*4.1.2. At the capillary level*

The posthypoxic recovery of an organ depends on the quality of its microcirculation and the re‐ sultant nutrient delivery and gaseous exchange. However, the microcirculation is the site of a paradoxical phenomenon called "no reflow", characterized by a major reduction in the capilla‐ ry density. Despite the reestablishment of complete blood flow, an incomplete and heterogene‐ ous perfusion of microcirculation persists. [85],[86] The capillaries are blocked by the parenchymatous and endothelial edema and the adhesion of the neutrophils and platelets to the surface of the endothelium, aided by the reduction in the production of nitric oxide. [15],[81], [85]-[87] Increased ROS and the depletion of ATP modify the cytoskeleton and the intercellular junctions, contributing to the loss of liquid from the vascular bed towards the interstitium. [88], [89] The phenomenon of no reflow persists several weeks after reperfusion. [85]

#### *4.1.3. At the postcapillary vein level*

The postcapillary veins are the sites of the inflammatory reaction. The margination and ex‐ travasation of the leukocytes are facilitated by the slower blood flow. Venous blood, arriving from the reperfused zones, is rich in proinflammatory mediators and activated neutrophils. These cause lesions both directly and indirectly through their interactions with platelets. [15],[90] Endothelial lesions prevent the intravascular oncotic pressure from recovering the excess liquid from the interstitium, thereby increasing the edema and contributing to the phenomenon of "no reflow".

### **4.2. Organs**

In pulmonary transplantation surgery, I/R-induced lung injury is characterized by non‐ specific alveolar damage, lung edema and hypoxemia. The most severe form may lead to primary graft failure and remains a significant cause of morbidity and mortality after lung transplantation.[91] Pulmonary microvascular permeability appears to have a bimo‐ dal pattern, peaking at 30 min and 4 h after reperfusion. [92] Mechanical ventilation, car‐ diopulmonary bypass during cardiac surgery and lung resection can also induce apoptosis and I/R-induced lung injury. [93]-[96]

**Author details**

**References**

Mont Godinne, Belgium

361: 1570-83

Maximilien Gourdin and Philippe Dubois\*

Nat Med 2011 17: 1391-401

Circ Physiol 2004; 287: H340-50

ol Pharmacol 1998; 76: 35-45

rats. Mech Ageing Dev 2002; 123: 275-85

teries. Circulation 1990; 82: 586-94

Am J Physiol Heart Circ Physiol 2007; 293: H3014-9

Department of Anaesthesiology, Université Catholique de Louvain, University Hospital of

Inflammation and Vasomotricity During Reperfusion

http://dx.doi.org/10.5772/54508

27

[1] Eltzschig HK, Eckle T: Ischemia and reperfusion--from mechanism to translation.

[2] Berthonneche C, Sulpice T, Boucher F, Gouraud L, de Leiris J, O'Connor SE, Herbert JM, Janiak P: New insights into the pathological role of TNF-alpha in early cardiac dysfunction and subsequent heart failure after infarction in rats. Am J Physiol Heart

[3] Hotchkiss RS, Strasser A, McDunn JE, Swanson PE: Cell death. N Engl J Med 2009;

[4] Moro C, Jouan MG, Rakotovao A, Toufektsian MC, Ormezzano O, Nagy N, Tosaki A, de Leiris J, Boucher F: Delayed expression of cytokines after reperfused myocar‐ dial infarction: possible trigger for cardiac dysfunction and ventricular remodeling.

[5] Garcia SC, Pomblum V, Gams E, Langenbach MR, Schipke JD: Independency of my‐ ocardial stunning of endothelial stunning? Basic Res Cardiol 2007; 102: 359-67

[6] Lefer AM, Tsao PS, Lefer DJ, Ma XL: Role of endothelial dysfunction in the patho‐ genesis of reperfusion injury after myocardial ischemia. Faseb J 1991; 5: 2029-34

[7] Qi XL, Nguyen TL, Andries L, Sys SU, Rouleau JL: Vascular endothelial dysfunction contributes to myocardial depression in ischemia-reperfusion in the rat. Can J Physi‐

[8] Besse S, Tanguy S, Boucher F, Bulteau AL, Riou B, de Leiris J, Swynghedauw B: Aort‐ ic vasoreactivity during prolonged hypoxia and hypoxia-reoxygenation in senescent

[9] Piana RN, Wang SY, Friedman M, Sellke FW: Angiotensin-converting enzyme inhibi‐ tion preserves endothelium-dependent coronary microvascular responses during

[10] Quillen JE, Sellke FW, Brooks LA, Harrison DG: Ischemia-reperfusion impairs endo‐ thelium-dependent relaxation of coronary microvessels but does not affect large ar‐

short-term ischemia-reperfusion. Circulation 1996; 93: 544-51

Perioperative acute renal failure is associated with a high incidence of morbidity and mortality. According to the type of surgery, IR injuries in the kidney are direct or indi‐ rect. [97] For example, acute renal failure is the most important complication of remote tissue damage following abdominal aortic surgery. [98] I/R induces renal tubular injuries and contributes to the decrease of glomerular filtration. Recent data suggest that 13% of patients with acute kidney injury (AKI) evolve to end-stage renal disease within 3 years. In the case of patients with preexisting renal disease, the progression to end-stage renal disease rises to 28% within the same period. [98] These results suggest that AKI predis‐ poses to chronic renal complication. I/R reduces blood vessel density and promotes renal fibrosis. The mechanisms mediating vascular loss are not clear but may be related to the lack of effective vascular repair responses. [99]

In cardiac surgery and in myocardial ischemia, cell death following I/R has features of apoptosis and necrosis. The loss of cardiomyocytes, which can hibernate in "no reflow" zones, and stunning, led by free radicals and calcium overload, explain the contractile posthypoxic dysfunction. The stunned cardiomyocytes can take several hours and days to recover. Intracellular ionic perturbation favors ventricular arrhythmias, such as ventricular fibrillation, ventricular tachycardia or ventricular extrasystole. [10 ]0 During ischemia, cardiomyocytes express ICAM-1. Neutrophils bind to this receptor and empty the contents of their granules onto the cells. [54],[55]

The mechanisms of I/R-induced brain injury have many similar aspects compared with those of I/R-induced myocardial injury. Many mediators and cytokines upregulated by I/R, such as bradykinin, purine nucleotides, nitric oxide and ROS, increase blood–brain barrier permea‐ bility and induce cerebral edema. [10 ]1 Although leukocyte infiltration into the ischemic brain increases cerebral damage, leukocyte accumulation in the microcirculation reduces reperfu‐ sion and increases the "no reflow" phenomenon.

The indirect repercussions of I/R on organs remote from the reperfused site are much more insidious. Neutrophils, complement activation, and massive production of cytokines and chemokines install a proinflammatory state that affects the functioning of other organs. During abdominal aortic surgery, I/R injuries are not only limited to the lower extremities but also cause damage to remote organs such as the lungs, kidneys, heart and bowel. [36],[97],[102- [104] Lung injuries following abdominal aortic aneurysm surgery are characterized by progressive hypoxemia, pulmonary hypertension, decreased lung compliance and nonhydro‐ static pulmonary edema, consistent with adult respiratory distress syndrome. [36],[103] In comparison with surgery, endovascular abdominal aortic aneurysm repair decreases I/R and I/R-induced-intestinal mucosal, renal and pulmonary dysfunction. [104]
