Internal Iliac Aneurysm Repair Outcomes Using a Modification of the Iliac Branch Graft.

OBJECTIVES: Iliac branch grafts (IBGs) are a validated option for the treatment of aorto-iliac aneurysms preserving internal iliac artery (IIA) flow. IIA aneurysm (IIAA) is a relative contraindication to IBG placement. The goal of this study was to review experience in managing aorto-iliac aneurysms with concomitant IIAAs with extension of the IIA branch stent graft into the superior gluteal artery (SGA). METHODS: This retrospective study between May 2009 and November 2014 includes consecutive patients who underwent placement of an IBG (Cook, Bloomington, IN, USA) with extension of the internal iliac component of the branch stent graft into the SGA because of aneurysmal IIA (>15 mm). The stent grafts used were Viabahn (Gore, Karlsruhe, Germany), Fluency (Bard, Flagstaff, AZ, USA), or iCast (Atrium, Hudson, NH, USA) proximally. Imaging follow up was with computed tomography angiography (CTA) within 30 days of device insertion and then annually. RESULTS: The procedure was performed on 15 patients with a mean age of 76.8 years (SD 6.1 years). Twenty IIAAs were treated with a mean IIA and common iliac artery (CIA) diameter of 33 mm (SD 13 mm) and 35 mm (SD 11 mm) respectively. Technical success rate was 100%. One patient who underwent simultaneous IBG and three vessel fenestrated endovascular aneurysm repair died of mesenteric ischemia 2 days after the procedure. Mean imaging follow up with CTA was 18.3 months (SD 15.1 months). Primary patency of the SGA stent grafts was 100%. There was one case of type II endoleak. All patients were free from buttock claudication at follow up (mean: 19.7 months). Two patients who had IIA embolization contralateral to the IBG placement suffered from unilateral lower limb monoparesis. CONCLUSIONS: Extension of the internal iliac component of IBGs into the SGA for distal seal is feasible and safe in the endovascular treatment of aorto-iliac aneurysms with concomitant IIAs. Long-term results are needed to further validate this technique.

Two cases of arteriovenous fistula formation between the external iliac vessels following endovenous laser therapy.

Minimally invasive treatment of varicose veins is becoming increasingly popular with both patients and physicians. Endovenous laser therapy has been shown to be safe and effective but the rare complication of iatrogenic creation of arteriovenous fistulas has been described. One case of fistulation between the external iliac artery and vein has been published. We report two further cases and describe their management.

Anomalous splenic artery aneurysm.

Aneurysms of the splenic artery are the most common visceral aneurysm. A splenomesenteric trunk, which involves the splenic artery arising from the superior mesenteric artery (SMA), is rare and occurs in less than 1% of patients. Thus splenic artery aneurysms (SAAs) with an anomalous origin from the SMA are quite rare. We report our experience with the surgical management of a 2.6-cm aneurysm involving a splenic artery arising from the SMA in a 40-year-old woman. This was treated with surgical resection with preservation of the spleen. A discussion about SAAs and the management of aneurysms arising from a splenomesenteric trunk follows.

Anomalous splenic artery aneurysm.

Aneurysms of the splenic artery are the most common visceral aneurysm. A splenomesenteric trunk, which involves the splenic artery arising from the superior mesenteric artery (SMA), is rare and occurs in less than 1% of patients. Thus splenic artery aneurysms (SAAs) with an anomalous origin from the SMA are quite rare. We report our experience with the surgical management of a 2.6-cm aneurysm involving a splenic artery arising from the SMA in a 40-year-old woman. This was treated with surgical resection with preservation of the spleen. A discussion about SAAs and the management of aneurysms arising from a splenomesenteric trunk follows.

Endovascular ruptured abdominal aortic aneurysm repair--setting up your hospital for an endovascular approach.

In recent years, major improvements have been made, making elective repair of abdominal aortic aneurysm (AAA) a safe procedure. In selected series, mortality rates are less than 5%. Many of the patients with AAA, however, remain asymptomatic until they present with rupture. Once rupture has occurred, the overall mortality approaches 90%. Despite many advances in the management of ruptured AAA, the mortality rate of conventional open surgery has not improved significantly during the last 15 years. Over the last decade, endovascular techniques have been used increasingly to repair AAA, and there is increasing evidence that endovascular aneurysm repair (EVAR) is technically feasible and safe for ruptured AAA. This review studies the evidence and aids the clinician in setting up a practice to manage rAAAs utilizing an endovascular approach.

C5 complement inhibition attenuates shock and acute lung injury in an experimental model of ruptured abdominal aortic aneurysm.

BACKGROUND: Ruptured abdominal aortic aneurysm (RAAA) is associated with a systemic inflammatory response syndrome and multiple organ dysfunction. The potential role of a novel C5 complement inhibitor in attenuation of pathological complement activation and tissue injury was explored in a model of RAAA. METHODS: Anaesthetized rats were randomized to sham (control) or shock and clamp (SC) groups. Animals in the SC group underwent 1 h of haemorrhagic shock (mean arterial pressure 50 mmHg or less), 45 min of supramesenteric aortic clamping and 2 h of reperfusion. They were randomized to receive an intravenous bolus of a functionally blocking anti-C5 monoclonal antibody (C5 inhibitor), at a dose of 20 mg/kg, or saline. Lung injury was assessed by permeability to 125I-labelled albumin, tissue myeloperoxidase (MPO) activity, and semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for mRNAs encoding tumour necrosis factor (TNF) alpha and interleukin (IL) 6. RESULTS: The lung permeability index was significantly increased in the SC compared with the sham group (P = 0.032); this was prevented by the C5 inhibitor (P = 0.015). Lung MPO activity was significantly increased in the SC compared with the sham group (P < 0.001), and this increase was attenuated by treatment with the C5 inhibitor (P < 0.001). Semiquantitative RT-PCR in SC group demonstrated downregulation of TNF-alpha mRNA (P = 0.050) and upregulation of IL-6 mRNA (P < 0.001), which were both prevented by the C5 inhibitor (P = 0.014 and P < 0.001 respectively). CONCLUSION: These results indicated that C5 complement inhibition can reduce shock and acute lung injury in an experimental model of RAAA.

Aortic and iliac reconstruction after kidney transplantation: experience with an algorithm for renal protection.

Advances in renal transplantation have allowed for improved survival and an increased age of recipients. This has resulted in more aortoiliac lesions requiring intervention. The optimal approach for renal protection during aortoiliac surgery remains unknown. A retrospective review of transplant patients admitted to Toronto General Hospital for aortoiliac reconstruction between 1990 and 2000 was performed. A total of 20 aortic reconstructions were carried out in 18 patients: 5 patients with ascending aortic repairs and 15 patients with aortoiliac reconstructions. Of the five ascending repairs, all had cardiopulmonary bypass and four were performed under hypothermic arrest. There was one allograft loss in the postoperative period and one mortality. Of the 15 aortoiliac reconstructions 12 had protection: 10 temporary axillofemoral artery bypasses and 2 renal cold perfusion. In the 10 patients with temporary bypass protection, there were no graft losses. There was no graft loss in the hypothermic perfusion group. Of the three patients without protection, there was one graft loss. The postoperative rise in serum creatinine was significantly higher (p <0.05) in the no-protection group than in those receiving temporary bypass protection. Our algorithm of (1). temporary axillofemoral bypass, (2). cold perfusion if temporary bypass cannot be performed, and (3). clamp and sew if the patient is too unstable allows for surgery with excellent graft survival.

p38 MAPK regulates group IIa phospholipase A2 expression in interleukin-1beta -stimulated rat neonatal cardiomyocytes.

Group IIa phospholipase A(2) (GIIa PLA(2)) is released by some cells in response to interleukin-1beta. The purpose of this study was to determine whether interleukin-1beta would stimulate the synthesis and release of GIIa PLA(2) from cardiomyocytes, and to define the role of p38 MAPK and cytosolic PLA(2) in the regulation of this process. Whereas GIIa PLA(2) mRNA was not identified in untreated cells, exposure to interleukin-1beta resulted in the sustained expression of GIIa PLA(2) mRNA. Interleukin-1beta also stimulated a progressive increase in cellular and extracellular GIIa PLA(2) protein levels and increased extracellular PLA(2) activity 70-fold. In addition, interleukin-1beta stimulated the p38 MAPK-dependent activation of the downstream MAPK-activated protein kinase, MAPKAP-K2. Treatment with the p38 MAPK inhibitor, SB202190, decreased interleukin-1beta stimulated MAPKAP-K2 activity, GIIa PLA(2) mRNA expression, GIIa PLA(2) protein synthesis, and the release of extracellular PLA(2) activity. Infection with an adenovirus encoding a constitutively active form of MKK6, MKK6(Glu), which selectively phosphorylates p38 MAPK, induced cellular GIIa PLA(2) protein synthesis and the release of GIIa PLA(2) and increased extracellular PLA(2) activity 3-fold. In contrast, infection with an adenovirus encoding a phosphorylation-resistant MKK6, MKK6(A), did not result in GIIa PLA(2) protein synthesis or release by unstimulated cardiomyocytes. In addition, infection with an adenovirus encoding MKK6(A) abrogated GIIa PLA(2) protein synthesis and release by interleukin-1beta-stimulated cells. These results provide direct evidence that p38 MAPK activation was necessary for interleukin-1beta-induced synthesis and release of GIIa PLA(2) by cardiomyocytes.

Hemorrhage-induced alpha-adrenergic signaling results in myocardial TNF-alpha expression and contractile dysfunction.

Hemorrhagic shock (HS), secondary to major blood loss, frequently precedes multiple organ dysfunction and is accompanied by a surge in circulating catecholamine levels. Expression of the cardiodepressant cytokine, tumor necrosis factor-alpha (TNF-alpha), has been observed in the heart after HS and resuscitation (HS/R) and alpha(1)-adrenergic blockade prevented translocation of the nuclear transcription factor, NF-kappa B, to the nucleus. We hypothesized that alpha(1)-adrenergic stimulation induces myocardial TNF-alpha expression, which results in depressed cardiac function after HS/R. The role of alpha(1)-adrenergic stimulation in myocardial TNF-alpha expression and depressed cardiac function after HS/R was assessed by treatment with the alpha(1)-adrenergic inhibitor, prazosin hydrochloride (1 mg/kg ip), for 1 h before the onset of hemorrhage. In addition, TNF-alpha was neutralized with a specific antibody (600 microl/kg iv) 5 min before hemorrhage. HS was induced by the withdrawal of blood to a mean blood pressure of 50 mmHg for 1 h. Contractile function was measured with the use of a Langendorff apparatus 2 h after the end of HS. HS/R led to significant decreases in left ventricular developed tension and in the maximal rate of pressure increase over time during both contraction and relaxation. Myocardial expression of TNF-alpha measured by enzyme-linked immunosorbent assay increased significantly after 30 min of hemorrhage and peaked after 60 min of HS and 45 min of resuscitation. Depression in cardiac function after HS/R was reversed by 85% in hearts from rats treated with a TNF-alpha neutralizing antibody and by 90% in hearts from rats treated with prazosin hydrochloride. We conclude that HS activates a alpha(1)-adrenergic pathway, resulting in TNF-alpha expression in the heart and depressed myocardial contractile function.

Role of TNF-alpha in myocardial dysfunction after hemorrhagic shock and lower-torso ischemia.

Ruptured abdominal aortic aneurysm (RAAA) repair, a combination of hemorrhagic shock and lower-torso ischemia, is associated with a 50-70% mortality. Myocardial dysfunction may contribute to the high rate of mortality after aneurysm repair. We attempted to determine whether RAAA repair results in cardiac dysfunction mediated by tumor necrosis factor-alpha (TNF-alpha). We modeled aortic rupture and repair in the rat by inducing hemorrhagic shock to a mean blood pressure of 50 mmHg for 1 h, followed by supramesenteric clamping of the aorta for 45 min. After 90 min of reperfusion, cardiac contractile function was assessed with a Langendorff preparation. Myocardial TNF-alpha, ATP and creatine phosphate (CP) levels, and markers of oxidant stress (F(2)-isoprostanes) were measured. Cardiac function in the combined shock and clamp rats was significantly depressed compared with sham-operated control rats but was similar to that noted in animals subjected to shock alone. Myocardial TNF-alpha concentrations increased 10-fold in the combined shock and clamp rats compared with sham rats, although there was no difference in myocardial ATP, CP, or F(2)-isoprostanes. TNF-alpha neutralization improved cardiac function by 50% in the combined shock and clamp rats. Hemorrhagic shock is the primary insult inducing cardiac dysfunction in this model of RAAA repair. An improvement in cardiac contractile function after immunoneutralization of TNF-alpha indicates that TNF-alpha mediates a significant portion of the myocardial dysfunction in this model.

Ruptured abdominal aortic aneurysm, a "two-hit" ischemia/reperfusion injury: evidence from an analysis of oxidative products.

PURPOSE: Ruptured abdominal aortic aneurysm (RAAA) remains a lethal condition despite improvements in perioperative care. The consequences of RAAA are hypothesized to result from a combination of two ischemia/reperfusion events: hemorrhagic shock and lower torso ischemia. Ischemia/reperfusion results in tissue injury by diverse mechanisms, which include oxygen free radical-mediated injury produced from activated neutrophils, xanthine oxidase, and mitochondria. Oxygen-free radicals attack membrane lipids, resulting in membrane and subsequently cellular dysfunction that contributes to postoperative organ injury/failure. The purpose of this investigation was to quantify the oxidative injury that occurs as a result of the ischemia/reperfusion events in RAAAs and elective AAAs. METHODS: Blood samples were taken from 22 patients for elective AAA repair and from 14 patients for RAAA repair during the perioperative period. Plasma F(2)-isoprostanes were extracted, purified, and measured with an enzyme immunoassay. Aldehydes and acyloins were purified and quantified. Neutrophil oxidative burst was measured in response to a receptor independent stimulus (phorbol 12-myristate 13-acetate) with luminol-based chemiluminescence. RESULTS: Plasma from patients with RAAAs showed significantly elevated F(2)-isoprostane levels on arrival at hospital and were significantly elevated as compared with the levels of patients for elective repair throughout the perioperative period (two-way analysis of variance, P <.0001). Multiple regression showed a significant relationship between the phagocyte oxidative activity and F(2)-isoprostane levels (P <.013). Total acyloin levels were significantly higher in patients with RAAAs as compared with the levels in elective cases. CONCLUSION: The F(2)-isoprostane levels, specific markers of lipid peroxidation, showed that patients with RAAAs had two phases of oxidative injury: before arrival at hospital and after surgery. The significant relationship between the postoperative increases in F(2)-isoprostane levels and the neutrophil oxidant production implicates neutrophils in the oxidative injury that occurs after RAAA. New therapeutic interventions that attenuate neutrophil-mediated oxidant injury during reperfusion may decrease organ failure and ultimately mortality in patients with RAAAs.

Coronary bypass and carotid endarterectomy: does a combined approach increase risk? A metaanalysis.

BACKGROUND: Patients with concomitant carotid and coronary artery disease present a surgical dilemma. We compared the stroke and mortality rates for combined coronary artery bypass grafting and carotid endarterectomy in which both procedures were performed under a single anesthetic, versus a staged approach, in which coronary artery bypass grafting and carotid endarterectomy were performed separately. METHODS: A computerized MEDLINE search supplemented with a manual bibliographic review was performed for all peer-reviewed English language publications that contained both combined and staged coronary artery bypass grafting/carotid endarterectomy patient cohorts. Outcomes of interest were stroke, death, and stroke or death; aggregation of outcome rates was performed with the Mantel-Haenszel method. RESULTS: Sixteen studies were identified with a total of 844 combined patients and 920 staged patients. None of the studies was completely randomized. The combined surgical group had a higher prevalence of unstable angina; the two groups had a similar prevalence of symptomatic carotid disease and severe carotid stenosis. Meta-analysis revealed a significantly increased risk of the composite end point, stroke or death, for patients undergoing combined procedures (relative risk 1.49; 95% confidence interval 1.03-2.15; p = 0.034). There was also a trend toward increased risk during combined procedures for the end points of stroke (relative risk 1.50; 95% confidence interval 0.97-2.32; p = 0.068) and death (relative risk 1.55; 95% confidence interval 0.94-2.53; p = 0.084) considered separately. The crude event rates for stroke were 6.0% versus 3.2% for combined versus staged procedure, 4.7% versus 2.9% for death, and 9.5% versus 5.7% for stroke or death. Two of the 16 individual studies showed a statistically significant increase in the risk of stroke or death for combined procedure (p < 0.05). CONCLUSIONS: Combined coronary artery bypass grafting and carotid endarterectomy may be associated with a higher risk of stroke or death than staged procedures. A randomized trial needs to be performed to determine the optimal management of patients with concomitant carotid and coronary artery disease.

A CD18 monoclonal antibody reduces multiple organ injury in a model of ruptured abdominal aortic aneurysm.

The role of CD18 antibody (anti-CD18) in remote and local injury in a model of ruptured abdominal aortic aneurysm repair was investigated. Rats were divided into sham, shock, clamp, and shock + clamp groups. Shock + clamp animals received anti-CD18 or a control monoclonal antibody. One hour of hemorrhagic shock was followed by 45 min of supramesenteric aortic clamping. Intestinal and pulmonary permeability to (125)I-labeled albumin was determined. Myeloperoxidase (MPO) activity, F(2)-isoprostane levels, and transaminases were also measured. Only shock + clamp resulted in statistically significant increases in pulmonary and intestinal permeability, which were associated with significant increases in MPO activity and F(2)-isoprostane levels. Treatment with anti-CD18 significantly decreased intestinal and pulmonary permeability in shock + clamp animals. These reductions were associated with significantly reduced intestinal and hepatic MPO activity and pulmonary F(2)-isoprostane levels and reduced alanine and aspartate aminotransferase levels; however, anti-CD18 had no effect on intestinal or hepatic F(2)-isoprostane levels or on pulmonary MPO activity. These results suggest CD18-dependent and -independent mechanisms of local and remote organ injury in this model of ruptured abdominal aortic aneurysm.

Effect of complement inhibition with soluble complement receptor 1 on pig allotransplant lung function.

BACKGROUND: Lung dysfunction after transplantation continues to be a significant clinical problem. Soluble complement receptor 1 (sCR1) is a potent inhibitor of complement activation. We evaluated the inhibitory effect of sCR1 on complement activation and reperfusion injury in pig lung allografts. METHODS: In a randomized and blinded study, left lung transplantation was performed in 13 pigs. Donor lungs were flushed and then stored for 30 hr at 4 degrees C. Control pigs (n=7) received saline, and the treatment group (n=6) received 15 mg/kg sCR1 1 hr before reperfusion. One hour after reperfusion, the right pulmonary artery was clamped for 10 min to assess the function of the transplanted lung. Pulmonary function was assessed again on day 3. RESULTS: Complement inhibition was 93% in the sCR1 group and returned to baseline (8% inhibition) after 3 days. There was a trend toward a higher partial pressure of oxygen at 1 hr in the sCR1 group compared with the control group (mean +/- SE: 408+/-42 mmHg vs. 288+/-69 mmHg, P = 0.19). Alveolar ventilation was better in the sCR1 group than in the control group (P = 0.01) at 1 hr. Mixed venous saturation was significantly lower in the control group at both 1 hr (P = 0.02) and 3 days (P = 0.001). The wet/dry weight of the lung tissue was lower in the sCR1 group compared with the control group on day 3 (P < 0.05). Chemiluminescence, an index of phagocyte priming, was lower in the sCR1 group when cells were stimulated with complement opsonized zymosan but not when stimulated with zymosan or phorbol myristate acetate. CONCLUSION: sCR1 improves ventilation, reduces pulmonary edema, and may be beneficial in improving posttransplant lung oxygenation.

Management of upper extremity central venous obstruction using interventional radiology.

Upper extremity central vein stenosis/occlusion is responsible for significant morbidity. The objective of this report is to review our management using interventional radiological techniques and to determine the long-term clinical results. All radiological interventions for central vein stenosis/occlusion (n = 59) between July 1991 and July 1996 at our institution were reviewed. The interventions consisted of thrombolytic therapy alone in 10 cases, PTA in 40 cases (combined with initial thrombolytic therapy in 6 cases), and deployment of a venous stent in 9 cases. At follow-up, the cumulative success (patency and relief of symptoms) was determined (Kaplan-Meier method). The involved vein was the subclavian, axillary, or innominate (SUB-AX-INN) in 45 cases and the superior vena cava (SVC) in 14 cases. The etiology was secondary to an indwelling foreign body (catheter, pacemaker lead) in 53 cases (90%), and spontaneous in only 6 cases (10%). The average follow-up after intervention was 17.2 months, with a cumulative success of 70 +/- 7.5% at 2 years, with rapid decline thereafter. Analysis of the failure quantiles revealed that 25% failed by 17 months, 50% failed by 26.6 months, and 75% failed by 33.8 months. There were no subgroup differences (log-rank test) for stenosis versus occlusion (p = 0.526), SUB-AX-INN versus SVC (p = 0.744), or if the intervention was begun < 5 days versus > or =5 days after symptom onset (p = 0.240), or whether or not a stent was deployed (p = 0.893). Interventional radiological techniques should be considered when symptoms from upper extremity central vein stenosis/occlusion are severe and disabling, or when veno-access or maintenance of patency of an ipsilateral arteriovenous (A-V) access is necessary. These results suggest an acceptable short-to medium-term solution.

The impact of multiple organ dysfunction on mortality following ruptured abdominal aortic aneurysm repair.

The in-hospital mortality for a patient with a ruptured abdominal aortic aneurysm (RAAA) ranges from 30% to 70% and remains unchanged despite aggressive surgical, anesthetic, and intensive-care management. The purpose of this investigation is to determine the relationship between the development of organ dysfunction and mortality in ruptured AAA patients. Eighty-eight consecutive patients admitted to the Toronto Hospital for repair of RAAAs were studied. APACHE II and multiple organ dysfunction (MOD) scores were calculated for all patients. The MOD scoring system measures daily alterations in the function of six key organs, with increased dysfunction indicated by an increasing score. The overall 30-day mortality rate was 40%; 10% of patient deaths occurred intraoperatively. ICU mortality was bimodal; 11.5% deaths occurred within the first 48 hours compared to 18.2% after 48 hours (late deaths). The APACHE II score was significantly higher in those who died within 48 hours of ICU admission (28.5 +/- 6.36) compared to both those who died late (17.2 +/- 5.7, p < 0.0001) and survivors (11.2 +/- 4.2, p < 0.0001). The survivors' daily mean MOD scores did not increase significantly, while the MOD scores for late deaths increased progressively (p < 0.01). The renal and hepatic dysfunction components of the MOD score were significantly lower in the survivors compared to late deaths (p < 0.001), however the respiratory MOD score did not differ between the groups (p > 0.05). The change in MOD (delta MOD) score over the intensive care stay was significantly greater in late deaths compared to survivors (p < 0.01). The rates of infection were similar in both groups and were not responsible for mortality. We conclude that mortality is better predicted following RAAA by the development of renal and hepatic dysfunction rather than by initial physiologic derangement measured by the APACHE II score.

Rupture of an abdominal aortic aneurysm causes priming of phagocytic oxidative burst.

PURPOSE: The purpose of this investigation was to determine whether rupture and repair of an abdominal aortic aneurysm induced activation of phagocyte oxidant burst, reflecting a systemic inflammatory state, when compared with elective abdominal aortic aneurysm (AAA) repair. METHODS: Blood samples were harvested from 22 patients with elective AAA and 15 patients with ruptured AAA. Phagocyte oxidant activity was measured in response to a panel of activators with luminol and lucigenin as chemiluminescent substrates. Activity of the complement pathways was measured with plasma levels of C3a des arg. RESULTS: Elective AAA repair resulted in significant elevation in phagocyte count and oxidative activity after surgery in response to maximal dose phorbol myristate acetate (PMA) when compared with the baseline sample. In patients with ruptured AAA the oxidative activity of phagocytes was significantly increased in response to both unopsonized zymosan (899.8 +/- 192 ruptured vs 300 +/- 40 elective, p < 0.01) and maximal dose PMA (8769 +/- 2011 vs 3508 +/- 382, p < 0.01) compared with elective cases at the initial sampling. Phagocyte priming has occurred by way of two distinct pathways: receptor-mediated (unopsonized zymosan, CR3 receptor) and receptor-independent (PMA, protein kinase c). CONCLUSIONS: Rupture of an AAA resulted in priming of the phagocyte oxidant capacity before operative repair compared with elective AAA. Phagocyte activation is a critical component of the systemic inflammatory response that may contribute to the high incidence of systemic organ dysfunction and death in this patient group.

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.

Sequential ischemia/reperfusion results in contralateral skeletal muscle salvage.

Sequential ischemia/reperfusion in a paired canine gracilis muscle model resulted in significant muscle salvage. In this model, one randomly chosen gracilis muscle was subjected to 5 h of ischemia followed by 48 h of in vivo reperfusion. The contralateral (second) muscle was then made ischemic and reperfused using the same protocol. Muscle necrosis was determined at the end of 48 h of reperfusion. A mean 60% reduction in muscle necrosis was observed in the second group of muscles. Analysis of tissue adenine nucleotides indicated that significant sparing of ATP utilization occurred in the second muscle group during ischemia. Preliminary analysis of tissue heat shock proteins (HSP) showed that the second group of muscles had a different pattern of HSP expression before the onset of ischemia. The results suggest that reduced ATP utilization and altered HSP expression in the second muscle play a role in the tissue salvage observed in this sequential muscle ischemia model.