S .De Marchi: Ischemia and adaptation in peripheral arterial disease: the recovery through the pain. Peripheral arterial disease (PAD) is widely present in general population and increases with ageing determining progressive inability and relevant social costs, with progression to more severe ischemia . This pathology presetns also high incidence of cardiovascular morbidity and mortality. Rehabilitation with exercise prescription and comprehensive secondary prevention has great benefits in patients with PAD in order to increase walking capacity and reducing cardiovascular morbidity. In patients with PAD, the reduction in tissue perfusion generates some potential adaptation mechanisms and other mechanisms are elicited by exercise. Functional impairment in PAD is determined by several mechanisms: arterial obstruction , inflammation with platelets/leukocyte activation, endothelial activation/dysfunction, blood rehology changes, modifications in skeletal muscle phenotype (mitochondrial dysfunction). Exercise can ameliorate these mechanisms and potentially prevent clinical deterioration. Training, with specific standardized protocols, especially using supervised sessions, has documented a great efficacy in increasing walking distance also in comparison with drugs and revascularization in claudicants. Exercise programs adopted in PAD treatment has some important goals: 1) to reduce symptoms at the legs; 2) to increase walking distance and improve; and (3) to prevents cardiovascular events. Physical training with standardized protocols has added into main international guidelines for the treatment of PAD. Reduction in blood flow is the main haemodynamic parameter determining PAD symptoms. The mechanism induced in claudication is certainly an imbalance between oxygen demand and supply. However inconsistency between occlusion extension and functional impairment suggests that some other mechanisms are involved. Endothelium dysfunction plays certainly a pivotal role in determining also functional impairment: in fact, nitric oxide reduced bioavailability produces a depressed hyperemic capacity, rise in inflammation and platelets/leukocyte adhesion. PAD symptoms are also linked to mitochondrial dysfunction. In the muscles of these patients, mitochondrial function is abnormal and energy production is reduced with high reactive oxygen species generation and consequent endothelial damage. Furthermore muscle cells have increased apoptosis, reduction in capillarization and in type I fibers content. Chronic inflammation, as demonstrated by elevation of C-reactive protein, interleukin-6 and ICAM-1, enhances the risk of developing PAD. Inflammation is also associated with higher rate of progression of PAD and with major cardiovascular event rate. Exercise training has demonstrated to improve these aspects; in particular it can increase arteriogenesis and angiogenesis with vessels enlargement and remodelling, this phenomenon can be activated by a more efficient nitric oxide production and growth factors release. Exercise improves also mithocondrial function with more efficient energetic production and ameliorated peroxisome proliferator–activated receptor-gamma coactivator-1 function that can improve endothelial function and capillary growth. Training can also improve carnitine metabolism. Inflammation has positive reduction by exercise with decrease of C-reactive protein, fibrinogen, ICAM-1 and interleukin-6. Exercise prescription is crucial and different types of protocols can elicit more or less these mechanisms. Some data suggest that reaching ischemia during training can be useful in stimulating some compensatory mechanisms, but a more profound ischemia may have some negative consequences. Although this point is object of research, we should consider muscle pain during exercise (marker if ischemia) as the referring point for grading rehabilitation program in order to stimulate compensatory systems without eliciting damage.

Ischemia and adaptation in peripheral arterial disease: the recovery through the pain.

DE MARCHI, Sergio
2013

Abstract

S .De Marchi: Ischemia and adaptation in peripheral arterial disease: the recovery through the pain. Peripheral arterial disease (PAD) is widely present in general population and increases with ageing determining progressive inability and relevant social costs, with progression to more severe ischemia . This pathology presetns also high incidence of cardiovascular morbidity and mortality. Rehabilitation with exercise prescription and comprehensive secondary prevention has great benefits in patients with PAD in order to increase walking capacity and reducing cardiovascular morbidity. In patients with PAD, the reduction in tissue perfusion generates some potential adaptation mechanisms and other mechanisms are elicited by exercise. Functional impairment in PAD is determined by several mechanisms: arterial obstruction , inflammation with platelets/leukocyte activation, endothelial activation/dysfunction, blood rehology changes, modifications in skeletal muscle phenotype (mitochondrial dysfunction). Exercise can ameliorate these mechanisms and potentially prevent clinical deterioration. Training, with specific standardized protocols, especially using supervised sessions, has documented a great efficacy in increasing walking distance also in comparison with drugs and revascularization in claudicants. Exercise programs adopted in PAD treatment has some important goals: 1) to reduce symptoms at the legs; 2) to increase walking distance and improve; and (3) to prevents cardiovascular events. Physical training with standardized protocols has added into main international guidelines for the treatment of PAD. Reduction in blood flow is the main haemodynamic parameter determining PAD symptoms. The mechanism induced in claudication is certainly an imbalance between oxygen demand and supply. However inconsistency between occlusion extension and functional impairment suggests that some other mechanisms are involved. Endothelium dysfunction plays certainly a pivotal role in determining also functional impairment: in fact, nitric oxide reduced bioavailability produces a depressed hyperemic capacity, rise in inflammation and platelets/leukocyte adhesion. PAD symptoms are also linked to mitochondrial dysfunction. In the muscles of these patients, mitochondrial function is abnormal and energy production is reduced with high reactive oxygen species generation and consequent endothelial damage. Furthermore muscle cells have increased apoptosis, reduction in capillarization and in type I fibers content. Chronic inflammation, as demonstrated by elevation of C-reactive protein, interleukin-6 and ICAM-1, enhances the risk of developing PAD. Inflammation is also associated with higher rate of progression of PAD and with major cardiovascular event rate. Exercise training has demonstrated to improve these aspects; in particular it can increase arteriogenesis and angiogenesis with vessels enlargement and remodelling, this phenomenon can be activated by a more efficient nitric oxide production and growth factors release. Exercise improves also mithocondrial function with more efficient energetic production and ameliorated peroxisome proliferator–activated receptor-gamma coactivator-1 function that can improve endothelial function and capillary growth. Training can also improve carnitine metabolism. Inflammation has positive reduction by exercise with decrease of C-reactive protein, fibrinogen, ICAM-1 and interleukin-6. Exercise prescription is crucial and different types of protocols can elicit more or less these mechanisms. Some data suggest that reaching ischemia during training can be useful in stimulating some compensatory mechanisms, but a more profound ischemia may have some negative consequences. Although this point is object of research, we should consider muscle pain during exercise (marker if ischemia) as the referring point for grading rehabilitation program in order to stimulate compensatory systems without eliciting damage.
ischemia-reperfusion injury; peripheral arterial disease; physical training
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11562/638751
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