**3. Pathophysiology of MACE related to revascularization procedure in patients with CLTI**

Almost CLTI patients need to be revascularization to salvage a functional limb and improve the quality of life [14, 35, 39]. Because the risk of perioperative MACE and other coexisting co-morbidities, some patients who indicate for limb revascularization are not candidate to perform the operation. Although, the novel medical technology including ET, medical risk optimization, the intensive care knowledge is significantly developed during the last century. The poor functional capacity and multiple co-morbidities patients are still very high risk of perioperative MACE during revascularization [3, 18, 37]. Active cardiac condition (including acute coronary syndrome including unstable angina (UA), non-ST elevation MI (NSTEMI) and

ST-elevation MI (STEMI) as well as symptomatic carotid stenosis are usually need for coronary and carotid revascularization before lower limb revascularization [3, 4, 14, 18, 35, 37, 39].

In healthy people, the systemic organs are functioning in parallel and simultaneously. The consequences of the organ functioning including (1) the stroke volume which is ejected from the heart and feeding to the various organs before entering the capillaries and venous system of the organ, (2) the arterial blood feeding each organ has the same composition, (3) the blood pressure at the entrance to each organ is the same, and (4) the blood flow to each organ can be controlled independently (local regulation of blood flow, namely, "autoregulation") [3, 41, 42]. The autoregulation is the human body physiologic response of functional hyperemia to maintain the blood flow to the vascular bed of the vital end-organ such as brain, kidney. The responsibility of the human body physiologic alteration and autoregulation after revascularization are impact to the incidence of perioperative MACE in patients with CLTI.

Physiologic changes and the autoregulation process after revascularization procedure by decreasing afterload (peripheral vascular resistance) are the burden to cardiovascular system. The cardiac reserve and response after lower limb revascularization, the anatomic distribution and severity of lower limb arterial occlusive disease as well as the type of revascularization are determining the risk of perioperative MACE [14, 37, 43].
