Pulmonary angiography for the diagnosis of thromboembolic events in the non-human primate.

Abstract

Evaluating possible thromboembolic events in the non-human primate has traditionally required euthanasia, significantly limiting the ability to conduct longitudinal studies. We hypothesized that pulmonary angiography could offer a safe, reproducible, and non-lethal means to assess for pulmonary embolus in the non-human primate. Eleven rhesus primates were studied using standard pulmonary angiography techniques. Five animals studied had previously received humanized anti-CD154 antibodies (associated with thromboembolism risk) in the context of skin transplantation 2 years before the angiography study. Four primates were studied after receiving mouse anti-human CD154 antibody following allogeneic islet or skin transplantation. Angiography was successful in all primates. We observed no complications, and all animals promptly recovered from the procedure. Angiographic findings consistent with thromboembolism were demonstrated in the three primates actively receiving anti-CD154 antibody and in one primate that last received anti-CD154 nearly 2 years before the study. The study was normal in both the streptozotocin-induced diabetic control animals. Histopathology of the lungs confirmed thrombus in two of the four primates, but no thromboembolus was identified in the other two. The first had limited pathologic evaluation without fine slices, and in the second (treated 2 years before with a humanized anti-CD154), ascariasis was found in the area identified as abnormal by the angiogram. Minimally invasive pulmonary angiography is a safe, reproducible, and inexpensive method to assess possible thromboembolic events in the non-human primate. This method may allow for the longitudinal assessment of non-human primates given novel agents that may promote thromboembolism.