Altered aortic protease and antiprotease activity in patients with ruptured abdominal aortic aneurysms

Aortic elastase, antiprotease (a-1-antitrypsin) and total protein were assayed in 37 patients who underwent an operation on the abdominal aorta for ruptured abdominal aortic aneurysms (AAA), an elective procedure for AAA or aortofemoral bypass for occlusive disease. Aortic elastase modified by local antiprotease activity (elastase/a-1-antitrypsin) was significantly higher in patients with a ruptured AAA compared with patients with an elective AAA or occlusive aortic disease: 241 nanograms per milligram of tissue in AAA-rupture versus 57 nanograms per milligram of tissue in AAA-elective versus 32 nanograms per milligram of tissue for occlusive (p less than 0.003). Patients with a ruptured AAA had the highest elastase activity (354 nanograms per milligram of tissue) and the lowest a-1-antitrypsin (1.07 nanograms per milligram of tissue) compared with patients with an elective AAA and occlusion (p less than 0.05). These data suggest that the homeostatic balance between elastase and antiprotease may be significantly altered in the aortic wall at the time of aneurysm rupture. Increased elastase unchecked by low antiprotease results in increased elastin breakdown which may be the inciting event for rupture of a compromised, thin aortic aneurysm wall.     

Urinary L-valyl proline in patients with aortic aneurysms

Recent evidence indicates that metabolism of elastin may be altered in patients with different types of infrarenal aortic disease and that the phenotypic expression of aortic disease may be dependent on the balance between aortic elastase and antiprotease activity. The dipeptide L-valyl proline (LVP) is a specific amino acid sequence for elastin and can be quantitated by high performance liquid chromatography analysis of the urine. This study was done to determine if alterations in systemic elastin metabolism could be detected in patients with different types of infrarenal aortic disease by quantitating urinary LVP. Patients were divided into one of five groups and had urine analyzed for LVP. These are control, no known aortic disease (n = 12); occlusive aortic disease (n = 10); elective abdominal aortic aneurysms (AAA) (n = 26); ruptured AAA (n = 5), and multiple aneurysms (n = 4). Urine values were correlated with aortic elastase and aortic antiprotease activity. Urinary LVP was significantly higher in patients with multiple aneurysms (1,209 micrograms per milliliter of urine) as compared with all of the other groups. Patients with elective AAA had significantly higher urinary LVP (40.5 micrograms per milliliter of urine) than patients with occlusive disease (9.1 micrograms per milliliter of urine) and those in the control group (4.2 micrograms per milliliter of urine). Patients with ruptured AAA did not have significantly elevated urinary LVP compared with other groups (18.6 micrograms per milliliter of urine). Urinary LVP increased significantly as aortic elastase and aortic elastase and antiprotease activity increased. These data suggest that elastin metabolism, as reflected by urinary LVP, is altered in patients with aortic aneurysmal disease and provide further evidence to support the concept that systemic elastin metabolism is altered in patients with different types of infrarenal aortic pathologic findings.     

Relationship between proteolytic enzymes and atherosclerosis in aortic aneurysms.

Aortic elastase and aortic collagenase were assayed in 38 patients who underwent an operation for thoracic or infrarenal aneurysm or infrarenal aortic occlusive disease and in 15 control patients (heart or kidney donors). Elastase was elevated in normal aortas of the infrarenal region (1.10 milliunits per gram, p less than 0.05), and in atherosclerotic descendens aneurysms (1.24 milliunits per gram, p less than 0.05), compared with the ascending aorta, when normal; aneurysmatic specimens revealed similar low elastolytic activities (0.10 milliunits per gram). The highest elastase content was found in infrarenal aneurysms (4.65 milliunits per gram). Collagenase assays yielded no significant differences, although higher activities were extracted from aortas of the infrarenal region. Coexistent atherosclerosis and wall destruction were evaluated by macroscopic and histologic investigation. All infrarenal specimens demonstrated severe atherosclerotic wall degeneration with depletion of elastic fibers. As the atherosclerotic specimens did not differ from normal aortas by protease assay, the higher elastase of infrarenal samples compared with the thoracic aorta suggests a more rapid fiber metabolism in the infrarenal region. The significantly elevated elastolytic activity of infrarenal aneurysms points to the decisive role of elastase in infrarenal aneurysm formation.     

Comparative analysis of retroperitoneal and transperitoneal aortic replacement for aneurysm

Transabdominal aortic replacement is the most widely accepted surgical approach in the treatment of infrarenal abdominal aortic aneurysms (AAA) with an enviable mortality rate of 2 to 5 per cent. This approach, however, is attended by significant intraoperative loss of fluid and subsequent translocation as well as impaired postoperative pulmonary function and ileus. Although the retroperitoneal exposure of the aorta was used for the first repair of an AAA by Dubost and has been championed more recently by others, it has not been widely accepted. Experience suggests, however, that the exposure is as good and that postoperative morbidity is significantly less than that with the transperitoneal approach. In the past five years, we have surgically treated 299 AAA, 106 by the transabdominal route and 193 by the extended retroperitoneal approach. In 133 of the 193 patients upon whom the retroperitoneal approach was used, the aneurysm was left intact after division of the infrarenal aorta for an end to end proximal anastomosis of an aortoaortic to iliac to femoral bypass. There has been a significant reduction in the intraoperative replacement of fluid and blood, in postoperative respiratory support, in length of time in the intensive care unit and in occurrence of postoperative ileus when compared with the transabdominal endoaneurysmorrhaphy approach. Furthermore, the exposure, particularly upon the obese patient, is superior. Findings from this experience using the retroperitoneal approach for repair of AAA indicate that it results in less over-all physiologic disturbance of the patient.     

Factors influencing the rupture of abdominal aortic aneurysms

The gross findings of 49,144 autopsies performed at two major hospitals in Rome were reviewed. There were 297 patients who were found to have atherosclerotic abdominal aortic aneurysm (AAA). The aneurysm was intact in 220 (74 per cent) and ruptured in 77 (26 per cent). The occurrence of aneurysm rupture was correlated to 17 variables by univariate and multivariate statistical analysis. Covariates found to be independently predictive of the rupture of AAA were the size of the aneurysm (p less than 0.001), arterial hypertension (p less than 0.001) and the presence of bronchiectasis (p less than 0.025.). Over-all, bronchiectasis was more common among patients with AAA than in the age-adjusted and sex-adjusted control population. The simultaneous presence of bronchiectasis and AAA suggests the presence of some inherited or acquired tendency to have ectasia of the connective tissue, aneurysm formation and rupture development.     

Injuries to the ascending aorta, aortic arch and great vessels

During the past decade (1977 to 1987), 46 patients with 51 arterial injuries to the ascending aorta, aortic arch and great vessels have been treated at our institution. There were 25 subclavian arterial, 17 common carotid arterial, five innominate arterial and four ascending aortic injuries. Sixteen (35 per cent) patients were hemodynamically unstable at admission and required immediate operative intervention. Two patients arrived in cardiac arrest, necessitating thoracotomy performed in the emergency room. Thirty (65 per cent) patients were hemodynamically stable and underwent emergent diagnostic angiography prior to arterial repair. Lateral or end to end arterial repairs were used in the majority. Two ascending aortic injuries required cardiopulmonary bypass. Forty-three of 46 patients survived. Prompt exploration in the unstable patient, diagnostic angiography in the stable patient and a systematic but flexible operative approach are the keys to the management of these potentially lethal injuries.     

Two year prospective analysis of the Oxford experience with surgical treatment of abdominal aortic aneurysm

During the two years from 1 November 1985 to 31 October 1987, 177 patients were admitted to a hospital in Oxford with the diagnosis of abdominal aortic aneurysm (AAA). The aneurysm had ruptured in 88 patients, of whom 75 underwent emergent surgical treatment, yielding an operative mortality rate of 36 per cent. Of the 13 patients who did not have surgical treatment, two died before transfer to the operating room; in the other 11 patients, a deliberate decision was made not to undertake surgical treatment--in ten patients, the reason was an age of 85 years or more and in one patient, severe debilitating Parkinson's disease. Emergent operations were done upon another 15 patients--11 who had acute aneurysm and four in whom symptoms were not caused by an aneurysm. Emergent operations for ruptured or acute aneurysms represented 55 per cent of all operations for AAA. This high proportion and large number of emergent operations is in marked contrast with the experience of comparable specialist vascular surgical units in the United States. The 24-fold difference in mortality rates between surgical procedures performed electively and for ruptured aneurysm suggests that a considerable impact on over-all mortality could be achieved by a substantial increase in referral of patients     

Acute acalculous cholecystitis complicating aortic aneurysm repair

In a series of 374 consecutive abdominal aortic aneurysmal repairs, the incidence of acute acalculous cholecystitis was 1.1 per cent. This complication occurred in only one of 352 patients (0.3 per cent) after elective aneurysmorraphy, as compared with three of 22 (13.6 per cent) after emergency repair of a ruptured aneurysm. This difference proved highly significant (p = 0.0001). All of the patients who had postoperative acute cholecystitis after aortic aneurysmal repair had acalculous disease. A mortality rate of 50 per cent was noted for this complication. Technetium cholescintigraphy proved the most valuable diagnostic study when acute cholecystitis was suspected.     

The use of the supraceliac aorta for hepatic arterial revascularization in transplantation of the liver

Thrombosis of the hepatic artery during the early post hepatic transplant period results in massive hepatocyte necrosis, bile duct damage and subsequent graft loss. The incidence of this complication is increased when hepatic arterial reconstruction is possible only by the placement of an interposition infrarenal iliac artery graft. We describe 45 hepatic transplants with difficult arterial reconstruction in which the supraceliac aorta was used for arterial reconstruction. Indications for using the supraceliac aorta as the primary site for arterial reconstruction were inadequate inflow through a narrow recipient common hepatic artery in 51 per cent, previously thrombosed common hepatic artery in 27 per cent, mechanical obstruction of the celiac axis in 13 per cent or intimal dissection in 9 per cent. Direct anastomosis of the donor hepatic artery to the supraceliac aorta was achieved in 22 patients, reducing the need for a graft by 49 per cent. Short segments of iliac artery graft (17 patients) or aortic conduit (six patients) to the supraceliac aortas were required because of insufficient length of the donor artery. The incidence of arterial thrombosis and graft loss were zero per cent in adults and 12.5 per cent in children, both significantly less when compared with the 23.0 to 70.0 per cent thrombosis rate when graft is placed in an infrarenal position. We conclude that routine use of the supraceliac aorta for difficult hepatic arterial reconstruction decreases the need for arterial grafts, the incidence of hepatic arterial thrombosis and loss of hepatic grafts.     

Proteomic analysis and characterisation of human cervico-vaginal fluid proteins

AIM: Cervico-vaginal fluid (CVF) may provide insight into the biochemical pathways of human reproduction and parturition. The aim of this study was to establish a 2-D electrophoretic map of human CVF in healthy, pregnant women at term. METHODS: CVF was collected, concentrated and processed by routine 2-D polyacrylamide gel electrophoresis using pH 4-7-immobilised pH gradient strips and 8-16% gradient polyacrylamide gels. Imaged gels were analysed, yielding more than 400 proteins. A total of 157 proteins were common to all gels with a subgroup of the most abundant proteins being excised and characterised either by MALDI or by electrospray ion-trap mass spectrometry. RESULTS: Twenty-one proteins were successfully identified, yielding 15 different proteins. These included blood transport proteins (albumin and transthyretin); a structural protein (beta-actin); proteins involved in fatty acid metabolism (fatty acid-binding protein and acetyl-CoA-binding protein); a calcium-binding protein (annexin III); an anti-inflammatory cytokine (interleukin-1 receptor antagonist); proteinase inhibitors (alpha-1-antitrypsin, monocyte/neutrophil elastase inhibitor, squamous cell carcinoma antigen-1 and cystatin A); and enzymes involved in oxidative stress defence (thioredoxin, peroxiredoxin 2, glutathione S-transferase P and copper,zinc superoxide dismutase). CONCLUSION: CVF is a complex body fluid consisting of both endogenous and environmental proteins. The putative role of some of these proteins in the human reproductive tract is discussed.     

Abdominal aortic aneurysm resection in patients more than 80 years old

Improvement in anesthetic and surgical techniques has prompted a more aggressive approach to repair of abdominal aortic aneurysms in patients more than 80 years old. In order to determine if surgical treatment is justified, all of the patients who were more than 80 years old admitted to the hospital during the ten year period from 1974 to 1983 with the diagnosis of abdominal aortic aneurysm were reviewed. A total of 90 patients were available for analysis. The mortality of the 18 patients treated conservatively for ruptured aortic aneurysms was 100 per cent. Ten of the 27 patients operated upon for a ruptured aneurysm died yielding a mortality of 37 per cent. Eleven patients with symptomatic aneurysms had urgent repair with a mortality of 27 per cent. Only one of the 34 patients undergoing elective aneurysm repair died. There was no difference in the size of aneurysms among the groups. Although the ruptured aneurysms required more blood (10.2 +/- 3.7 units), there was no difference between the other two groups (symptomatic 4.5 +/- 3.1 units, elective 4.6 +/- 2.8 units). There was significantly fewer myocardial and renal complications in the elective group, although the sole death in this group was from myocardial infarction. Based upon these observations, we recommend aggressive elective therapy for selected patients who are more than 80 years of age with asymptomatic abdominal aortic aneurysms. Although the mortality is higher in those patients with symptomatic or ruptured aneurysms, it is not formidable, and therefore, repair should not be ruled out on the basis of age alone.     

A suggested classification and reappraisal of mortality statistics for ruptured atherosclerotic infrarenal aortic aneurysms

A retrospective review of 80 ruptured infrarenal abdominal aortic aneurysms with classification of the patients into clinical groups based upon the findings at laparotomy was undertaken. Patients with small hematomas confined to the area of rupture were uniformly salvaged. Those with free intraperitoneal blood almost invariably died. Intermediate groups had mortalities od 37.5 and 62.5 per cent. It is concluded that operative mortality is related to the clinical group to which the patient belongs. Attention must be focused upon the potentially salvageable intermediate groups, with regard to early laparotomy and prompt, effective proximal and distal control of the aorta before entering the retroperitoneal hematoma. Major improvements in survival have occurred with smaller ruptures but little has been achieved with larger ruptures during the past 25 years.     

Operation for late complications of aortic grafts

In a period of seven years, 120 revision operations were performed for complications occurring in 1,284 aortic bifurcation grafts. The reasons cited for operation were: graft limb occlusion or stenosis in 82 patients, false aneurysm in 28 and symptomatic disease distal to the graft in ten. Preferred operations were replacement of the graft and distal anastomosis for occlusion or complete reconstruction of the anastomosis with fresh graft material for a false aneurysm. The operative mortality rate was 1.6 per cent and three patients (2.5 per cent) underwent amputation after multiple procedures. This group of 120 patients with complications was compared with a random sample of 300 patients with aortic bifurcation grafts with no complications. In the group with complications, there were significantly fewer patients who underwent sympathectomy or profundaplasty and significantly more with an iliac rather than a femoral artery graft insertion. Those patients who had graft complications develop also had a significantly higher hematocrit level at the first procedure.     

Retroperitoneal in-line aortic bypass for treatment of infected infrarenal aortic grafts.

Since 1970, we have treated 43 patients with infected aortic grafts. Early in the series, four patients were treated with resection of the fistula or erosion and systemic and topical antibiotics without removal of the graft. All four patients died. Thirty-two patients were treated by conventional therapy; there were 13 deaths (40 percent). More recently, seven patients were managed by the left retroperitoneal placement of a new in-line polytetrafluoroethylene (PTFE) aortic graft through clean tissue planes, followed by the immediate transperitoneal removal of the infected graft without cross-contamination. Patients were maintained postoperatively on antibiotics for a minimum of two weeks. All seven patients survived without septic complications, with a mean follow-up time of 36 months (six months to four years). The surgical technique consists of initial suprarenal control of the aorta, followed by infrarenal division and oversewing of the distal aorta. A PTFE bifurcation graft is placed connecting the proximal aorta and the appropriate femoral vessels, the right limb tunneled through the space of Retzius. After closure of the incisions, through the space of Retzius. After closure of the incisions, the patient is placed in the supine position and the infected graft is removed transperitoneally. We believe that retroperitoneal in-line aortic bypass for treatment of an infected aortic graft offers a favorable alternative to conventional therapy by avoiding the use of an extra-anatomic bypass and associated risk of stump blowout.     

Immediate preoperative phlebotomy with autologous blood donation for aortic replacement

The preferential use of autologous blood provided by phlebotomy can reduce the need for homologous blood transfusion in patients undergoing extensive elective operations. This blood is usually provided either by intraoperative isovolemic hemodilution or phlebotomy one to two weeks preoperatively. To minimize the intraoperative time delay or preoperative period between phlebotomy and operation required in these patients, we performed preoperative isovolemic hemodilution in 69 patients one to two days prior to elective aortic replacement for infrarenal aneurysmal disease. Patients underwent phlebotomy a mean of 0.57 +/- 0.01 liter of whole blood; volume was replaced with lactated Ringer's solution. Hematocrit levels decreased from a mean value of 42.9 +/- 0.4 per cent to 33.7 +/- 0.3 per cent. Mean intraoperative blood loss was 1.2 +/- 0.05 liters. Hemodynamic parameters (blood pressure, cardiac output, pulmonary capillary wedge pressure, central venous pressure, oxygen delivery and systemic vascular resistance) remained stable throughout the perioperative and intraoperative time periods. In addition, we evaluated the technical modification of exclusion aneurysmorrhaphy (n = 50) versus open aneurysmorraphy (n = 19) on reduction of intraoperative homologous blood transfusion in these patients. Seventy-two per cent (36 of 50) of patients whose aneurysms were excluded received no homologous blood intraoperatively. Blood loss was decreased in the excluded versus open aneurysmorraphy group, 920 +/- 90 milliliters versus 2,030 +/- 250 milliliters, as were homologous blood transfusion requirements, 175 +/- 35 milliliters versus 570 +/- 119 milliliters. Two patients died (2.9 per cent mortality rate), and there was no increase in morbidity. Surgical treatment of large aortic aneurysms is frequently performed on an urgent basis; thus, provision of autologous blood for this operation in a short period of time may be beneficial. Isovolemic hemodilution performed during the immediate preoperative period can reduce homologous blood requirements and be safely performed without adverse effects on mortality, morbidity and myocardial performance. Exclusion aneurysmorrhaphy may further reduce dependence on homologous blood.     

Twenty-one years' experience with ruptured abdominal aortic aneurysms.

The surgical experience with 107 ruptured abdominal aortic aneurysms at this hospital during the years 1953 to 1975 has been reviewed. The operative mortality rate during the first ten years of this study was 86 per cent, but since 1966, it has fallen to 40 per cent. These improved mortality statistics are related primarily to improved techniques for controlling operative blood loss and minimizing the time of aortic cross clamping. The use of an intra-aortic balloon has been useful in this regard. Twenty-four additional patients died from ruptured aneurysms without undergoing operation, all before 1966. Only seven had a correct diagnosis prior to death, and these seven serve to emphasize the importance of being alert to the diagnosis of ruptured aneurysm which often masquerades as urologic or orthopedic problems because of the frequent symptoms of back, abdominal, flank or groin pain. Since the operative mortality rate for elective resection of the aneurysm has been less than 1 per cent at this institution during the last eight years, we believe we are justified in encouraging prompt resection of aneurysms on an elective basis to eliminate the high mortality rate that still accompanies rupture of the aneurysm.     

Zero operative mortality rate in 109 consecutive elective aortic operations performed by residents

One hundred and nine consecutive elective abdominal aortic operations were performed at the Veterans Administration Medical Center San Diego between 1984 and 1987. All of the operating surgeons were residents in general surgery who were assisted by attending staff. The mean age of the patients was 66.1 years and 34 patients were 70.0 years or older. The indication for operation was aortic aneurysm in 69 and aortoiliac occlusive disease in 40. Fifteen patients underwent highly complex procedures. The mean duration of operation was 5.6 hours, mean aortic clamp time was 72 minutes and mean volume of blood replacement was 1,186 milliliters. There was no operative mortality. Twenty-nine patients had 32 nonfatal complications. Patency of the graft was 100 per cent at discharge. We conclude that excellent clinical results with complex elective aortic operations can be achieved by surgical residents with appropriate supervision.     

Elastin metabolism in pelvic tissues: is it modulated by reproductive hormones?

OBJECTIVE: The purpose of this study was to investigate the effect of relaxin on extracellular matrix protein expression in pelvic fibroblasts that were cultured from women with stress urinary incontinence compared with asymptomatic control subjects. STUDY DESIGN: Periurethral vaginal wall fibroblasts from premenopausal women with stress urinary incontinence and continent women (in both the proliferative and secretory phase of the menstrual cycle) were stimulated with increasing concentrations of relaxin (0-500 ng/mL). The supernatant was sampled for matrix metalloproteinase-2 and -9 by zymography. Tissue inhibitors of metalloproteinase-1 and -2 and alpha-1 antitrypsin were evaluated with Western blot. Total elastase activity was measured by generation of free amino groups from succinylated elastin. Increasing concentrations of alpha-1 antitrypsin were added to cell lysate to evaluate total elastase activity inhibition. RESULTS: Proliferative-phase stress urinary incontinence fibroblasts demonstrated an increase in matrix metalloproteinase-2 and no change in matrix metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 and -2 expressions with increasing relaxin concentrations. Cells from control subjects showed increased expression of matrix metalloproteinase-2 and -9, but no change in tissue inhibitors of metalloproteinases. Secretory-phase stress urinary incontinence fibroblasts showed no response in matrix metalloproteinase or tissue inhibitors of metalloproteinase expressions with relaxin stimulation. Secretory-phase control fibroblasts reacted by increasing matrix metalloproteinase-2 and -9 and tissue inhibitors of metalloproteinase-2. With respect to total elastase activity and alpha-1 antitrypsin expression, increasing doses of relaxin appear to increase elastolytic activity in stress urinary incontinence cells by decreasing the expression of alpha-1 antitrypsin in proliferative phase cells or increasing the total elastase activity in secretory phase cells. Fibroblast total elastase activity was inhibited by increasing concentrations of alpha-1 antitrypsin. CONCLUSION: Elastase activity appears to be increased in relaxin-stimulated stress urinary incontinence fibroblasts by either decreased inhibitor (alpha-1 antitrypsin) production or increased elastase activity.     

Transperitoneal approach and right retroperitoneal dissection for abdominal aortic aneurysm

Most abdominal aortic aneurysms can be resected through a standard transperitoneal approach. In patients with large aneurysms, supra-renal extension of the aneurysm, those requiring renal reconstructive procedures and in patients who have had previous extensive intra-abdominal operations, alternative approaches have been recommended. We exposed the abdominal aorta in ten of these difficult patients using a midline transperitoneal incision and right retroperitoneal dissection that provided excellent exposure of the suprarenal aorta. We recommend this technique for performance of complicated abdominal aortic aneurysm resections.     

Clinical observations and lessons learned in the treatment of patients with thoracoabdominal aortic aneurysms

Thoracoabdominal aortic aneurysms can be repaired successfully with acceptable rates of morbidity and mortality. Twenty-three men and seven women (an average age of 67 years) underwent 23 elective and seven emergency operations. Pulmonary complications were the most common, but renal insufficiency and paraplegia were the most serious postoperative problems. The average time of suprarenal aortic occlusion was 47 minutes, but neither renal insufficiency nor paraplegia was directly related to suprarenal clamp time. Four deaths occurred after elective procedures, two from postoperative bleeding (one death from a technical error) and two deaths from multisystem organ failure. Four late deaths were caused by myocardial infarction. The remaining patients are alive at two to 79 months after infarction. DeBakey's technique (multiple sidearm grafts from the main aortic graft) was used in the first three procedures, and the graft inclusion technique of Crawford, in the remainder. The graft inclusion technique reduced operating time and loss of blood by 50 per cent and intraoperative fluid requirements by 33 per cent. Hypothermia was minimized by extraperitoneal, rather than intraperitoneal, abdominal aortic exposure, heated ventilation and warmed intravenous fluids. Selective renal cooling was performed by catheter perfusion of the renal arteries. Extreme care must be taken in making openings and attaching grafts to visceral arteries to avoid troublesome hemorrhage. In contrast with patients with infrarenal aneurysms, those with thoracoabdominal aneurysms require prolonged ventilatory support and have considerably higher fluid requirements. Precise surgical technique is mandatory.