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Arterialization of the venous system in a rat lower limb model
Britrsh Journal of Plastic Surgery (I 997), 50,402-407 0 1997 The British Association of Plastic Surgeons
Arterialization of the venoussystemin a rat lower limb model C. Ozek*‘, F. Zhang’, W. C. Lineaweaver*, B. T. Chin+, L. Newlint, T. Eimanr and H. J. Buncket *Division of Plastic and Reconstructive Surgery, Stanford University Medical Center, Stanford, ‘Division of Microsurgical Replantation-Transplantation and IDepartment of Pathology, Davies Medical Center, San Francisco, California, USA SUMMARY Creation of alternative vascular conduits has been one of the most challenging subjects in the history of vascular surgery. In the past, afferent arteriovenous fistulas have been used by vascular surgeons to rescue ischaemic extremities. We have undertaken a comprehensive investigation to characterize arterialization of the venous system at different levels of the rat lower limb. In Group 1 (n = 28), we performed an end-to-end anastomosis between the proximal saphenous artery and the distal saphenous vein (Superficial venous system), and ligated all other branches of the femoral artery. In Group 2 (n = 28), we performed an end-to-end anastomosis between the proximal saphenous artery and the distal femoral vein (Deep venous system). In Group 3 (n = 24), the control group, the femoral artery was ligated proximal to its trifurcation into the saphenous, epigastric, and distal femoral vessels. Group 4 (n = lo), the normal group, underwent no surgery. Animals were sacrificed at the first, third, and eighth postoperative weeks. Arteriographic, India ink injection, latex injection, and histological studies were performed on all groups. Successful arterialization of veins, significant neovascularization, and less ischaemic injury of muscles were noted in the arterialized vein groups (Groups 1 and 2) when compared with the ligated group (Group 3). This model appears to depict successfully arterialization of the lower limb venous system in a small animal model.
Salvage of ischaemic limbs by vascular reconstruction is a surgical problem with a long history and intense current interest. Historically, an early technique for rescue of an ischaemic extremity was creation of an arteriovenous tistula between the venous and arterial systems of the extremity, following which the venous system serves as a route of arterial inflow. After earlier work by Berard and Carrel in 1902, Carrel and Guthrie reported arterialization of the venous system of the limbs in dogs.’ In the years following, Carrel’s technique was used by many surgeons for treatment of ischaemic conditions of the extremities such as thromboangiitis obliterans and Raynaud’s disease, as well as for treatment of ischaemic conditions resulting from tumour resections and trauma.*-” Most of the studies on this subject were reported from the early 1900s to the 1960s. Although a small number of good results was reported, the technique lost its popularity because of a generally low overall salvage rate. Beginning in the mid-l 970s revolutionary improvements in microvascular surgical techniques and equipment allowed surgeons to re-evaluate the efficacy of this technique experimentally and clinically.‘2~‘5In the present study, we have undertaken a comprehensive investigation to study arterialization of the venous system at different levels of the rat lower limb in order to see if a small animal model of this technique is feasible.
care of laboratory animals were followed. The animals were anaesthetized with 60 mg/kg intraperitoneal sodium pentobarbital injections. Ninety animals were randomly divided into four groups to compare the effects of arterialization of the venous system at different levels of the rat hind limb. In Group 1 (n = 28), we performed an end-to-end anastomosis between the proximal saphenous artery and the distal saphenous vein (Superficial venous system) and ligated all other branches of the femoral artery. In Group 2 (n = ZS), an end-to-end anastomosis was performed between the saphenous artery and the distal femoral vein (Deep venous system). In Group 3 (n = 24), the control group, the femoral artery was ligated proximal to its trifurcation into the saphenous, epigastric, and distal femoral vessels. Group 4 (n = lo), the normal group,‘underwent no surgery. Eight animals in each group were sacrificed at postoperative weeks 1, 3 and 8. Arteriographic, India ink injection, latex injection, and histological studies were performed on all groups. A histological control study was performed for both arterialized groups (Groups 1 and 2, four animals in each group) at 3 months. Arteriography and India ink injection techniques Immediately following sacrifice, microangiographies were performed to visualize the vascular networks of the arterialized limbs. Following exposure of the dorsal aorta and heart, 18-gauge catheters were inserted into both the dorsal aorta and right ventricle. A 30 ml 1: 1 mixture of lidocaine and heparin was injected, and
Materials and methods
We used 450-550 g adult Long-Ewans rats. The National Research Council’s guidelines for the use and 402
Arterialization of the venous system 60 cc of -35°C saline was perfused through the dorsal aorta catheter. Simultaneously, the animal’s blood was removed by applying continuous suction through the right ventricle catheter until perfusion of clear saline was observed. Once the animal’s vasculature had been completely flushed, a mixture of lead oxide and latex was injected through the dorsal aorta catheter (30 g of lead oxide [Pb,O,] was added to 60 ml of latex; 10 cc of this mixture was injected to each animal). Following the lead oxide-latex injection, the specimens were stored at 4°C for 2 hours at which time hind-limb radiographs were obtained. India ink injections were performed using the same technique.
Results
In the anastomosis groups (Groups 1 and 2) together, an overall anastomosis patency rate of 91.8% was observed. Separately, the arterialized saphenous (Group 1) and arterialized distal femoral (Group 2) groups exhibited patency rates of 27128 (96.4%) and 25/28 (89.3%), respectively. Gross examination revealed mild oedema in the arterialized legs; this effect was more marked in the arterialized distal femoral group (Deep venous system).
Fig. 1 Figure l-Latex Arterialization
injection of 8 weeks arterialized saphenous vein. of the venous system can be seen down to the foot.
India ink injections Latex injections
In the arterialized venous groups (Groups 1 and 2), latex injections demonstrated successful arterialization of the veins and anastomosis patency, and provided evidence of neovascularization (Fig. 1). In the ligated group (Group 3), the latex injections demonstrated absence of circulation in the distal parts of the ligated vessels (epigastric, saphenous, and distal femoral) at postoperative weeks 1 and 3; however, significant circulation was observed at week 8.
At weeks 1 and 3, significant colour differences were observed between the arterialized venous groups (Groups 1 and 2) and the ligated group (Group 3). While the arterialized groups showed colour similar to that of the normal group, no colour changes were noted in the ligated group following injection of India ink (Fig. 2). At week 8, however, similar colour was observed in the ligated and arterialized groups. No significant colour differences were observed in the arterialized groups between weeks 1, 3 and 8.
Fig. 2 Figure Z-India ink injections at 3 weeks. Saphenous: Arterialized saphenous vein (Group I). Arteria (Group 3). Distal femoral: Arterialized femoral vein (Group 2). Normal: Group 4. Significant colour and ligated groups can be seen.
ligated: Ligated femoral artery differences between the arterialized
British Journal of Plastic Surgery
404
vein groups. Focal areas of ischaemic damage persisted but the general condition of the muscles was much better than those in the ligated group (Fig. 5). Neovascularization was significant in both of the arterialized groups. In the ligated group, muscle ischaemic damage was slightly less at week 8 than at week 3. The vessel walls of the arterialized veins exhibited thickening, such that the veins resembled arteries, and muscle hypertrophy was observed (Fig. 6). At 3 months, arterialized venous groups (Groups 1 and 2, histological control) exhibited focal areas of muscle ischaemic damage. The muscles in general were much better than at weeks 1 and 3 and appeared almost identical to those from the same group observed at week 8. Vessel walls were thickened and resembled arteries, as did those observed at week 8.
Angiography Anastomosis patency, vein arterialization, and neovascularization were observed in the arterialized venous groups (Group 1 and 2). Although there was no circulation in the distal portion of the ligated vessels (epigastric, saphenous, and distal femoral) at weeks 1 and 3 (Fig. 3A), circulation was observed at week 8 (Fig. 3B). Gradual thickening of the arterialized vein walls as well as gradual neovascularization was observed at weeks I, 3 and 8 (Fig. 4). Best results were observed at week 8 in the arterialized vein groups (Figs 4 C, E). Histology At week I, focal ischaemia was observed in the skeletal muscle of both arterialized groups as well as in the ligated group. Ischaemic injury was more severe in the ligated group than in the arterialized groups. Slight muscle hypertrophy was observed in the media of the arterialized vein groups. At week 3, ischaemic injury was more severe than at week 1 in the ligated group, but the skeletal muscle appeared more healthy than at week 1 in the arterialized groups. Nevertheless, areas of focal ischaemia were still evident in the skeletal muscle of the arterialized groups. Also, some degree of neovascularization was observed in these groups. Finally, significant muscle hypertrophy and vein wall thickening were observed in the arterialized veins. No differences in skeletal muscle condition were observed between weeks 3 and 8 in the arterialized
Discussion
Francois-Frank, in 1881, made the first attempt to produce a functional arteriovenous anastomosis in animals.’ Success was not reported until 1902, when Carrel, after advancing the techniques of experimental vascular surgery, made the first successful anastomosis between the jugular and carotid vessels in a dog.’ In 1905, Carrel and Guthrie reported a series of 13 arteriovenous anastomoses in dogs without a single failure. ’ In 1912, Bernheim reported success in 15 of 52 patients recorded in the literature, including 6 of his own, who had had arteriovenous anastomoses.3
Fig. 3 Figure WA) 8 weeks after
Angiography of 3 weeks femoral ligation of the femoral artery.
artery
ligated
leg. There
is no circulation
in the distal
portion
of ligated
vessel. (B) Circulation
Arterialization of the venous svstem
Fig. 4 Figure &(A) Angiography of normal leg. (B) Angiography of 1 week arterialized distal femoral vein leg. (C) Angiography arterialized distal femoral vein leg, Significant thickening of arterialized vein wall and neovascularization. (D) Angiography arterialized saphenous vein leg. (E) Angiography of 8 weeks arterialized saphenous vein leg. There are significant differences arterialized vein groups (Groups 1 and 2) and the ligated artery group (Group 3) (Fig. 3).
Zweifach, in 1940, showed successful exchange of small molecules” and Heimbecker et al. demonstrated oxygen uptake with reverse perfusion.” Until the 195Os, this procedure was popular with some surgeons but lost its appeal because of the low patency rates associated with the technique. With the advent of improved
of 8 weeks of 1 week between the
microsurgical techniques and widespread use of the operating microscope, arteriovenous anastomosis has reappeared. In addition to recent experimental work,‘3.‘4 Pederson” reported improvement of symptoms and healing of ulcers in four of six patients who had arterialization of the venous system for treatment
British
406
Journal
of Plastic
Surgery
Fig.
Fig. 6 Figure 5-(H&E x 160) (A) Horizontal section of 8 weeks arterialized saphenous vein muscle. Good muscle condition: nuclei periphery, cytoplasm is smooth, just focal cracking. (B) Horizontal section of 8 weeks ligated artery group. Diffuse ischaemia, of nuclei, prominent distortion of cytoplasm. Figure b(H&E x 250) (A) Cross-section of normal saphenous artery and vein. (B) Arterialized distal and media are significantly thickened. (C) Arterialized saphenous vein at 8 weeks. Muscle hypertrophy vein almost looks like an artery, except for the elastic lamina.
of end-stage ischaemia of the upper limb, with multiple segmental occlusion of the arteries and poor outflow vessels. In our study, anastomosis patency and successful arterialization of the venous system were confirmed by the angiographic and latex and India ink injection
on the degeneration
femoral vein at 8 weeks. The intima and thickening of the vein wall. The
studies. Vein valves were clearly incompetent against reversed flow. Absence of severe oedema upon gross examination suggested no venous return problems both for deep and superficial venous groups. The vessel wall thickening and hypertrophy indicate that the arterialized veins had successfully initiated adaptive
Arterialization of the venous system changes to withstand the increased stress experienced in their new roles as arterial conduits. The histological evidence shows clearly that in both experimental groups arterialization of the venous system can significantly curb ischaemic injury to extremity muscles which have suffered loss of arterial supply. This study demonstrates that venous arterialization in the rat can successfully and adequately serve as a substitute method of blood delivery to distal extremities which have lost their arterial supplies, with minimal to negligible tissue and vessel damage. The rat model can be used to study venous system arterialization for up to eight weeks, at which time circulation begins to re-establish itself in the distal part of the ligated arteries. While more experimental and eventually clinical studies are clearly necessary, it is our hope that the revisited technique for re-establishing tissue perfusion might eventually be applicable to trauma, replantation, transplantation, and reconstructive surgery patients.
401 7. Horsley JS, Whitehead RH. A study of reversal of the circulation in the lower extremity. JAMA 1915; 64: 873-7. 8. Horsley JS. Operative treatment for threatened gangrene of the foot, with special reference to reversal of the circulation. JAMA 1916; 67: 492-9. 9. Bernheim BM. Arteriovenous anastomosis: follow-up after eighteen years of “successful reversal of the circulation in all four extremities of the same individual”. JAMA 193 I: 96: 1296-7. 10. Szilagyi DE, Jay GD, Munnel ED. Femoral arteriovenous anastomosis in the treatment of occlusive arterial disease. Arch Surg 1951; 63: 435-51. 1. Heimbecker P, Vivien T, Blalock A. Experimental reversal of capillary flow. Circulation 1951; 4: 116-23. 2. Matolo NM, Cohen SE, Wolfman EF. Use of an arteriovenous fistula for treatment of the severely ischemic extremity: experimental evaluation. Ann Surg 1976: 184: 62225. 13. Johansen K, Bernstein EF. Revascularization of the ischemic canine hindlimb by arteriovenous reversal. Ann Surg 1979: 190: 243-53. 1,4. Nichter LS, Haines PC. Arterialized venous perfusion of composite tissue. Am J Surg 1985: 150: 191-6. 1 5. Pederson WC. Microsurgical management in end-stage ischaemia of the upper extremity. In: Proceedings of 12th Symposium, International Society of Reconstructive Microsurgery, Singapore 1996; 471-2.
Acknowledgement Support for this study of the Davies Medical
was provided by the Microsurgery Foundation Center, and Ege University. Izmir, Turkey.
References I. Carrel A, Guthrie CC. The reversal of the circulation in a limb. Ann Surg 1906; 43: 203-15. 2. Horsley JS. Reversal of the circulation in the low extremities. JAMA 1915; 64: 277-9. 3. Bernheim BM. Arteriovenous anastomosis: successful reversal of the circulation in all lower extremities in the same individual. JAMA 1913; 60: 360-I. 4. Bernheim BM. Arteriovenous anastomosis-reversal of the circulation-as a preventive of gangrene of the extremities. Ann Surg 1912; 55: 195-207. 5. Goodman C. Arteriovenous anastomosis of the femoral vessels for impending gangrene. Ann Surg 1914; 60: 62-87. 6. Lilienthal H. Arteriovenous anastomosis for thrombo-angeitis obliterans. Ann Surg 1914; 58: 303-8.
The Authors Cuneyt Ozek MD Feng Zhang MD, PhD William C. Lineaweaver Brian T. Chin MS Leonard Newlin MS Thomas Eiman MD Harry J. Buncke MD
MD
Division of Plastic and Reconstructive Surgery, Stanford University Medical Center, Stanford, California. Division of Microsurgical Replantation-Transplantation and Department Pathology, Davies Medical Center, San Francisco, California. Correspondence to William C. Lineaweaver Plastic and Reconstructive Surgery, Stanford Center, NC 104. Stanford, CA 94305, USA. Paper received 13 November 1997. Accepted 2 I April 1997. after revision
MD, Division of University Medical
of
Arterialization of the venoussystemin a rat lower limb model C. Ozek*‘, F. Zhang’, W. C. Lineaweaver*, B. T. Chin+, L. Newlint, T. Eimanr and H. J. Buncket *Division of Plastic and Reconstructive Surgery, Stanford University Medical Center, Stanford, ‘Division of Microsurgical Replantation-Transplantation and IDepartment of Pathology, Davies Medical Center, San Francisco, California, USA SUMMARY Creation of alternative vascular conduits has been one of the most challenging subjects in the history of vascular surgery. In the past, afferent arteriovenous fistulas have been used by vascular surgeons to rescue ischaemic extremities. We have undertaken a comprehensive investigation to characterize arterialization of the venous system at different levels of the rat lower limb. In Group 1 (n = 28), we performed an end-to-end anastomosis between the proximal saphenous artery and the distal saphenous vein (Superficial venous system), and ligated all other branches of the femoral artery. In Group 2 (n = 28), we performed an end-to-end anastomosis between the proximal saphenous artery and the distal femoral vein (Deep venous system). In Group 3 (n = 24), the control group, the femoral artery was ligated proximal to its trifurcation into the saphenous, epigastric, and distal femoral vessels. Group 4 (n = lo), the normal group, underwent no surgery. Animals were sacrificed at the first, third, and eighth postoperative weeks. Arteriographic, India ink injection, latex injection, and histological studies were performed on all groups. Successful arterialization of veins, significant neovascularization, and less ischaemic injury of muscles were noted in the arterialized vein groups (Groups 1 and 2) when compared with the ligated group (Group 3). This model appears to depict successfully arterialization of the lower limb venous system in a small animal model.
Salvage of ischaemic limbs by vascular reconstruction is a surgical problem with a long history and intense current interest. Historically, an early technique for rescue of an ischaemic extremity was creation of an arteriovenous tistula between the venous and arterial systems of the extremity, following which the venous system serves as a route of arterial inflow. After earlier work by Berard and Carrel in 1902, Carrel and Guthrie reported arterialization of the venous system of the limbs in dogs.’ In the years following, Carrel’s technique was used by many surgeons for treatment of ischaemic conditions of the extremities such as thromboangiitis obliterans and Raynaud’s disease, as well as for treatment of ischaemic conditions resulting from tumour resections and trauma.*-” Most of the studies on this subject were reported from the early 1900s to the 1960s. Although a small number of good results was reported, the technique lost its popularity because of a generally low overall salvage rate. Beginning in the mid-l 970s revolutionary improvements in microvascular surgical techniques and equipment allowed surgeons to re-evaluate the efficacy of this technique experimentally and clinically.‘2~‘5In the present study, we have undertaken a comprehensive investigation to study arterialization of the venous system at different levels of the rat lower limb in order to see if a small animal model of this technique is feasible.
care of laboratory animals were followed. The animals were anaesthetized with 60 mg/kg intraperitoneal sodium pentobarbital injections. Ninety animals were randomly divided into four groups to compare the effects of arterialization of the venous system at different levels of the rat hind limb. In Group 1 (n = 28), we performed an end-to-end anastomosis between the proximal saphenous artery and the distal saphenous vein (Superficial venous system) and ligated all other branches of the femoral artery. In Group 2 (n = ZS), an end-to-end anastomosis was performed between the saphenous artery and the distal femoral vein (Deep venous system). In Group 3 (n = 24), the control group, the femoral artery was ligated proximal to its trifurcation into the saphenous, epigastric, and distal femoral vessels. Group 4 (n = lo), the normal group,‘underwent no surgery. Eight animals in each group were sacrificed at postoperative weeks 1, 3 and 8. Arteriographic, India ink injection, latex injection, and histological studies were performed on all groups. A histological control study was performed for both arterialized groups (Groups 1 and 2, four animals in each group) at 3 months. Arteriography and India ink injection techniques Immediately following sacrifice, microangiographies were performed to visualize the vascular networks of the arterialized limbs. Following exposure of the dorsal aorta and heart, 18-gauge catheters were inserted into both the dorsal aorta and right ventricle. A 30 ml 1: 1 mixture of lidocaine and heparin was injected, and
Materials and methods
We used 450-550 g adult Long-Ewans rats. The National Research Council’s guidelines for the use and 402
Arterialization of the venous system 60 cc of -35°C saline was perfused through the dorsal aorta catheter. Simultaneously, the animal’s blood was removed by applying continuous suction through the right ventricle catheter until perfusion of clear saline was observed. Once the animal’s vasculature had been completely flushed, a mixture of lead oxide and latex was injected through the dorsal aorta catheter (30 g of lead oxide [Pb,O,] was added to 60 ml of latex; 10 cc of this mixture was injected to each animal). Following the lead oxide-latex injection, the specimens were stored at 4°C for 2 hours at which time hind-limb radiographs were obtained. India ink injections were performed using the same technique.
Results
In the anastomosis groups (Groups 1 and 2) together, an overall anastomosis patency rate of 91.8% was observed. Separately, the arterialized saphenous (Group 1) and arterialized distal femoral (Group 2) groups exhibited patency rates of 27128 (96.4%) and 25/28 (89.3%), respectively. Gross examination revealed mild oedema in the arterialized legs; this effect was more marked in the arterialized distal femoral group (Deep venous system).
Fig. 1 Figure l-Latex Arterialization
injection of 8 weeks arterialized saphenous vein. of the venous system can be seen down to the foot.
India ink injections Latex injections
In the arterialized venous groups (Groups 1 and 2), latex injections demonstrated successful arterialization of the veins and anastomosis patency, and provided evidence of neovascularization (Fig. 1). In the ligated group (Group 3), the latex injections demonstrated absence of circulation in the distal parts of the ligated vessels (epigastric, saphenous, and distal femoral) at postoperative weeks 1 and 3; however, significant circulation was observed at week 8.
At weeks 1 and 3, significant colour differences were observed between the arterialized venous groups (Groups 1 and 2) and the ligated group (Group 3). While the arterialized groups showed colour similar to that of the normal group, no colour changes were noted in the ligated group following injection of India ink (Fig. 2). At week 8, however, similar colour was observed in the ligated and arterialized groups. No significant colour differences were observed in the arterialized groups between weeks 1, 3 and 8.
Fig. 2 Figure Z-India ink injections at 3 weeks. Saphenous: Arterialized saphenous vein (Group I). Arteria (Group 3). Distal femoral: Arterialized femoral vein (Group 2). Normal: Group 4. Significant colour and ligated groups can be seen.
ligated: Ligated femoral artery differences between the arterialized
British Journal of Plastic Surgery
404
vein groups. Focal areas of ischaemic damage persisted but the general condition of the muscles was much better than those in the ligated group (Fig. 5). Neovascularization was significant in both of the arterialized groups. In the ligated group, muscle ischaemic damage was slightly less at week 8 than at week 3. The vessel walls of the arterialized veins exhibited thickening, such that the veins resembled arteries, and muscle hypertrophy was observed (Fig. 6). At 3 months, arterialized venous groups (Groups 1 and 2, histological control) exhibited focal areas of muscle ischaemic damage. The muscles in general were much better than at weeks 1 and 3 and appeared almost identical to those from the same group observed at week 8. Vessel walls were thickened and resembled arteries, as did those observed at week 8.
Angiography Anastomosis patency, vein arterialization, and neovascularization were observed in the arterialized venous groups (Group 1 and 2). Although there was no circulation in the distal portion of the ligated vessels (epigastric, saphenous, and distal femoral) at weeks 1 and 3 (Fig. 3A), circulation was observed at week 8 (Fig. 3B). Gradual thickening of the arterialized vein walls as well as gradual neovascularization was observed at weeks I, 3 and 8 (Fig. 4). Best results were observed at week 8 in the arterialized vein groups (Figs 4 C, E). Histology At week I, focal ischaemia was observed in the skeletal muscle of both arterialized groups as well as in the ligated group. Ischaemic injury was more severe in the ligated group than in the arterialized groups. Slight muscle hypertrophy was observed in the media of the arterialized vein groups. At week 3, ischaemic injury was more severe than at week 1 in the ligated group, but the skeletal muscle appeared more healthy than at week 1 in the arterialized groups. Nevertheless, areas of focal ischaemia were still evident in the skeletal muscle of the arterialized groups. Also, some degree of neovascularization was observed in these groups. Finally, significant muscle hypertrophy and vein wall thickening were observed in the arterialized veins. No differences in skeletal muscle condition were observed between weeks 3 and 8 in the arterialized
Discussion
Francois-Frank, in 1881, made the first attempt to produce a functional arteriovenous anastomosis in animals.’ Success was not reported until 1902, when Carrel, after advancing the techniques of experimental vascular surgery, made the first successful anastomosis between the jugular and carotid vessels in a dog.’ In 1905, Carrel and Guthrie reported a series of 13 arteriovenous anastomoses in dogs without a single failure. ’ In 1912, Bernheim reported success in 15 of 52 patients recorded in the literature, including 6 of his own, who had had arteriovenous anastomoses.3
Fig. 3 Figure WA) 8 weeks after
Angiography of 3 weeks femoral ligation of the femoral artery.
artery
ligated
leg. There
is no circulation
in the distal
portion
of ligated
vessel. (B) Circulation
Arterialization of the venous svstem
Fig. 4 Figure &(A) Angiography of normal leg. (B) Angiography of 1 week arterialized distal femoral vein leg. (C) Angiography arterialized distal femoral vein leg, Significant thickening of arterialized vein wall and neovascularization. (D) Angiography arterialized saphenous vein leg. (E) Angiography of 8 weeks arterialized saphenous vein leg. There are significant differences arterialized vein groups (Groups 1 and 2) and the ligated artery group (Group 3) (Fig. 3).
Zweifach, in 1940, showed successful exchange of small molecules” and Heimbecker et al. demonstrated oxygen uptake with reverse perfusion.” Until the 195Os, this procedure was popular with some surgeons but lost its appeal because of the low patency rates associated with the technique. With the advent of improved
of 8 weeks of 1 week between the
microsurgical techniques and widespread use of the operating microscope, arteriovenous anastomosis has reappeared. In addition to recent experimental work,‘3.‘4 Pederson” reported improvement of symptoms and healing of ulcers in four of six patients who had arterialization of the venous system for treatment
British
406
Journal
of Plastic
Surgery
Fig.
Fig. 6 Figure 5-(H&E x 160) (A) Horizontal section of 8 weeks arterialized saphenous vein muscle. Good muscle condition: nuclei periphery, cytoplasm is smooth, just focal cracking. (B) Horizontal section of 8 weeks ligated artery group. Diffuse ischaemia, of nuclei, prominent distortion of cytoplasm. Figure b(H&E x 250) (A) Cross-section of normal saphenous artery and vein. (B) Arterialized distal and media are significantly thickened. (C) Arterialized saphenous vein at 8 weeks. Muscle hypertrophy vein almost looks like an artery, except for the elastic lamina.
of end-stage ischaemia of the upper limb, with multiple segmental occlusion of the arteries and poor outflow vessels. In our study, anastomosis patency and successful arterialization of the venous system were confirmed by the angiographic and latex and India ink injection
on the degeneration
femoral vein at 8 weeks. The intima and thickening of the vein wall. The
studies. Vein valves were clearly incompetent against reversed flow. Absence of severe oedema upon gross examination suggested no venous return problems both for deep and superficial venous groups. The vessel wall thickening and hypertrophy indicate that the arterialized veins had successfully initiated adaptive
Arterialization of the venous system changes to withstand the increased stress experienced in their new roles as arterial conduits. The histological evidence shows clearly that in both experimental groups arterialization of the venous system can significantly curb ischaemic injury to extremity muscles which have suffered loss of arterial supply. This study demonstrates that venous arterialization in the rat can successfully and adequately serve as a substitute method of blood delivery to distal extremities which have lost their arterial supplies, with minimal to negligible tissue and vessel damage. The rat model can be used to study venous system arterialization for up to eight weeks, at which time circulation begins to re-establish itself in the distal part of the ligated arteries. While more experimental and eventually clinical studies are clearly necessary, it is our hope that the revisited technique for re-establishing tissue perfusion might eventually be applicable to trauma, replantation, transplantation, and reconstructive surgery patients.
401 7. Horsley JS, Whitehead RH. A study of reversal of the circulation in the lower extremity. JAMA 1915; 64: 873-7. 8. Horsley JS. Operative treatment for threatened gangrene of the foot, with special reference to reversal of the circulation. JAMA 1916; 67: 492-9. 9. Bernheim BM. Arteriovenous anastomosis: follow-up after eighteen years of “successful reversal of the circulation in all four extremities of the same individual”. JAMA 193 I: 96: 1296-7. 10. Szilagyi DE, Jay GD, Munnel ED. Femoral arteriovenous anastomosis in the treatment of occlusive arterial disease. Arch Surg 1951; 63: 435-51. 1. Heimbecker P, Vivien T, Blalock A. Experimental reversal of capillary flow. Circulation 1951; 4: 116-23. 2. Matolo NM, Cohen SE, Wolfman EF. Use of an arteriovenous fistula for treatment of the severely ischemic extremity: experimental evaluation. Ann Surg 1976: 184: 62225. 13. Johansen K, Bernstein EF. Revascularization of the ischemic canine hindlimb by arteriovenous reversal. Ann Surg 1979: 190: 243-53. 1,4. Nichter LS, Haines PC. Arterialized venous perfusion of composite tissue. Am J Surg 1985: 150: 191-6. 1 5. Pederson WC. Microsurgical management in end-stage ischaemia of the upper extremity. In: Proceedings of 12th Symposium, International Society of Reconstructive Microsurgery, Singapore 1996; 471-2.
Acknowledgement Support for this study of the Davies Medical
was provided by the Microsurgery Foundation Center, and Ege University. Izmir, Turkey.
References I. Carrel A, Guthrie CC. The reversal of the circulation in a limb. Ann Surg 1906; 43: 203-15. 2. Horsley JS. Reversal of the circulation in the low extremities. JAMA 1915; 64: 277-9. 3. Bernheim BM. Arteriovenous anastomosis: successful reversal of the circulation in all lower extremities in the same individual. JAMA 1913; 60: 360-I. 4. Bernheim BM. Arteriovenous anastomosis-reversal of the circulation-as a preventive of gangrene of the extremities. Ann Surg 1912; 55: 195-207. 5. Goodman C. Arteriovenous anastomosis of the femoral vessels for impending gangrene. Ann Surg 1914; 60: 62-87. 6. Lilienthal H. Arteriovenous anastomosis for thrombo-angeitis obliterans. Ann Surg 1914; 58: 303-8.
The Authors Cuneyt Ozek MD Feng Zhang MD, PhD William C. Lineaweaver Brian T. Chin MS Leonard Newlin MS Thomas Eiman MD Harry J. Buncke MD
MD
Division of Plastic and Reconstructive Surgery, Stanford University Medical Center, Stanford, California. Division of Microsurgical Replantation-Transplantation and Department Pathology, Davies Medical Center, San Francisco, California. Correspondence to William C. Lineaweaver Plastic and Reconstructive Surgery, Stanford Center, NC 104. Stanford, CA 94305, USA. Paper received 13 November 1997. Accepted 2 I April 1997. after revision
MD, Division of University Medical
of