Daniel S. Rush

Lower extremity ischemia in adults younger than forty years of age: A community-wide survey of premature atherosclerotic arterial disease

A retrospective community-wide survey identified 109 patients younger than 40 years of age with lower extremity ischemia: 72 men and 37 women, mean age 36 years (range 25 to 40 years), black-to-white ratio-1:1. Initially, 66 patients had claudication and 43 had severe ischemia. Cardiovascular risk factors were smoking (85%), hypertension (47%), coronary artery disease (30%), hyperlipidemia (27%), diabetes (25%), and visceral arteriopathy (17%). Unique risk factors included hypercoagulability (15%) and clinical arterial hypoplasia (15%). Twenty-three (21%) patients were treated medically; 74 (68%) underwent primary revascularization and 12 (11%) primary major limb amputation. Forty-six (53%) patients required secondary procedures, of which 34 (74%) were performed within 1 year of primary intervention. A total of 29 (27%) patients ultimately required amputation (10 bilateral). Women had higher prevalence of diabetes (p < 0.01), arterial hypoplasia (p < 0.05), and tendency for more severe ischemia (p = 0.11). No racial differences in severity of symptoms or outcome of treatment were found. By multiple logistic regression analysis, typical cardiovascular risk factors did not predict severity of symptoms, need for surgical treatment, or outcome. However, diabetes was associated with tissue loss (p < 0.05) and primary amputation (p < 0.001). Further, adjusted odds ratios indicate that arterial hypoplasia had a protective effect on distal vasculature (p < 0.05) and predicting need for revascularization (p < 0.05), but not on treatment failure. Hypercoagulability had the highest predictive value for presence of severe ischemia (p < 0.05), need for primary amputation (p < 0.01), and early failure of surgical treatment (p < 0.05).

Does open fasciotomy contribute to morbidity and mortality after acute lower extremity ischemia and revascularization

A retrospective review was undertaken of 127 lower extremity fasciotomies performed for compartment syndrome after acute ischemia and revascularization in 73 patients with vascular trauma and 49 patients with arterial occlusive disease. One hundred twelve (88%) fasciotomies were performed early (at the time revascularization); 15 (12%) were delayed because of late compartment syndrome diagnosis. Ninety-four (77%) patients had more than one accepted indication for fasciotomy. Double-incision fasciotomy was used in 98 (77%) extremities, single-incision fasciotomy was used in 19 (15%), and fasciotomy-fibulectomy was used in 10 (8%). Fasciotomies were closed in 88 (69%) patients an average of 14 days after surgery. Seven patients needed multiple skin grafting procedures or myocutaneous flaps to close the wound; none compromised limb salvage. Five other patients had minor wound infections that resolved. Functional status returned to preoperative levels by the time of discharge from the hospital in 59 (48%) patients. Thirty-one (24%) patients had residual lower extremity disability related to delayed union of the fracture (five), chronic neuropathy (20), leg swelling (one), or ischemic nonhealing fasciotomy wounds (three); two patients had unrelated disabilities. Fourteen (11%) amputations were required for refractory limb ischemia; two (1.6%) were required for wet gangrene of the foot, which infected the fasciotomy site; the others had open noninfected incisions. Eighteen (15%) patients died of cardiopulmonary failure or multisystem failure or both, without fasciotomy-related problems. Open fasciotomy for compartment syndrome after acute lower extremity ischemia and revascularization was associated with an increased risk of minor wound morbidity. However, limb loss and death resulted from persistent ischemia and underlying systemic disease processes or injuries, but not from open fasciotomy wound complications.

Prostacyclin, thromboxane A2, and prostaglandin E2 formation in atherosclerotic human carotid artery.

Prostaglandin (PG) formation In 16 atherosclerotic human carotid endarterectomy specimens was compared systematically with that of normal carotid artery from seven white pigs and six rhesus monkeys. Prostacyclin (PGI2) formation (plcomoles 6-keto- PGF1a/2 mln/100 μg homogenate protein plus 2 mM glutathlone [GSH]) of nonatheromatous Intlma adjacent proximal (276 ± 32, mean ± SEM) or distal (271 ± 14) to carotid plaque was comparable to that of normal carotid artery from white pig (272 ± 25, NS) and rhesus monkey (219 ± 41, NS), and was greater than stenotlc Intlma (156 ±17, p<0.01), sublntlmal plaque (168 ± 14, p<0.01), and ulceratlon (65 ± 16, p<0.01). GSH modulated PGI2 synthesis In all carotid specimens except areas of ulceratlon (p<0.05), but did not restore PGI2 formation In atheromatous fractions to basal level. No detectable arterial thromboxane A2 (TXA2) formation or GSH-dependent PGE2 Isomerase activity was observed. The decrement In atherosclerotic carotid artery PGI2 formation was focal (confined to the plaque) and may have been related to loss of effective GSH modulation. These conditions could contribute to a localized Imbalance between arterial PGI2 and platelet TXA2 with adverse vascular thromboregulatory consequences.

The safety, efficacy, and durability of external carotid endarterectomy

Results of 21 external carotid endarterectomies (ECEAs) in 19 patients with symptoms were reviewed retrospectively. No patients died or had new strokes referable to ECEA within 30 days of surgery. Overall, six (32%) patients died during an average 41 months of follow-up (range 1 to 134 months). Persistent symptoms followed five (71%) of seven ECEAs performed for cerebrovascular insufficiency or transient ischemic attacks. One patient treated urgently for an evolving stroke failed to improve and died after hospital discharge. Another patient with crescendo transient ischemic attacks had a preoperative deficit that did not resolve for 6 months and had a second stroke 2 years later. Another patient had a stroke after a contralateral carotid reconstruction but recovered. In contrast, only two (14%) of 14 ECEAs performed for monocular amaurosis fugax had persistent symptoms after surgery. Durability of 16 ECEAs was evaluated by arteriography or duplex scanning. Of six ECEAs closed primarily, three (50%) occluded, one has 60% restenosis, and only two (33%) had no restenosis (mean follow-up 36 months). Of 10 ECEAs closed by patch angioplasty, none occluded, 2 had 20% restenosis, and eight (80%) had no restenosis (mean follow-up 47 months). Life-table analysis indicated improvement in ECEA patency and durability with patch angioplasty (p = 0.011). From these data, ECEA can be performed with relative safety but is more effective for treatment of monocular amaurosis fugax in patients with a microembolic source at the external carotid origin. Patients with any other indications for ECEA did not benefit consistently from this operation.

Increased prostacyclin and thromboxane A2 formation in human varicose veins.

Increased urinary metabolites of the antiaggregatory vasodilator prostacyclin (PGI2) and the proaggregatory vasoconstrictor thromboxane A2 (TXA2) have been reported in deep vein thrombosis; however, the tissue(s) of origin is uncertain. Because little is known about the formation of PGI2 or TXA2 from its common precursor, prostaglandin (PG) endoperoxide H2 (PGH2), by varicose veins, we determined the formation of 6-keto-PGF1 alpha (the stable metabolite of PGI2), TXB2 (the stable metabolite of TXA2), and PGE2. Segments of normal saphenous vein and varicose vein (nine and six patients, respectively) were incubated with 10 microM [14C]PGH2 for 2 min at 37 degrees C; products were separated by thin-layer chromatography. Surface area and mass of normal and varicose vascular segments were 19.5 +/- 0.8 versus 18.8 +/- 0.6 mm2 and 11.6 +/- 1.4 versus 10.7 +/- 0.7 mg, respectively. Formation of 6-keto-PGF1 alpha and TXB2 by the segments of varicose vein was significantly increased over that of normal vein: 157 +/- 14 versus 243 +/- 17 pmole of 6-keto-PGF1 alpha (P less than 0.005) and 22 +/- 3 versus 35 +/- 5 pmole of TXB2 (P less than 0.01). The formation of PGE2 by segments of varicose vein was not significantly different from that of normal vein (201 +/- 9 vs 219 +/- 11, respectively). Deoxyribonucleic acid (DNA) content of normal and varicose vein was 1.69 +/- 0.12 and 1.51 +/- 0.13 mg per gram of tissue, respectively. The data suggest that the increased PGI2 formation may reflect increased activity or content of PGI2 synthase. The increase in TXA2 formation may reflect increased productivity or an increased presence of residual platelets or microemboli.

Prostacyclin and thromboxane A2 formation by atherosclerotic carotid artery: Comparison with normal aorta, saphenous vein, and platelets *

Prostacyclin (PGI2) and thromboxane A2 (TxA2) formation by whole-tissue segments of nine carotid endarterectomy specimens (CES), five normal aortic specimens (NAS), six saphenous vein specimens (SVS), and four platelet samples were determined by incubation with 10 mumol/L 1-14C-radiolabeled prostaglandin endoperoxide H2 (PGH2), and in other experiments with and without 10 mumol/L of CGS 13080, a TxA2 synthase inhibitor. PGI2 formation (expressed as picomoles 6-keto-PGF1 alpha/2-min incubation per sample) by nonatheromatous proximal intima of CES (307 +/- 23, mean +/- standard error) and distal intima of CES (260 +/- 22) was not statistically different; however, it was greater than atheromatous transitional plaque (159 +/- 13 pmol) (p less than 0.01) and ulceration regions (140 +/- 15 pmol) (p less than 0.01) of CES, NAS (204 +/- 16 pmol) (p less than 0.01), and SVS (165 +/- 9 pmol) (p less than 0.01). TxA2 formation (expressed as picomoles TxB2/2-min incubation per sample) by CES ulceration (51 +/- 2 pmol) was low but greater than proximal (17 +/- 2 pmol) (p less than 0.01), distal (19 +/- 3 pmol) (p less than 0.01), and transitional (23 +/- 3 pmol) (p less than 0.01) regions. TxA2 formation by NAS and SVS was not detected (less than 10 pmol). CGS 13080 inhibited TxA2 formation by CES below the limits of detection. Incubation of 1.9 x 10(5) intact platelets with 10 mumol/L of PGH2 formed a quantity of TxA2 equal to that of CES ulceration.(ABSTRACT TRUNCATED AT 250 WORDS)

Prostacyclin synthetase activity in human diabetic and nondiabetic vascular tissue

A decrease in the formation of prostacyclin (PGI2), a potent vasodilating and platelet antiaggregatory substance, has been implicated in the pathogenesis of diabetic vasculopathy. This defect, as well as others, may contribute to imbalances in the thrombo-regulatory system resulting in enhanced platelet aggregability, accelerated atherosclerosis, and subsequent vessel injury. Until recently the major thrust of relevant literature has been directed toward abnormalities in PGI2 quantity or function in vascular tissue from experimentally induced diabetic animal models. For the past 2 years our laboratory has studied prostaglandin metabolism in human diabetic and nondiabetic blood vessels. We determined prostacyclin synthetase (PGI2ase) activity in saphenous veins of diabetic and nondiabetic patients (HSV-D and HSV-ND) undergoing coronary artery bypass grafts and in tibial arteries and tibial veins of diabetic patients (HTA-D and HTV-D) and nondiabetic patients (HTA-ND and HTV-ND) undergoing limb amputation for arterial disease of the lower extremity. Carbon 14-labeled prostaglandin endoperoxide (PGH2) was incubated for 2 minutes with vascular microsomal protein. The products were separated via thin-layer chromatography and quantified by radiochromatographic scan. PGI2ase activity was determined by the formation of 6-keto-PGF1 alpha, the stable breakdown product of PGI2. Results of this study indicate that the microsomal fractions of all vascular tissues studied contain an active PGI2ase capable of forming PGI2; formation is enzymatic, as the amount of product increased with increasing microsomal protein concentration; there is no significant difference in PGI2ase activity between HSV-D and HSV-ND; PGI2ase activity in HTA-D and HTV-D is less than in HSV-D and HSV-ND.(ABSTRACT TRUNCATED AT 250 WORDS)

Lower Extremity Amputations in Adults Less Than Forty Years of Age: An Underestimated Risk from Premature Atherosclerosis:

Between 1987 and 1992, 57 patients aged twenty-five to forty (average, 34.0 ±4.5 years) underwent major lower extremity amputations in five community hospitals, including a Level II Trauma Center. Only 19 (33%) patients had traumatic amputations, 3 (5%) had malignant tumors, and 4 (7%) had juvenile-onset diabetes mellitus without atherosclerotic involvement of the large arteries. Thirty (53%) patients had premature atherosclerosis (PAS) of the lower extremities with end-stage renal disease (ESRD) present in half and related to diabetes in 12. All patients with ESRD required continuous dialysis therapy. Overall 19 (33%) patients in this study had diabetes. Of 32 patients < thirty-five years of age, 47% had traumatic amputations, and PAS was diagnosed in 28%. However, PAS was diagnosed in 84% of 25 patients > thirty-six years of age (OR= 14.3; P < 0.001). In total, 67 amputations were done. Twenty-one (68%) of 31 above-knee amputations (AKA) were performed in patients with PAS, and 26% of AKA were related to trauma. Of 10 bilateral amputations, 9 (90%) were done in patients with PAS. Patients with PAS had a high prevalence of risk factors for cardiovascular disease including smoking (87%), diabetes (50%), hypertension (50%), and hyperlipidemia (30%). Nine (30%) of the patients with PAS had hypercoagulable states. PAS was identified as the leading cause for major amputations among young adults in this community and was frequently associated with heavy smoking, diabetes, end-stage renal disease, and hypercoagulability.

Prostaglandin Endoperoxide Metabolism by the Human Carotid Artery

Prostacyclin (PGI2) synthesis is associated with maintenance of normal vascular function, and a fall in human vascular PGI2 synthesis has been associated with atherosclerosis (1,2). It has been proposed that a decrease in PGI2 production results in the loss or impairment of the vascular defense mechanism against platelet deposition which might favor thrombosis and the progression of atherosclerosis (1). A decrease in bioassayable PGI2 production by vascular sections from fatty streak (pre-atherosclerotic) and advanced atherosclerotic lesions has been reported (3). Little if any information is available concerning the activity of prostacyclin synthetase in vascular tissue immediately adjacent to advanced atherosclerotic plaques. An increase or decrease in the PGI2 generating capacity of these adjacent areas could represent a protective mechanism against or a predisposing factor for, respectively, the progression of atherosclerotic disease into these areas.

Ruptured Solitary Iliac Artery Aneurysms: A "Silent" Killer? Report of Four Cases and Review of the Literature

Between 1982 and 1991, 38 cases of ruptured solitary iliac artery aneurysm (SIAA) were reported in the English literature. Iliac artery aneurysms are frequently found in conjunction with abdominal aortic aneurysm (AAA); however SIAA is a rare entity. Review of the literature and 4 new cases revealed a diversity of clinical presentation that may be partially explained by various mechanisms of SIAA rupture. Different from rupture of the AAA, symptoms of ruptured or leaking SIAA may be obscure and even present as a chronic disease. Emergent operative management is mandatory and requires endoaneurysmorrhaphy with interposition graft for the common and external iliac aneurysms or ligation of internal iliac aneurysms. The reported mortality of up to 75% reflects the delay in diagnosis, lack of operative experience with this particular entity, and frequent associated complications.