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• W2086564607 abstract "The technique of liver transplantation has become relatively standardized. Although not commonly practiced, arterial reperfusion has been shown in both animal and human trials to offer hemodynamic and functional benefits to liver allograft recipients. Whether this is the result of shortening the time to re-establishing arterial perfusion or an effect of the sequence which the liver is revascularized remains unknown. Further randomized clinical trials are needed to answer this question and support our practice of arterial reperfusion. The technique of liver transplantation has become relatively standardized. Although not commonly practiced, arterial reperfusion has been shown in both animal and human trials to offer hemodynamic and functional benefits to liver allograft recipients. Whether this is the result of shortening the time to re-establishing arterial perfusion or an effect of the sequence which the liver is revascularized remains unknown. Further randomized clinical trials are needed to answer this question and support our practice of arterial reperfusion. Liver transplantation is the accepted treatment for end-stage liver disease and although the operative procedure has become relatively standardised, a number of technical variations have emerged that may have an impact on early and late graft function. Whilst surgical attention over the recent years has focused on piggyback techniques, interest is returning to arterial reperfusion of the liver allograft. The liver is unique in that it receives both arterial and venous inflow from the hepatic artery and portal vein, respectively. The first description of orthotopic liver transplantation (OLT) reported hepatic arterial followed by portal venous reperfusion (1Starzl TE Marchioro TL von Kaulla KH et al.Homotransplantation of the liver in humans..Surg Gynaecol Obstet. 1963; 117: 659-676Google Scholar). Currently the majority of centres undertake initial portal venous reperfusion followed by arterial reperfusion to try and minimize warm ischemia. Thus, there is a variable period of at least 20–60 min, or longer, during which the graft is exclusively perfused by portal blood. During this period of time, the liver appears mildly ‘congested’ and in fatty/marginal grafts it may become hard and poorly perfused (2Hickman R Innes CR The relevance of the order of revascularisation in liver grafting..Hepatology. 1990; 11: 471-476Crossref PubMed Scopus (12) Google Scholar). With subsequent arterial reperfusion, there is noticeable improvement in the appearance of the liver that becomes less ‘full’ (congested) and softer. The portal vein drains blood from the splanchnic venous bed and accounts for approximately 75% of the total liver blood flow (3Guyton AC, Hall JE. Textbook of medical physiology. Philadelphia, WB Saunders, 2000.Google Scholar). Oxygen saturation in the portal vein is low, but by virtue of its greater blood flow, the supply of oxygen provided to the liver is comparable to that from the hepatic artery (3Guyton AC, Hall JE. Textbook of medical physiology. Philadelphia, WB Saunders, 2000.Google Scholar). During liver transplantation, perfusion of the splanchnic circulation is reduced as a result of cardiac re-distribution leading to a measurable reduction in gastric mucosal pH and an increase in the oxygen extraction ratio in portal venous blood (4Tallgren M Makisalo H Hockerstedt K et al.Hepatic and splanchnic oxygenation during liver transplantation..Crit Care Med. 1999; 27: 2383-2388Crossref PubMed Scopus (18) Google Scholar). Furthermore, in the absence of veno-venous bypass or porto-caval shunting, there is congestion within the splanchnic venous bed leading to accumulation of toxic metabolites and an increase in portal venous pressure. Consequently at the time of liver reperfusion there is rapid re-warming of the graft leading to an increase in the oxygen requirement. In a liver solely perfused by the portal vein, this may potentially result in hepatic hypoxia and cytokine release, causing systemic hypotension and a reduction in splanchnic blood flow, which will further compromise hepatic perfusion at the time arterial flow is re-established. In contrast, arterial reperfusion of the liver, via the hepatic artery, provides a smaller volume of highly oxygenated blood, which results in slower re-warming and greater delivery of oxygen to an aerobically deprived organ (4Tallgren M Makisalo H Hockerstedt K et al.Hepatic and splanchnic oxygenation during liver transplantation..Crit Care Med. 1999; 27: 2383-2388Crossref PubMed Scopus (18) Google Scholar,5Brockmann JG August C Wolters HH et al.Sequence of reperfusion influences ischaemia/reerfusion injury and primary graft function following porcine liver transplantation..Liver Transpl. 2005; 11: 1214-1222Crossref PubMed Scopus (35) Google Scholar). Our observation is that this results in less severe reperfusion injury. Whether this has functional consequences remains a topic of debate. Initial arterial reperfusion appears to give a more uniform perfusion compared to the portal vein (2Hickman R Innes CR The relevance of the order of revascularisation in liver grafting..Hepatology. 1990; 11: 471-476Crossref PubMed Scopus (12) Google Scholar). At a functional level, the effect of arterial perfusion is less clear. To date, three studies have been published looking at the effect of revascularization in a porcine model (2Hickman R Innes CR The relevance of the order of revascularisation in liver grafting..Hepatology. 1990; 11: 471-476Crossref PubMed Scopus (12) Google Scholar,5Brockmann JG August C Wolters HH et al.Sequence of reperfusion influences ischaemia/reerfusion injury and primary graft function following porcine liver transplantation..Liver Transpl. 2005; 11: 1214-1222Crossref PubMed Scopus (35) Google Scholar,6Van As AB Lotz Z Kahn D Effect of early arterialisation of the porcine liver allograft on reperfusion injury, hepatocellular injury, and endothelial cell dysfunction..Liver Transpl. 2001; 7: 32-37Crossref PubMed Scopus (19) Google Scholar). Two papers show beneficial effects in performing primary arterial perfusion (2Hickman R Innes CR The relevance of the order of revascularisation in liver grafting..Hepatology. 1990; 11: 471-476Crossref PubMed Scopus (12) Google Scholar,6Van As AB Lotz Z Kahn D Effect of early arterialisation of the porcine liver allograft on reperfusion injury, hepatocellular injury, and endothelial cell dysfunction..Liver Transpl. 2001; 7: 32-37Crossref PubMed Scopus (19) Google Scholar). Hickman et al. demonstrated that initial arterialisation was associated with a significantly lower peak serum AST level compared to portal revascularization (2Hickman R Innes CR The relevance of the order of revascularisation in liver grafting..Hepatology. 1990; 11: 471-476Crossref PubMed Scopus (12) Google Scholar). However, after a period of either warm or cold ischemia, the biochemical advantage of arterial reperfusion was lost (2Hickman R Innes CR The relevance of the order of revascularisation in liver grafting..Hepatology. 1990; 11: 471-476Crossref PubMed Scopus (12) Google Scholar). This may be the result of poor organ preservation as the liver allografts were flushed with a combination of Ringers Lactate and Euro Collins solution, neither of which are now considered suitable for liver preservation (2Hickman R Innes CR The relevance of the order of revascularisation in liver grafting..Hepatology. 1990; 11: 471-476Crossref PubMed Scopus (12) Google Scholar). All liver allografts have preservation–reperfusion injury; however, with the use of better organ preservation, the degree of preservation injury may have been lessened so as to allow for the beneficial effect of arterialization to persist. Using the same model, van As et al. showed that early arterialization (20 min prior to portal reperfusion) was associated with less reperfusion injury, hepatocyte damage and improved liver endothelial cell function compared to those re-arterialized 60 min after portal reperfusion (6Van As AB Lotz Z Kahn D Effect of early arterialisation of the porcine liver allograft on reperfusion injury, hepatocellular injury, and endothelial cell dysfunction..Liver Transpl. 2001; 7: 32-37Crossref PubMed Scopus (19) Google Scholar). In contrast to these two studies, Brockmann et al. showed that primary hepatic artery reperfusion was associated with a higher peak AST level, less bile production, greater histological evidence of hepatocyte injury compared to simultaneous or primary portal reperfusion (5Brockmann JG August C Wolters HH et al.Sequence of reperfusion influences ischaemia/reerfusion injury and primary graft function following porcine liver transplantation..Liver Transpl. 2005; 11: 1214-1222Crossref PubMed Scopus (35) Google Scholar). The authors could not account for the difference in their findings compared to the two previous published reports. Five studies have been published comparing the effect of arterial and venous reperfusion in humans (7Sadler KM Walsh TS Garden OJ Lee A Comparison of hepatic artery and portal vein reperfusion during orthotopic liver transplantation..Transplantation. 2001; 72: 1680-1684Crossref PubMed Scopus (23) Google Scholar, 8Noun R Sauvanet A Belghiti J Appraisal of the order of revascularization in human liver grafting: A controlled study..J Am Coll Surg. 1997; 185: 70-73Crossref PubMed Scopus (0) Google Scholar, 9Ducerf C Mechet I Landry JL et al.Hemodynamic profiles during piggyback liver grafts using asterial or portal revascularisation..J Am Coll Surg. 2000; 190: 89-93Crossref PubMed Scopus (26) Google Scholar, 10Walsh TS Garden OJ Lee A Metabolic, cardiovascular and acid base status after hepatic artery or portal vein reperfusion during orthotopic liver transplantation..Liver Transpl. 2002; 8: 537-544Crossref PubMed Scopus (26) Google Scholar, 11Moreno C Sabate A Hemodynamic profile and tissular oxygenation during liver transplantation: Influence of the order in vascular clamp release. (Letter to Editor)..Liver Transpl. 2002; 8: 1201-1202Crossref PubMed Scopus (3) Google Scholar). Two have reported the short- and medium-term effects of primary arterial reperfusion (7Sadler KM Walsh TS Garden OJ Lee A Comparison of hepatic artery and portal vein reperfusion during orthotopic liver transplantation..Transplantation. 2001; 72: 1680-1684Crossref PubMed Scopus (23) Google Scholar,8Noun R Sauvanet A Belghiti J Appraisal of the order of revascularization in human liver grafting: A controlled study..J Am Coll Surg. 1997; 185: 70-73Crossref PubMed Scopus (0) Google Scholar). In a retrospective review of 26 patients who had undergone OLT with hepatic artery reperfusion and 26 patients reperfused via the portal vein, Sadler et al. found no clinically or statistically significant differences in indices of graft function, reperfusion injury or outcome (7Sadler KM Walsh TS Garden OJ Lee A Comparison of hepatic artery and portal vein reperfusion during orthotopic liver transplantation..Transplantation. 2001; 72: 1680-1684Crossref PubMed Scopus (23) Google Scholar). Although there were more early deaths in the primary hepatic artery perfused group, this was not statistically significant (7Sadler KM Walsh TS Garden OJ Lee A Comparison of hepatic artery and portal vein reperfusion during orthotopic liver transplantation..Transplantation. 2001; 72: 1680-1684Crossref PubMed Scopus (23) Google Scholar). Similarly, Noun et al. did not demonstrate a difference in graft function or morbidity, but initial arterial perfusion was associated with less blood product transfusion and a shorter time to completion of the procedure after revascularisation (8Noun R Sauvanet A Belghiti J Appraisal of the order of revascularization in human liver grafting: A controlled study..J Am Coll Surg. 1997; 185: 70-73Crossref PubMed Scopus (0) Google Scholar). Three clinical studies have examined the hemodynamic effects of arterial reperfusion (9Ducerf C Mechet I Landry JL et al.Hemodynamic profiles during piggyback liver grafts using asterial or portal revascularisation..J Am Coll Surg. 2000; 190: 89-93Crossref PubMed Scopus (26) Google Scholar, 10Walsh TS Garden OJ Lee A Metabolic, cardiovascular and acid base status after hepatic artery or portal vein reperfusion during orthotopic liver transplantation..Liver Transpl. 2002; 8: 537-544Crossref PubMed Scopus (26) Google Scholar, 11Moreno C Sabate A Hemodynamic profile and tissular oxygenation during liver transplantation: Influence of the order in vascular clamp release. (Letter to Editor)..Liver Transpl. 2002; 8: 1201-1202Crossref PubMed Scopus (3) Google Scholar). These demonstrated that initial arterial perfusion was associated with more stable hemodynamics, less vasopressor requirement and a lower cardiac output and mean pulmonary arterial pressure compared to patients who underwent initial portal venous reperfusion. Taken together, these studies suggest that arterial reperfusion does not appear to be associated with significant benefit; however, it seems to be at least as safe as portal vein reperfusion. Rather than the order in which the liver is reperfused, the time taken to re-establishing arterial perfusion may be critical in the development of reperfusion injury. The transplanted liver is critically dependant upon the hepatic artery to maintain biliary integrity (12Puhl G Schaser K-D Pust D et al.The delay of rearterilaisation after initial portal reperfusion in living donor liver transplantation significantly determines the development of microvascular graft dysfunction..J Hepatol. 2001; 41: 299-306Abstract Full Text Full Text PDF Scopus (28) Google Scholar). A delay in re-establishing arterial inflow in an exclusively portal perfused liver potentially prolongs the warm ischaemia time to the bile ducts and has been postulated as a contributory factor in the development of biliary strictures (13Sankary HN McChesney L Frye E Cohn E Foster P Williams J A simple modification in operative technique can reduce the incidence of nonanastomotic strictures after orthotopic liver transplantation..Hepatology. 1995; 21: 63-69Crossref PubMed Google Scholar). In a rat model of liver transplantation, 8 min of exclusive portal perfusion induced microcirculatory damage and impairment of hepatocellular excretory function, associated with increased Kupffer cell activation and leukocyte adherence (14Post S Palma P Gonzalez AP Rentsch M Menger MD Timing of arterialisation in liver transplantation..Ann Surg. 1994; 220: 691-698Crossref PubMed Scopus (61) Google Scholar). In human liver allograft recipients, the time interval between portal venous and hepatic arterial reperfusion has been shown to be more important at predicting changes in the graft microcirculation than the anhepatic period or cold ischemic time (12Puhl G Schaser K-D Pust D et al.The delay of rearterilaisation after initial portal reperfusion in living donor liver transplantation significantly determines the development of microvascular graft dysfunction..J Hepatol. 2001; 41: 299-306Abstract Full Text Full Text PDF Scopus (28) Google Scholar). Six clinical trials have been published examining the effect of simultaneous and sequential revascularization of liver allografts (9Ducerf C Mechet I Landry JL et al.Hemodynamic profiles during piggyback liver grafts using asterial or portal revascularisation..J Am Coll Surg. 2000; 190: 89-93Crossref PubMed Scopus (26) Google Scholar, 10Walsh TS Garden OJ Lee A Metabolic, cardiovascular and acid base status after hepatic artery or portal vein reperfusion during orthotopic liver transplantation..Liver Transpl. 2002; 8: 537-544Crossref PubMed Scopus (26) Google Scholar, 11Moreno C Sabate A Hemodynamic profile and tissular oxygenation during liver transplantation: Influence of the order in vascular clamp release. (Letter to Editor)..Liver Transpl. 2002; 8: 1201-1202Crossref PubMed Scopus (3) Google Scholar, 13Sankary HN McChesney L Frye E Cohn E Foster P Williams J A simple modification in operative technique can reduce the incidence of nonanastomotic strictures after orthotopic liver transplantation..Hepatology. 1995; 21: 63-69Crossref PubMed Google Scholar, 15Massarollo PC Mies S Raia S Simultaneous arterial and portal revascularisation in liver transplantation..Transplant Proc. 1998; 30: 2883-2884Crossref PubMed Scopus (31) Google Scholar, 16Polak WG Miyamoto S Nemes BA et al.Sequential and simultaneous revascularisation in adult orthotopic piggyback liver transplantation..Liver Transpl. 2005; 11: 934-940Crossref PubMed Scopus (35) Google Scholar,13Sankary HN McChesney L Frye E Cohn E Foster P Williams J A simple modification in operative technique can reduce the incidence of nonanastomotic strictures after orthotopic liver transplantation..Hepatology. 1995; 21: 63-69Crossref PubMed Google Scholar,15Massarollo PC Mies S Raia S Simultaneous arterial and portal revascularisation in liver transplantation..Transplant Proc. 1998; 30: 2883-2884Crossref PubMed Scopus (31) Google Scholar,16Polak WG Miyamoto S Nemes BA et al.Sequential and simultaneous revascularisation in adult orthotopic piggyback liver transplantation..Liver Transpl. 2005; 11: 934-940Crossref PubMed Scopus (35) Google Scholar). Three clinical trials examined the hemodynamic effect of simultaneous reperfusion and did not look at graft function (9Ducerf C Mechet I Landry JL et al.Hemodynamic profiles during piggyback liver grafts using asterial or portal revascularisation..J Am Coll Surg. 2000; 190: 89-93Crossref PubMed Scopus (26) Google Scholar,11Moreno C Sabate A Hemodynamic profile and tissular oxygenation during liver transplantation: Influence of the order in vascular clamp release. (Letter to Editor)..Liver Transpl. 2002; 8: 1201-1202Crossref PubMed Scopus (3) Google Scholar). Of the three studies that examined the effect of arterial reperfusion on graft function, two showed that simultaneous arterial and portal perfusion was associated with a lower incidence of non-anastomotic biliary strictures (13Sankary HN McChesney L Frye E Cohn E Foster P Williams J A simple modification in operative technique can reduce the incidence of nonanastomotic strictures after orthotopic liver transplantation..Hepatology. 1995; 21: 63-69Crossref PubMed Google Scholar,15Massarollo PC Mies S Raia S Simultaneous arterial and portal revascularisation in liver transplantation..Transplant Proc. 1998; 30: 2883-2884Crossref PubMed Scopus (31) Google Scholar). Of the 45 patients that had simultaneous arterial and venous reperfusion, only one (2.2%) developed a non-anastomotic biliary stricture, compared to a historical rate of 15 of 131 (8.5%) patients who had arterial reconstruction after partial revascularization of the liver with portal venous blood (13Sankary HN McChesney L Frye E Cohn E Foster P Williams J A simple modification in operative technique can reduce the incidence of nonanastomotic strictures after orthotopic liver transplantation..Hepatology. 1995; 21: 63-69Crossref PubMed Google Scholar). Even more striking, Massarollo et al. reported a biliary complication rate of 34.6% in patients undergoing portal reperfusion compared to 2.0% in patients that received simultaneous arterial and portal reperfusion (15Massarollo PC Mies S Raia S Simultaneous arterial and portal revascularisation in liver transplantation..Transplant Proc. 1998; 30: 2883-2884Crossref PubMed Scopus (31) Google Scholar). Interestingly, six of the nine biliary complications were reported as anastomotic strictures and only one patient was reported to have a non-anastomotic stricture. One of the three studies that examined the effects of simultaneous or sequential revascularisation on graft function reported no difference in the incidence of biliary complications on graft outcome (16Polak WG Miyamoto S Nemes BA et al.Sequential and simultaneous revascularisation in adult orthotopic piggyback liver transplantation..Liver Transpl. 2005; 11: 934-940Crossref PubMed Scopus (35) Google Scholar). The reasons for the difference in these findings are not clear. With an improvement in organ preservation and peri-operative care, any beneficial effect of arterial or venous reperfusion may be difficult to demonstrate. Reperfusion injury results in a loss of some graft function. To date all the animal and human studies investigating the effects of primary arterial reperfusion have been performed in good quality/normal livers where a 5%–10% loss of graft function cannot be recognized early and is of no clinical significance. However, in the context of increasing use of marginal grafts, the loss of 5%–10% of graft function may be critical in determining graft and patient survival. It is this group of patients that need to be recruited into further trials before a consensus can be reached on the sequence with which liver allografts should optimally be reperfused. What is clear from the data published to date is that the sequence of liver allograft revascularization needs to be questioned. Although the data are sparse, primary arterial reperfusion has been demonstrated in both porcine and clinical trials to have both hemodynamic and functional advantages over primary portal reperfusion. Whether this is a result of shortening the time to re-establishing arterial perfusion or an effect of the sequence with which the graft is reperfused remains to be found. Further prospective randomized trials are needed to answer this question and support our practice of primary arterial reperfusion." @default.
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• W2086564607 title "Reperfusion of the Liver Allograft with Blue Blood: Is It Still the Royal Perfusate?" @default.
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