Abstract: BACKGROUND: Preliminary work applied extracorporeal circulation and pressurized perfusion to treat ischemic lesions. While establishing lower extremity collateral circulation, it also improved the distal microcirculation of the extremities by increasing the blood perfusion volume of the lower extremities. This technique has achieved good clinical results.  
OBJECTIVE: To explain the principle of extracorporeal circulation compression perfusion in the reconstruction of limb microcirculation from the mechanism of mechanical and chemical signal transduction by designing an animal model of diabetes with peripheral arterial disease.
METHODS:  The models of diabetes mellitus complicated with peripheral arterial disease were established in 24 Bama miniature pigs and were randomly divided into four groups (n=6): blank control group, model group, extracorporeal circulation perfusion group (close to normal limb mean arterial pressure perfusion) (normobaric perfusion group), and extracorporeal circulation compression perfusion group (twice mean arterial pressure perfusion) (compression perfusion group). The limb blood flow of the four groups of experimental animals was measured at six time points: successful establishment of the model, 30 minutes of perfusion, 1 hour of perfusion, 2 hours of perfusion, 5 hours of perfusion, and 7 hours of perfusion. Arterial blood samples of experimental animals were taken to detect the contents of interleukin-8, nitric oxide and endothelin-1 by enzyme-linked immunosorbent assay. Two weeks after the end of the experiment, the tibialis anterior muscle of the right hindlimb was stained with hematoxylin and eosin to observe the capillary density. The tibialis anterior muscle of the right hindlimb was taken from the right hindlimb, and the relative expression of vascular endothelial growth factor A/ vascular endothelial growth factor receptor 2 protein was detected by western blot assay.  
RESULTS AND CONCLUSION: (1) The skin blood flow of the compression perfusion group was significantly higher than that of other three groups after 7 hours of perfusion (P < 0.05). The serum nitric oxide level in compression perfusion group was significantly higher than that in the other three groups (P < 0.05). The serum endothelin-1 value in compression perfusion group was significantly higher than that in the model group, lower than that in blank control group and normal pressure perfusion group (P < 0.05). The serum interleukin-8 level in compression perfusion group was higher than that in the model group and lower than that in the blank control group and normal pressure perfusion group, and the difference was statistically significant (P < 0.05). (2) Two weeks after the end of the experiment, pathological examination showed that the microvessel density count of tibialis anterior muscle tissue in compression perfusion group (18.33±1.51)/mm2 was significantly higher than that in the other three groups (P < 0.05). The relative expression of vascular endothelial growth factor A/ vascular endothelial growth factor receptor 2 protein in the tibialis anterior muscle tissue in the compression perfusion group was significantly higher than that in the other three groups (P < 0.05). (3) By increasing the perfusion compression and increasing the shear force of blood flow to vascular endothelial cells, the shear force acted as a mechanical stimulation signal to initiate complex mechanical and chemical signal transduction so as to promote the formation of collateral circulation, thereby effectively improving microcirculation.

Key words: diabetes mellitus complicated with peripheral arterial disease, extracorporeal circulation compression perfusion, microcirculation, shear force, capillaries