The mother lode of liver transplantation, with particular reference to our new journal

Starzl, Thomas E.

doi:10.1002/lt.500040101

Cited by 6 publications

(1 citation statement)

References 103 publications

(104 reference statements)

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“…The liver became the key organ in unmasking the secrets of acquired tolerance because of its large content of immunocompetent leukocytes (see earlier and Allograft Acceptance versus Acquired Tolerance, below). In addition, the functional complexity of the liver and its metabolic interactions with other abdominal viscera have made hepatic transplantation a "mother lode" for physiologic studies [243].…”

Section: Life Sciencesmentioning

confidence: 99%

History of Clinical Transplantation

Starzl

2000

World j. surg.

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153

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The emergence of transplantation has seen the development of increasingly potent immunosuppressive agents, progressively better methods of tissue and organ preservation, refinements in histocompatibility matching, and numerous innovations in surgical techniques. Such efforts in combination ultimately made it possible to successfully engraft all of the organs and bone marrow cells in humans. At a more fundamental level, however, the transplantation enterprise hinged on two seminal turning points. The first was the recognition by Billingham, Brent, and Medawar in 1953 that it was possible to induce chimerism-associated neonatal tolerance deliberately. This discovery escalated over the next 15 years to the first successful bone marrow transplantations in humans in 1968. The second turning point was the demonstration during the early 1960s that canine and human organ allografts could self-induce tolerance with the aid of immunosuppression. By the end of 1962, however, it had been incorrectly concluded that turning points one and two involved different immune mechanisms. The error was not corrected until well into the 1990s. In this historical account, the vast literature that sprang up during the intervening 30 years has been summarized. Although admirably documenting empiric progress in clinical transplantation, its failure to explain organ allograft acceptance predestined organ recipients to lifetime immunosuppression and precluded fundamental changes in the treatment policies. After it was discovered in 1992 that long-surviving organ transplant recipients had persistent microchimerism, it was possible to see the mechanistic commonality of organ and bone marrow transplantation. A clarifying central principle of immunology could then be synthesized with which to guide efforts to induce tolerance systematically to human tissues and perhaps ultimately to xenografts.

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Section: Life Sciencesmentioning

confidence: 99%

History of Clinical Transplantation

Starzl

2000

World j. surg.

Self Cite

153

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The effect of mechanically enhancing portal venous inflow on hepatic oxygenation, microcirculation, and function in a rabbit model with extensive hepatic fibrosis

et al. 1999

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Enhancing the portal venous blood flow (PVBF) has been shown to reduce portal pressure and intrahepatic vascular resistance and to improve liver function in isolated cirrhotic rodent livers in vitro. The aim of this study was to assess the short-term effect of mechanically pumping the portal inflow on hepatic microcirculation (HM), oxygenation, and function in an animal model of extensive hepatic fibrosis. New Zealand white rabbits underwent laparotomy and exposure of the liver: group 1 (n ‫؍‬ 7) were normal controls; group 2 (n ‫؍‬ 7) had hepatic fibrosis. Total hepatic blood flow (THBF) and HM was measured along with continuous monitoring of intrahepatic tissue oxygenation using near infrared spectroscopy (NIRS). Baseline hepatic hemodynamics and liver function were measured in both groups. PVBF was then increased by 50% over a 3-hour period in the hepatic fibrosis group using a miniature portal pump designed for human implantation, and the hemodynamics were monitored continuously. Liver function tests were repeated after portal pumping. In comparison with normal controls, animals with hepatic fibrosis had a higher portal pressure (13.0 ؎ 3.6 vs. 3.7 ؎ 1.4 mm Hg, P F .001, mean ؎ SD vs. controls), reduced PVBF (52.4 ؎ 24.6 vs. 96.9 ؎ 21.1 mL/min, P ‫؍‬ .003), and increased portal vascular resistance (P ‫؍‬ .001). THBF and flow in the HM was lower than in controls, and liver function tests were abnormal. After a 3-hour period of enhanced portal flow in animals with hepatic fibrosis, the portal pressure greatly reduced (13.0 ؎ 3.6 to 2.5 ؎ 1.1 mm Hg, P F .001) as did the intrahepatic portal resistance ( Current aims in the management of portal hypertension are to reduce portal venous pressure (PVP), to increase blood flow through hepatic parenchyma, 1 and to decompress esophageal and gastric varices. 2,3 Reduction of PVP minimizes the risk of bleeding from varices, the likelihood of hepatic encephalopathy and problems relating to first pass uptake of drugs. 4 Reduced portal pressure also decreases intestinal venous congestion and could increase blood flow through the hepatic parenchyma and hence increase liver function. 5 In 1991, Habib et al. 6 first introduced the concept of mechanical pumping of portal blood to enhance hepatic portal inflow. Since then, we have seen a number of publications in this field. 7-10 Cardoso et al. [7][8][9] showed that augmenting portal inflow to isolated perfused cirrhotic rat and human livers decreased intrahepatic resistance without a change in intrahepatic shunting and resulted in liver function improvement. Bernadich et al. 10 found that in rats with portal hypertension owing to portal vein stenosis, mechanical portal pumping decreased portal pressure and portal-systemic shunting without having a significant effect on systemic hemodynamics. In cirrhosis, several early studies provided evidence that it was vasoactive mediators coupled with the extensive destruction of hepatocytes and nodular regeneration that contributed to the pathogenesis of portal hypertension. [11][12][13]...

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History of Clinical Transplantation

Starzl¹

2008

Surgery

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The mother lode of liver transplantation, with particular reference to our new journal

Cited by 6 publications

References 103 publications

History of Clinical Transplantation

History of Clinical Transplantation

The effect of mechanically enhancing portal venous inflow on hepatic oxygenation, microcirculation, and function in a rabbit model with extensive hepatic fibrosis

History of Clinical Transplantation

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