Small vessel ischaemia induced by microbead embolization in the sheep hind limb

Peripheral ischaemia may be caused by small vessel disease but there has been no satisfactory experimental model for studying this condition. We have developed a model in which microbeads are embolized to the distal vascular bed of a sheep. This model induces ischaemia proportional to the volume of microbead infusion and allows the pathophysiology and therapy of small vessel occlusion to be studied.

Gradual reduction of femoral artery blood flow by 50% and 75% in unilateral hind limbs of eight sheep was achieved by slow introduction of latex microbeads (mean size = 400 microns) into the peripheral vascular bed. The other hind limb served as a control. Measurements of blood flow, subcutaneous temperature and arterial and venous blood gases were recorded in both hind limbs after each level of flow reduction. Angiography confirmed small vessel occlusion. Muscle samples were analysed for ultrastructural changes by transmission microscopy.

A linear correlation was found between the amount of microbeads infused and the reduction in the blood flow. Significant subcutaneous temperature and venous pO2 changes were observed in the embolized limb at both 50% and 25% flow levels compared to baseline (P < 0.05, ANOVA). Angiography demonstrated abrupt cut-off images of the small vessels. Transmission microscopy showed graded levels of muscle cell damage from ischaemia.

Latex microbead embolization induces reproducible controlled small artery occlusion. The degree of outflow obstruction and the extent of ischaemia can be varied by delivering measured quantities of microbeads. This model should be useful for studying the pathophysiology of ischaemia and for assessing the efficacy of treatment, especially the use of pharmacological agents.