Annals of Vascular Surgery
Volume 20, Issue 2 , Pages 237-242, March 2006

The Relationship between Gestational Age and Compliance in Human Umbilical Vein and Its Possible Application in Vascular Grafting

  • Wenchun Li, MD

      Affiliations

    • Laboratory of Medical Biomechanics, Yunyang Medical College, Shiyan, Hubei, People's Republic of China
    • Department of Surgery, Taihe Hospital, Yunyang Medical College, Shiyan, Hubei, People's Republic of China
    • ,
  • Tiezhu Huang, MD

      Affiliations

    • Laboratory of Medical Biomechanics, Yunyang Medical College, Shiyan, Hubei, People's Republic of China
    • ,
  • Yanjun Zeng, PhD

      Affiliations

    • Biomechanics and Medical Information Institute, Beijing University of Technology, Beijing, People's Republic of China
    • Corresponding Author InformationCorrespondence to: Yanjun Zeng, PhD, Biomechanics and Medical Information Institute, Beijing University of Technology, Beijing, 100022, People's Republic of China
    • ,
  • Zhongjun Yao, MD

      Affiliations

    • Department of Surgery, Taihe Hospital, Yunyang Medical College, Shiyan, Hubei, People's Republic of China

Article Outline

The aim of this study was to provide a theoretical basis, using biomechanical properties, for the clinical application of human umbilical vein (HUV) as material for vascular grafting. This was a nonrandomized, noncontrolled in vitro study. The experiment was conducted in the Laboratory of Medical Biomechanics, Yunyang Medical College. HUVs of 50 normal fetuses were collected on spontaneous miscarriage or labor with the pregnant women's permission by the Department of Obstetrics and Gynecology, Taihe Hospital, Shiyan, Hubei Province. Gestational aged ranged 24–42 weeks, and parturients were 20–30 years old. The pressure-volume (P-V) relationship of HUV was measured on the biomechanical experiment stand for soft tissues, and then compliance was calculated. The P-V relationship of HUV corresponded to a parabolic curve. The compliance of HUV increased gradually with gestational age [24–27 weeks (2.22 ± 0.34) × 10−4 mL/(kPa • cm), 28–32 weeks (3.65 ± 0.46) × 10−4 mL/(kPa • cm), 33–36 weeks (4.22 ± 0.55) × 10−4 mL/(kPa • cm), 37 weeks (7.63 ± 0.48) × 10−4 mL/(kPa • cm), 38 weeks (8.32 ± 0.76) × 10−4 mL/(kPa • cm)]. However, after 39 weeks of gestation, compliance decreased gradually with gestational age [39 weeks 7.61 ± 0.46) × 10−4 mL/(kPa • cm), 40 weeks (7.53 ± 0.72) × 10−4 mL/(kPa • cm), 41 weeks (4.13 ± 0.35) × 10−4 mL/(kPa • cm), 42 weeks (2.25 ± 0.62) × 10−4 mL/(kPa • cm)]. The compliance of HUVs collected at 37–40 weeks of gestational age was similar. When the HUVs older than 42 weeks or under 28 weeks were compared, there was significant difference in their compliance (F = 65.84–86.52, p < 0.01). The results of the present study suggest that HUVs collected at 37–40 weeks of gestational age have good compliance, i.e., a good P-V relationship, and therefore may be a suitable material for vascular grafting. HUV is one of several graft materials that may be used when autogenous saphenous vein is absent or inadequate. HUV is very biocompatible and shows promise for use in orthopedic implants.

 

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INTRODUCTION 

Advances in vascular surgery are closely related to the development of biomaterials.1, 2, 3 Success in vascular transplantation depends to some extent on finding an ideal blood vessel substitute.4, 5, 6 The rate of patency is commonly used as a criterion for evaluating the success or failure of vascular surgery.7 Many studies indicate that anastomosis, plerosis, and transplantation of an artery are involved in alterations in the mechanical characteristics of blood vessel walls and, therefore, will in turn affect the patency rate of a reconstructed blood vessel after operation either directly or indirectly.8, 9, 10 In recent years, with the development of biomechanics in medicine, clinicians have increasingly paid attention to the mechanical properties of blood vessels. Since Dardik and Dardik11 began in the United States to use human umbilical vein (HUV) in artery transplantation in 1973, researchers in China and other countries12, 13, 14, 15, 16 have performed experimental and clinical studies on the application of HUV for arterial transplantation. However, little is known about the relationship between the compliance of HUV and gestational age.16 Vascular compliance, which accommodates blood pressure changes without rupture under pressure or force, is an important marker that reflects the mechanical characteristic of a blood vessel. In this study, we measured the pressure-volume (P-V) relationship of HUV from fetuses. The results provide a reference for the use of HUV in transplantation procedures.

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MATERIALS AND METHODS 

Materials 

The experiment was completed in the Laboratory of Medical Biomechanics, Yunyang Medical College. HUVs of 50 normal fetuses were collected on spontaneous miscarriage or labor with the pregnant women's permission by the Department of Obstetrics and Gynecology, Taihe Hospital, Shiyan, Hubei Province. The gestational age of fetuses ranged 24–42 weeks, and the pregnant women were aged 20–30 years. Among them, eight cases had gestational age of 24–27 weeks, seven cases 28–32 weeks, eight cases 33–36 weeks, four cases 37 weeks, five cases 38 weeks, five cases 39 weeks, five cases 40 weeks, four cases 41 weeks, and four cases 42 weeks.

Methods 

The umbilical cords were not dragged or clipped in any manner after fetal disengagement. A 2 cm long segment of each umbilical cord was measured and labeled at both ends. Then, they were cut off and put into normal saline (NS). The HUV was carefully stripped from the cord and its two ends were fixed on the biomechanical experiment stand of soft tissues (produced by the Center of Technology, Dongfeng Automobile, Shiyan, China). One end of the HUV was connected to the triplet assembly of the pressure transducer. Pressure was increased by a dynamic state electric resistance strain meter and input into a computer. Gas in the fluid pressure system was exhausted, and the mobilization trestle was inserted and adjusted so that the HUV achieved its original length. An injection syringe was used to adjust intravascular pressure to zero. Then, equivalent saline was pulled in and out at constant speed with an injection syringe to alter the intravascular relative volume. Meanwhile, the corresponding pressure was recorded by computer through a pressure converter. One pressure circulation was determined by one cycle of loading and unloading. Furthermore, the process was completed within 20 sec; there was a 1 min interval between measurements. After the HUV was pretreated through circulation compression and decompression five times, four components of pressure circulation were measured as formal data of the P-V relationship. During the whole process, the tested HUV was put in a thermostatic saline bath at 37 ± 0.5°C, and all experiments were completed within 10 hr after the cord was harvested. Then, coefficients a, b, and c; multiple correlative coefficient r; and compliance (C) were calculated according to (1), (2) below:17

(1)
(2)

where a, b, and c stand for coefficients, and dV/dP represents the variance of the volume of vessel when the pressure changes by one unit.

Statistical Analysis 

The measured data were analyzed statistically by different gestational age groups. SPSS (Chicago, IL; version 11) for Windows software was used for data analysis according to the instructions of the Department of Preventive Medicine, Yunyang Medical College. Measurement data were expressed as means ± SD. Single-factor analysis of variance was performed for comparison among different groups, firstly, and then a significance test (Neuman-Keuls method) was performed for one group versus another. The difference was considered statistically significant at p < 0.05.

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RESULTS 

Descriptive Statistics 

The umbilical cord is sufficient to provide material selected by examination. All 50 HUVs entered the experiment with no loss in the midway; all data were entered for analysis.

Measuring the P-V Relationship of HUV 

P-V curves measured at different gestational ages for the HUV are shown in Figure 1, where V indicates the volume per unit length of the blood vessel (the total volume of liquid injected into the vessel divided by the length of the vascular segment). The HUV curves at different gestational ages showed that when the pressure was within the physiological range, the curvature of the P-V curve was larger and its nonlinear character was obvious; when the pressure was beyond the physiological range, the linear character became gradually obvious. P-V curves of HUVs aged 37–40 weeks were similar to each other. However, P-V curves of HUVs aged 28 weeks or 42 weeks descended in amplitude obviously. The P-V curves obtained via actual measurement of the veins at different gestational ages were all closely similar to the upstroke of the parabola, which can be indicated by the second parabola relation (equation 1).

Curve fitting was done for the measured data for each HUV, and coefficients a, b, and c and multiple correlative coefficient r (Table I) between the measured data of P-V and fitting degree of equation 1 were obtained through regression analysis. There was a significant correlation in regression effect between P and V (t [test of regression coefficient] = 4.38; p < 0.01); its multiple correlative coefficient was greater than 0.96 without exception. This result indicated that the P-V data measured at different gestational ages for HUV preferably fit with the parabolic equation.

Table I. Results of secondary regression of P-V of HUV at different gestational ages (mean ± SD)
Gestational age (weeks)na (×10−6)b (×10−4)c (×10−3)r
24–278−0.84 ± 0.512.40 ± 0.660.51 ± 0.330.9834 ± 0.0117
28–327−1.49 ± 1.253.97 ± 1.991.95 ± 1.290.9723 ± 0.0447
33–368−1.73 ± 1.114.59 ± 1.194.95 ± 2.100.9864 ± 0.0542
374−3.22 ± 1.788.32 ± 3.617.43 ± 2.350.9658 ± 0.0342
385−3.69 ± 2.239.11 ± 4.759.29 ± 6.210.9772 ± 0.0192
395−3.47 ± 1.288.35 ± 0.308.48 ± 5.530.9735 ± 0.0249
405−3.21 ± 1.908.22 ± 2.262.13 ± 1.050.9699 ± 0.0123
414−0.73 ± 0.114.29 ± 0.190.49 ± 0.190.9946 ± 0.0015
424−0.47 ± 0.322.35 ± 0.620.69 ± 0.433

a, b, and c represent coefficients described in the text.

It is clearly shown in Table I that when the gestational age of the HUV was 38 weeks, its absolute values of P-V regression coefficients a, b, and c were maximal; and these coefficients decreased with increase or decrease of gestational age.

Compliance of HUV at Different Gestational Ages 

When the secondary parabolic curve was applied for fitting to P-V, the corresponding blood vessel compliance was calculated using equation 2.

When P = 0, C = b; i.e., it expresses zero pressure compliance.

Table II shows that HUV compliance at different gestational ages decreased with increasing pressure. HUV compliance at the age of 38 weeks was the greatest under the same pressure, and the compliance decreased with the increase or decrease of gestational age. HUV compliance was closely similar at ages 37–40 weeks. When HUVs older than 42 weeks or younger than 28 weeks were compared, there was a significant difference in compliance (F = 65.84–86.52, p < 0.01).

Table II. Changes in compliance of HUVs at different gestational ages [×10−4 mL/(kPa · cm), mean ± SD]
Gestational age (weeks)nPressure kPa (mm Hg) 0 (0)5.3 (40)10.7 (80)13.3 (100)
24–2782.40 ± 0.53*2.31 ± 0.41*2.22 ± 0.34*2.18 ± 0.35*
28–3273.97 ± 0.61*3.81 ± 0.62*3.65 ± 0.46*3.57 ± 0.49*
33–3684.59 ± 0.74**4.41 ± 0.41**4.22 ± 0.55**4.13 ± 0.64**
3748.32 ± 0.587.98 ± 0.787.63 ± 0.487.46 ± 0.59
3859.11 ± 0.578.72 ± 0.918.32 ± 0.768.13 ± 0.43
3958.35 ± 0.477.98 ± 0.447.61 ± 0.467.43 ± 0.44
4058.22 ± 0.527.88 ± 0.537.53 ± 0.727.37 ± 0.54
4144.29 ± 0.38**4.21 ± 0.62**4.13 ± 0.35**4.10 ± 0.61**
4242.35 ± 0.57*2.30 ± 0.51*2.25 ± 0.62*2.23 ± 0.58*

* p < 0.01 vs. weeks 37–40.

** p < 0.05 vs. weeks 37–40.

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DISCUSSION 

The P-V relationship of arteries in the systemic circulation could be described using a parabola equation. Our experiment showed that when fitting was performed for the measured P-V data of HUVs by applying a parabolic equation, the multiple correlative coefficients were greater than 0.96. This demonstrates that the P-V relationship of HUV could also be described by a parabolic equation. The nonlinear character of HUV P-V curves was within the physiological range, which indicates that HUV compliance alters with changes in pressure, an advantage for the fetal blood supply. Previous studies have shown that compliance of the vein was approximately 24 times that of the corresponding artery. The results of our previous study showed that the compliance of HUV was two to three times greater than that of the human umbilical artery.16 The idea that HUV has properties similar to those of the common medium artery was supported indirectly. The HUV wall may be divided into intima, media, and adventitia. Intima was thin; it consisted of an endothelium cell layer, a subendothelium layer, and an endoplastic membrane. Endoplastic membrane was integrated and separated by intima and media. On the transverse section of HUV, it looked like piled fans because of the contraction of the vascular wall. Media was composed of 14–23 layers of smooth muscle arranged longitudinally inside and in circles outside; it was thicker than common moderate veins but similar to moderate arteries.18

The compliance-age curves of aorta (5–71 years of age) showed that compliance would increase with age from birth, attain its maximum at 25 years or so, and afterward decrease progressively with age.19 The present study showed that HUV compliance increased with gestational age and attained its maximum at 38 weeks. Afterward, it decreased with increasing gestational age. HUV compliance was similar at 37–40 weeks of gestation, but over 42 weeks or under 28 weeks of gestational age it decreased obviously. According to the principle of compliance = expansile degree × original volume, we believe that the lower compliance of HUV aged less than 28 weeks can be attributed to a smaller caliber, which leads to a smaller volume of unit length. On the other hand, it was likely that dysplasia of HUV caused a reduction in elastic fibers. The lower compliance of HUV aged 42 weeks was likely associated with the aging of the placenta. Quantitative analysis of microstructural components of HUV is of particular significance in the study of HUV function. The collagen/elastic (C/E) ratio can indirectly reflect vascular elasticity, and a higher C/E ratio suggests lower compliance. Before week 28, the percentage of collagenous fiber was more than that of elastic fiber in the HUV wall; therefore, a higher C/E ratio led to lower compliance. After week 42, a higher C/E ratio and lower compliance were, on the one hand, connected with smooth muscle transformation and, on the other hand, with excessive fetal maturation and a disproportionate increase of collagenous fibers.18

Autogenous vessel is an ideal material for vascular transplantation; however, the supply is limited. Dardik and Dardik20 first reported their early experience with HUV bypass grafts in 1976. Several studies have since reported favorable patency rates for HUV femoral-popliteal bypass grafts, with long-term primary patency rate ranging 61–75%.21, 22 Bypasses using a sequential HUV-composite technique were reviewed for graft patency. Primary patency and secondary patency rates at 1, 2, 3, and 4 years were 71%, 61%, 53%, and 53% and 89%, 80%, 73%, and 67%, respectively.23 Between 1983 and 1988,24 members of the Department of Veterans Affairs were randomized to receive either an externally supported polytet-rafluoroethylene (PTFE), HUV, or saphenous vein (SV) for an above-knee femoral-popliteal bypass graft. The cumulative assisted primary patency rates were statistically similar among the different conduit types at 2 years (SV, 81%; HUV, 70%; PTFE, 69%). After 5 years, SV bypass grafts had a significantly better patency rate (73%) than HUV bypass grafts (53%), which had a significantly better patency rate than PTFE bypass grafts (39%). The number of bypass graft thromboses and major amputations within the first 30 days was highest in the HUV group. Patency failure also included bypass grafts that were removed because of an infection or aneurysmal degeneration. The study suggested that the SV should be considered as the bypass graft of choice for femoral-popliteal reconstruction and that, when a prosthetic bypass graft is used, an HUV should also be considered as an alternative choice to PTFE. However, the overall study did not include the relationship between HUV and gestational age. Our studies suggest that HUVs aged 37–40 weeks have good compliance and, therefore, may be a good option for use in vascular transplantation. Many studies25, 26 have shown that difference in compliance between host artery and transplantation material was one of the most important factors leading to alteration in hemodynamics, intimal hyperplasia, and even failure of transplantation. With increased compliance, the blood vessel can deal with changes in blood pressure. In contrast, with decreased compliance, the blood vessel will not be able to accommodate changes in blood pressure. The compliance of other vascular conduits is known:27, 28, 29 brachial artery, 4.35 × 10−4 mL/(kPa • cm) at 100 mm Hg; femoral artery, 3.80 × 10−4 mL/(kPa • cm) at 100 mm Hg; human greater SV, 5.82 × 10−4 mL/(kPa • cm) at 40 mm Hg, etc. In addition, HUVs are so widely available that they may become suitable material for vascular grafting. In this regard, besides matching in compliance between the HUV and the host artery, the relationship between compliance and gestational age should be considered.

The preferred conduit for lower limb bypass grafting is the greater SV, but it remains unclear which alternate graft should be used when this vein is unavailable to the surgeon. Often, a policy of using all-autogenous tissue grafts has been adopted, but this implies harvesting veins from distant sites and constructing spliced vein grafts. Because the use of nonautologous grafts has the appeal of reducing operating time and the need for multiple incisions, the plausible superiority of using alternate autologous veins needs proof. In the absence of such proof, HUV grafts have been used liberally.

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CONCLUSIONS 

The results of the present study suggest that HUVs collected at 37–40 weeks of gestational age have good compliance, i.e., a good P-V relationship, and therefore may be suitable material for vascular grafting. HUV is one of several graft materials that may be used when autogenous SV is absent or inadequate. HUV is very biocompatible and shows promise for use in orthopedic implants.

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This work was supported by the Key Program of the Hubei Provincial Bureau of Public Health (WJ01539).

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REFERENCES 

  1. Heyligers JM , Arts CH , Verhagen HJ , de Groot PG , Moll FL . Improving small-diameter vascular grafts: from the application of an endothelial cell lining to the construction of a tissue-engineered blood vessel . Ann Vasc Surg . 2005;19:448–456
  2. Stoltz JF , Lehalle B , Blondel WC , Bensoussan D , Paulus F . Introduction to vascular engineering . J Mal Vasc . 2001;26:183–190
  3. Nerem RM , Ensley AE . The tissue engineering of blood vessels and the heart . Am J Transplant . 2004;4:36–42
  4. Liu SQ , Tieche C , Alkema PK . Neointima formation on vascular elastic laminae and collagen matrices scaffolds implanted in the rat aortae . Biomaterials . 2004;25:1869–1882
  5. MacNeill BD , Pomerantseva I , Lowe HC , Oesterle SN , Vacanti JP . Toward a new blood vessel . Vasc Med . 2002;7:241–246
  6. Lamm P , Juchem G , Milz S , Schuffenhauer M , Reichart B . Autologous endothelialized vein allograft: a solution in the search for small-caliber grafts in coronary artery bypass graft operations . Circulation . 2001;104(Suppl 1):I108–I114
  7. Calles-Vazquez MC , Uson JM , Viguera FJ , Sun F , Paz JI , Uson-Gargallo J . Vascular closure stapler clips versus polypropylene sutures in end-to-end anastomoses of growing arteries and veins . Ann Vasc Surg . 2005;19:320–327
  8. Sierra J , Beghetti M , Kalangos A . Truncus arteriosus repair with double aortic homograft . J Card Surg . 2004;19:252–253
  9. Pascual G , Martinez S , Garcia-Honduvilla N , Corrales C , Bellon JM , Bujan J . Long-term behaviour of cryopreserved arterial grafts versus prosthetic micrografts . Eur. J Vasc Endovasc Surg . 2004;27:423–431
  10. Nishinari K , Wolosker N , Yazbek G , et al.   Vascular reconstruction in limbs associated with resection of tumors . Ann Vasc Surg . 2003;17:411–416
  11. Dardik I , Dardik H . Vascular heterograft: human umbilical cord vein as an aortic substitute in baboon. A preliminary report . J Med Primatol . 1973;2:296–301
  12. Dardik H , Wengerter K , Qin F , et al.   Comparative decades of experience with glutaraldehyde-tanned human umbilical cord vein graft for lower limb revascularization: an analysis of 1275 cases . J Vasc Surg . 2002;35:64–71
  13. Vlessis AA , Hovaguimian H , Arntson E , Starr A . Use of autologous umbilical artery and vein for vascular reconstruction in the newborn . J Thorac Cardiovasc Surg . 1995;109:854–857
  14. Aslan R , Sevin B , Dernek S , Manti Z . Human umbilical cord vein grafts for replacement of the superior vena cava . J Cardiovasc Surg (Torino) . 1992;33:154–159
  15. Pennati G . Biomechanical properties of the human umbilical cord . Biorheology . 2001;38:355–366
  16. Li W , Huang T , Zeng F , Zhou L . Biomechanical properties of human umbilical vessels at different gestational ages and their clinical significanc . Sheng Wu Yi Xue Gong Cheng Xue Za Zhi . 2001;18:530–533
  17. Shigemi K . Vascular responses to hypercapnia in anesthetized dogs . J. Anesth . 1988;2:1–7
  18. Li WC , Wang J , Tang J . Quantitative analysis of histological structure of umbilical cord vein for assessing the feasibility as arteriole transplantation substitute . ZhongGuo Lin Chuang Kang Fu . 2005;9:216–219
  19. Lanne T , Sonesson B , Bergqvist D , Bengtsson H , Gustafsson D . Diameter and compliance in the male human abdominal aorta: influence of age and aortic aneurysm . Eur. J. Vasc. Surg. . 1992;6:178–184
  20. Dardik H , Dardik II . Successful arterial substitution with modified human umbilical vein . Ann Surg . 1976;183:252–258
  21. Dardik H , Miller N , Dardik A , Ibrahim IM . A decade of experience with the glutaraldehyde-tanned human umbilical cord vein graft for revascularization of the lower limb . J Vasc Surg . 1998;7:336–346
  22. Anderson LI , Nielson OM , Hansen Buchardt HJ . Umbilical vein bypass in patients with severe lower limb ischemia: a report of 121 consecutive cases . Surgery . 1985;97:294–299
  23. Daniel J , Abe K , McFetridge PS . Development of the human umbilical vein scaffold for cardiovascular tissue engineering applications . ASAIO J . 2005;51:252–261
  24. Johnson WC , Lee KK . A comparative evaluation of polytetrafluoroethylene, umbilical vein, and saphenous vein bypass grafts for femoral-popliteal above-knee revascularization: a prospective randomized Department of Veterans Affairs cooperative study . J Vasc Surg . 2000;32:268–277
  25. Morasch MD , Dobrin PB , Dong QS , Mrkvicka R . Mechanics of spatulated end-to-end artery-to-vein anastomoses . Ann Vasc Surg . 1998;12:55–59
  26. Haruguchi H , Teraoka S . Intimal hyperplasia and hemodynamic factors in arterial bypass and arteriovenous grafts: a review . J Artif Organs . 2003;6:227–235
  27. Huang TZ , Chen EY , Yu HY . Changes of compliance and morphology of human brachial artery at different elongations and their clinical significance . Sheng Wu Yi Xue Gong Cheng Xue Za Zhi . 1995;12:295–299
  28. Yu HY , Chen EY , Zhu XH . Compliance changes of human femoral arterial segment after stretching . Zhongguo Sheng Wu Yi Xue Gong Cheng Xue Bao . 1993;12:285–289
  29. Stooker W , Gok M , Sipkema P , Niessen HW , Baidoshvili A , Westerhof N . Pressure-diameter relationship in the human greater saphenous vein . Ann Thorac Surg . 2003;76:1533–1538

PII: S0890-5096(06)60037-X

doi:10.1007/s10016-006-9020-4

Annals of Vascular Surgery
Volume 20, Issue 2 , Pages 237-242, March 2006

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