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A new portacaval shunt
A New Portacaval Shunt
JACOB
T. KISSINGER, HERMAN E. GRIFFIN, SARAH A. CAMPBELL, HOWARD C.
HUGHES, AND MARGARETS. LANDI
A new prosthetic, segmented polyether polyurethane
portacaval shunt featuring quick-connect anastomotic ends was constructed and evaluated as part of a shortterm pharmacokinetic study, The shunts were easily implanted, did not require the use of anticoagulants, and decreased the operative time normally required for this surgical preparation. There was no evidence of thrombosis or venous stasis associated with the shunts. Key Words:
Portacaval shunt; Extrahepatic drug metabolism;
Portal vein
INTRODUCTION
Pharmacokinetic studies of extrahepatic drug metabolism require the isolation of the liver from the systemic circulation. Since the simple ligation of the portal vein and hepatic artery can result in systemic circulatory collapse (Warren, 4980)‘ isolation of the liver is best accomplished by ligating the hepatic artery and diverting the blood supply from the portal vein directly to the inferior vena cava (IVC). The conventional method for creating these portacaval shunts consists of suturing the portal vein and vena cava together in a side-by-side fashion, after which a stoma is created between the vessels with a cutting suture (Hofmeyer and irwin, 1965). An alternate technique employs an end-to-side anastomosis between the portal vein and the IVC (Donovan and Covey, 1978). Although these techniques are reliable for creating chronic animal models, their meticulous dissection and suture techniques can unnecessarily prolong the operative time when only a short-term, nonsurvival model is required. Problems associated with this increased surgical time, such as ischemia and hypothermia, can adversely affect the experimental preparation. The purpose of this study was to evaluate a new nonthrombogenic, reusable, prosthetic portacaval shunt designed to decrease operative time and reduce morbidity.
From the Department of Laboratory Animal Science, Smith Kline and French Laboratories, King of Prussia, Pennsylvania (J.T.K., S.A.C., H.C.H., M.S.L.), and Department of Pathology and Experimental Toxicology, Warner Lambert Company, Ann Arbor, Michigan (H.E.C.). Address reprint requests to: Jacob T. Kissinger, Department of Laboratory Animal Science, Smith Kline & French Laboratories, P.O. Box 1539, Mail Code L620, King of Prussia, PA 19406-0939. Received January 4, 1988; revised and accepted April 13, 1988.
Journal of Pharmacological
Methods
0 1988 Elsevier Science Publishing
20,329-333
(1988)
Co., inc., 655 Avenue of the Americas,
New York, NY f@J70
330
J. T. Kissinger et al.
Shunt Fabrication The portacaval shunts (6-mm internal diameter and 5.5 cm long) were fabricated from a segmented polyether polyurethane (SPU), (Cardiac Control Systems, Inc., Palm Coast, FL), and chosen for its strength, durability, and low thrombogenicity (Hughes et al., 1983; Kissinger and Hughes, 1984). Two coats of 20% solvent-dissolved SPU are dipcoated into glass molds and dried. The polymer’s solvent is N,NDimethylacetamide, and in this case the molds were 6-mm diameter glass rods, which were cut to working lengths of 12 cm (the rod ends are polished to remove any sharp edges). After soaking in distilled water, the SPU tubes are removed from the molds, turned inside out (making the air-dried, less thrombogenic surface the lumen), returned to the molds, and dried. Two handmade 0.35-mm stainless steel rings are slid over each end of the tubes, placed 4 mm apart, and bonded down with a running bead of 20% SPU. The ends of the SPU tubes are then trimmed, pulled back over the two rings, and beaded down with 15% SPU. Since the portal vein and inferior vena cava run essentially parallel to one another, the shunts are next molded in a bent configuration (Figure 1) which allows an end-to-end anastomosis to the portal vein and an end-to-side anastomosis with the inferior vena cava. This is accomplished by soaking the dried shunts in distilled water, removing them from the straight molds, putting them onto bent-glass molds, and then heatsetting them in an autoclave at 250” for 45 min. A final 24-hr water soak is used to leach out any remaining solvent and facilitate removal of the shunts from the molds. Surgical Procedure These shunts, or grafts, were used to create acute portacaval shunt models in five dogs (two beagles and three mongrels) weighing between IO-20 kg each. The mongrels were anesthetized with sodium pentobarbital (Veterinary Laboratories, Inc., Lenexa, KS), while the beagles, which were subsequently used in a short-term (2 hr) pharmacokinetic drug study, were anesthetized by induction with sodium thiamylal (Boehringer lngelheim Animal Health, Inc., St. Joseph, MO) (35 mg/kg), intubated, and maintained on isoflurane (BOC Health Care, Anaquest, Madison, WI) (1.5%) inhalation anesthesia. The animals were placed on a water-circulatingheating pad in dorsal recumbency and a IS-cm ventral-midline incision was used to enter the abdomen. Working from the right side of the abdomen we retracted the intestines medially to allow the hepatic artery, portal vein, and inferior vena cava to be identified and dissected free. In preparation of the end-to-side anastomosis a caval vascular clamp was used to isolate a 2-cm segment of the ventral half of the IVC. The occluded area of the cava was as small as was practical in order to minimize the disturbance of blood flow through the vessel. Total occlusion of the IVC cannot be used, since it would prevent approximately two-thirds of the venous blood from returning to the heart, resulting in rapid hypovolemic shock and death. A 6-mm longitudinal incision was made in the section of isolated caval wall and a purse-string suture of 4-O polypropylene was preplaced around the wound edges. One end of the shunt was then guided through
331
332
J. T. Kissinger et al.
the incision into the cava (Figure 2) and the purse-string suture was tightened down on the shunt in the area between the two rings. A straight vascular clamp was next placed across the middle of the prosthesis, and the caval clamp was released. The shunt was now ready for anastomosis to the previously isolated portal vein. First the portal vein and any of its branches were ligated cranially with 2-O silk and cross-clamped as far caudally as possible. A 5-mm-transverse incision was made in the vein’s wall, and the shunt’s free end was inserted through the incision into the vessel lumen. A preplaced circumferential ligature (2-O silk) was then tied down over the vessel in the area of separation between the shunt’s rings (Figure 3). With both anastomoses completed, the vascular clamps were slowly removed from the prosthesis and portal vein to gradually reintroduce the pooled portal venous blood into the circulation. To totally eliminate blood flow to the liver, the hepatic artery was ligated using 2-O silk suture. In order to maintain normal splanchic blood flow and body temperature, the abdominal organs were then returned to their correct anatomical position, and the skin incision was closed using 2-O gut.
FIGURE 2. Diagram showing shunt end positioned for insertion through the incised, isolated caval wall (purse-string suture around incision not shown).
Portacaval Shunt
FIGURE 3. Diagram of the end-to-end anastomosis between the shunt and portal vein. The shunt is secured within the vessel by a circumferential ligature.
RESULTS AND
DISCUSSION
The primary advantage of these shunts is that their quick-connect anastomotic design decreases implant time considerably when compared to conventional portacaval shunt preparations. With proper-sized shunts available, the entire surgical procedure, from incision to closure, can be accomplished in 75-90 min. Certain characteristics of the SPU polymer such as its strength, elasticity, nonporosity, and low thrombogenicity also promote these shunts as an ideal interface with the vascular system. The polymer’s lack of porosity prevents bleeding and allows for easy cleaning and reuse. Another attractive property of the shunts is their which allows for custom fabrication of curves or bends as re“heat-setability,” quired. In addition, anticoagulants are not necessary with the use of these devices. The shunts used in the acute pharmacokinetic study functioned well during their 2-hr implant duration. Their curved configuration minimized the chances of kinking so that unimpeded flow from the portal vein to the vena cava was maintained. In addition, at the conclusion of the study, the shunts were removed, and, upon examination, their lumens revealed no evidence of fibrin buildup or associated thrombosis.
REFERENCES Donovan AJ, Covey PC (1978) Early history of the portacaval shunt in humans. Surg Cynecol Obstet 147:423-430. Hofmeyer CF, Irwin DH (1965) Liver and biliary tract. In Canine Surgery. Ed., J Archibald. Wheaton, III.: American Veterinary Publications Inc., pp. 688-689. Hughes HC, Bertolet RD, Kissinger JT, Brownlee RR (1983) A new polyurethane and process for pacer
leads. In Cardia facing. Ed., K Steinbach. Darmstat: Steinkoff-Verlag, p. 323. Kissinger JT, Hughes HC (1984) Fabrication method for endotracheal tubes for sheep, goats, and calves. Lab Anim Sci 34:97-98. Warren WD (1980) Presidential address: Reflections on the early development of portacaval shunts. Ann Surg 191:519-527.
333
JACOB
T. KISSINGER, HERMAN E. GRIFFIN, SARAH A. CAMPBELL, HOWARD C.
HUGHES, AND MARGARETS. LANDI
A new prosthetic, segmented polyether polyurethane
portacaval shunt featuring quick-connect anastomotic ends was constructed and evaluated as part of a shortterm pharmacokinetic study, The shunts were easily implanted, did not require the use of anticoagulants, and decreased the operative time normally required for this surgical preparation. There was no evidence of thrombosis or venous stasis associated with the shunts. Key Words:
Portacaval shunt; Extrahepatic drug metabolism;
Portal vein
INTRODUCTION
Pharmacokinetic studies of extrahepatic drug metabolism require the isolation of the liver from the systemic circulation. Since the simple ligation of the portal vein and hepatic artery can result in systemic circulatory collapse (Warren, 4980)‘ isolation of the liver is best accomplished by ligating the hepatic artery and diverting the blood supply from the portal vein directly to the inferior vena cava (IVC). The conventional method for creating these portacaval shunts consists of suturing the portal vein and vena cava together in a side-by-side fashion, after which a stoma is created between the vessels with a cutting suture (Hofmeyer and irwin, 1965). An alternate technique employs an end-to-side anastomosis between the portal vein and the IVC (Donovan and Covey, 1978). Although these techniques are reliable for creating chronic animal models, their meticulous dissection and suture techniques can unnecessarily prolong the operative time when only a short-term, nonsurvival model is required. Problems associated with this increased surgical time, such as ischemia and hypothermia, can adversely affect the experimental preparation. The purpose of this study was to evaluate a new nonthrombogenic, reusable, prosthetic portacaval shunt designed to decrease operative time and reduce morbidity.
From the Department of Laboratory Animal Science, Smith Kline and French Laboratories, King of Prussia, Pennsylvania (J.T.K., S.A.C., H.C.H., M.S.L.), and Department of Pathology and Experimental Toxicology, Warner Lambert Company, Ann Arbor, Michigan (H.E.C.). Address reprint requests to: Jacob T. Kissinger, Department of Laboratory Animal Science, Smith Kline & French Laboratories, P.O. Box 1539, Mail Code L620, King of Prussia, PA 19406-0939. Received January 4, 1988; revised and accepted April 13, 1988.
Journal of Pharmacological
Methods
0 1988 Elsevier Science Publishing
20,329-333
(1988)
Co., inc., 655 Avenue of the Americas,
New York, NY f@J70
330
J. T. Kissinger et al.
Shunt Fabrication The portacaval shunts (6-mm internal diameter and 5.5 cm long) were fabricated from a segmented polyether polyurethane (SPU), (Cardiac Control Systems, Inc., Palm Coast, FL), and chosen for its strength, durability, and low thrombogenicity (Hughes et al., 1983; Kissinger and Hughes, 1984). Two coats of 20% solvent-dissolved SPU are dipcoated into glass molds and dried. The polymer’s solvent is N,NDimethylacetamide, and in this case the molds were 6-mm diameter glass rods, which were cut to working lengths of 12 cm (the rod ends are polished to remove any sharp edges). After soaking in distilled water, the SPU tubes are removed from the molds, turned inside out (making the air-dried, less thrombogenic surface the lumen), returned to the molds, and dried. Two handmade 0.35-mm stainless steel rings are slid over each end of the tubes, placed 4 mm apart, and bonded down with a running bead of 20% SPU. The ends of the SPU tubes are then trimmed, pulled back over the two rings, and beaded down with 15% SPU. Since the portal vein and inferior vena cava run essentially parallel to one another, the shunts are next molded in a bent configuration (Figure 1) which allows an end-to-end anastomosis to the portal vein and an end-to-side anastomosis with the inferior vena cava. This is accomplished by soaking the dried shunts in distilled water, removing them from the straight molds, putting them onto bent-glass molds, and then heatsetting them in an autoclave at 250” for 45 min. A final 24-hr water soak is used to leach out any remaining solvent and facilitate removal of the shunts from the molds. Surgical Procedure These shunts, or grafts, were used to create acute portacaval shunt models in five dogs (two beagles and three mongrels) weighing between IO-20 kg each. The mongrels were anesthetized with sodium pentobarbital (Veterinary Laboratories, Inc., Lenexa, KS), while the beagles, which were subsequently used in a short-term (2 hr) pharmacokinetic drug study, were anesthetized by induction with sodium thiamylal (Boehringer lngelheim Animal Health, Inc., St. Joseph, MO) (35 mg/kg), intubated, and maintained on isoflurane (BOC Health Care, Anaquest, Madison, WI) (1.5%) inhalation anesthesia. The animals were placed on a water-circulatingheating pad in dorsal recumbency and a IS-cm ventral-midline incision was used to enter the abdomen. Working from the right side of the abdomen we retracted the intestines medially to allow the hepatic artery, portal vein, and inferior vena cava to be identified and dissected free. In preparation of the end-to-side anastomosis a caval vascular clamp was used to isolate a 2-cm segment of the ventral half of the IVC. The occluded area of the cava was as small as was practical in order to minimize the disturbance of blood flow through the vessel. Total occlusion of the IVC cannot be used, since it would prevent approximately two-thirds of the venous blood from returning to the heart, resulting in rapid hypovolemic shock and death. A 6-mm longitudinal incision was made in the section of isolated caval wall and a purse-string suture of 4-O polypropylene was preplaced around the wound edges. One end of the shunt was then guided through
331
332
J. T. Kissinger et al.
the incision into the cava (Figure 2) and the purse-string suture was tightened down on the shunt in the area between the two rings. A straight vascular clamp was next placed across the middle of the prosthesis, and the caval clamp was released. The shunt was now ready for anastomosis to the previously isolated portal vein. First the portal vein and any of its branches were ligated cranially with 2-O silk and cross-clamped as far caudally as possible. A 5-mm-transverse incision was made in the vein’s wall, and the shunt’s free end was inserted through the incision into the vessel lumen. A preplaced circumferential ligature (2-O silk) was then tied down over the vessel in the area of separation between the shunt’s rings (Figure 3). With both anastomoses completed, the vascular clamps were slowly removed from the prosthesis and portal vein to gradually reintroduce the pooled portal venous blood into the circulation. To totally eliminate blood flow to the liver, the hepatic artery was ligated using 2-O silk suture. In order to maintain normal splanchic blood flow and body temperature, the abdominal organs were then returned to their correct anatomical position, and the skin incision was closed using 2-O gut.
FIGURE 2. Diagram showing shunt end positioned for insertion through the incised, isolated caval wall (purse-string suture around incision not shown).
Portacaval Shunt
FIGURE 3. Diagram of the end-to-end anastomosis between the shunt and portal vein. The shunt is secured within the vessel by a circumferential ligature.
RESULTS AND
DISCUSSION
The primary advantage of these shunts is that their quick-connect anastomotic design decreases implant time considerably when compared to conventional portacaval shunt preparations. With proper-sized shunts available, the entire surgical procedure, from incision to closure, can be accomplished in 75-90 min. Certain characteristics of the SPU polymer such as its strength, elasticity, nonporosity, and low thrombogenicity also promote these shunts as an ideal interface with the vascular system. The polymer’s lack of porosity prevents bleeding and allows for easy cleaning and reuse. Another attractive property of the shunts is their which allows for custom fabrication of curves or bends as re“heat-setability,” quired. In addition, anticoagulants are not necessary with the use of these devices. The shunts used in the acute pharmacokinetic study functioned well during their 2-hr implant duration. Their curved configuration minimized the chances of kinking so that unimpeded flow from the portal vein to the vena cava was maintained. In addition, at the conclusion of the study, the shunts were removed, and, upon examination, their lumens revealed no evidence of fibrin buildup or associated thrombosis.
REFERENCES Donovan AJ, Covey PC (1978) Early history of the portacaval shunt in humans. Surg Cynecol Obstet 147:423-430. Hofmeyer CF, Irwin DH (1965) Liver and biliary tract. In Canine Surgery. Ed., J Archibald. Wheaton, III.: American Veterinary Publications Inc., pp. 688-689. Hughes HC, Bertolet RD, Kissinger JT, Brownlee RR (1983) A new polyurethane and process for pacer
leads. In Cardia facing. Ed., K Steinbach. Darmstat: Steinkoff-Verlag, p. 323. Kissinger JT, Hughes HC (1984) Fabrication method for endotracheal tubes for sheep, goats, and calves. Lab Anim Sci 34:97-98. Warren WD (1980) Presidential address: Reflections on the early development of portacaval shunts. Ann Surg 191:519-527.
333