SMALL VESSEL ISCHEMIA-INDUCED BY MICROBEAD EMBOLIZATION IN THE SHEEP HIND-LIMB

Background: Peripheral ischaemia may be caused by small vessel disease but there has been no satisfactory experimental model for studying th is condition. We have developed a model in which microbeads are emboli zed to the distal vascular bed of a sheep. This model induces ischaemi a proportional to the volume of microbead infusion and allows the path ophysiology and therapy of small vessel occlusion to be studied. Metho ds: Gradual reduction of femoral artery blood flaw by 50% and 75% in u nilateral hind limbs of eight sheep was achieved by slow introduction of latex microbeads (mean size = 400 mu m) into the peripheral vascula r bed. The other hind limb served as a control. Measurements of blood flow, subcutaneous temperature and arterial and venous blood gases wer e recorded in both hind Limbs after each level of flow reduction. Angi ography confirmed small vessel occlusion. Muscle samples were analysed for ultrastructural changes by transmission microscopy. Results: A li near correlation was found between the amount of microbeads infused an d the reduction in the blood flow. Significant subcutaneous temperatur e and venous pO(2) changes were observed in the embolized limb at both 50% and 25% flow levels compared to baseline (P < 0.05, ANOVA). Angio graphy demonstrated abrupt cut-off images of the small vessels. Transm ission microscopy showed graded levels of muscle cell damage from isch aemia. Conclusions: Latex microbead embolization induces reproducible controlled small artery occlusion. The degree of outflow obstruction a nd the extent of ischaemia can be varied by delivering measured quanti ties of microbeads. This model should be useful for studying the patho physiology of ischaemia and for assessing the efficacy of treatment, e specially the use of pharmacological agents.