo was catheter-delivered into 1 thrombosed iliac artery, while low-dose tPA (tisokinase, 50,000 IU) was catheter-delivered into the other thrombosed artery.…”

“…74 One study demonstrated that a secondary generation thrombolytic (alteplase) and a third-generation thrombolytic (reteplase) were both superior to the first-generation drug streptokinase. 99 Interestingly, although 3 studies demonstrated that alteplase was superior to the first generation drugs urokinase or single-chain urokinase, 16,17,75 other studies suggested superiority of urokinase 77 or pro-urokinase 32 over tPA. Each of the included studies is described in more detail below.…”