ISSN:0894-1939    

DOI:10.3109/08941939409018277

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

In recent years, considerable research efforts have been directed at elucidating the mechanisms underlying the pathophysiologic alterations associated with reperfusion (reoxygenation) of ischemic (hypoxic) skeletal muscle. This intensive effort has led to the accumulation of a large body of evidence supporting the concept that reactive oxygen metabolites, generated at the onset of reperfusion, initiate the formation and release of proinflammatory agents, which subsequently attract and activate granulocytes. The activated neutrophils adhere to the microvascular endothelium, extravasate, and release cytotoxic oxidants and hydrolytic enzymes. As a consequence of these pathologic events, vascular permeability and transcapillary fluid filtration are increased and the no-reflow phenomenon (ie, some capillaries fail to reperfuse upon reinstitution of blood flow) becomes apparent. These microvascular alterations may be of considerable functional importance since the marked accumulation of fluid in the interstitial spaces, coupled with the incomplete and maldistributed blood flow, increases the functional diffusion path length for nutrients. Thus cellular nutrition is limited during reperfusion. which in turn impairs the functional recovery of postischemic muscles. Moreover, the infiltrating neutrophils are able to direct a focussed attack on myocytes, thereby exacerbating contractile dysfunction and tissue injury during reperfusion. These observations indicate that alterations in the microcirculation play a critical role in the genesis of ischemia/reperfusion injury in skeletal muscle. This review summarizes the evidence we have accumulated in support of the view that reactive oxygen metabolites and neutrophils contribute to production of postischemic microvascular dysfunction and describes the experimental models we have used to examine the mechanisms involved in the pathogenesis of ischemia and reperfusion.

ISSN:0894-1939    

DOI:10.3109/08941939409018278

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

The bilateral canine gracilis muscle has been studied as a model of acute skeletal muscle ischemia. Early investigations demonstrated that preparation of the model did not alter the energy profile of the muscle. Changes in energy metabolism during ischemia and after reperfusion have been extensively investigated using this model. Further investigations are reviewed that have explored the mechanisms of injury during reperfusion, including oxygen free radical production, calcium influx, neutrophil infiltration, and complement activation. These experiments have furthered our understanding of the pathophysiologic changes that occur in skeletal muscle afer ischemia and laid the groundwork for future experiments to reduce reperfusion injury and salvage ischemic skeletal muscle.

ISSN:0894-1939    

DOI:10.3109/08941939409018279

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Animal models of skeletal muscle ischemia-reperfusion injury have led to a better understanding of the pathophysiology of this condition and are necessary, for the evaluation of potential therapeutics. This study presents a new, well-controlled model of ischemia-reperfusion that more accurately simulates acute arterial occlusions in humans. In rabbits, a whole hindlimb is rendered reversibly ischemic by occlusion of primary and collateral arterial inflow and then reperfused for an extended period of 48 h. Ischemic injuries are standardized by defining and controlling ischemic time, limb temperature, and the extent of collateral circulation. We have characterized this model by measuring anterior tibial and soleus muscle necrosis and edema formation in groups of animals subjected 10 4 h of ischemia at either 32 or 36°C, with one of two extents of collateralization and with or without muscle compartment release (fasciotomy). Our results indicate the following: (1) muscle necrosis is significantly worsened by restricting the extent of collateral blood supply or by elevating ischemic temperature; (2) anterior tibial muscle is inherently more sensitive than soleus muscle to ischemic injury; (3) fasciotomy may reduce muscle necrosis by more than 50%; and (4) the amount of’edema present in muscles is an unreliable indicator of actual muscle necrosis. We conclude that this new model is a practical, well-controlled, and clinically relevant preparation useful, for the investigation of ischemic muscle injury.

ISSN:0894-1939    

DOI:10.3109/08941939409018280

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Ischemia-reperfusion injury remains a difficult problem facing vascular surgeons because of its associated high morbidity and mortality. The basis for tissue injury during ischemia depends on depletion of tissue oxygen and energy substrates. Cell injury, as documented cellular edema and lysosomal degranulation, begins after only 30 min of ischemia. Irreversible cellular changes occur after 4–6 h of skeletal muscle ischemia. Following acute arterial occlusion, the restoration of blood flow heralds the onset of biochemical events, forming the basis of what is known as the reperfusion syndrome. This tissue injury is maximal in areas with the greatest blood flow during reperfusion. Endothelium-leukocyte interactions play an important role in ischemia-reperfusion injury. Both endothelial and white blood cells have the biochemical machinery and capacity to generate molecular signals, to express adhesion proteins, and to produce toxic metabolic by-products. Since the microcirculatory changes in ischemia-reperfusion injury parallel those seen in inflammation, the leukocyte-endothelial interaction can explain many of the reactions associated with the early phases of ischemia-reperfusion injury.

ISSN:0894-1939    

DOI:10.3109/08941939409018281

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

The study of new approaches for the treatment of limb-threatening ischemia has been hampered by the lack of a suitable animal model of persistent limb ischemia. We describe the development and evaluation of an animal model of persistent hindlimb ischemia, in which ischemia WNS induced in the left hindlimb of 28 rabbits by ligation of the distal external iliac artery arid excision of the common and superficial femoral arteries. The severity of the ischemia and its relief in each animal were evaluated every 10 days postoperatively until day 40 (all animals) or day 90 (five animals). Nine minds developed superficial tissue necrosis in the foot, but no deaths were attributable to the ischemia-inducing procedure. Angiography demonstrated minimal collateralization and sluggish filling of distal vessels up to postoperative day 90. This was accompanied by a decrease at rest in the raw blood flow ratio (p<0.005 vs day 0), an increase in lactic acid in the femoral venous blood (left vs right side, p<0.002) up to postoperative day 40, and a decrease in the calf blood pressure ratio (p<0.0001 vs day 0) up to day 90. Histologic study of the gastrocnemius muscle demonstrated evidence of atrophy und fibrosis in the left hindlimb. This model can be used to evaluate direct and indirect approaches to the treatment of chronic limb ischemia.

ISSN:0894-1939    

DOI:10.3109/08941939409018282

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Revascularization after prolonged complete limb ischemia may result in severe damage to skeletal muscle and systemic alterations (postischemic syndrome). Our previous experimental studies have shown that this injury can be reduced substantially by treating the jeopardized extremity by controlling the conditions of reperfusion and composition of the initial reperfusate. In the present study this concept of controlled limb reperfusion was applied in patients with prolonged severe limb ischemia, Controlled limb reperfusion was used in 14 patients after prolonged complete uni- or bilateral ischemia. The ischemic interval ranged from 5 to 21 h. Two patients were in cardiogenic shock, 11 had associated cardiac disease, and seven coexistent peripheral vascular disease. After systemic heparinization, standard thromboembolectomy was done using N Fogarty catheter. Cannulas were placed into the iliac, profunda, and superficial femoral arteries and were connected to a reperfusion set. Oxygenated blood was drawn from the iliac artery and mixed with an asanguineous solution (ratio 6:1). This controlled reperfusate was delivered into the profunda and superficial femoral arteries using a single rollerpump. The system allows control of the composition of the reperfusate (calcium, pH, osmolarity, glucose, substrate, pO2, free radical scavengers) and the conditions of reperfusion (pressure, flow, temperature). After 30 min of controlled limb reperfusion, the cannulas were removed and normal blood reperfusion started. All 12 patients who were stable hemodynamically before the operation survived the revascularization. Eleven patients, including one with acute aortic occlusion for several hours, were discharged with functional recovery of their extremities. Despite the severe ischemic insult, controlled limb reperfusion avoided amputation and profound systemic complications. Two patients who were in cardiogenic shock preoperatively died from progressive cardiac failure. We conclude that controlled arterioarterial limb reperfusion may reduce the local manifestations of the postischemic syndrome after prolonged periods of ischemia, may salvage limbs thought previously to be damaged irreversibly by prolonged ischemia, and can be done easily in the operating room.

ISSN:0894-1939    

DOI:10.3109/08941939409018283

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0894-1939    

DOI:10.3109/08941939409018276

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor