Abdominal aortic aneurysm surgery in a district general hospital: a 15-years experience

The incidence of patients presenting with both ruptured abdominal aortic aneurysm (RAAA) and elective abdominal aortic aneurysm (EAAA) increases with age. The aim of our study was to find out the incidence of RAAA, age and sex groups of patients at risk, and 30-day all-cause perioperative mortality associated with RAAA as well as EAAA repair in a busy district general hospital over a 15-year time period. All patients operated for AAA during 1989-2003, both elective and ruptured, were included in the study. Patients who died in the community from RAAA were also included. The data were collected from the hospital information system, theater logbooks, intensive therapy unit records, postmortem register, and patients' medical notes. We divided the data for RAAA into two groups of 7.5 years each to see if there was any improvement over time in 30-day postoperative mortality. There were 816 cases of AAA, which included 468 RAAAs (57%) and 348 EAAAs (43%). Out of 468 RAAAs, 243 patients had emergency repair, of whom 213 were males. There were 201 patients who had RAAA postmortem (43%). Median age (range) was 73 (54-94) years in males and 77 (52-99) years in females, with a male-to-female ratio of 7:1. The peak incidence of RAAA was over 60 years of age in males and 70 years in females. Incidence of RAAA was 7.3/100,000/year in males and 5/100,000/year in females. For RAAA, 30-day perioperative mortality was 43% (105/243) while overall mortality was 70% (330/468), which includes deaths in the community. There was no improvement in 30-day mortality over time after comparing data for the first 7.5 years (50/115, 43.5%) with those for the second set of 7.5 years (55/128, 43%). There were 348 patients who had EAAA repair over the same period, comprising 282 males, with a male:female ratio of 4.3:1. The 30-day mortality in the elective group was 7.75%. Incidence and mortality of RAAA remain high. A high proportion of patients with AAA remain undiagnosed and die in the community. More lives may be saved if a screening program is started for AAA.     

Outcomes of endovascular treatment of ruptured abdominal aortic aneurysms

INTRODUCTION: The successful application of endovascular techniques for the elective repair of abdominal aortic aneurysms (AAAs) has stimulated a strong interest in their possible use in dealing with a long-standing surgical challenge: the ruptured abdominal aortic aneurysm (RAAA). The use of a conventional open procedure to repair ruptured aneurysms is associated with a high operative mortality of 45% to 50%. In this study, we evaluated the current frequency of endovascular repair of RAAAs in four large states and the impact of this technique on patient outcome. METHODS: We examined discharge data sets from 2000 through 2003 from the four states of California, Florida, New Jersey, and New York, whose combined population represents almost a third of the United States population. Proportions and trends were analyzed by chi2 analysis and continuous variables by the Student's t test. RESULTS: We found that since the year 2000, endovascular repair has begun to emerge as a viable treatment option for RAAAs, accounting for the repair of 6.2% of cases in 2003. During the same period, the use of open procedures for RAAAs declined. The overall mortality rate for the 4-year period was significantly lower for endovascular vs open repair (39.3% vs. 47.7%, P = .005). Moreover, compared with open repair, endovascular repair resulted in a significantly lower rate of pulmonary, renal, and bleeding complications. Survival after endovascular repair correlated with hospital experience, as assessed by the overall volume of elective and nonelective endovascular procedures. For endovascular repairs, mortality ranged from 45.9% for small volume hospitals to 26% for large volume hospitals (P = .0011). Volume was also a determinant of mortality for open repairs, albeit to a much lesser extent (51.5% for small volume hospitals, 44.3% for large volume hospitals; P < .0001). CONCLUSION: We observed a benefit to using endovascular procedures for RAAAs in institutions with significant endovascular experience; however, the analysis of administrative data cannot rule out selection bias as an explanation of better outcomes. These data strongly endorse the need for prospective studies to clarify to what extent the improved survival in RAAA patients is to be attributed to the endovascular approach rather than the selection of low-risk patients.     

Renal effects of N-acetylcysteine in patients at risk for contrast nephropathy: decrease in oxidant stress-mediated renal tubular injury.

BACKGROUND: N-Acetylcysteine has been shown to protect against contrast nephropathy, although the mechanisms underlying such an effect are unclear. Surprisingly, studies have shown that post-radiocontrast renal function actually improves in chronic renal failure patients receiving N-acetylcysteine. However, there have been no studies investigating the cause of this improvement. METHODS: In a double-blind, placebo-controlled study, 24 patients (aged 65+/-2 years) suffering from stable mild-to-moderate renal insufficiency and undergoing elective coronary angiography were randomized to receive either placebo or N-acetylcysteine. All received similar hydration. Renal function parameters were assessed 48 h before and 48 h after radiocontrast administration. Urinary 15-isoprostane F2(t), a specific marker of oxidative stress, was measured immediately before and after the procedure. Expression of urinary alpha-glutathione S-transferase protein, a specific proximal tubular injury marker, was assessed after the procedure. RESULTS: Comparing creatinine clearance values before and after angiography, a significant increase was seen in N-acetylcysteine patients (44.7+/-4.2 vs 57.2+/-6.3 ml/min/1.73 m(2); P = 0.02), whereas placebo patients presented no change (46.6+/-5.0 vs 46.9+/-4.3 ml/min/1.73 m(2); P = 0.90). After radiocontrast, urinary 15-isoprostane F2(t) levels in placebo patients increased significantly over baseline values (2.9+/-0.7 vs 10.3+/-2.1 ng/mg creatinine; P = 0.007), whereas urinary 15-isoprostane F2(t) levels in N-acetylcysteine patients remained basically unchanged (3.5+/-0.5 vs 4.1+/-0.9 ng/mg creatinine; P = 0.63). Furthermore, N-acetylcysteine treatment led to lower levels of alpha-glutathione S-transferase than did placebo treatment (0.8+/-0.2 vs 2.4+/-0.7 micro g/g; P = 0.046). CONCLUSIONS: In chronic renal failure patients, the improvement in renal function induced by post-radiocontrast administration of N-acetylcysteine is strongly associated with suppression of oxidant stress-mediated proximal tubular injury.     

Relationships between cerebrospinal fluid markers of excitotoxicity, ischemia, and oxidative damage after severe TBI: the impact of gender, age, and hypothermia

Excitotoxicity and ischemia can result in oxidative stress after TBI. Female sex hormones are hypothesized to be neuroprotective after TBI by affecting multiple mechanisms of secondary injury, including oxidative damage, excitotoxicity and ischemia. Ca2+ mediated oxidative stress increases with age, and hypothermia is known to attenuate secondary injury. The purpose of this study was to determine if the relationship between cerebral spinal fluid (CSF) markers of excitotoxicity, ischemia, and oxidative damage are gender and age specific and the role of hypothermia in affecting these relationships. F2-isoprostane, glutamate, and lactate/pyruvate, were assessed in CSF from adults (n = 68) with severe TBI (Glasgow coma scale [GCS] score 相似文献   

Ruptured abdominal aortic aneurysm in a well-defined geographic area

OBJECTIVE: Despite an increasing number of elective operations on abdominal aortic aneurysms (AAAs), the age- and sex-standardized mortality rate of ruptured AAA (RAAA) continues to increase. In the Pirkanmaa region, population 440,000, all aortic surgery is performed at Tampere University Hospital (TAUH). Procedures have been collected into the vascular registry. The purpose of this study was (1) to establish the incidence, modes of treatment, and mortality of RAAA in a defined geographic area; (2) to evaluate the prerupture history to determine if there are any ways to prevent rupture; and to make a forecast about the increase of RAAAs in the next decades. METHODS: Population and outcome data in the Pirkanmaa region and information on all patients who died of RAAA during 1990-1997 were provided by Statistics Finland. All operated RAAAs that underwent procedures during 1990 to 1999 were identified from the local vascular registry. To make a forecast for the next decades, an incidence of RAAA was calculated separately for each age group in 5-year intervals. RESULTS: From 1990 to 1997, 221 patients presented with RAAA. The mean incidence was 6.3/100,000 inhabitants. The incidence in the population over 65 years was 35.5/100,000. The total RAAA mortality was 76.9%. A total of 139 patients reached TAUH and 111 underwent emergency surgery. The overall hospital mortality in TAUH was 63.3%. The calculated annual number of RAAA will increase 49.6% in the next 2 decades, and the overall incidence will increase from 6.3 to 8.9/100,000 inhabitants. According to the vascular registry, 166 patients were operated on for RAAA during 1990 to 1999 in TAUH. The 30-day mortality was 50.6%. A minority of the patients (n = 18, 10.8%) had a previously documented AAA. The median diameter at the time of rupture was 7 cm. Seven (5.0%) men and six (24.0%) women had a diameter of less than 5.5 cm. CONCLUSION: The incidence of RAAA in the Pirkanmaa region in 1990s was the Finnish average. In the next two decades, the number of individuals with RAAA will increase significantly. One quarter of women had a diameter of AAA at the time of rupture that was under the current threshold indicator for elective operation.     

Endovascular approaches to ruptured infrarenal aorto-iliac aneurysms

BACKGROUND: Ruptured abdominal aortoiliac aneurysms (RAAAs) carry a high mortality when treated by open surgical repair. Since 1994, we have employed endovascular approaches to treat this entity. METHODS: Patients with presumed RAAAs were treated with restricted fluid resuscitation (hypotensive hemostasis), rapid transport to the operating room, placement of a transbrachial or transfemoral guidewire under local anesthesia, and urgent arteriography. In patients with suitable anatomy, endovascular graft repair was performed. If the anatomy was unsuitable, standard open repair was performed. If the patient had circulatory collapse, proximal balloon control was employed. RESULTS: Of 31 patients managed in this fashion, 25 underwent endovascular graft repair. Six required open repair. Total operative mortality was 9.7% (3 patients). Only 10 patients required proximal balloon aortic control. CONCLUSIONS: Endovascular techniques (proximal balloon control and endografts) may improve treatment outcomes for RAAAs. Restricted resuscitation (hypotensive hemostasis) can be effective in the RAAA setting.     

Inadequate myocardial protection with cold cardioplegic arrest during repair of tetralogy of Fallot

Postoperative low cardiac output is the most common cause of death in patients undergoing elective repair of tetralogy of Fallot. The incidence is much higher than in elective adult bypass operations for coronary artery disease. To explain this difference, we investigated 16 children having elective repair of tetralogy (mean age 6.3 years). Myocardial biopsy specimens obtained during bypass before arrest, at the end of cold arrest by blood cardioplegia, and after 30 minutes of reperfusion were studied for adenosine triphosphate and lactate levels. Myocardium was submitted for microscopic study shortly after the onset of ischemia. The operation was successful in reducing right ventricular-pulmonary artery gradients from 82 +/- 28 to 9 +/- 1 mm Hg, yet seven patients required significant inotropic support (dopamine, greater than 5 micrograms/kg/min) for more than 24 hours and 12 patients needed prolonged use of digoxin and diuretics for right ventricular failure. Tissue levels of adenosine triphosphate and lactate in the tetralogy groups were compared with those in 20 adults with coronary artery disease having similar myocardial protection techniques. Adenosine triphosphate levels in the tetralogy group decreased during cross-clamping (41 +/- 8 minutes) from 24 +/- 3 to 16 +/- 2 mmol/kg dry weight (mean +/- 1 standard error), with a marked further drop after reperfusion to 9 +/- 2 mmol/kg (p less than 0.01). Adenosine triphosphate levels in the group with coronary disease also decreased from 20 +/- 1 to 16 +/- 1 mmol/kg after a longer cross-clamp time (70 +/- 17 minutes) but remained at 15 +/- 2 mmol/kg after reperfusion. Tissue lactate levels in the tetralogy group rose markedly during ischemia and remained elevated after reperfusion. In contrast, lactate levels in the group with coronary disease rose moderately during ischemia and returned to normal early on reperfusion. Microscopic study revealed focal myocyte necrosis in tetralogy of Fallot. Our findings, which demonstrate inadequate myocardial protection of patients with tetralogy during repair, with depression of adenosine triphosphate and increased lactate during ischemia and reperfusion, suggest a defect in oxidative metabolism. The drop in adenosine triphosphate after reperfusion in the patients with tetralogy implicates reperfusion injury as a mechanism of myocardial damage.     

Ruptured abdominal aortic aneurysm in the Huntingdon district: a 10-year experience.

A study was undertaken to establish the true incidence of ruptured abdominal aortic aneurysms (RAAA) in the Huntingdon districts. RAAAs in the Huntingdon district between 1986 and 1995 were studied retrospectively. Data were collected from hospital records and hospital and community autopsies. There was a total of 139 cases of RAAA; 119 were males and 20 females, giving a M:F ratio of 6:1. The incidence of RAAAs was 17.8/100,000 person years (py) in males and 3.0/100,000 py in females. Mean age at rupture was 75.5 years in men (95% confidence intervals (CI) 74-78 years) and 80.2 in women (95% CI 78.8-83 years). There was an age-specific increase in incidence after the age of 65 years in men and after 80 years in women, although 12.6% of all RAAAs occurred in men under 65 years. In all, 100 patients were confirmed to have died of RAAA during the 10-year period. This represents 79% of all ruptures discovered. Almost three-quarters of patients did not reach the operating theatre. Of the 61 patients operated on, 29 survived (48%). The size of the aneurysm at rupture was recorded in 68 cases (49%). The mean size was 8.14 cm (SD 2.0 cm). In five cases (7.4%), rupture occurred in AAAs smaller than 6 cm. The overall mortality from RAAA in Huntingdon health district is approximately 80% and three-quarters of all deaths occurred without an operation.     

Clamp before you cut: Proximal control of ruptured abdominal aortic aneurysms using endovascular balloon occlusion--Case reports

While the mortality rate for elective abdominal aortic aneurysm (AAA) repair has declined over the last several decades, the rate for ruptured abdominal aortic aneurysm (RAAA) has unfortunately remained disturbingly high. Undiagnosed aneurysms may present with little warning until abdominal pain, syncope, and hypotension signify rupture. Fifty percent of patients with ruptured aneurysms die before reaching a medical facility, and their survival is highly dependent on hemodynamic stability at presentation. The degree of rupture containment and comorbid status of the patient determine hemodynamic stability. Endovascular stent grafting has significantly improved perioperative morbidity and mortality rates for elective AAA repair, and some of the same endovascular techniques can be used to obtain proximal control in patients presenting with RAAA. We describe 3 consecutive cases of RAAA where proximal control was obtained using a percutaneously placed, transfemoral aortic occlusion balloon before induction of anesthesia.     

A statewide, population-based time-series analysis of the outcome of ruptured abdominal aortic aneurysm.

OBJECTIVES: The purpose of this study was to perform the first statewide, population-based, time-series analysis of the frequency of ruptured abdominal aortic aneurysm (RAAA), to determine the outcomes of RAAA, and to assess the association of patient, physician, and hospital factors with survival after RAAA. The hypotheses of the study were as follows: 1) the rate of RAAA would increase over time and 2) patient, surgeon, and hospital factors would be associated with survival. BACKGROUND: Ruptured abdominal aortic aneurysm is a life-threatening emergency that presents the surgeon with a technically demanding challenge that must be met and surmounted in a short time if the patient is to survive. METHODS: Data were obtained from the following four separate data sources: 1) the North Carolina Hospital Discharge database, 2) the North Carolina American Hospital Association database, 3) the North Carolina State Medical Examiner's database, and 4) the Area Resource File. All patients with the diagnosis of an abdominal aortic aneurysm (AAA) were selected for initial assessment. Patients were grouped into those with and those without rupture of the abdominal aneurysm. RESULTS: During the 6 years of the study, 14,138 patients were admitted with a diagnosis of AAA. Of these, 1480 (10%) had an RAAA. The yearly number of patients with elective AAAs increased 33% from 1889 in 1988 to 2518 in 1993. The yearly number of RAAAs increased 27% from 203 to 258. The mortality rate for AAA was 5%, as compared with 54% in RAAA patients. The patient's age was found to be the most powerful predictor of survival. Univariate logistic regression analyses demonstrated an association of the surgeon's experience with RAAA and patient survival after RAAA. Analysis of the survival rates of board-certified and nonboard-certified surgeons demonstrated that patients with RAAAs who were treated by board-certified surgeons had significantly better survival. When the survival was compared in small (less than 100 beds) and large (more than 100 beds) hospitals, survival was significantly better in the larger hospitals. CONCLUSIONS: Ruptured abdominal aortic aneurysm remains a highly lethal lesion, even in the best of hands. Despite the many improvements in the care of seriously ill patients, there was no significant improvement in the survival of RAAA during this study. This suggests that early diagnosis is the best hope of survival in these patients. The study demonstrated that survival after RAAA was related most strongly to patient age at the time of the RAAA. The physician's and the hospital's experience with RAAA, the physician's background as measured by board certification, and the type of hospital at which the operation was performed (small vs. large) also may be associated with survival. These findings may have important implications for the regionalization of care and the education and credentialling of physicians. Given the lack of recent progress of improving the outcome of RAAA, aggressive efforts to treat patients before rupture are appropriate.     

The reduced tolerance of rat fatty liver to ischemia reperfusion is associated with mitochondrial oxidative injury

BACKGROUND: Oxidative stress contributes to the pathogenesis of hepatic ischemia-reperfusion injury. This study aimed to determine whether fatty degeneration affects the oxidative damage during warm ischemia reperfusion and whether mitochondria, the major intracellular site of energy synthesis, represent a preferential target of this injury. MATERIALS AND METHODS: Fed rats with control or fatty liver induced by choline deficiency underwent 60' lobar ischemia and reperfusion. Oxidative damage was assessed by measuring in whole liver tissue and in isolated mitochondria the thiobarbituric acid-reactive substances (TBARs), protein carbonyls (PC), and total and oxidized glutathione (GSH and GSSG) concentrations. The mitochondrial F0-F1-ATPase content and the oxidative phosphorylation activity were also determined. Rat survival and ALT release were assessed as parameters of liver injury. RESULTS: In the whole liver tissue, with the exception of TBARs, no differences were observed for GSH, GSSG, and PC between the two groups throughout all of the experiment. In contrast, in isolated mitochondria, fatty infiltration was associated with a mild oxidative imbalance already under basal conditions. The preischemic differences in the mitochondrial TBARs, PC, and GSSG levels were significantly amplified by reperfusion in the presence of steatosis. The enhanced oxidative damage was associated to a reduced F0-F1-ATPase content and oxidative phosphorylation activity in fatty liver mitochondria. Finally, serum ALT levels were significantly greater and survival significantly lower in rats with steatotic liver. CONCLUSIONS: Fatty infiltration exacerbates mitochondrial oxidative injury during warm ischemia reperfusion. The increased oxidative stress can alter mitochondrial functions, including key processes for ATP synthesis, thus, contributing to the reduced tolerance to reperfusion injury.     

Interstitial F(2)-isoprostane 8-iso-PGF(2α) as a biomarker of oxidative stress after severe human traumatic brain injury

Oxidative stress is a major contributor to the secondary injury process after experimental traumatic brain injury (TBI). The importance of oxidative stress in the pathobiology of human TBI is largely unknown. The F(2)-isoprostane 8-iso-prostaglandin F(2α) (8-iso-PGF(2α)), synthesized in vivo through non-enzymatic free radical catalyzed peroxidation of arachidonic acid, is a widely used biomarker of oxidative stress in multiple disease states, including TBI and cerebral ischemia/reperfusion. Our hypothesis is that harvesting of biomarkers directly in the injured brain by cerebral microdialysis (MD) is advantageous because of its high spatial and temporal resolution compared to blood or cerebrospinal fluid sampling. The aim of this study was to test the feasibility of measuring 8-iso-PGF(2α) in MD, ventricular cerebrospinal fluid (vCSF), and plasma samples collected from patients with severe TBI, and to compare the MD signals with MD-glycerol, implicated as a biomarker of oxidative stress, as well as MD-glutamate, a biomarker of excitotoxicity. Six patients (4 men, 2 women) were included in the study, three of whom had a focal/mixed TBI, and three a diffuse axonal injury (DAI). Following the bedside analysis of routine MD biomarkers (glucose, lactate:pyruvate ratio, glycerol, and glutamate), two 12-h MD samples per day were used to analyze 8-iso-PGF(2α) from 24?h up to 8 days post-injury. The interstitial levels of 8-iso-PGF(2α) were markedly higher than the levels obtained from plasma and vCSF (p<0.05), supporting our hypothesis. The MD-8-iso-PGF(2α) levels correlated strongly (p<0.05) with MD-glycerol and MD-glutamate, which are widely used biomarkers of membrane phospholipid degradation/oxidative stress and excitotoxicity, respectively. This study demonstrates the feasibility of analyzing 8-iso-PGF(2α) in MD samples from the human brain. Our results support a close relationship between oxidative stress and excitotoxicity following human TBI. MD-8-iso-PGF(2α) in combination with MD-glycerol may be useful biomarkers of oxidative stress in the neurointensive care setting.     

Long-term survival and late complications after repair of ruptured abdominal aortic aneurysms

Purpose:Long-term survival and late vascular complications in patients who survived repair of ruptured abdominal aortic aneurysms (RAAA) is not well known. The current study compared late outcome after repair of RAAA with those observed in patients who survived elective repair of abdominal aortic aneurysms (AAA). Methods:The records of 116 patients, 102 men and 14 women (mean age: 72.5 (8.3 years), who survived repair of RAAA (group I) between 1980 to 1989 were reviewed. Late vascular complications and survival were compared with an equal number of survivors of elective AAA repair matched for sex, age, surgeon, and date of operation (group II). Survival was also compared with the age and sex-matched white population of west-north central United States. Results:Late vascular complications occurred in 17% (20/116) of patients in group I and in 8% (9/116) in group II. Paraanastomotic aneurysms occurred more frequently in group I than in group II (17 vs. 8,p = 0.004). At follow-up, 32 patients (28%) were alive in group I (median survival: 9.4 years) and 53 patients (46%) were alive in group II (median survival: 8.7 years). Cumulative survival rates after successful RAAA repair at 1, 5, and 10 years were 86%, 64%, and 33%, respectively. These were significantly lower than survival rates at the same intervals after elective repair (97%, 74%, and 43%, respectively, p = 0.02) or survival of the general population (95%, 75%, and 52%, respectively,p < 0.001). Coronary artery disease was the most frequent cause of late death in both groups. Vascular and graft-related complications caused death in 3% (3/116) in group I and 1% (1/116) in group II. Cox proportional hazards modeling identified age p = 0.0001), cerebrovascular disease p = 0.009), and number of days on mechanical ventilation p = 0.01) to be independent prognostic determinants of late survival in group I. Conclusions:Late vascular complications after repair of RAAA were higher and late survival rates lower than after elective repair. These data support elective repair of AAA. As two-thirds of the patients discharged after repair of RAAA are alive at 5 years, aggressive management of RAAA remains justified. (J Vasc Surg 1998;27:813-20.)     

F2-isoprostane and neuron-specific enolase in cerebrospinal fluid after severe traumatic brain injury in infants and children

It has been hypothesized that oxidative stress plays an important role in mediating secondary damage after traumatic brain injury (TBI). To study the relationship between lipid peroxidation, clinical variables, and neuronal damage in pediatric TBI, we measured levels of F2-isoprostane, a marker of lipid peroxidation, and neuron-specific enolase (NSE), a marker of neuronal damage, in serial cerebrospinal fluid (CSF) samples from 23 infants and children with severe TBI (Glasgow Coma Scale score <8). These were compared to CSF samples from 10 uninjured pediatric controls. On d1 after injury, F2-isoprostane was increased 6-fold vs. control (36.59+/-8.96 pg/ml vs. 5.64+/-8.08 pg/ml, p=0.0035) and NSE was increased 10-fold (100.62+/-17.34 ng/ml vs. 8.63+/-2.76 ng/ml, p=0.0002). Multivariate analysis of F2-isoprostane levels and selected clinical variables showed a trend toward an inverse association with time after injury (p=0.0708). Multivariate analysis of NSE levels and selected variables showed a positive association between d1 NSE and F2-isoprostane (p=0.0426). CSF F2-isoprostane increases early after TBI in infants and children and is correlated with NSE, supporting a role for oxidative stress in the evolution of secondary damage early after severe TBI in infants and children.     

The effect of warm ischemic time on renal function and injury in the isolated hemoperfused kidney

BACKGROUND: The precise effect of warm ischemia on renal allograft function remains unclear and leads to variable warm ischemic time (WIT) limits advocated by transplant programs. This study aims to investigate the relationship between WIT, renal ischemia reperfusion injury, and graft function using a hemoperfused kidney model. METHODS: Porcine kidneys were perfused with normothermic blood on an isolated organ perfusion system. Kidneys were divided into four groups (n=6) and subjected to 7, 15, 25, and 40 min WIT. Physiological parameters were measured throughout the 6 hr perfusion period. Serum, tissue, and urine samples were analyzed for histological and biochemical markers of ischemia reperfusion injury. RESULTS: Creatinine clearance, urine output, renal hemodynamics, and oxygen consumption deteriorated proportionally with increasing WIT. A significant increase in plasma carbonyl levels during perfusion was seen after 25 and 40 min WIT only. Plasma 8-isoprostane levels were higher after 40 min WIT (2.5+/-1.6) vs. 7, 15, and 25 min WIT (0.65+/-0.43, 0.25+/-0.12, and 0.62+/-0.21, respectively; P<0.05). A negative correlation was shown between urine output and plasma carbonyls (r=-0.415, P<0.05) and between 8-isoprostane levels and creatinine clearance (r=-0.649, P<0.005). Caspase-3 activity was significantly higher after 7 min WIT compared with the other groups, correlating positively with creatinine clearance, urine output, and renal blood flow. CONCLUSION: The isolated organ perfusion system successfully delineated a clear WIT-dependent variation in renal function which correlated accurately with oxidative injury markers. This model may represent a clinically applicable tool for assessing graft viability.     

A monoclonal antibody against cytokine-induced neutrophil chemoattractant attenuates injury in the small intestine in a model of ruptured abdominal aortic aneurysm

PURPOSE: Ruptured abdominal aortic aneurysm (RAAA) continues to be a major source of aneurysm-related morbidity and mortality. Neutrophils have been implicated in RAAA repair-induced organ injury; however, the agents responsible for neutrophil activation and organ sequestration have not been identified. This study investigated the role of cytokine-induced neutrophil chemoattractant (CINC) in organ injury in an RAAA model. METHODS: Rats were subjected to 1 hour of hemorrhagic shock with resuscitation, followed by 45 minutes of lower torso ischemia and 2 hours of reperfusion, and randomly were selected to receive saline solution or anti-rat CINC monoclonal antibody at the start of hemorrhagic shock. Another group of animals underwent sham operation, and served as a control group. Intestinal and lung permeability, intestinal and lung myeloperoxidase (MPO) activity, intestinal and lung CINC, and tumor necrosis factor-alpha (TNF-alpha) levels, resuscitation fluid requirements, and histologic mucosal injury were evaluated in all groups. RESULTS: The RAAA model resulted in increased lung and intestinal permeability to radiolabeled albumin and lung MPO activity (P <.01), with increases in intestinal TNF-alpha (P <.001) and CINC (P <.01) levels, when compared with sham-operated animals. Treatment with anti-rat CINC monoclonal antibody attenuated the increases in intestinal permeability and histologic mucosal injury (P <.01), gut TNF-alpha level (P <.001), and resuscitation fluid volume required (P <.05), without significantly affecting lung and intestinal MPO activity, lung permeability, and intestinal CINC level (P = NS), compared with animals given saline solution. CONCLUSION: Neutralization of CINC by the anti-rat CINC monoclonal antibody attenuated intestinal injury and induction of intestinal TNF-alpha, but failed to significantly attenuate remote pulmonary injury in this model of RAAA.     

Existing delays following the presentation of ruptured abdominal aortic aneurysm allow sufficient time to assess patients for endovascular repair.

OBJECTIVES: The greatest benefit of endovascular AAA repair (EVAR) may be in the management of rupture (RAAA). However, the detailed anatomical assessment required for EVAR has lead to concerns of surgical delay and death during cross-sectional imaging. In this study, we prospectively assessed patients with RAAA and correlated time of hospital arrival with time of surgery or death to ascertain whether these concerns are justified. METHODS: All patients presenting with RAAA between October 2000 and December 2002 were included. The hospital arrival time, onset of surgery or time of death, were recorded, as were demographic and physiological parameters. RESULTS: One hundred consecutive patients were studied, median age 75 years (range 54-94). Seventy-nine patients underwent attempted conventional surgical repair and 21 were palliated. The median delay from arrival to operation was 159 min (range 16-1450 min). Mortality in the surgical group was not affected by the length of delay (p = 1.0) or by CT scanning (p = 0.34). The median time from arrival to death in the non-surgical group was 435 min (15 min-6 days). CONCLUSIONS: Most patients who present with ruptured AAA experience a significant delay prior to surgery. This study suggests it is safe to assess the majority of RAAA patients for EVAR.     

Chronic lower extremity ischemia: a human model of ischemic tolerance.

BACKGROUND: Ischemic preconditioning (IPC) has been found in animals to have a protective effect against future ischemic injury to muscle tissue. Such injury is unavoidable during some surgical procedures. To determine whether chronic ischemia in the lower extremities would imitate IPC and reduce ischemic injury during vascular surgery, we designed a controlled clinical study. PATIENTS AND METHODS: Two groups of patients at a university-affiliated medical centre with chronic lower-extremity ischemia served as models of IPC: 6 patients awaiting femoral distal bypass (FDB) and 4 scheduled for aortobifemoral (ABF) bypass grafting for aortoiliac occlusive disease. Seven patients undergoing elective open repair of an infrarenal abdominal aortic aneurysm (AAA) were chosen as non-IPC controls. Three hematologic indicators of skeletal-muscle injury, lactate dehydrogenase (LDH), creatine kinase (CK) and myoglobin, were measured before placement of the proximal clamp, during surgical ischemia, immediately upon reperfusion, 15 minutes after and 1 hour after reperfusion, and during the first, second and third postoperative days. RESULTS: Baseline markers of skeletal-muscle injury were similar in all groups. In postreperfusion samples, concentrations of muscle-injury markers were significantly lower in the 2 PC groups than in the control group. For example, at day 2, LDH levels were increased by about 30% over baseline measures in the elective AAA (control) group, whereas levels in the FDB and ABF groups remained statistically unchanged from baseline. Myoglobin in controls had increased by 977%, but only by 160% in the FDB and 528% in the ABF groups. CK levels, in a similar trend, were 1432% higher in the control group and only 111% (FDB) and 1029% (ABF) in the study groups. Taken together, these data represent a significant level of protection. CONCLUSIONS: Patients with chronic lower-extremity ischemia suffered less severe ischemic injury after a period of acute ischemia than those with acute ischemia alone. Ischemic preconditioning is one proposed mechanism to help explain this protective effect.     

Is there a selection bias in applying endovascular aneurysm repair for rupture?

Accumulating data suggest that endovascular repair (EVAR) of ruptured abdominal aortic aneurysms (RAAAs) leads to reduced mortality, but concern exists that this may reflect selection bias. We reviewed our overall rupture experience early after our protocol was instituted to explore this question. We instituted a defined protocol for RAAA with emphasis on EVAR in July 2002, which included device availability (consignment), preoperative training, 24-hr access to our surgical endosuite and ability to operate imaging in an emergency, and immediate availability of a transbrachial balloon cutdown cart for all cases. Charts of all RAAA patients who arrived in the operating room alive since institution of our protocol were reviewed. Computed tomographic (CT) scans were re-reviewed to assess potentially suitable anatomic candidates. From July 2002 to May 2006, a total of 52 RAAAs were treated at our institution: 15 pararenal RAAAs, all treated by open repair (PR-OPEN), and 37 infrarenal RAAAs, 20 treated by open repair (IR-OPEN) and 17 treated by EVAR (IR-EVAR, 32% of all ruptures). Mortality rates in the three groups were 47%, 75%, and 35% (p < 0.02 vs. IR-OPEN), respectively. Although mortality was significantly lower in the EVAR group, overall mortality was 53% (28/52). On re-review of the operative notes and CT scans, it is estimated that more than half of those cases repaired using open techniques could have been repaired using EVAR based on anatomic criteria alone. The most common reason for open repair was hemodynamic instability preoperatively; only a minority of cases were excluded from EVAR based on unfavorable anatomy after CT scan review in the emergency room. In conclusion, during our early experience EVAR for rupture was associated with significantly reduced mortality. However, our overall mortality was no different from historical values, and this fact along with the extremely high mortality seen in the IR-OPEN group suggest that we are simply selecting patients with the greatest chance of survival to undergo EVAR. It also appears that many patients who are anatomically suitable for EVAR are undergoing open operation because of hemodynamic instability. If EVAR for rupture truly decreases mortality in all patients, a much more aggressive attitude toward EVAR may be required to lower the overall mortality rate.     

Plasma F2-isoprostane levels are elevated in chronic hemodialysis patients

AIMS: Cardiovascular mortality has been reported to be 10- to 20-fold higher in chronic dialysis patients than in the age-matched general population. It has been suggested that increased oxidant stress and resulting vascular wall injury due to uremia and the hemodialysis procedure may be one of the mechanisms predisposing to these cardiovascular complications. Further, hemodialysis membrane bioincompatibility can contribute to increased oxidative stress and prevalence of inflammation. MATERIALS: We studied 18 chronic hemodialysis (CHD) patients (age 62.8 +/- 14.7 years, 39% male, 61% African-American, 44% insulin-dependent diabetic, 61% smokers, 61% with documented coronary artery disease) during hemodialysis with 2 membranes with different flux and complement activating properties. METHODS: We have measured free and phospholipid-bound F2-isoprostane (F2-IsoP) levels, a sensitive marker of oxidative stress, in CHD patients and compared them to levels in healthy subjects. We have also examined the acute effects of the hemodialysis procedure using both biocompatible and bioincompatible membranes on F2-IsoP levels. RESULTS: The results indicated that, compared to controls, both free (96.2 +/- 48.8 pg/ml versus 37.6 +/- 17.2 pg/ml) and bound F2-IsoP (220.4 +/- 154.8 pg/ml versus 146.8 +/- 58.4 pg/ml) levels were significantly higher (p < 0.05 for both). There was a statistically significant decrease in free F2-IsoP concentrations at 15 and 30 minutes of HD, which rebounded to baseline levels at the completion of the procedure. There were no significant differences in F2-IsoP concentrations between the 2 study dialyzers at any time point. Age, smoking status, diabetes mellitus and presence of cardiovascular disease were also not correlated with F2-IsoP levels in this patient population. There was a significant association between predialysis F2-IsoP and C-reactive protein concentrations. CONCLUSION: Using a sensitive and specific assay for the measurement of F2-IsoP, we demonstrated that CHD patients are under increased oxidative stress. During a single hemodialysis treatment, the hemodialysis membrane appears to have no discernable effect on oxidative stress status. Measurement of F2-isoprostanes may be a useful biomarker of oxidative stress status as well as in developing new therapeutic strategies to ameliorate inflammatory and oxidative injury in this patient population.