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1 The significance of calf muscle function in venous ulceration pump Clifford T. Arald, PhD, Thomas L. Back, MS, RVT, Frank T. Padberg, MD, Peter N. Thompson, MD, Zafar Jamil, MD, Bing C. Lee, MD, Walter N. Duran, PhD, and Robert W. Hobson II, MD, Newark and East Orange, N.J. Purpose: Patients with clinically evident chronic venous insufficiency were evaluated to relate the degree of insufficiency and calf muscle pump dysfunction to venous ulceration. Methods: Sixty-nine limbs in 55 patients with chronic venous insufficiency by Society for Vascular Surgery/International Society for Cardiovascular Surgery classification were compared in three groups: classes 1 and 2 with no history of ulceration (19 limbs); class 3 with healed ulceration (20 limbs); and class 3 with active ulcers (30 limbs). Air plethysmography measurements of outflow fraction, venous volume, venom filling time, venous filling index, ejection fraction, ejection volume, residual volume fraction, and residual volume were made. In 62 of the 69 limbs, color-flow duplex ultrasonography was used to determine the pattern of reflux. Results: The outflow fraction was normal in 84%, 75%, and 77% ofnonulcerated, healed, and ulcerated limbs. The venous filling index was abnormal in most limbs (nonulcerated 95%, healed 90%, ulcerated 98%) but not significantly different among groups. Differences in calf muscle pump fimction were significant. Ulcerated limbs had significantly poorer ejection fractions (p = ) and greater residual volume fractions (p = ) than nonulcerated or healed limbs. By ultrasonography, deep and superficial vein incompetence was present in most limbs and was not statistically different among groups. Although venous insufficiency was not measurably different among groups, limbs with active venous ulcers had significantly poorer calf musde pump function than those with healed ulcers or with no history of ulceration. Conclusion: Venous insufficiency is necessary but not sufficient to cause ulceration, and a deficiency of the calf muscle pump is significant to the severity of venous ulceration. (J VAsc SURG 1994;20:872-9.) Chronic venous insufficiency (CVI) often results in substantial ankle edema, skin changes, and ulceration. The cause of ulceration with CVI is poorly understood. The conditions of patients with edema, lipodermatosclerosis, and hyperpigmentation may remain stable without ulceration, whereas the conditions of patients with less obvious skin changes may progress to ulceration. Sustained venous hyperten- From the Section of Vascular Surgery (Drs. Araki, Padberg, Thompson, Jamil, Lee, Duran, and Hobson), University of Medicine and Dentistry of New Jersey and New Jersey Medical School, Newark, and the Department of Veterans Affairs Medical Center (Mr. Back and Drs. Padberg and Thompson), East Orange. Presented at the Eighth Annual Meeting of the Eastern Vascular Society, Montreal, Quebec, Canada, May 12-15, Reprint requests: Clifford T. Araki, PhD, Section of Vascular Surgery, Department of Surgery, Medical Science Bldg., G-532, University of Medicine and Dentistry of New Jersey, 145 S. Orange Ave., Newark, NJ /6/60347 sion, necessary for the development of CVI, is believed to be caused by varying combinations of venous reflux, venous obstruction, and a poorly functioning calf muscle pump.1 However, the interaction between venous hypertension and the calf muscle pump remains ill defined. Refinements in the use of air plethsymography (APG) have allowed more convenient measurement of venous volume changes in control and CVI populations and have standardized the quantitation of venous incompetence and calf muscle pump function? Still, studies have noted inconsistencies in the ability of APG to separate quantitatively the different classes of CVI. 1'3"5 We evaluated groups of patients with different degrees of CVI by using APG and color-flow duplex ultrasonography to determine how these inconsistencies in APG may instead be defining the importance of some underlying factors in the development of venous ulceration. 872

2 Volume 20, Number 6 Araki et al. 873 Table I. Incompetence and calf muscle pump function by APG (means SEM) No. Age OF VFI VV VFT90 EF EV R VF R V Nonulcerated ~ * 46 4 * 81 8 Healed ulcer _ * _ 3 ~ 70 _ 9 ~ Active ulcer _ _ _ 6 Significantly different from active ulcer group (p < 0.05). Table II. Incidence of venous incompetence among limbs by color-flow duplex ultrasonography No. None (%) S (%) D (%) S D (%) Nonulcerated Healed ulcer Active ulcer None, No incompetence; S, superficial incompetence only; D, deep incompetence only; S D, superficial and deep incompetence. METHODS Subjects. A retrospective review of noninvasive tests performed over an 18-month period identified 69 limbs in 55 male patients with CVI that were tested for venous incompetence by APG. Patients ranged in age from 35 to 86 years, with a mean age of 61 years. With the classifications recommended by the Society for Vascular Surgery and the International Society for Cardiovascular Surgery, 6 limbs were grouped according to their presenting symptoms: group 1-19 limbs, class 1 or 2, with chronic swelling, induration, hyperpigmentation, and no history of ulceration; group 2-20 previously ulcerated limbs, class 3, with healed ulcers at the time of testing; group 3-30 limbs, class 3, with active ulcers at the time of testing. Limbs with ankle brachial indexes less than 0.9 or with previous arterial reconstruction were excluded from the study. Air plethysmography. APG measurements were made with the protocol described by Christopoulos et al.2 with use of commercially available instrumentation (APG-1000C; ACI Medical Inc, Sun Valley, Calif.).4,s,7 All measurements were made without the application of a thigh tourniquet. The following parameters were measured: Venous volume (VV), the increase in calf volume that occurs when the patient shifts between the supine position with leg elevated and the standing position with leg unweighed. 90% Venous flling time (VFTg0), the time required to fill 90% venous volume, which includes the time to mobilize the patient from the supine position to standing. Ejection volume (EV), the amount of volume removed from the calf with a single, sustained tiptoe maneuver. Residual volume (RV), the amount of volume retained in the calf during a rapid series of 10 tiptoe maneuvers. As measured, RV is not the difference between EV and W but is an estimate of the venous volume that cannot be eliminated from the calf by exercise. Indexes are calculated from the measured parameters to normalize differences in venous volume among subjects. The following indexes are calculated: OuOelow fraction (OF), the relative rate of calf vein emptying is calculated as the percentage of calf volume that is expelled within 1 second after the release of a proximal occluding cuff. The patient!ls tested in the supine position with the leg elevated. The proximal cuff pressure is 80 mm Hg. OF is normal if greater than 40% (no evidence of outflow obstruction). Venous filling index (VFI), the average rate of increase in calf blood volume (ml/sec) between the supine position and standing. VFI is a combined measure of venous reflux and arterial inflow (VFI = 0.9 W/VFT90). Normal VFI is less than 2 ml/sec. Ejection fraction (EF), the proportion of VV removed from the calf with a single, sustained tiptoe maneuver. EF estimates calf muscle pump efficiency as the percentage VV ejected by the calf with each contraction (EFp = [EV/VV] x 100). Normal EF is 60% or greater. ResiduaI volume fraction (RVF), an estimate of the dependent leg fluid volume that cannot be extracted by exercise. RVF = (RV/VV) x 100. Normal RVF is less than 35%. Color-flow duplex ultrasonography. Patterns of valvular incompetence and venous obstruction were also determined by color-flow duplex ultrasonography to supplement the APG measurements. Ultrasound testing was performed on 19 of IL9 nonulcerated limbs, 18 of 20 healed limbs, and 25 of 30 ulcerated limbs. Valvular competency was examined in the deep system: common femoral, deep femoral, superficial femoral, popliteal, posterior

3 IOURNAL OF VASCULAR SURGERY 874 Araki et al. December 1994 Table III. Incidence (%) of incompetence among vein segments by color-flow duplex ultrasonography Deep Superficial Thigh Calf Nonulcerated Healed ulcer Active ulcer Table IV. Incompetence and calf muscle pump function by author Author Category No. W VFI EF R VF Neglen is Class ± 15 ~ Welkie s Class ± ± ± 2.8t Neglen is Class ± 15 ~ vanbemmelen s Dermatitis _ ± 17" Welkie s Class _ 2.7t Cordts 4 Class ± ± t:~ Neglen Is Class ± ~ Welkie ~ Class ± ± Welkie 16 Ulcer t Katz z Ulcer _ ± 6.1" vanbemmelen s Ulcer ~ Current series (healed & active) Ulcer ± I *Data presented as means SD. tdata presented as means _ SEM. :~Age adjusted. tibial, peroneal, and anterior tibial veins. In the superficial system, vein competency was tested in the saphenofemoral junction, above-knee greater saphenous, below-knee greater saphenous, and lesser saphenous veins. Patients were first examined in the semifowler position with the back raised 45 degrees and the examined leg externally rotated with the knee slightly flexed. The leg was scanned by two-dimensional imaging from the common femoral to tibioperoneal vein for the presence of chronic disease. Testing for vein incompetence was started at the common femoral vein with use of Valsalva to elicit reflux. Where Valsalva produced clear evidence of reflux, scanning was continued through increasingly distal segments of both superficial and deep venous systems until the effects of Valsalva were not clearly demonstrated. Testing for valvular incompetence was then continued with the application of manual, distal compression with use of methods previously described, s Femoral and popliteal vein incompetence was evaluated with patients standing. Peroneal, posterior, and anterior tibial and lesser saphenous vein incompetence was assessed in the lower calf with the patient in the semi-fowler position. Because foot compression did not appear adequate for tibia/vein assessment, calf compressions proximal to the imaging probe were performed to elicit reflux in the lower calf veins. All measurements were made with a 5 MHz imaging/5 MHz pulsed-wave Doppler color-flow system (Quantum 2000; Siemens Medical Systems, Inc., Issaquah, Wash.). Reflux was principally determined by reversals in color flow that clearly lasted longer than 1 second. Color-flow images were taken at a medium flow setting, with adjustments set to maximize the sensitivity of detecting reverse flow. Where reversals were of equivocal duration, timing was performed by Doppler spectral display. Testing was performed to an observable endpoint in reflux or valve closure with reversal times greater than 0.5 second considered evidence of reflux. 9 Absolute values for duration and velocity were not considered in the data analysis. Data were tabulated as binary (yes/no) variables for competence or reflux in the imaged vein segments. Statistical analysis. All comparisons were performed with the SAS statistical package (SAS Institute, Inc., Cary, N.C.). APG data were compared among three groups through analysis of variance (ANOVA), with post hoc testing by Tukey's studentized range test. The incidence of reflux among limbs

4 Volume 20, Number 6 Araki et al. 87!5 and vein segments noted through ultrasonography were compared by use of Fisher's exact and Kruskal- WaUis tests, with the latter for nonparametric, ranked data comparisons. 1 Stepwise logistic regression was used to compare APG parameters for correlation with CVI severity. All data are presented as mean standard error of the mean (SEM), unless otherwise indicated. RESULTS OF was normal in 84%, 75% and 77% of nonulcerated, healed, and ulcerated limbs respectively (Fig. 1, A). Venous incompetence, as determined by VFI, was present in most limbs (nonulcerated 95%, healed 90%, ulcerated 98%) and was not significantly different among groups (Fig. 1, B). EF and RVF were also abnormal in most limbs (Fig. 2). Thirty percent or more of nonulcerated and healed limbs demonstrated normal EF and RVF. Only 7% of ulcerated limbs were normal by either EF or RVF. By Fisher's exact test, differences in EF and RVF were significant. ANOVA comparisons revealed no significant difference in age, OF, VV, VFT90, and VFI among groups (Table I). Although parameters estimating outflow obstruction and venous incompetence were similar, measures of calf muscle pump function were significantly different among the three groups. In all cases where differences were significant, they were between the active ulcer group and one or both of the other two groups (Table I). Limbs with active ulceration had significantly lower EV and EF (p = for EF) and significantly higher RV and RVF (p = for RVF) than either nonulcerated or healed limbs. There were no significant differences between nonulcerated and healed limbs in any of the measured or calculated parameters. Univariate analysis showed that the only significant parameters were those associated with calf mnscle pump fianction. Stepwise logistic regression showed that among APG parameters EF was the principal parameter correlating with disease severity, if the level of severity was assumed to increase between nonulcerated, healed, and active ulceration. Other variables did not contribute significantly to the regression. As demonstrated by color-flow ultrasonography, most limbs had combined superficial and deep vein incompetence (Table II). Among all groups, the incidence of isolated deep or superficial vein incompetence was relatively rare. Overall, deep vein reflux was present in 79% of nonulcerated limbs, 94% of limbs with healed ulceration, and 91% of ulcerated OF (%) VFI (ml/sec) 25~ 20: 15 i 10 o 4- :1: :1:,! CVI Healed Active 4- * 4- CVI Healed Active Fig. 1. OF (A) and VFI (B) in individual limbs of three groups: CVI (class 1 or 2, with no history of ulceration), healed (class 3 with healed ulcer), and active (class 3 with open ulcer). Normal values denoted by horizontal lines :are OF greater than 40% and VFI less than 2 ml/sec. limbs. Superficial vein incompetence was found in 84%, 94%, and 71% of nonulcerated, healed, and ulcerated limbs, respectively. Thus combined superficial and deep vein incompetence was found in the large majority of limbs in all groups. Statistical comparison showed no difference in the proportion of limbs with superficial, deep, or combined superficial and deep vein incompetence among the three groups. Statistical comparisons were also made on the incidence of deep (thigh and calf), superficial (thigh and calf), thigh (superficial and deep), and calf (superficial and deep) vein reflux among groups. By coding the imaged vein segments for the presence or absence of reflux, the proportion of vein segme.nts noted as insufficient were determined and compared (Table III). In all comparisons (Kruskal-Wal]Lis), A B

5 876 Araki et al. December 1994 EF (%) o 40 ~ 20-0 lo RVF (%) CVI Healed Active CVI Healed Active Fig. 2. EF (A) and RVF (B) in individual limbs of three groups: CVI (class i or 2, with no history of ulceration), healed (class 3 with healed ulcer), and active (class 3 with open ulcer). Normal values denoted by horizontal lines are EF greater than 60% and RVF less tahn 35%. there were no significant differences among groups in the proportion of incompetent vein segments in superficial, deep, thigh, or calf veins. DISCUSSION Although VFI has been shown to increase with increasing severity of CVI, 1 other studies have not found VFI to differ significantly among limbs with differing CVI classification. 4,5 The validity of assessing venous hemodynamics of patients with CVI through APG testing has been questioned because of its inability to distinguish limbs with varicose veins from limbs with deep venous incompetence. In this series, comparing groups with different degrees of CVI and stages of ulceration, we were also unable to demonstrate differences in VFI between A limbs with mild to moderate CVI and limbs with venous ulceration. All three groups had abnormal VFI, but differences were not significant. By duplex ultrasound examination of the same limbs, nonulcerated limbs tended to have less deep vein incompetence and more superficial incompetence, but this was not significant and the patterns of superficial, deep, thigh, and calf vein insufficiency were similar among groups. Most limbs in all categories demonstrated a combination of superficial and deep vein incompetence (Table II), with superficial vein incompetence a significant factor in all groups. Although a thigh tourniquet applied in the APG protocol may have allowed us to separate the effects of deep and superficial vein incompetence, we chose not to use the tourniquet. Its utility has been questioned, 5 and, according to Christopoulos et al.,2 the distribution of reflux between superficial and deep systems is of minor importance compared with the magnitude of reflux. Previous reports have not demonstrated a distinct pattern of valvular incompetence in ulcerative limbs TM by use of ultrasound techniques. Studies have demonstrated involvement of both superficial and deep vein incompetence. The lack of significant differences in reflux pattern, by ultrasonography, and rate of reflux, by APG, suggest that differences in venous insufficiency among classes of CVI must be small relative to the wide variability in presentation among limbs of the same class. Our results demonstrate a significant reduction in calf muscle pump function in patients with active ulceration. Although most limbs in all three groups demonstrated poor calf muscle pump fimction, the significantly lower EF and increased RVF found in ulcerated limbs suggest a greater deficiency in that group's calf pump function. Overall, these results suggest that instead of lacking the ability to discriminate among classes of CVI, the APG may be demonstrating that differences in the level of incompetence among CVI classifications may be small despite pronounced differences in the severity of symptoms. Once a certain degree of insufficiency is attained, the severity of symptoms may be dependent on other factors. Others 3'4 have suggested that there is more involved in the development of venous ulcers than can be explained by APG testing. These factors are as yet unknown. Our results demonstrated a significantly greater impairment of the calf muscle pump in limbs with active ulceration. Limbs with healed ulcers had greater similarity to limbs without previous ulcer-

6 Volume 20, Number 6 Araki et al. 877' ations than to limbs with active ulcers. It is possible but unlikely that limbs with healed ulcers spontaneously improved a once-poor calf muscle pump. It seems more likely that healed limbs contained less calf pump dysfunction and were thus able to heal their ulcers more readily. A review of laboratory records revealed that actively ulcerated limbs had a mean history of ulceration of 144 _ 31 months with the current ulcer open an average of 11 _ 3 months before testing. Records confirmed that, for the most part, these patients had long-standing ulcerations with short intervals of healing. In healed limbs, testing was performed an average of months after the most recent ulcer had healed. Although the interval between the date of first ulcer and the date of study was 101 _ 35 months in the healed group, ulcer recurrence was not as severe. Significant reductions in EF and increases in RVF with venous ulceration have not been reported by others. 3-s Table IV summarizes the means in APG measurements reported in the literature and includes a recalculation of our data to reflect the combined means for healed and actively ulcerated limbs. Data from the combined group are well within the range of reported data for limbs with class 3 CVI. Differences between healed and actively ulcerated limbs suggest that patients with venous ulcers have widely varying degrees of calf pump impairment. Those with the most intractable ulcers appear to suffer from a measurably poor calf muscle pump. By combining all class 3 limbs, previous studies may have hidden this impairment by including limbs with severe but less debilitating disease. If these findings are confirmed by others, the underlying cause of calf muscle pump dysfunction must be determined. From this series it appears that differences in EF and RVF were mainly due to differences in EV and RV because VV among the three groups were not significantly different (Table I). Although superficial vein incompetence is capable of influencing both EV and RV, color-flow duplex evaluation did not demonstrate significant differences in superficial vein incompetence among the tested groups, which suggests that superficial vein incompetence does not strongly influence calf pump function. This is supported by the findings of Gillespie et al.,14 who were unable to demonstrate a significant change in calf muscle pump function with superficiai vein ligation and stripping. Elucidating the factors influencing EF and RVF may be important to understanding the mechanism by which venous hemodynamics influence ulcer formation. From these data, we conclude that venous incom.- petence is necessary but not sufficient to cause ulceration. Once a certain degree of insufficiency is reached, impairment of the calf muscle pump, and possibly other factors are necessary for the development of venous ulcerative disease. We thank Mr. Martin Feuerrnan of UMDNJ, Academic Computing Service for the statistical analysis. REFERENCES 1. Christopoulos D, Nicolaides AN, Cook A, et al. Pathogenes]~s of venous ulceration in relation to the calf muscle pump function. Surgery 1989;106: Christopoulos DG, Nicolaides AN. Noninvasive diagnosis and quantitation of popliteal reflux in the swollen and ulcerated leg. J Cardiovasc Surg 1988;29: Welkie JF, Comerota AJ, Kerr RP, et al. Hemodynarrfic deterioration in chronic venous disease. J VASC SURG 1992; 16: Cordts PR, Hartono C, LaMorte WW, Menzoian JO. Physiologic similarities between extremities with varicose veins and with chronic venous insufficiency utilizing air plethysmography. Am J Surg 1992;164: vanbemmelen PS, Mattos MA, Hodgson KJ, et al. Does air plethsymography correlate with duplex scanning in patients with chronic venous insufficiency? ~ VASC SURG 1993;1;8: Porter JM, Rutherford RB, Clagett GP, et al. Reporting standards in venous disease. J VASC SUlVG 1988;8: Katz ML, Comerota AJ, Kerr R. Air plethsymorgraphy (APG): a new technique to evaluate patients with chronic venous insufficiency. J Vasc Tech 1991;15: Araki CT, Back TL, Padberg FT, et al. Refinements in l~he ultrasonic detection of popliteal vein reflux. J VASC SuIm 1993;18: van Bemmelen PS, Beach K, Bedford G, Strandness DE. The mechanism of venous valve closure. Arch Surg 1990;125: Conover WJ. Practical nonparametric statistics. 2nd ed. New York: John Wiley, 1980: Hanrahan LM, Araki CT, Rodriguez AA, et al. Distribution of val~alar incompetence in patients with venous stasis ulceration. J VASC SUIVG 1991;13: Weingarten MS, Branas CC, Czeredarczuk M, et al. Distribution and quantification of venous reflux in lower extremity chronic venous stasis disease with duplex scanning. J VAsc SUinG 1993;18: Moore DJ, Himmel PD, Sumner DS. Distribution of venous valvular incompetence in patients with the postphlebiitic syndrome. J VAsc SURG 1986;3: Gillespie DL, Cordts PR, Hartono C, et al. The role of air plethysmography in monitoring results of venous surgery. J VAsc SURG 1992;16: Neglen P, Raju S. A rational approach to detection of significant reflux with duplex Doppler scanning and air plethysmography. J VAse SURG 1993;17: Welkie IF, Comerota AJ, Kerr R_P, et al. The hemodynamics of venous ulceration. Ann Vasc Surg 1992;6:1-4. Submitted May 31, 1994; accepted Sept. 2, 1994.

7 j'ournal OF VASCULAR SURGERY 878 Araki et al. December 1994 DISCUSSION Dr. Harry Schanzer (New York, N.Y.). The study by Araki et al. discusses what determines the use of APG and duplex scanning and what function and factors could relate with a degree of severity of chronic venous stasis. As is well known, normal function depends on an adequate outflow and good muscle pump. The latter is a function of the integrity of the valvular system and the ability of having good calf muscle contraction. Chronic outflow obstruction or failure of the muscle will eventually result in increased capillary pressure with a consequent production of edema, liposclerosis, pigmentation, and ultimate skin ulceration. One of the functional tests that allows assessment of the quality of venous outflow and the presence of reflux and provides a quantitative ideal of the efficiency of the muscle pump with this technique, Araki et al. have found that patients with active ulcers have a significant deterioration in muscle pump as determined by measurements ofef, RVF, EV, and RV. They implied that the presence of an active ulcer is a manifestation of severe venous insufficiency and that the main factor responsible for this arrangement is a defective muscle pump. Duplex results show that more than two thirds of patients with CVI have combined superficial and deep venous reflux. This distribution is equally present whether the patients have ulcers or not. The field of venous stasis is crowded with confusing and often misleading terms. The authors use the term venous insufficiency as a synonym for reflux. I suggest the use of the word reflux instead of venous insufficiency to promote clarity. The authors have demonstrated that muscle contraction is the main factor most significantly affected by the present ulcer. Venous reflux is equally influenced in all groups of patients. Is the decrease in muscle function seen in patients with an active ulcer a manifestation of primary severe venous stasis or is it the secondary result of inability of the patient to exercise properly during the performance of the test because of the discomfort that the ulcer is producing? The authors have found that less than 10% of patients with venous stasis have an isolated superficial venous system affected. This is a contradiction to results coming from the United Kingdom where more than 50% of patients with venous stasis have been described as having their superficial venous system refluxing with a normal deep system. Are these different results a manifestation of different methods being used for the evaluation or are we dealing with a different genetic population or different environmental factors? Finally, the authors focused their attention on the superficial and deep system without mentioning the perforating system. There is evidence that this third system is very important in the pathogenesis of chronic venous stasis and ulceration. Do you have any comments on this? Dr. Clifford T. Araki. I tend to use the term venous insufficiency a little bit liberally. This has been noted by others in our group. With regard to whether patients with active ulcerations may be experiencing discomfort and that may be causing the decrease in the EF, I do not believe that that's the case. Instead we find that these people who had the more chronic debilitating ulcers did have a greater difficulty ambulating, which is more a part of the disease process that contributes to the development of increased venous pressures. I don't think that the APG measurement itself is what is causing the problem. In terms of the superficial system, we chose specifically to stay away from people who only had superficial vein varicosities and tried to pick people within the CVI group who had definite evidence of induration, which would put them into a different category. In terms of the perforating system, that is something that we didn't have time to study adequately within this protocol. It is something that we have examined in the past and should be included. Dr. Syde A. Taheri (Buffalo, N.Y.). Six years ago we evaluated limb output by femoral defusion technique. During our study with 20 patients determining CVI from grade I to 3, it was interesting that our finding was similar to what you have seen. These patients had increased limb output and increased residual capacity of the lower extremity. But the interesting part of the work was the muscle biopsy. Those patients who had ulceration and grade 3 CVI also had muscle atrophy. We believe that the problem of ulceration at the ankle area is due to substances generate d from the PMN. Perhaps this can help other substances caught in this ulceration. Have you had any experience with muscle flaps? Do you have any experience with amounts of the skin ulcer to see that supervision was there? Dr. Araki. The muscle atrophy you mention is something that may be present in the patients whom we tested, where it seems likely that there is a debilitating effect on the muscle that may be affecting the venous pump mechanism. There are people in our group who are working actively on white blood cell involvement in venous ulceration. I am not as familiar with it as I should be. Dr. Richard K, Spence (Camden, N.J.). We have had difficulty in using APG and trying to reproduce some of the results that have been generated in the United Kingdom. As a result, rather than throw it out, we looked at how you used this method to best advantage in trying to make sense of it. I think what you have shown us represents another step forward and tries to define how APG can help us define what is going on in the patient with venous disease. To that end, with the numbers that you have shown with volumes, EF, and RVF, a number of these patients may have some kind of occlusion or resistance to outflow. We found a similar kind of thing with our patients, in fact with superficial compression, we measured patients with and without stockings and were able to show that in those

8 Volume 20, Number 6 Araki et al. 879 patients there was indeed proximal obstruction. We can't see that with the APG. You can't really identify it very well and a lot of times you can't identify it with duplex scanning. I think you either go to venography and look at the pelvic veins, etc. I wonder if you have done that or if you have the ability to tell us about proximal obstruction and how much of it might be playing a role here. Dr. Arald. We haven't studied the patients' venography results. Measurements by APG and duplex scanning, appear to correlate fairly well in estimating proximal obstruction. We are not seeing much venous obstruction in these patients. The duplex scanning--derived data and the APG data both seem to hold true. Whether there is some obstructive process within the calf veins that we are not picking up, I'm not sure. In terms of the APG measurement itself, people are interpreting the test as maybe not being sensitive enough to give us an idea of what is going on with reflux and insufficiency. But we are looking at it from a different view point. Maybe it is telling us that there real]ly aren't that many differences between groups, that such wide variability is really existing in the patients. AVAILABILITY OF JOURNAL BACK ISSUES As a service to our subscribers, copies of back issues of JOURNAL OF VASCULAR SURGERY for the preceding 5 years are maintained and are available for purchase from the publisher, Mosby-Year Book, Inc., at a cost of $10.00 per issue. The following quantity discounts are available: 25% off on quantities of 12 to 23, and one third off on quantities of 24 or more. Please write to Mosby-Year Book, Inc., Subscription Services, Westline Industrial Drive, St. Louis, MO , or call (800) or (314) for information on availability of particular issues. If unavailable from the publisher, photocopies of complete issues are available from University Microfilms International, 300 N. Zeeb Rd., Ann Arbor, MI 48106, or call (313)

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