Assessment of antithrombotic properties of sodium ibuprofen.

The effect of sodium ibuprofen on platelet activity in vivo and the lysability of ex vivo thrombi was investigated. The formation of a hemostatic platelet plug in the rabbit mesentery and platelet embolism as a response to a laser-induced injury in the ear chamber of rabbits were used as models for determining platelet activity. Ibuprofen at a dose of 25 mg/kg i.v. was found to increase the primary (PHT) and the total hemostatic plug formation time (THT). The same dose decreased the number of cumulative emboli over a 10 min period after a laser injury to arterioles. A dose of 10 mg/kg i.v. did not affect the formation of the hemostatic platelet plug. In dogs, doses of 10, 25 und 50 mg/kg did not enhance the release of 125I-FDP from the thrombi after incubation in plasmin, but the largest dose which is approximately five times the recommended dose in humans, did significantly decrease the thrombus weight 90 and 180 min after the drug administration. In conclusion, sodium ibuprofen was shown to have an inhibitory effect on platelet function in vivo and in large doses was also found to diminish the thrombus weight.

Male hypoplastic infrarenal aorta and premature atherosclerosis.

Hypoplasia of the abdominal aorta distal to the origin of the renal arteries may be a contributing factor in the development of early atherosclerosis. The abnormal aortic configuration and resultant increased stress forces may account for the localization of the disease to the aortoiliac segment. The increased frequency of single bifurcating lumbar arteries at the L4-L5 level, easily demonstrable on conventional arteriograms, suggests that the aortic hypoplasia may result from excessive fusion of the paired dorsal aortas during embryonic life. Hypoplasia of the infrarenal aorta is present in 9% of females with aortoiliac disease, and it is believed to be uncommon in males. A review of 408 peripheral arteriograms of males revealed 18 cases (4.4%) of hypoplasia of the abdominal aorta. Males with hypoplastic aortas develop symptoms 10 years earlier than those with normal-sized aortas and 10 years later than females with similar narrowing of the distal aorta.

Aspirin failure in symptomatic atherosclerotic carotid artery disease.

Over a 26-month period 27 urgent carotid endarterectomies were performed on patients who had been taking antiplatelet aggregating drugs for 6 months to 2 years. Angiography confirmed an original diagnosis of symptomatic extracranial carotid artery stenosis and ulceration in all patients. Nineteen had been started on dosages of aspirin from 325 to 1,300 mg/day, and eight started on aspirin plus persantine. Compliance to aspirin use appeared high. All had partial or total resolution of the ischemic symptoms after aspirin therapy was instituted. On readmission three patients had early stroke in evolution, and 24 had crescendo transient ischemic attacks. Reevaluation included cerebral angiography which confirmed progression of carotid artery disease to 90% or greater stenosis in each instance. All patients underwent successful carotid endarterectomies. A review of history of these 27 in the urgent group as opposed to the 45 symptomatic carotid patients who were electively operated on in the same time period revealed no significant (P greater than 0.10) differences in incidence of risk factors for atherosclerosis. However, none of the elective group had regularly taken aspirin. It would appear that aspirin decreased ischemic symptoms in the patients who underwent urgent operation by its antithromboxane effect, inhibiting platelet aggregation and embolization. However, aspirin appeared to have a deleterious effect on these patients by allowing their carotid disease to progress to a dangerous state by eliminating the symptoms of progressive carotid artery atherosclerosis or by accentuating the process of atherosclerosis possibly by inhibition of arterial prostacyclin.

Reduced thrombogenic characteristics of expanded polytetrafluoroethylene and polyurethane arterial grafts after heparin bonding.

The effect of bonding of heparin, via a glutaraldehyde-stabilized ionic complex, on the early thrombogenicity of polyurethane (PU) and expanded polytetrafluoroethylene (PTFE) (Gore-tex) as well as covalent bonding of heparin on PTFE was studied in vivo. Grafts 6 cm long and 4 mm in diameter were placed in the carotid arteries of sheep and perfused for 4 hours at 25 ml/min in order to accelerate thrombus formation. The thrombogenicity was determined by calculation of the percent of the luminal surface free of thrombus and patency. In addition, 32P-labelled platelet accumulation was determined in some of the grafts. The stabilized ionic bonding of heparin significantly reduced the early thrombogenicity of PU but had little effect on PTFE grafts; but the thrombogenicity of the latter was markedly decreased following covalent bonding of heparin. A regional distribution of platelet accumulation was found with the distal anastomoses showing the highest platelet deposition. By choice of an appropriate method of heparinization, a significant reduction of the thrombogenicity of PU and PTFE grafts was achieved.

Surgically induced carotid subclavian steal syndrome. Diagnosis by video dilution technique.

A rare occurrence of carotid subclavian steal syndrome following carotid subclavian bypass for arm ischemia was described. Blood flows in the carotid artery and carotid subclavian bypass, at rest and following arm exercise, were determined by video dilution technique during the angiographic procedure. There was no obstruction of the inflow or outflow of the proximal or distal anastomoses to account for the steal (55%). Rather, increased arterial flow to the subclavian artery due to the patient's status as a bilateral amputee was thought to be the cause. The diagnosis and subsequent correction by takedown of this bypass and conversion to an axillary-to-axillary bypass were performed. Video dilution technique offers a unique and accurate way to study steal phenomena in conjunction with routine angiography and does not add to the patient's cost or risk.

Carcinoma obstructing the left side of the colon.

The clinical course, operative treatment, and results of 129 patients with carcinoma obstructing the left side of the colon were reviewed. There were 64 cases of incomplete obstruction, all secondary to primary adenocarcinoma of the colon. Sixty-five patients had complete obstruction; 37 of these had primary adenocarcinoma of the colon, and the rest, cancer from other primary sites, largely the genitourinary tract. The operations involving colostomy only or colostomy as part of a staged resection resulted in high operative mortality and low long-term survival, in addition to a high rate of postoperative sepsis. Results of operations involving primary resection of obstructing tumor were superior in all the above factors studied.

Automated data management for clinicians. A low-cost approach.

A self-instructional general purpose clinical data management system using a low-cost microcomputer has been developed specifically for use by clinicians not famililar with computers. The system was designed to resemble the traditional manual method of data analysis, while the time-consuming and repetitive procedures intrinsic to the manual method have been replaced by automation. This system has been used to analyze a variety of clinical problems, including patient chart review, collation of laboratory research data, initiating a vascular registry, and calculations with trending of physiological and laboratory data in the intensive care unit. User acceptance has been uniformly positive.

Dynamic isotope aortoiliac assessment. Clinical, doppler, and arteriographic correlation.

In the presence of multiple tandem arteriosclerotic stenoses of the distal aorta, iliac, and lower extremity arteries, it may be difficult to ascertain which lesions are clinically and surgically important. Usually the history, physical examination, and arteriogram will resolve this issue. However, a recent report has stated that the rapid transit time of isotope from the distal aorta to the femoral arteries may be helpful. The relevance of this technique in surgical candidates with different clinical stages of vascular disease has yet to be demonstrated. We compared the use of this technique in surgical candidates with their clinical state and assessment of vascular disease by standard angiographic and directional transcutaneous Doppler techniques. Only modest benefit from the isotope transit was found, particularly when compared with the patient's clinical status of asymptomatic, claudicating, or limb salvage categories. We conclude that isotope transit times as currently measured are not as clinically important as previously reported. With further development, some trends may prove to be useful.

Effect of lumbar sympathectomy in distal arterial obstruction.

We developed a model that simulates distal arterial occlusive disease to determine the effects of sympathectomy on certain hemodynamic changes. Two groups of seven dogs each received unilateral distal popliteal artery ligation. Intra-arterial BPs, angiography, pulse volume recordings (PVRs), and photoplethysmograms were taken of the distal hind limb throughout the experiment. After ligation, PVR and distal hind limb pressures were lowered to less than half of the preligation values. Four days after unilateral distal popliteal artery ligation, group 2 dogs received lumbar sympathectomy on the same side as the ligation. One week after sympathectomy, the PVR amplitudes and pressures showed a transient significant rise. Two weeks after sympathectomy, the PVR pressures and amplitudes returned to the previous, diminished postligation values.

Malnutrition in veterans administration surgical patients. Updated standards.

A prospective nutritional assessment of 106 hospitalized Veterans Administration surgical patients was performed; 60 healthy, age-matched outpatient veterans were studied for controls. Standard biochemical and anthropometric indices were measured. Malnutrition was defined for each index as a value more than 2 SD below the mean established from the VA control population, the values from which were also compared with conventionally accepted published standards of malnutrition. Striking discrepancies in the incidence of abnormal nutritional indices in our patients were observed, depending on which standard was used. The frequencies of abnormal in our surgical patients using VA control values or published norms, respectively, were: albumin level, 43% vs 19%; hematocrit value, 38% vs 27%; total iron-binding capacity, 30% vs 37%; arm muscle circumference, 11% vs 0%; and triceps skin fold, 19% vs 35%. Future studies of nutritional assessment in hospitalized patients should use control subjects closely related to the target population in age and other demographic variables.

Recurrence of femoral anastomotic aneurysms.

Forty-two noninfected femoral anastomotic aneurysms that occurred after aortobifemoral bypass were repaired during a 7 year period. Twenty of these were recurrent aneurysms. In an attempt to define the cause of recurrence, a number of factors were studied including infection, suture failure, graft deterioration, defective graft manufacture, graft dilatation, and arterial degeneration. Five grafts in the primary group failed because of inherent defects in the graft structure. Two lightweight Dacron grafts showed generalized graft dilatation, and three unwrapped expanded polytetrafluoroethylene grafts had linear tears at the anastomosis. We believe that such graft degeneration does not represent a current problem because the polytetrafluoroethylene grafts now used are reinforced, and lightweight Dacron grafts are no longer made. Two primary femoral anastomotic aneurysms resulted from broken polypropylene suture. No infections were found in the primary or recurrent groups of aneurysms. Arterial degeneration adjacent to the anastomosis, consisting of a decrease in wall thickness due to loss of smooth muscle with proliferation of elastic fibers and disruption of elastic laminae, was a consistent finding in the remaining 15 primary femoral anastomotic aneurysms and all recurrent femoral anastomotic aneurysms. In many instances of primary femoral anastomotic aneurysm and in all instances of recurrent aneurysms dilatation of the Dacron graft with secondary arterial degeneration was believed to be the cause of aneurysm formation. Graft dilatation without fiber deterioration is an inherent problem in Dacron grafts and reportedly varies from 10 to 50 percent of the original graft diameter. This dilatation plus the use of initial graft diameters larger than the host artery leads to increased tension at the anastomotic site with subsequent arterial degeneration. For the aforementioned reasons, our current practice and recommendation is that repair of all anastomotic aneurysms be with expanded polytetrafluoroethylene grafts sized to approximate the host artery since its dilatation at sites of arterial pressure is minimal.

Occurrence of occlusive intimal changes in an expanded polytetrafluoroethylene graft.

A case report is presented demonstrating pathologic changes in the neointima that formed when a polytetrafluoroethylene (PTFE) graft was placed in a 35 year old white male with severe arteriosclerosis. Representative sections of the patient's artery and graft were taken which demonstrated considerable smooth muscle proliferation in both along with full wall healing in the latter. Partial oclusion of the total length of the PTFE graft by a process similar to that occurring in the patient's own arteriosclerotic arteries was found. The consistency and extent of the involvement (> 10 cm in length) would appear to preclude entities such as neointimal fibrous hyperplasia and may point to another consequence of intimal injury and full wall graft healing which may be an undesirable effect of arteriosclerotic metabolism in the human. It is conceivable that full wall graft healing in an arteriosclerotic individual may have untoward events that need to be further investigated as new graft materials are developed.

Alternative management of isolated iliac artery aneurysms.

Isolated iliac artery aneurysms are uncommon and frequently remain undetected until they reach significant size. Often their first clinical presentation is with rupture of the aneurysm. Direct surgical intervention has been the usual mode of treatment. Successful treatment of iliac aneurysms by alternative approaches in two elderly, debilitated patients is reported. Extra-anatomic bypass and catheter embolization were used in both resulting in a minimal in-hospital stay for the patients without morbidity or mortality.

Correction and monitoring of postoperative cerebral vasospasm.

There have been several case reports in which various hypertension-inducing regimens have been used in the treatment of postoperative cerebral vasospasm. Regimens have included the used of metaraminal bitarate, norepinephrine with intravascular volume expansion, and high-dose dopamine with mannitol and volume expansion. Clinical response has been very favorable. Our patient improved markedly after administration of dopamine and intravascular volume expansion. Little work has been done to document vasospasm as the cause of the ischemia or to demonstrate increased cerebral blood flow following treatment. We suggest that noninvasive Doppler flow velocity studies may be an ideal tool for the further assessment of these patients.

New techniques in the evaluation of cerebrovascular disease.

Numerous reports in the literature indicate that various noninvasive vascular techniques can now be used to evaluate atherosclerosis at the carotid bifurcation. This article reviews noninvasive screening techniques currently available and being developed. Particular emphasis has been placed on the practicality of these techniques as well as their limitations. Our conclusions are that noninvasive techniques cannot be used as definitive screening tests for cerebrovascular disease. Although these tests are frequently useful when positive, the false negative rate of these tests would appear to be significant and variable in different hands. Nonstenotic ulcers are usually not detected and total occlusion often not differentiated from stenosis. These tests should be viewed as the beginning rather than the end result of a developing field. At present, contrast arteriography remains the definitive test to evaluate the presence and significance of extracranial cerebrovascular disease.

Arterial wall thromboxane: dominance after surgery predisposes to thrombosis.

Ibuprofen reduces early occlusion and surface thrombogenicity of small-diameter polytetrafluoroethylene (PTFE) grafts in sheep. The following experiments were designed to determine the effects of cyclooxygenase inhibition by ibuprofen on long-term patency and arterial wall and graft neointima prostaglandin synthesis. Crossover PTFE grafts (internal diameter 4 mm) were interposed between the carotid arteries of 18 sheep. Nine animals were used as controls, and nine received ibuprofen, 10 mm/kg intravenously, 1 hour prior to surgery and then every 8 hours for the duration of the experiment. Grafts were removed either when they became occluded or routinely at 60 days. Arterial segments adjacent to anastomoses were removed at graft insertion and at graft removal for assay of arterial wall production of the prostaglandins 6-keto-PGF1 alpha and thromboxane B2 (TxB2). There was no difference in patency between control animals (four out of nine) and ibuprofen-treated (five out of nine) animals. Arterial segments removed before the administration of ibuprofen produced 2.59 +/- 1.48 nM/mg protein/20 min of 6-keto-PGF1 alpha and 2.59 +/- 1.38 nM/mg protein/20 min of TxB2. A single dose of ibuprofen reduced the levels of 6-keto-PGF1 alpha to 0.30 +/- 0.12 nM/mg protein/20 min and the levels of TxB2 to 0.78 +/- 0.41 nM/mg protein/20 min (p less than 0.01). When the grafts were removed, control animals showed a reduction of 6-keto-PGF1 alpha to 1.69 +/- 0.86 nM/mg protein/20 min, whereas TxB2 levels remained unchanged at 2.54 +/- 1.23 nM/mg protein/20 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental carotid stenosis due to fibrous intimal hyperplasia.

Although fibrous intimal hyperplasia has been reported to be involved in up to one-third of recurrences of carotid restenosis following endarterectomy, little is known of its origin. This prompted us to attempt to produce it experimentally. Fibrous intimal hyperplasia could not be induced in the canine carotid model using simple endarterectomy or endarterectomy with an autogenous vein patch angioplasty. Polytetrafluoroethylene graft angioplasties in the same model produced this lesion readily and usually led to stenosis or occlusion. The experimental and clinical lesion of fibrous intimal hyperplasia of the carotid artery and the lesion of intimal fibrous hyperplasia that occurs when prosthetic arterial grafts are placed into small and medium size arteries appear histologically similar and may be due to a common factor. A review of the factors available in our series, as well as those of others, leads us to believe that the common denominator is hemodynamic in nature. The experimental data showing stenotic fibrous intimal hyperplasia occurring with polytetrafluoroethylene patch angioplasties has been previously reported. These data indicate that polytetrafluoroethylene should cautiously be used for small and medium diameter arterial patch angioplasties.

Platelet function and coagulation parameters in sheep during experimental vascular surgery.

Various clotting parameters (prothrombin time, activated coagulation time, activated partial thromboplastin time, platelet counts, and platelet aggregation) were obtained from unanesthetized sheep and from sheep at various times during 5 hours of vascular surgery. The values obtained were not influenced by anesthesia and surgery and were consistent between sheep. Ovine platelets were less prone to aggregate in the presence of collagen, epinephrine, and ristocetin than those of man. Platelet aggregation induced by adenosine diphosphate was similar to that seen in man. Based on these parameters, the sheep would seem to be a reasonable model for experimental vascular surgery when results are to be applied to man.