Magnetic resonance spectroscopy of normal and diseased muscles.

Phosphorus magnetic resonance spectroscopy (P MRS) affords and innovative approach to the study of the oxidative enzyme content of normal and diseased muscles. Examples of the evaluation of the enzyme content of normal muscles by an exercise protocol are provided. The protocol affords a hyperbolic work/cost profile, the Vmax of which is calculated by the reciprocal plots giving the enzyme content and the "effective Michaelis constant" with an evaluation of the resting metabolism. This steady state protocol clearly illustrates enzyme adaptation, on the one hand, and tissue atrophy particularly in the case of tissue injury, Duchenne's dystrophy, and genetic deletion of specific enzymes, on the other hand. The method is rapid, safe, and affords a quantitative evaluation of the disease process and possibilities for following appropriate therapies. So far, approx 1000 examinations of normal and diseased human limbs have been carried out in our laboratory in over the past four years.

Adrenergic blockade and renal hemodynamics.

An isolated blood perfused kidney preparation was used to study the influence of intrarenal adrenergic receptors on renal hemodynamics, renal function, and the renin-angiotensin system. Beta adrenergic blockade with propranolol resulted in a reduction of fractional sodium excretion, and alpha blockade with phentolamine had no effect on sodium excretion despite significant increases in cortical flow and glomerular filtration rate. The changes in sodium excretion after beta blockade were not felt to be due to a direct tubular effect but rather were secondary to preferential perfusion of nephrons in the juxtamedullary cortex, which is known to have higher sodium reabsorptive capacity. These changes appeared to be direct effects of adrenergic blockade on the renal vasculature and were independent of any effects on renin secretion.

Improved renal function and inhibition of renin and aldosterone secretion following peritoneovenous (LeVeen) shunt.

Twelve patients with cirrhosis, refractory ascites, and varying degrees of renal failure (creatinine clearance, 5 to 44 ml/min) were studied before and up to 2 weeks following peritoneovenous shunt. Creatinine clearance increased 60% or more in seven patients (group I) and 22% or less in five patients (group II). There were no significant differences in maximum urine output or sodium excretion between groups (group I, 4,272 ml/14 hr, 372 mEq/24 hr; group II, 3,722 ml/24 hr, 255 mEq/24 hr). Aldosterone and renin concentrations were higher in group I and showed a greater decrease after shunting. Renin substrate levels also were higher in group I and rose following shunt insertion, while group II remained low. Ascitic fluid was found to contain renin substrate in concentrations of approximately 25% to 50% of plasma concentrations. Patients with the greatest increase in creatinine clearance showed the largest rise in substrate concentration and fall in renin and aldosterone secretion, suggesting a dynamic relationship between these factors. That a diuresis could occur without significant change in these parameters in five of 12 patients suggests independent control mechanisms for renal salt and water excretion and glomerular filtration in the ascitic patient.

Value of routine vascular laboratory studies to identify vein graft stenosis.

Thirty-three stenotic lesions were found in 30 vein grafts (17 femoral-popliteal, 13 femoral-tibial) 3 months to 8 years postoperatively--77% appeared within 1 year of surgery. Seventeen (57%) of the patients presented with normal distal pulses, and a similar number were asymptomatic. Only eight (26%) presented with unequivocal clinical evidence of graft stenosis based on decreased pulses and return of ischemic symptoms. Forty percent were completely asymptomatic with normal distal pulses. The mean postoperative ankle systolic pressure index (ASPI) was 0.83 +%- 0.03 (SEM); it fell to 0.57 +/- 0.04 (SEM) when stenosis developed. The peripheral vascular laboratory measurements were the key factor influencing the decision for repeat arteriography in many of these patients and reinforced the need for a repeat arteriogram when the clinical diagnosis was unclear. Early diagnosis of vein graft lesions prior to graft occlusions allowed 24 of 30 of these stenotic grafts to be treated primarily by percutaneous transluminal angioplasty (PTA); 80% remained patent 24 months after PTA. Since most vein graft stenoses can be treated by such a simple, nonoperative technique (PTA), every effort should be made to diagnose and treat lesions prior to graft occlusion. Our experience indicates that frequent vascular laboratory measurements of ASPI are more sensitive then clinical examinations in detecting early vein graft stenosis.

Treatment of acute peripheral arterial and graft thromboses with low-dose streptokinase.

Seventeen patients with acute peripheral arterial or graft occlusion were treated with local low-dose intra-arterial streptokinase. The series includes eight patients with native vessel occlusion, six patients with vein graft occlusion, two patients with prosthetic graft occlusion, and one patient with renal allograft artery occlusion. The duration of occlusion prior to streptokinase therapy varied from 2 hours to 5 weeks. The treatment was successful in 14 of the 17 instances. In conjunction with the successful thrombolytic therapy, percutaneous transluminal angioplasty was performed subsequently in 10 of the patients and reconstructive surgery in three. One major and five minor hemorrhagic complications occurred and were considered to be secondary to the streptokinase therapy. In follow-up of up to 9 months, 11 of the 14 successfully treated patients continued to have a good result, without any indication of recurrent arterial occlusion. Two patients have died of causes unrelated to thrombolytic therapy and one patient required bypass grafting for recurrent thrombosis. None of the successfully treated patients lost a limb. Of the three patients in whom thrombolysis was unsuccessful, two required amputation. Local intra-arterial low-dose streptokinase appears to be a promising alternative to immediate operative treatment in carefully selected cases of arterial occlusion. Definitive treatment of the underlying cause of the thrombus usually is required and changes of success may be enhanced by the thrombolytic therapy.

Diagnostic accuracy of ocular pneumoplethysmography attachment for pulse volume recorder.

The ocular pneumoplethysmography (OPG) attachment for the Life Sciences Pulse Volume Recorder (OPG-LS) is a widely distributed instrument, but no results have been published on its accuracy in diagnosing carotid artery lesions. One hundred twelve patients were studied with the OPG-LS using lateralizing criteria and a curve of ophthalmic artery systolic pressure (OAP) to brachial systolic pressure (BP) for normal carotid arteries, which served as a discriminant between normal and stenotic vessels. Two hundred nineteen carotid arteries were visualized on arteriography and percentage of diameter stenosis was measured. Lateralizing criteria by themselves gave poor diagnostic accuracy, but when combined with OAP-BP data, positive diagnosis was made for lesions having greater than 60% diameter stenosis in 89.6% of patients and 80.8% of arteries. False-positive results for 0% to 30% diameter stenotic lesions occurred in 11.1% of arteries and in 13.6% of patients.

Noninvasive techniques in the assessment of lower-extremity arterial occlusive disease. The advantages of proximal and distal thigh cuffs.

We studied 209 limbs angiographically and noninvasively to determine whether measurements of upper-thigh (UT) and lower-thigh (LT) segmental pressures (four-cuff technique), combined with segmental pulse-volume recordings (PVRs), offered any advantage over the standard single-thigh cuff (three-cuff technique) and PVR in the diagnosis of aortoiliac (AI) and superficial femoral artery (SFA) occlusive disease. Angiographic stenosis of 50% or greater and occlusions were considered to be hemodynamically significant lesions in this study. In the absence of SFA disease, sensitivity to AI disease was high (96%) and not significantly different using three- or four-cuff measurements. However, in the presence of SFA-segment disease, four-cuff measurements, both with and without PVR, were significantly more sensitive to AI disease (100%) and more specific for a normal AI segment (76%) than the three-cuff, PVR technique. Plethysmography alone was most sensitive to SFA disease (90%), even in the presence of AI disease, and sensitivity was not improved by additional segmental pressure measurements. The four-cuff system enhances the physician's ability to diagnose AI disease in the presence of SFA lesions, while PVR is most useful in detecting SFA lesions in the presence of AI disease.

Hypertrophic osteoarthropathy as indication of aortic graft infection and aortoenteric fistula.

Diagnosis of an infected bifurcation graft or aortoenteric fistula can be extremely difficult, and delay in diagnosis may lead to the lethal complication of a ruptured aortoenteric fistula. Hypertrophic osteoarthropathy limited to the lower extremities was the initial symptom of aortoenteric fistula in two of our patients with infected aortic bifurcation grafts. Review of the literature discovered six additional patients with a similar diagnosis, indicating its possible value as an early diagnostic sign of aortoenteric fistula.

Balloon dilation of iliac stenosis with distal arterial surgery.

Seven patients with concomitant atherosclerotic iliac stenosis and femoral artery occlusive disease were treated with polyvinyl balloon catheter dilation of the iliac artery and subsequent distal operative arterial reconstruction. The iliac lesions were short, localized, common and external iliac stenoses and the femoral lesions were superficial femoral artery occlusions in six patients and a common femoral occlusion in another. All seven iliac stenoses were successfully dilated. Subsequent operative femoral artery reconstruction was successful in these patients, with restoration of popliteal or pedal pulses and relief of ischemic symptoms over a follow-up period of two to 14 months. One patient's femoral popliteal bypass graft thrombosed four months postoperatively.

Thoracoabdominal aneurysm resection after previous infrarenal abdominal aortic aneurysmectomy.

Thoracoabdominal aneurysms in 51 patients were repaired over 5 years ending in February 1991. Fourteen (27%, 14 of 51) patients had a prior infrarenal aneurysm resection (PRA); their data are analyzed separately. The average age of patients who had undergone PRA was 67 years (range: 56 to 86 years). The mean aneurysm diameter was 8.6 cm (range: 5 to 12 cm), and the mean time interval between initial aneurysm surgery and subsequent resection of the thoracoabdominal aneurysm was 8.5 years (range: 2 to 17 years). Three patients in the PRA group were operated on emergently, two because of clinical evidence of rupture; the other patients underwent elective repair. Early mortality (30 days) in the PRA group was significantly related to age (72 years or older versus younger than 72 years: 75% versus 10%, p = 0.04), proximal extent of aneurysm (above diaphragm versus below diaphragm: 50% versus 0%, p = 0.05), ruptured aneurysm (ruptured versus nonruptured: 100% versus 16%, p = 0.06), and a cardiac history of myocardial infarction (57% versus 0%, p = 0.03), congestive heart failure (66% versus 0%, p = 0.01), or arrhythmia (80% versus 0%, p = 0.005). Similar results were seen with the entire group of patients with thoracoabdominal aneurysms except that the proximal extent of the aneurysm was not related to mortality. These results demonstrate that thoracoabdominal aneurysm resection after prior infrarenal aneurysmectomy is not associated with increased mortality or morbidity.

Occluded infrainguinal grafts: when to choose lytic therapy versus a new bypass graft.

BACKGROUND: The published results of thrombolysis for occluded bypass grafts, including a prospective multicenter trial, have been disappointing, prompting many investigators to proceed directly to a new bypass rather than attempt graft salvage. Our series of 61 occluded grafts treated with lytic therapy, however, identified a subgroup that justified attempted graft salvage. METHOD: The grafts consisted of saphenous vein 59% (36/61), other vein (arm or composite vein) 21% (13/61), and polytetrafluoroethylene (PTFE) 29% (13/61). The data analysis was designed to identify the graft subgroup that would benefit from lytic therapy by using cumulative survival analysis techniques with the Wilcoxon (Gehan) test for univariate analysis and Cox proportional hazards model for multivariate analysis. Specific variables examined by univariate analysis were graft age (defined as the interval from initial bypass to graft lysis), graft material, graft type (femoropopliteal versus femorotibial), diabetes, symptoms (claudication versus salvage) and duration of occlusion prior to lysis. RESULTS: Complete lysis was achieved in 72% (44/61) of the grafts, and 86% (38/44) had an underlying stenosis that was treated by percutaneous balloon angioplasty (28/38) or surgery (7/38). Three stenotic outflow lesions were not treated. Cumulative 5-year patency for all 61 grafts was 23% +/- 0.075 (SE). Only graft age < 10 versus > 10 months was significant (P < 0.004) by univariate analysis, and it was also the only significant variable found by multivariate analysis; it indicated a 1.58 increase in relative risk of occlusion for the younger grafts. The combination of a saphenous vein graft that was also > 10 months old resulted in a 45% 5-year patency, compared to 21% for < 10-month-old saphenous vein grafts (P < 0.008). A review of 161 bypass grafts performed at our institution over the past 10 years revealed a 52% 5-year secondary patency in previously bypassed limbs, which varied with graft material (67% saphenous, 50% alternative vein, 31% prosthetic). Lysed graft patency was comparable to that of a second bypass using other veins or PTFE conduit. CONCLUSIONS: In the absence of an intact saphenous vein for a second bypass, thrombolytic therapy is an alternative to surgery.

Tobacco. Its impact on vascular disease.

The role of smoking in vascular disease is multifactorial and complex. Research continues to further elucidate the mechanisms involved and advance treatment options. What remains clear throughout is that smoking cessation has multiple health benefits. In a recent public health projection study of mortality and disability by cause, tobacco use was marked as the potentially largest health problem to be expected in the year 2020. Although smoking cessation is not simple, in the years spanning 1993 to September 1997, 1720 articles were published under the key words "smoking cessation," reflecting the difficulty of this endeavor and lack of a satisfying answer to this health problem. Nonetheless, approaches to patient smoking cessation should be attempted by all physicians. A protocol for physicians to assist patients with smoking cessation from the National Cancer Institute can serve as a general guide (Fig. 3). Some of the programs available to assist patients in smoking cessation are listed in Table 7.

Determination of carotid plaque risk by ultrasonic tissue characterization.

This in vitro study investigated the ability of ultrasonic tissue characterization (UTC) to discriminate between plaques from asymptomatic and symptomatic patients and to compare UTC findings with quantitative measurements of plaque morphology. A total of 34 plaque specimens removed at carotid endarterectomy were scanned transversely at intervals of 1 mm, and compared to tissue cross-sections examined by optical microscopy employing computer-assisted planimetry. UTC was performed by spectral analysis of backscattered radiofrequency signals. The slope, intercept and total power parameters of the spectrum were evaluated. Discriminant analysis was used to compare the ability of the UTC spectral parameters and morphological constituents to correctly classify plaques according to their symptom group membership. UTC correctly classified 88.2% of the plaques. Thrombus was present in 93.9% of the plaques, and there was little difference in the morphological constituents of plaques from asymptomatic and symptomatic patients. Morphological constituents correctly classified 60.7% of the plaques. We conclude, in this preliminary study, that UTC can discriminate between carotid plaques from asymptomatic and symptomatic patients with moderate accuracy, despite a similarity in their morphological composition. UTC discrimination is not related to differences in the type or amount of morphological constituents in the plaques.

Economic impact of transluminal angioplasty.

Using actual bills and follow-up records we attempted to determine the economic impact of percutaneous transluminal angioplasty. The patients selected included forty angioplasties performed early in our experience as well as forty comparable patients who had operations in the same period of time. Clinical follow-up was obtained over four years. The statistics obtained demonstrate the hospital bills for angioplasty were only 24% that of surgical treatment for femoral lesions ($1,329.00 versus $6,112.00) and 16% for iliac lesions ($1,353.00 versus $7,732.00). Using this patient sample and readily available statistical data, we calculated direct national savings for using angioplasty on all patients suitable and used a standard value of life analysis to estimate the value of lives saved by doing the less dangerous procedure. The sum total savings in the United States from using angioplasty in all suitable candidates as opposed to surgery would be $180 million per year for femoral lesions and $117 million for iliac lesions. This could produce a significant savings in medical costs over the coming years.