Plasma activation of neutrophil CD18 after skeletal muscle ischemia: a potential mechanism for late systemic injury.

Reperfusion of acutely ischemic skeletal muscle is associated with neutrophil activation, which may augment local injury or cause damage to distant organs. Polymorphonuclear neutrophil glycoprotein CD18 plays a role in this injury, since its blockade substantially reduces damage; however, its mechanisms of control during reperfusion are poorly understood. The purpose of this study was to investigate the importance of circulating plasma factors to CD18-dependent neutrophil function during reperfusion and to relate these to quantitative expression of CD18. Eight rabbits were subjected to hindlimb ischemia for 5 h, followed by 48 h of reperfusion. Plasma collected at seven intervals was incubated with unstimulated neutrophils from uninjured rabbits. CD18-specific neutrophil activation was evaluated by quantifying adherence to protein-coated polystyrene and by measuring oxidant production, detected by chemiluminescence after exposure to complement-opsonized zymosan. CD18 was quantified cytofluorometrically. Plasma collected at end ischemia and during early reperfusion affected no significant alterations of adhesion, oxidant production, or CD18. Late reperfusion plasma (between 8 and 48 h) significantly increased adherence and oxidant production (to 4.11 +/- 0.61 and 2.60 +/- 0.32 times the values of preischemic plasma, P < 0.006). Peak adherence, oxidant production, and CD18 expression were evoked synchronously by 24 h plasma. CD18 expression increased only at 24 h and did not increase proportional to increases in adherence and oxidant production. Control plasma (nonischemic, n = 5) elicited no significant differences of any inflammatory measure during sham ischemia or reperfusion. These results indicate that endogenous mediators may evoke a progressive systemic inflammatory response after ischemia by stimulating CD18-dependent neutrophil function in a delayed but prolonged manner.

Determinants of ischemic injury to skeletal muscle.

PURPOSE: Ischemic injuries to the lower extremity are often graded in severity according to their duration. Other determinants may also influence the extent of an injury, however, and may be equally significant contributors to the final outcome. The purpose of this study was to compare the relative influences of ischemic time, temperature, residual blood flow, muscle location, and fiber type on postischemic necrosis in a rabbit model of skeletal muscle ischemia-reperfusion injury. METHODS: Animals' hindlimbs were rendered ischemic under differing conditions of each determinant and then reperfused for 48 hours. Necrosis in the rectus femoris, semimembranosus, anterior tibial, and soleus muscles was determined by nitroblue tetrazolium staining and computerized planimetry. The severity of each animal's injury was quantified by calculating the cumulative percentage of necrosis by weight of all muscles excised from the ischemic limb. RESULTS: Four hours of ischemia at room temperature resulted in an average of 21% +/- 7% necrosis. Lengthening the ischemic interval to 5 hours increased necrosis to 61% +/- 4% (p < 0.01 vs 4 hours); however injuries were equally or more significantly influenced by changes in ischemic temperature or small changes in ischemic limb residual (collateral) blood flow. The most severe injuries of any encountered were observed when limbs were maintained at body temperature during ischemia (92% +/- 9% necrosis after 5 hours of ischemia, p < 0.01 vs room temperature ischemia), whereas extremely small improvements in ischemic period residual flow (by allowing pelvic collateral cross-flow during ischemia) resulted in significant salvage in all muscles studied. Muscles predominating in fast-twitch fibers had significantly greater necrosis than did those richer in slow-twitch fibers; this difference was apparent only after longer periods (5 hours) of ischemia. Thigh muscles sustained significantly greater injuries than did distal hindlimb muscles, except in animals subjected to body temperature ischemia, where the distribution of necrosis was uniform. CONCLUSIONS: The results of this study indicate that muscle necrosis accompanying an ischemic event can be significantly influenced by numerous determinants in addition to ischemic time, each of which warrants careful clinical scrutiny when appraising the extent of an injury.

A clinically relevant small-animal model of skeletal muscle ischemia-reperfusion injury.

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 to 4 h of ischemia at either 32 or 36 degrees 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.

Salvage of postischemic skeletal muscle by monoclonal antibody blockade of neutrophil adhesion molecule CD18.

Reperfusion of ischemic skeletal muscle is associated with neutrophil (PMN) adherence to damaged endothelium and PMN-mediated tissue destruction. Neutrophils may attach to endothelium through surface adhesive molecules, such as CD18. The purpose of this study was to determine whether monoclonal antibody blockade of CD18 would reduce skeletal muscle necrosis associated with ischemia and reperfusion. In rabbits, an entire hindlimb was rendered ischemic for 4 hr, followed by 48 hr of in vivo reperfusion. Animals were allocated to one of five treatment groups: ischemia/reperfusion without treatment (I/R controls), I/R plus treatment with the anti-CD18 antibody IB4 (end-ischemic 2 mg/kg dose), I/R plus treatment with an identical dose of isotype-matched control Ig, I/R plus anterior compartment fasciotomy, or I/R plus both IB4 and fasciotomy. After 48 hr of reperfusion anterior tibial muscle necrosis was assessed (by tetrazolium staining and computerized planimetry), wet:dry muscle weights (W:D) were determined, and muscle PMN sequestration was measured by myeloperoxidase (MPO) activity. IB4-treated animals exhibited markedly reduced muscle MPO activity, compared to untreated animals. Although all interventions reduced edema formation (W:D ratios), none did so significantly. IB4 treatment reduced muscle necrosis when used alone (to 28 +/- 7%, vs. 48% +/- 6% in untreated controls), however this was not statistically significant (P = 0.06).2+ Fasciotomy significantly reduced necrosis (to 22 +/- 2%, P < 0.05); however, the addition of IB4 to fasciotomy resulted in necrosis that was significantly lower than that after fasciotomy alone (12 +/- 4%, P < 0.05 vs fasciotomy group) and the least necrosis of any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Sartorius myoplasty in the treatment of exposed arterial grafts.

The long-term success of sartorius myoplasty in 14 of 16 patients who presented with an exposed vascular graft in an infected groin is described. The presenting complications were wound dehiscence (ten patients), hemorrhage (two), skin erosion (two), late bilateral fistulas (one) and false aneurysm (one). Ten grafts were prosthetic and six autogenous. Positive cultures were obtained from 15 wounds; four grew Staphylococcus epidermidis, the remainder mixed or Gram-negative bacteria. Each groin was radically debrided, including the surface of the arterial graft, and, if possible, closed immediately with a sartorius myoplasty applied directly to the graft. Twist, fan and loop myoplasties were equally effective. Grossly infected wounds were debrided initially and obviously infected grafts were replaced in situ before myoplasty. Sartorius myoplasty is recommended as an elegant solution for the infected groin in which there is an exposed arterial graft.

Sartorius myoplasty for deep groin wounds following vascular reconstruction.

Groin wound infections following vascular reconstructive surgery prolong hospital admission and convalescence and may lead to more serious morbidity with prosthetic graft infection, false aneurysm formation, or hemorrhage. Therefore, it is imperative to achieve wound closure as expeditiously as possible. Herein, we describe 11 patients with complicated groin wounds and report our management using sartorius myoplasty. Five of these patients had underlying prosthetic grafts at risk. All patients underwent wound closure with sartorius myoplasty after adequate debridement of necrotic and infected soft tissue. Success of wound closure with complete primary healing was observed in nine patients, while in two, adequate early coverage of femoral vessels was achieved, but extended wound care for superficial skin separation was necessary with eventual complete healing. There was no morbidity or mortality related to the added surgical procedure. One patient underwent late repair of a femoral false aneurysm. There were no other complications seen after an average follow-up of 20 months (range: 6 to 49 months). In summary, we recommend that sartorius myoplasty be considered for wound infections to hasten groin closure, decrease hospital stay, and reduce the chance of infectious complications.