Transcutaneous oxygen measurements predict a beneficial response to hyperbaric oxygen therapy in patients with nonhealing wounds and critical limb ischemia.

Hyperbaric oxygen (HBO) therapy may be a useful adjunct in the treatment of patients with wounds associated with critical limb ischemia. These patients either cannot undergo a successful bypass or may not heal after vascular reconstruction alone. Identification of patients likely to benefit from HBO is essential before treatment, as this therapy is time-consuming, costly, and not without risk. Transcutaneous oxygen measurements (TCOM) can be used to evaluate the degree of hypoxia in ischemic tissue. In this study we evaluated whether TCOM could be used to identify those patients who would or would not benefit from HBO therapy. Our hypothesis is that a difference in transcutaneous oxygen tension readings measured near the ischemic lesion with the patient breathing room air and while breathing 100 per cent oxygen at ambient pressure may be predictive of wound healing with adjunctive hyperbaric oxygen therapy. Thirty-six patients with critical limb ischemia and nonhealing ulcers were referred for HBO therapy. They were deemed either nonreconstructible from a vascular surgical viewpoint, had failed prior revascularization attempts, or could not achieve complete wound healing even after a successful revascularization. Pretreatment assessment included a room air and post-100 per cent-O2 challenge TCOM reading obtained in the vicinity of the open wound. Hyperbaric oxygen treatments at 2.0 to 2.5 atm were then administered until healing occurred or failure was confirmed. All patients undergoing HBO had a baseline TCOM of <40 torr. Twenty-seven patients had an increase in TCOM of >10 torr with oxygen inhalation at initial evaluation. Of these patients, 19 (70%) healed their wounds with HBO therapy. Conversely the increase in TCOM was <10 torr in nine patients, and only one of these patients (11%) ultimately healed (P < 0.01). Patients with nonhealing ischemic extremity wounds may heal with adjunctive HBO therapy. We can predictably identify patients who are likely to benefit from this modality using TCOM at the time of initial evaluation. An increase of tissue O2 tension of > or =10 torr when breathing pure O2 suggests that the patient may benefit from HBO therapy. Those patients with an increase of <10 torr are unlikely to receive benefit from this treatment modality.

Supervised training of general surgery residents in carotid endarterectomy performed on awake patients under regional block is safe and desirable.

Previous studies have documented the safety and efficacy of general surgery residents and vascular fellows performing carotid endarterectomy (CEA) under the supervision of an attending surgeon. With the proper supervision of the attending surgeon, these operations can be performed with an acceptably low perioperative stroke and mortality rate. The question remains, however, whether these desirable results can be obtained by general surgery residents when operating on awake patients under regional block (RB) anesthesia. We set out to determine whether it is prudent to promote this technique in this teaching setting. We analyzed 128 CEAs performed at a community teaching hospital training three chief residents a year. These operations were performed by residents under the direct supervision of a single attending vascular surgeon. RB was preferred and was used in 67 operations. General anesthesia (GA) was used in the remaining 61 procedures. Overall mortality was 0 per cent. Patients in the RB group were converted intraoperatively to GA in 4 of 67 (6%) procedures. There was one perioperative stroke in this series (1/128, 0.78%), occurring in a patient under RB (1/67, 1.5 %) leaving the patient with a minor sensory deficit. No strokes occurred in the GA group. There were five temporary cranial nerve deficits (3.9%). Three were in the RB group (4.5%) and two in the GA group (3.3%). General surgery residents can be trained in the performance of carotid endarterectomy using regional block anesthesia in awake patients without compromising patient safety. Suggestions to the effect that only attending physicians and/or vascular fellows can perform these procedures under regional block are without merit.

Increased oxygen extraction as adaptation to acute renal ischemia.

Acute renal ischemia is an infrequently encountered clinical entity with occasionally devastating consequences. The renal compensation to acute ischemia is unknown and is the purpose of this report. Eight pigs were anesthetized and ventilated. Left atrial, aortic, CVP, left renal venous, and ureteral catheters were inserted. Renal blood flow (RBF) reduction was accomplished by the graded constriction of the left renal artery using a balloon occluder. Renal oxygen extraction ratio (RER, %), renal oxygen delivery (RO2D, cc/min per 100 gm), renal oxygen consumption (RVO2, cc/min/100 gm), creatinine clearance (CrCl, ml/min), and renal lactate production (delta [L], mg/min per hgm) were measured at baseline and following sequential 90-minute intervals of moderate and then severe left renal flow reduction. Significant increases in renal oxygen extraction were observed when RBF was severely limited (.30 +/- .05 vs .64 +/- .06, p < .01). CrCl decreased precipitously (16.5 +/- 4.6 vs 0.2 +/- 0.07, p < .05). Lactate production by the ischemic organs correlated with blood flow reduction (r = .546, p = .0034). In severe ischemia, healthy kidneys increase oxygen extraction to preserve oxygen consumption.

In-vitro assessment of the behavior of magnetic resonance angiography in the presence of constrictions.

RATIONALE AND OBJECTIVES: Time-of-flight magnetic resonance angiography (TOF/MRA) is increasingly used to assess the nature and severity of stenotic blood vessels. Flow artifacts associated with high flows and/or narrow constrictions may confuse the interpretation of these studies. Accurate TOF/MRA evaluations demand an understanding of the nature of these flow effects. METHODS: A two-dimensional TOF pulse sequence was used to acquire images of five smoothly constricted phantoms at various flows. Analysis included assessment of phantom appearance and quantification of apparent constriction diameter and signal variations. RESULTS: Most notable flow phenomena were a cone-shaped region of high signal, a region of signal void, and signal preservation along the wall. When visible, constriction diameter was accurately measured. CONCLUSIONS: The behavior observed in TOF/MRA images can be understood by considering the contributing mechanisms of phase dispersion, turbulence, poststenotic flow eddies, flow reversal, and flow separation.

Abnormalities in the biosynthesis of type III procollagen in cultured skin fibroblasts from two patients with multiple aneurysms.

We examined the synthesis of collagenous proteins by cultured skin fibroblasts taken from 14 patients with an abdominal aortic aneurysm and either an aneurysm at a second site (8 patients) or a first order relative with an abdominal aortic aneurysm (6 patients). Fibroblasts were labeled with [3H] proline and, following pepsin digestion of media proteins, the ratio of type I/III collagen was examined by denaturing polyacrylamide gel electrophoresis (SDS-PAGE). With the exception of two patients, the ratio of type I/III collagen in the media of fibroblasts from aneurysm patients was similar to control values (6 controls). In two of the patients, the type I/III collagen ratio was greater than 3 standard deviations from the mean of both control ratios and those of other aneurysm patients. mRNA levels coding for type III procollagen, however, were normal in both patients. Patient #1 (ME) showed reduced type III procollagen on SDS-PAGE analysis of intracellular proteins. Intracellular and media type III procollagen levels were normal in patient #2 (HR), but media type III collagen was reduced by over 50% after digestion with a combination of trypsin and alpha-chymotrypsin for 5 minutes at 36 degrees C. Control type III collagen was only reduced after digestion at 39 degrees C. These data suggest an altered thermal stability of the type III collagen trimer synthesized by this patient, probably due to a mutation in the amino acid sequence. The data presented in this paper suggest that some forms of common abdominal aortic aneurysms may be caused by mutations in the gene coding for type III procollagen.

The comparative evaluation of three-dimensional magnetic resonance for carotid artery disease.

Conventional angiography is the current standard for the evaluation of carotid artery disease. The excellent resolution of this invasive study is offset by the potential for contrast-related, embolic, and puncture site complications. Three-dimensional magnetic resonance angiography may offer a noninvasive diagnostic alternative. We examined this possibility by performing both conventional angiography and three-dimensional magnetic resonance angiography in 13 patients. Cervical duplex scans were also obtained in these patients. Contiguous transverse cervical magnetic resonance images were acquired in a 1.5 tesla magnet, by use of a posterior neck coil and a gradient echo pulse sequence. These "raw" data were transferred to a real-time workstation where three-dimensional cervical arterial images were reformatted, magnified, and examined from multiple angles. Total study time from patient positioning to image generation was approximately 30 minutes. In all patients, on three-dimensional magnetic resonance angiography the common, external, and internal carotid arteries and distal vertebral arteries were easily discernable and correctly identified as patent, stenotic, or occluded. Three-dimensional magnetic resonance angiography was not accurate in detecting carotid ulcers. The degree of internal carotid artery stenosis measured from the three-dimensional magnetic resonance angiography studies correlated well with the internal carotid artery stenosis measured with conventional angiography (r = 0.866, r2 = 75.1%, p = less than or equal to 0.0001). This recent technologic advance represents significant progress toward achieving the goal of completely noninvasive vascular assessment in this patient population.

Hypertension sustains plaque progression despite reduction of hypercholesterolemia.

To assess the effect of hypertension on diet-induced coronary artery plaques after a return to a nonatherogenic diet, 10 cynomolgus monkeys were fed an induction regimen containing 2% cholesterol and 25% peanut oil for 6 months and then were subjected to midthoracic aortic coarctation to induce hypertension. The animals were then fed a nonatherogenic "prudent" ration for 6 additional months (hypertension-regression group). Twelve additional monkeys were fed the atherogenic diet for 6 months; six were killed (lesion-induction control group) and six were changed to the prudent diet for 6 additional months without coarctation (normotension-regression control group). At the end of the induction period, cholesterol levels averaged 744 +/- 178 mg/dl for the 22 animals and were similar for the three groups throughout the induction period. For the animals restored to the nonatherogenic diet (hypertension-regression and normotension-regression groups), serum cholesterol levels fell to 486 +/- 252 mg/dl at 1 month, to 341 +/- 162 mg/dl at 2 months, and to 234 +/- 78 mg/dl at 6 months. There was no significant difference between the hypertensive and normotensive animals. Six months after coarctation, blood pressure proximal to the coarctations for the hypertension-regression group ranged from 100/60 to 220/145 mm Hg with a mean of 166/103 +/- 36/28 mm Hg. Cross-sectional area of coronary plaques was somewhat lower for the normotension-regression control group compared with the lesion-induction control group, but the difference was not significant. Plaque area was, however, markedly greater in the hypertension-regression group than in either the lesion-induction or the normotension-regression groups (p less than 0.05 for each) despite progressive reduction in hyperlipidemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Interleaved magnetic resonance and ultrasound by electronic synchronization.

Increasing attention has been directed toward using magnetic resonance imaging (MRI) to assess blood flow velocity. Complete acceptance of this application requires validation of MRI-derived flow measurements against an accepted flow measurement technique such as Doppler ultrasound in an in vivo situation. To provide an accurate correlation in the presence of rapid changes in blood flow, the MR acquisition should be made nearly simultaneously with the ultrasonic measurements. Unfortunately, standard ultrasound equipment generates radio frequency signal which interferes with MRI. Near-simultaneous acquisition of MR data and ultrasonic blood flow data should be possible if the two measurements are properly synchronized. In the technique presented, ultrasound is made to peacefully coexist with MRI by gating the ultrasound so that it is disabled during the time of MR data acquisition. Phantom and animal experiments confirm the use of this procedure. Although we did not specifically test new fast-scan MR techniques, our technique is completely general and should work equally well with spin-echo as well as newer fast scanning MRI techniques.

Can intraoperative prebypass arteriography substitute for the preoperative arteriogram?

Preoperative contrast arteriography is presently considered a requirement when planning infrainguinal arterial reconstructions in patients with limb-threatening ischemia. We reviewed the clinical data from 22 infrainguinal bypasses done in 20 patients to see if appropriate decisions concerning operability and the nature of the operation could be made from the physical examination and noninvasive data supplemented by a limited intraoperative on-table prebypass arteriogram. The presence of a normal femoral pulse with either a normal thigh pulse volume tracing or a normal high-thigh index assured adequate inflow to the groin level. The presence of an arterial Doppler signal at the ankle level, heard with a hand held Doppler, confirmed the presence of patent outflow vessels for the distal anastomosis. The exact site of the distal anastomosis could be determined with the on-table prebypass arteriogram. In patients with limb-threatening ischemia due to occlusive disease limited to the infrainguinal arterial tree, an appropriate operative bypass may be performed without the aid of the preoperative arteriogram.

One hundred percent oxygen reverses muscle hypoxia in a rat hindlimb model of acute arterial occlusion.

Significant morbidity results from extremity ischemia after acute arterial occlusion. Reestablishment of arterial flow is considered to be the ideal treatment, yet substantial tissue loss can occur before this is accomplished. Using a rat hindlimb model we investigated whether the administration of 100% oxygen would decrease tissue hypoxia from acute arterial occlusion. Adult male Sprague-Dawley rats were used, and Po2 recordings were taken from the gastrocnemius muscle by use of an oxygen electrode. Baseline muscle Po2 was recorded, and then the femoral artery was occluded. Repeat recordings were made after 20 minutes of ventilation with room air and after an additional 20 minutes of ventilation with 100% oxygen (N = 10). Control groups consisted of animals undergoing occlusion but continued on room air (N = 3) and animals undergoing sham occlusion but receiving the period of 100% oxygen ventilation (N = 3). Femoral artery occlusion produced a reduction in muscle Po2 from 28.0 +/- 1.4 to 6.1 +/- 2.0 (mean +/- SEM, p less than 0.001). Ventilation with 100% oxygen reversed the tissue hypoxia produced by occlusion (27.3 +/- 2.0, p less than 0.001). The administration of 100% oxygen without femoral artery occlusion resulted in a higher tissue Po2 than the occluded + oxygen group (94 +/- 12 vs 27.3 +/- 2.0, p less than 0.001). Mean arterial blood pressure increased in the experimental group concomitant with the administration of 100% oxygen, but there was no correlation between final blood pressure and final tissue oxygen tension.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic resonance imaging of acute occlusive intestinal ischemia.

The mortality of acute superior mesenteric artery occlusion and mesenteric infarction remains high, in part because of the failure to identify the patients with the disorder. A reliable noninvasive diagnostic study may facilitate earlier definitive diagnosis and therapy. Proton magnetic resonance imaging may offer a noninvasive diagnostic alternative. We examined this possibility by using an experimental rabbit model of acute superior mesenteric artery occlusion in this study. Animals were scanned 1 hour after the ischemic insult. Relative intestinal wall signal intensity was increased in experimental (ischemic) animals when compared to sham operated controls on T2-weighted (4.35 +/- 0.5 vs 2.57 +/- 0.31, p less than 0.02) and proton spin density-weighted images (2.1 +/- 0.2 vs 1.4 +/- 0.21, p less than 0.05). Significant increases in image intensity were found on T2-weighted and proton spin density images when compared to control animals. Differences between groups could be further highlighted after the administration of a paramagnetic contrast agent gadolinium diethyltriamine pentacetic acid on T1-weighted images. The data from this preliminary study demonstrate that proton magnetic resonance imaging may be used to discriminate between ischemic and nonischemic small intestine. This noninvasive tool may someday become clinically useful to enhance our diagnostic capabilities when a diagnosis of acute superior mesenteric artery occlusion is being entertained.

Catheter occlusion of a mycotic renal artery aneurysm with cure of associated renovascular hypertension.

We describe successful transcatheter occlusion of a mycotic renal artery aneurysm. The patient's hypertension resolved following occlusion of the aneurysm and infarction of the renal parenchyma in the distribution of the aneurysmal vessel.

Shear stress regulation of artery lumen diameter in experimental atherogenesis.

We studied the adaptive response of the arterial wall and intimal thickening under conditions of increased flow in an atherogenic model. Blood flow was increased by construction of an arteriovenous fistula between the right iliac artery and vein in six cynomolgus monkeys fed a diet containing 2% cholesterol and 25% peanut oil. The left iliac artery served as the control. Serum cholesterol increased from 135 +/- 22 mg/dl to 880 +/- 129 mg/dl during the experiment. After 6 months, blood flow in the right iliac artery (420 +/- 95 ml/min) was 10 times greater than in the left iliac artery (44 +/- 9 ml/min, p less than 0.005). Flow velocity in the right iliac artery (31 +/- 6 cm/sec) was more than twofold greater than in the left (12 +/- 1 cm/sec, p less than 0.05). Despite the marked difference in blood flow and flow velocity, calculated wall shear stress was the same in both the right (16 +/- 4 dynes/cm2) and left iliac vessels (15 +/- 2 dynes/cm2) because of a twofold increase in lumen diameter (p less than 0.001) of the right iliac artery. Shear stress in the aorta was also normal (12 +/- 2 dynes/cm2). There was no difference in plaque deposition or mean intimal thickness between the right and left iliac arteries. In the right iliac artery there was a twofold increase in media cross-sectional area (p less than 0.001) but no change in media thickness or total wall thickness. Tangential wall tension and tangential wall stress were two times greater on the right than on the left (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

31P nuclear magnetic resonance spectroscopy: noninvasive biochemical analysis of the ischemic extremity.

The biochemical effects of peripheral vascular disease on skeletal muscle have not been characterized precisely because of the lack of satisfactory noninvasive analytic methods. 31P nuclear magnetic resonance (NMR) spectroscopy was used to measure the high-energy phosphate compounds, phosphocreatine (PCr) and adenosine triphosphate, as well as metabolic byproducts, such as inorganic phosphates (Pi) and phosphate monoesters in calf muscles of 214 limbs with peripheral vascular disease. Intracellular pH was also measured. The NMR index (Pi[PCr + Pi]) was used to quantitate the impairment of oxidative phosphorylation as a result of ischemia. Studies done at rest documented the impairment of oxidative metabolism only in limbs with severe ischemia (ankle-brachial pressure index (API) less than 0.4). Exercise resulted in a significant elevation of the NMR index in all limbs and the rate of return of this value toward normal following exercise was prolonged even in limbs with moderate ischemia (0.4 less than or equal to API less than or equal to 0.9). Correlation of 31P NMR parameters with arteriograms showed that infrapopliteal occlusions resulted in prolonged recovery times only when the superficial femoral artery was occluded and emphasized the metabolic consequences of multisegmental disease. Accumulation of glycolytic pathway intermediates correlated with the decrease in muscle cell pH observed with exercise. Despite immediate improvement in symptoms and hemodynamic parameters following revascularization, return to normal biochemical function occurs over a prolonged period of time. This study demonstrates that 31P NMR spectroscopy can successfully measure noninvasively the important phosphorus-containing compounds involved in the bioenergetics of skeletal muscle in vivo rapidly enough to permit real-time determination during exercise and recovery.

Increased collagenase activity in early aneurysmal dilatation.

Increased collagenase activity has been implicated as a basic abnormality in aortic aneurysm formation. We studied a localized aneurysmal change, poststenotic dilatation, and its relation to collagenase and elastase activity of the aortic wall. Cynomolgus monkeys underwent midthoracic aortic coarctation to produce poststenotic dilatation. Serial angiography showed that poststenotic dilatation was minimal or absent at 10 days, just discernible at 3 months, and prominent at 6 months. At the 3-month time interval, collagenase activity in the region of the poststenotic dilatation increased twofold compared with the same region in aortas from animals without poststenotic dilatation (p less than 0.05). There was no change in aortic elastase activity. These data indicate that collagenolysis and aneurysmal dilatation may be induced by local modifications of pressure and/or flow. Increased collagenase activity associated with abdominal aortic aneurysms may not represent an intrinsic metabolic defect but rather a response to altered hemodynamic conditions.

Role of medial lamellar architecture in the pathogenesis of aortic aneurysms.

The human abdominal aorta is particularly susceptible to the formation of aneurysms with atrophic walls. This aortic segment normally has fewer medial lamellar units than would be expected for a mammalian aorta of comparable diameter as well as far fewer medial vasa vasorum than would be expected for an aortic wall of comparable thickness. To test the hypothesis that ischemia and/or loss of normal lamellar architecture are predisposing factors for aneurysm formation, we used the pig thoracic aorta, which is furnished with 75 medial layers and vasa supplying the outer two thirds. Vasal blood flow was surgically ablated, and crushing injury was used to reduce the number of intact lamellar units. Mural ischemia alone resulted in necrosis of cells in the medial zone furnished by vasa but did not lead to aneurysmal dilatation, and all the fibrous tissue layers persisted during the 2-month observation period. Mechanical injury resulted in aneurysms in both ischemic and nonischemic aortic segments, but only if fewer than 40 intact lamellae remained and the average tension per lamellar unit exceeded three times the normal value of 1316 +/- 202 dynes/cm (4543 +/- 1624 for ischemic and 4087 +/- 871 for nonischemic segments; p less than 0.01 for each). We conclude that a critical reduction in the number of intact lamellar units results in aneurysmal dilatation. Protracted medial ischemia due to intimal plaque formation in the avascular abdominal aorta may eventually reduce the number of intact lamellae and favor the development of aneurysms.