Haem oxygenase activity in human umbilical cord and rat vascular tissues.

Carbon monoxide (CO) has been shown to affect vascular tone in smooth muscle cells and thus, may regulate regional or systemic blood pressure as well as fetoplacental vascular tone and fetal blood delivery. To assess the potential of vascular tissue to produce CO, we determined haem oxygenase (HO) activity through in vitro quantitation of CO production with gas chromatography and its inhibition by 33-66 microm of chromium mesoporphyrin (CrMP) in homogenate preparations of rat aorta and vena cava and human umbilical cord tissues. We compared these results to HO activity in rat heart and liver. We also discuss normalization of HO activity on a per mg protein as well as per g fresh weight (FW) tissue basis. We found that both rat vascular tissue HO activities (per g FW) were equal, but greater than that of heart (x3) and less than that of liver (x0.2). For human cord tissues, HO activities of artery and vein were equal, but greater than that of Wharton's jelly. Also, HO activity in rat vascular tissues was 3x greater than that of the human cord tissues. HO activity was completely inhibited by CrMP in rat heart (90 per cent) and liver (96 per cent), but incompletely (50-66 per cent) in both rat and human vascular tissues. We established that it is unlikely that other non-haem CO-generating processes account for this unique insensitivity of HO to CrMP inhibition. In fact, high concentrations of other potent metalloporphyrin inhibitors affected vascular tissue HO even less. We found that the degree of in vitro HO inhibition appeared to be related to the concentration of haem in the reaction medium. We conclude that the presence of HO activity in cord tissues supports the possibility that CO plays a role in fetoplacental blood flow regulation.

A study of nephrotoxin-induced acute tubular necrosis with 31P magnetic resonance spectroscopy.

Phosphorus magnetic resonance spectroscopy (31P MRS) was used to obtain in vivo spectra from rat kidneys undergoing acute tubular necrosis induced by a nephrotoxic dose of cephaloridine (CLD). Spectra were obtained 0, 24, and 48 h after injection of CLD (experimental group, n = 6) or saline vehicle (control group, n = 6). The nephrotoxicity of CLD was demonstrated by severely increased serum creatinine levels and the development of extensive proximal tubular necrosis in the CLD-injected rats, and the lack of such changes in the controls. 31P MRS showed an increase in the inorganic phosphate region signal (Pi, p = 0.004) and a decrease in the phosphodiester region signal (PDE, p = 0.01) in the experimental group by 48 h, whereas these parameters did not vary significantly in the control group during the experiment. Significant correlations were found between serum creatinine and the same two 31P MRS parameters. In summary, rat kidneys which have developed severe CLD-induced proximal tubular necrosis exhibit changes in the 31P spectrum 48 h after administration of the drug. The causes of these changes were not determined.

Staged infrainguinal revascularization: initial prosthetic above-knee bypass followed by a distal vein bypass for recurrent ischemia. A valid concept for extending limb salvage?

Optimal infrainguinal revascularization should provide limb salvage for the longest duration of time. It is not known whether limb salvage is longer with an initial below-knee popliteal or tibial in situ saphenous vein graft or with staged bypasses; that is, an initial above-knee popliteal prosthetic bypass if feasible, followed by a more distal vein graft should the above-knee prosthetic graft fail. A retrospective review of 197 lower extremity vascular reconstructions performed since 1976 utilizing polytetrafluoroethylene (PTFE), umbilical vein, or in situ saphenous vein was completed. The data were analyzed for differences in limb salvage and prevention of limb threatening ischemia among three subgroups: above-knee prosthetic bypass, below-knee or tibial in situ saphenous vein bypass, and staged reconstructions (above-knee prosthetic bypass with subsequent in situ bypass). The groups were similar with respect to severity of limb threatening ischemia as indicated by mean preoperative ankle-brachial indices. Cumulative secondary limb salvage at 36 months was 73 percent for prosthetic grafts in the above-knee position, 78 percent for in situ saphenous vein grafts in the below-knee or tibial position, and 87 percent for staged reconstruction with an initial prosthetic graft to the above-knee position followed by a distal in situ vein bypass when the prosthetic graft fails.

Efficacy of tissue plasminogen activator and urokinase in a canine model of prosthetic graft thrombosis.

Tissue plasminogen activator and urokinase were evaluated in a model of prosthetic graft thrombosis. In addition, the effects of thrombus age on lysability and the effect of thrombolytic agents on endothelium were examined. Polytef (polytetrafluoroethylene [PTFE]) grafts (3 mm X 3.5 cm) were placed in femoral arteries of dogs and graft thrombosis was induced. Grafts were treated with a local infusion of either urokinase or tissue plasminogen activator (4000 units/min) and the times for initial flow, complete thrombolysis, and anastomotic bleeding were noted. The luminal surfaces of the grafts and the proximal arterial segments were assayed for the production of thromboxane A2 and prostacyclin and examined with scanning electron microscopy. No difference in the ease of graft lysis was observed, but 50% of tissue plasminogen activator-treated vs 0% of urokinase treated grafts had extravasation of blood through the wall. Grafts treated with tissue plasminogen activator produced less thromboxane A2 and had less thrombus than those treated with urokinase. No differences between arteries exposed to either agent and control arteries were seen. Grafts treated 1,3,5, and 7 days after thrombosis were progressively more difficult to lyse. We conclude that tissue plasminogen activator is an effective thrombolytic agent, but has a potential for local bleeding complications. Grafts of PTFE are thrombogenic after lysis, but may be less so with tissue plasminogen activator than with urokinase. No effect on arterial endothelium was seen, and our studies confirm the clinical impression that older thrombi are more difficult to lyse.

The natural history of endothelial structure and function in arterialized vein grafts.

When the saphenous vein is used in the in situ position for arterial bypass surgery, it is associated with more optimal preservation of the endothelial lining and with improved graft patency compared with reversed vein grafts. However, it is not clear whether preservation of endothelial integrity persists after arterialization. The goal of this study was to establish whether preservation of the endothelium before arterialization is a critical factor in the development of late functional and morphologic abnormalities of autogenous vein grafts. Paired reversed and in situ vein grafts were created in 75 mongrel dogs. Veins to be used in the reversed position were excised and stored in either heparinized whole blood at 37 degrees C or saline solution at 4 degrees C. Veins were studied before and after arterialization. The veins were arterialized by anastomosis to the carotid artery and excised at intervals of 1 day to 12 weeks for studies of the luminal production of prostacyclin and thromboxane A2 in addition to luminal morphology. Before arterialization, normothermic whole blood preserved biochemical function of the endothelium significantly better than hypothermic saline solution, but not as well as the in situ vein procedure. Soon after arterialization, all three vein grafts showed significant functional and morphologic abnormalities consistent with injury of the vein graft. Morphologic healing of the endothelial monolayer progressed slowly back to normal; however, the biochemical capacity of the vein graft never matched that of the prearterialized vein, nor that of normal host arteries. Regardless of surgical technique, all vein grafts exhibited a period of abnormal structure and function, which exposed them to the risk of thrombogenesis. This period of potential leukocyte or platelet interaction with the vein wall could lead to release phenomena as well as proliferative changes in the vessel wall.

The role of computed tomography in symptomatic aortic aneurysms.

Forty-seven patients with an abdominal aortic aneurysm (AAA) and recent onset of abdominal or back pain were evaluated by emergency computed tomography (CT) to identify those patients with a confined rupture, and unstable aneurysm, nonaneurysmal cause of pain and a stable AAA. CT suggested that 25 per cent of these had a confined rupture and should undergo emergency surgical treatment. Rupture was confirmed at operation in one-half of these instances. Thirteen per cent avoided operation since other significant pathologic factors were identified. The remaining 47 per cent benefited from optimal preoperative evaluation and semielective surgical treatment. No patient ruptured an AAA during the delay for complete preoperative evaluation and preparation. Additionally, a preoperative CT is useful to identify patients with an unsuspected iliac, suprarenal, thoracic or inflammatory aneurysm. Thus, we believe that CT has a particularly important role in the evaluation of the symptomatic AAA, adding it to the list of indications for CT evaluation of difficult aortic disorders.

Venous stasis ulceration. Effectiveness of subfascial ligation.

Forty-seven extremities with recurrent venous ulceration were treated by subfascial ligation of incompetent perforating veins. The limbs were observed for an average of 8.5 years (range, 0.5 to 13 years). The risk for recurrence was 22%, 41%, and 51% at 1, 3, and 5 years, respectively. Patients with bilateral ulceration or prior venous ligation were at the highest risk for recurrence, while those with prior excision of prominent varicose veins had a reduced risk. There has been no loss of limbs or life secondary to this venous problem during the 398 cumulative years of observation.

Intrahepatic pyogenic abscesses: treatment by percutaneous drainage.

During a 6 year period, 18 liver abscesses in 12 patients were identified by computerized tomography. Five patients had presumed hematogenous seeding. Five patients previously had bilioenteric anastomoses, stents, or both to relieve obstructive jaundice. Four patients with abscesses had recent abdominal operations. Diagnosis was established by guided needle aspiration and treatment was provided by percutaneous catheter drainage. Organism-specific antibiotics were administered to all patients. Patients were evaluated for recurrence by serial computerized tomographic studies and were clinically followed up for a minimum of 15 months. Ten of 12 patients (83 percent) and 16 of 18 abscesses (89 percent) were successfully treated by percutaneous catheter drainage. Two failures required operative intervention. In summary, the low morbidity and high success rate in treating hepatic abscesses by percutaneous drainage suggests that this therapy be tried before operative intervention is considered.

In situ saphenous vein bypass grafts for limb salvage. A current fad or a viable alternative to reversed vein bypass grafts?

Revascularization of the lower extremity using the in situ saphenous vein bypass graft has resurfaced as a clinical alternative to reversal of the saphenous vein. Early patency rates have been excellent, however, concern has been raised about the durability of the in situ technique. Our total experience with this technique has been reviewed to evaluate its effectiveness on a teaching vascular service. Seventy-six limbs in 71 patients were revascularized using the in situ technique. The distal anastomosis was created at the below-the-knee popliteal level in 26 limbs and at the infrapopliteal level in 50 limbs. Operative assessment of the vein quality showed 42 percent to be phlebitic or less than 4 mm in diameter. Hospital mortality was 0 and late mortality was 8 percent. Cumulative life table analysis showed the graft patency rate to be 89 percent 1 month postoperatively, 82 percent at 1 year, 77 percent at 2 years, and 72 percent up to 4 year postoperatively. Patency was independent of runoff to the pedal arch and the level of the distal anastomosis. Limb salvage at 4 years was 83 percent for distal popliteal grafts and 79 percent for infrapopliteal reconstructions. Our results indicate that the long-term durability of the in situ saphenous vein graft is excellent despite suboptimal veins and poor runoff. When performed properly, it is the preferred technique for arterial reconstruction below the knee joint.

Expanded criteria for percutaneous abscess drainage.

The original criteria for percutaneous abscess drainage were limited to simple abscesses (well-defined, unilocular) with safe drainage routes. We expanded these entry criteria to include complex abscesses (loculated, ill-defined, or extensively dissecting abscesses), multiple abscesses, abscesses with enteric fistulas or whose drainage routes traversed normal organs, as well as complicated abscesses (appendiceal, splenic, interloop, and pelvic). Using these expanded criteria, cure was achieved nonoperatively in 92 (73.6%) of 125 abscesses with ten deaths (9%), and 11 complications (9%). Cure was achieved in 82% of simple abscesses, but only 45% of complex abscesses. There was no correlation between size, depth, drainage route, or etiology of the abscess (spontaneous v postoperative) with either cure or complications. We recommend a trial of percutaneous drainage in all simple abscesses and most complex abscesses with clinical response as the key determinant of the need for operative intervention.

Luminal release of prostacyclin and thromboxane A2 by arteries distal to small-caliber prosthetic grafts.

Myointimal hyperplasia distal to prosthetic grafts may be due to a local imbalance of prostacyclin and thromboxane A2 that exaggerates platelet adherence. This study evaluated prostacyclin and thromboxane A2 production by arteries distal to prosthetic grafts. In 12 dogs, control segments of both iliac arteries were excised and a 5 cm segment of polytetrafluoroethylene was grafted end to end. One iliac artery was circumferentially dissected from the distal anastomosis to the inguinal ligament. The contralateral artery was not dissected. Of the 24 grafts, 19 remained patent and the arteries distal to these grafts were studied. After excision, each artery was analyzed for its ability to produce prostacyclin and thromboxane A2. Our data indicate that the luminal surface of a normal artery spontaneously produces both prostacyclin and thromboxane A2 and that the arterial wall distal to a prosthetic graft produces increased levels of these arachidonic acid metabolites. However, only those arteries not surgically dissected maintain a normal balance of prostacyclin and thromboxane A2. The dissected artery may thus be more susceptible to platelet interaction and myointimal hyperplasia.

Percutaneous drainage of infected pancreatic pseudocysts.

After diagnostic needle aspiration guided by computed tomography and/or ultrasound, 11 infected pseudocysts in ten patients were treated nonoperatively by percutaneous catheter drainage and intravenously administered antibiotics. Nine infected pseudocysts resolved after 11 to 37 days (mean, 21 days) with no recurrences at follow-up 16 to 42 months (mean, 24.4 months) later. All were confirmed by Gram's stain, culture, and elevated amylase levels. Ten of the pseudocysts were acute; one was chronic; five were polymicrobial; six had a single organism. There were no major complications. There was one failure when a pancreatic abscess developed in a patient who died following operative drainage. There was one successful palliation of a postoperative-infected pseudocyst in a patient with an obstructing nonresectable carcinoma of the head of the pancreas. A trial of percutaneous catheter drainage is indicated in patients with infected pancreatic pseudocysts.

Functional injury of vein graft endothelium. Role of hypothermia and distention.

The cause of endothelial injury during vein harvesting and preservation is complex. Hypothermia is thought necessary to preserve cell viability but has been implicated in morphologic injury to the endothelium. This study explored the effect of temperature on preserving endothelial function using prostacyclin production as a metabolic marker. Canine veins were atraumatically excised and matched segments were stored at three temperatures using either nutrient medium or heparinized saline. After storage, endogenous production of prostacyclin by the luminal surface of each vein was collected in a closed perfusion system at 37 degrees C and assayed by radioimmunoassay. Optimal prostacyclin production was observed in veins stored in tissue culture medium at normothermia. Preservation of normal endothelial function may require revision of traditional vein graft-harvesting techniques.

Stroke after carotid endarterectomy: risk as predicted by preoperative computerized tomography.

In patients undergoing carotid endarterectomy, the role of preoperative computerized tomographic head scanning in predicting the risk of postoperative neurologic deficit was determined by a retrospective evaluation of a select group of 107 consecutive patients with preoperative scans. Patients with infarction determined preoperatively by computerized tomography were found to be at a significantly higher risk for postoperative neurologic deficit than patients with a normal preoperative computerized tomographic scan. History and physical examination alone detected only 66 percent of the infarctions found with preoperative computerized tomographic scanning in these patients. Because the incidence of infarction revealed computerized tomography in patients with symptoms of a reversible ischemic neurologic deficit was 22 percent, we have proposed a new definition of reversible ischemic neurologic deficit to include the necessary finding of a normal computerized tomographic scan. Patients who presented with transient ischemic attack and the unexpected finding of a subclinical infarction on the preoperative scan were at the same significantly higher risk for postoperative stroke and a permanent neurologic deficit. Computerized tomographic scanning of potential carotid endarterectomy patients is of benefit not only to rule out other sources of neurologic symptoms, but also to predict more accurately the risk of postoperative neurologic deficit.

Favorable balance of prostacyclin and thromboxane A2 improves early patency of human in situ vein grafts.

Graft thrombosis soon after reconstruction remains a major obstacle to the use of reversed vein grafts in infrapopliteal reconstruction. Our clinical experience with in situ vein grafts corroborates Leather's results by demonstrating an overall graft patency of 95% below the knee at 1 year and 94% in the infrapopliteal group. It has been postulated that this improved early patency rate of in situ vein grafts is the result of more optimal preservation of the endothelium of the vein graft. To investigate this hypothesis, human saphenous veins were handled by an in situ and a reversed technique. The intact vein segments were then tested for luminal production of prostacyclin and thromboxane A2 and fixed for scanning electron microscopic analysis of the surface morphology. This study demonstrated that endothelial cell prostacyclin release is enhanced in human in situ vein segments but not in reversed vein segments. In addition, luminal production of thromboxane A2 is significantly greater in the reversed than in the in situ vein segments. These findings are associated with marked endothelial structural damage in the reversed veins and minimal endothelial disruption in the in situ veins. Therefore the ratio of the antiaggregatory vasodilator prostacyclin to the proaggregatory vasoconstrictor thromboxane A2 is significantly more favorable for the in situ vein segment than for the reversed vein segment. The observed excellent early patency of the in situ vein grafts in our poor-risk patient population may in part be the result of this favorable balance of prostacyclin and thromboxane A2 and the more optimally preserved endothelial morphology.

Combined operative angiodilation and arterial reconstruction for limb salvage.

Fifteen high-risk patients with threatened limb loss underwent combined operative iliac angiodilation and infrainguinal vascular reconstruction for iliac and femoropopliteal occlusive disease. The patients were poor candidates for combined surgical inflow and outflow reconstruction because of associated cardiopulmonary disease. The mean systolic pressure gradient across the iliac stenosis was 34 +/- 5 mm Hg. Iliac artery angiodilation was accomplished intraoperatively and reduced all gradients to zero. Stenoses in the distal portion of the deep femoral artery were endarterectomized in nine patients, and six cross-femoral and six distal popliteal or tibial grafts were constructed. Life-table analysis at 36 months showed iliac patency in 86% of cases and successful distal reconstruction in 76%. Our limb salvage rate of 86% suggests that combined intraoperative angiodilation by the angiographer and arterial reconstruction by the vascular surgeon may provide effective therapy for high-risk patients.

Prevalence of normal serum amylase levels in patients with acute alcoholic pancreatitis.

Acute alcoholic pancreatitis is uncommonly diagnosed when the serum amylase level is normal. We defined acute alcoholic pancreatitis as a clinical syndrome in which hyperamylasemia was not a necessary component and sought support for the diagnosis by ultrasonography and computed tomography of the pancreas. In 68 episodes of acute alcoholic pancreatitis identified in a one-year period, the serum amylase level was normal at the time of hospital admission in 32%. In 40 episodes, we performed ultrasonography and computed tomography within 48 hr of admission. The diagnosis was supported by ultrasonography in 43%, by computed tomography in 68%. Ultrasonography and computed tomography supported the diagnosis as frequently in patients with normal serum amylase levels as in patients with hyperamylasemia. We conclude that patients with acute alcoholic pancreatitis frequently have normal serum amylase levels. The widespread clinical practice of relying solely on hyperamylasemia to establish the diagnosis of acute alcoholic pancreatitis is unjustified and should be abandoned.

Direct venous surgery for venous valvular insufficiency of the lower extremity.

Seven patients had severe deep venous insufficiency and recurrent ulceration in eight lower extremities. All incompetent perforating veins had been previously ligated. All limbs were evaluated by dynamic venous pressure measurements. The venous pressure reduction with exercise was recorded, as well as the recovery time. The most accurate indicator of venous valvular incompetence was a short postexercise recovery time. Abnormal hemodynamic findings were correlated with ascending and descending venographic findings. Based on these anatomic and pathophysiologic abnormalities, patients underwent valvular transposition, superficial femoral vein valvuloplasty, or superficial femoral vein ligation. Immediate postoperative recovery time (mean +/- SEM) was improved to 34.5 +/- 18.3 s from 7.9 +/- 2.9 s preoperatively. Postoperative venography demonstrated patency of all anastomoses and absence of reflux into previously incompetent venous systems. All limbs were symptomatically improved after operation, and no venous thrombosis or pulmonary emboll developed. Persistent ulceration, however, continued in one limb.

Distal in situ saphenous vein grafts for limb salvage. Increased operative blood flow and postoperative patency.

Early failure remains a major obstacle to successful distal bypass surgery using vein grafts for limb salvage. Thirty distal bypass graft procedures were performed for limb salvage using the in situ technique. Grafts were anastomosed to the distal popliteal artery in 13 patients and to the infrapopliteal artery in 17 patients. Sixteen patients had inadequate saphenous veins for reversed vein grafts. The mean blood flow measured through these grafts (n = 20) was 164 +/- 22 ml/min and increased to 278 +/- 31 ml/min after administration of 30 mg of papaverine. All grafts were patent at the time of hospital discharge and patients were followed for 1 to 28 months. Life table analysis of the 30 procedures shows a patency of 100 percent at 18 months follow-up. One graft subsequently failed at 22 months. Long-term limb salvage was achieved in 100 percent of the patients in this series. The excellent blood flow through these grafts suggests that the in situ vein graft technique may be more favorable for arterial reconstruction than the reversed vein graft technique. Our preliminary data confirm the observations of Leather et al [3,4], that the rates of vein utilization and graft patency are higher with the in situ technique.