**7. The state of foot collaterals: a key principle in modern CLI wound treatment**

The TASC II recommendation [3] for prompt revascularization in CLI is generally accepted [1, 27], however, do all these interventions address similar extent of ischemic threat? Do all these interventions bear then, equivalent expectations for tissue recovery? [49] More concretely, does the modern vascular interventionist truly control all hemodynamic *macro-* and *microvascular* changes at the wound level while performing CLI revascularization? [49, 61, 97] Up-to-date research reveals that not all proven lower limb ischemic ulcers share the same TASC II/CLI criteria [3] and, consequently, harbor the corresponding amount of ischemic burden! [2, 31, 49, 61, 118, 119] Owning steady improvement in diagnostic and treatment, modern practitioners start to adapt current CLI standards to each type of arterial pathology [1, 35, 73, 107], and to resize ischemic ulcer appraisal in deeper *macro-* and *microcirculatory* perception [39, 59–61, 97, 106]. The contemporary medical community is now facing *a novel* challenge wherein specific strategies for revascularization in CLI patients *with* and *without* a convenient foot *collateral network* [92, 96–100, 119]. Thorough research in diabetic CLI treatment had already evinced good tissue cicatrization since topographic revascularization is performed in subjects having a poor collateral reserve [26, 92, 96–100, 119]. It is known that DFS currently alter common foot cutaneous, the underlying tissue and bony presentation, by iterative inflammation, scars, ischemic necrosis, sensorimotor neuropathy, and local pressure aggressions [57–60]. Even though that CLI/DFS severely distorts the "classically pictured" angiosomal foot vasculature [23–25, 96–98], *wound-targeted revascularization* using the *surviving collateral system* represents a valuable solution for better tissue regeneration [92, 96–100, 119].

Today's evidence suggests that both *macro-* and *microcirculation* evaluation should be routinely considered in each ischemic ulcer presentation toward deeper CLI understanding, as a whole limb circulatory pattern [39, 105].

### **7.1. Compensatory** *collateral systems* **relying the foot angiosomes and derived wound healing implications**

arterial branches (the "dormant" collaterals) that gradually reveal during CTO recanalization

It becomes clearer that since all tibial trunks become occluded, the tipping point between hypoxic tissue regeneration versus chronic ulceration and necrosis hinges upon *the remnant individual collateral reserve* and ways to deliberately use it in addressing the ischemic threat [24,

Despite encouraging results to date [91–93, 96], the angiosome concept may provide better, yet

Topographic WDR for ulcer healing remains an enthralling subject of discussion. Certainly, alike similar new openings of flourishing interest in tissue regeneration, the scarcer the available evidence, the acrider the current debate, mostly based on heterogeneous retrospec-

**7. The state of foot collaterals: a key principle in modern CLI wound**

The TASC II recommendation [3] for prompt revascularization in CLI is generally accepted [1, 27], however, do all these interventions address similar extent of ischemic threat? Do all these interventions bear then, equivalent expectations for tissue recovery? [49] More concretely, does the modern vascular interventionist truly control all hemodynamic *macro-* and *microvascular* changes at the wound level while performing CLI revascularization? [49, 61, 97] Up-to-date research reveals that not all proven lower limb ischemic ulcers share the same TASC II/CLI criteria [3] and, consequently, harbor the corresponding amount of ischemic burden! [2, 31, 49, 61, 118, 119] Owning steady improvement in diagnostic and treatment, modern practitioners start to adapt current CLI standards to each type of arterial pathology [1, 35, 73, 107], and to resize ischemic ulcer appraisal in deeper *macro-* and *microcirculatory* perception [39, 59–61, 97, 106]. The contemporary medical community is now facing *a novel* challenge wherein specific strategies for revascularization in CLI patients *with* and *without* a convenient foot *collateral network* [92, 96–100, 119]. Thorough research in diabetic CLI treatment had already evinced good tissue cicatrization since topographic revascularization is performed in subjects having a poor collateral reserve [26, 92, 96–100, 119]. It is known that DFS currently alter common foot cutaneous, the underlying tissue and bony presentation, by iterative inflammation, scars, ischemic necrosis, sensorimotor neuropathy, and local pressure aggressions [57–60]. Even though that CLI/DFS severely distorts the "classically pictured" angiosomal foot vasculature [23–25, 96–98], *wound-targeted revascularization* using the *surviving collateral system* represents a

Today's evidence suggests that both *macro-* and *microcirculation* evaluation should be routinely considered in each ischemic ulcer presentation toward deeper CLI understanding, as a whole

not complete, ischemic tissue control [35, 61, 72, 118].

valuable solution for better tissue regeneration [92, 96–100, 119].

limb circulatory pattern [39, 105].

tive deliberations [35, 72, 92, 96–98, 118].

264 Wound Healing - New insights into Ancient Challenges

[24, 35, 56].

30, 34, 59].

**treatment**

An impressive compensatory collateral network interconnecting neighboring foot and ankle angiosomes was thoroughly documented by previous publications [23, 24, 101, 102], available as to counterbalance any possible ischemic threat [23, 24, 98].

The central *arterial-arterial* communicants relying upon different leg angiosomes encompass numerous *small* to *large* collaterals (the above-described *levels III and IV*), beyond the arterioles (*level V)* in a sequential model of perfusion [35, 101]. Numerous "large" foot collaterals hold particular importance in supplying adjacent angiosomes [24, 39, 118]. They also seem to play a pivotal role in intentional "wound-directed" revascularization and appropriate tissue regeneration [35, 96–98, 118]. These vessels assemble the *foot arches*, (acknowledging eventual 5–9% anatomical variations, Section 6.3) [108–114], the *metatarsal perforators*, the anterior *communicants*, and other sizable *arterial-arterial* branches such as the dorsal foot-to-plantar, or the peroneal-to-posterior tibial *rescue* heel collaterals (*level III* of perfusion) [35, 101].

In the same design, yet with narrow compensatory significance (Section 6.3), the *medium-* and *small*-sized muscular collateral arteries (*level IV*) [35] and *the arterioles* (*level V*), also contribute in vital tissue flow preservation [103, 105, 106]. These "rescue" connections were also implicated in the "initiatory" phase of revascularization (Section 4.1) [35, 105] and actively partake throughout the vast "choke vessels" salvage system [23, 24], before or during the angio- and arteriogenesis processes [104–106]. Regardless individual variations, the following groups of arterial-arterial collateral connections were appointed in CLI flow compensation [24, 35, 39, 102, 118]:


All these briefly schematized *arterial-arterial* communications constitute but a small part of the whole natural foot compensatory system against ischemic aggression [23, 24, 35]. Although severely compromised in distinct CLI categories of patients (diabetes, ESRD, and inflammatory arteritis) [59–61, 104], all these "rescue branches" [35, 59, 101, 102] or "choke-vessels" [23, 24] provide noticeable flow assistance during miscellaneous ischemic injuries. Their appropriate evaluation affords valuable diagnostic and therapeutic knowledge for better tissue preservation and limb salvage [39, 56–59].

In this exhaustive "regional view" of ischemic tissue perfusion, albeit more precise than blunt angiographic assessment (Section 4.5), it appears that *not all foot areas may express similar ischemic affliction* [59–61, 104]. Even more surprisingly, the ulcer's area could not always stand for the lowest perfusion point in the ischemic limb, since severe neuropathy, inflammatory swelling, sepsis, and local skin trauma may add complementary hindrance to main CLI threat [26, 27, 31, 33].

Future diagnostic tools focusing on *superficial* and *deep* tissue "wound-oriented" arterial flow may eventually complete this unique holistic view of the neuro-ischemic diabetic foot [33, 39, 53, 59].

We know today that diabetic and renal CLI patients express serious tissue regeneration handicap, inflicted by specific infragenicular arterial collateral depletion [29–31]. This significant decay in tissue regeneration also appears proportionate with the *type* and *time* of ischemic suffering [1, 2, 27, 30, 59]. In this perspective, recent researchers advise reasonable adaptation of current revascularization indications upon individual *macro* [3, 41] and *microvascular* CLI characteristics [29–31, 39], weighted in patients *with* and *without* available collateral reserve [29, 39, 59].
