Hepatic artery

Intraarterial infusion of microspheres containing adriamycin was used for the local treatment of breast cancer and recurrent breast cancer with liver metastases (123). A reduction in tumor size was noted when the microspheres were injected into the internal and lateral thoracic arteries for treatment of the primary tumor. However, hepatic artery injection for liver metastases resulted in improvement in only one of three patients treated. 

The liver is a wedge-shaped organ of some 1.5 kg in adult humans, which, in terms of blood circulation, is interposed between the gastrointestinal tract and the rest of the body. The blood supply to the liver is from the hepatic portal vein (80%) and the hepatic artery (20%), the former bringing a rich supply of nutrients direct from the intestinal tract and the latter supplying the liver with oxygen. Blood drains from the liver by the hepatic vein. The position of the liver enables it to act as a processor of the absorbed nutrients, and to control their storage... 

The most common adverse events reported with sirolimus are leukopenia (20%), thrombocytopenia (13% to 30%), and hyperlipidemia (38% to 57%).11,31 Other adverse effects include delayed wound healing, anemia, diarrhea, arthralgias, rash, and mouth ulcers. Sirolimus has an FDA black-box warning in newly transplanted liver and lung recipients.11 In liver transplant recipients, use of sirolimus immediately after transplant is associated with an increased risk of hepatic artery thrombosis, graft loss, and death. In lung transplant... 

The hepatic artery supplies the liver with 300 ml/min of oxygenated blood from the aorta. The remaining 1050 ml/min of blood flow is delivered by the hepatic portal vein. This blood comes directly from the digestive tract. It is low in oxygen but contains a high concentration of nutrients absorbed from the intestines. 

Kornmann M, Link KH, Lenz H-J, Pil-lasch J, Metzger R, Butzer U et al. Thymidylate synthase is a predictor for response and resistance in hepatic artery infusion chemotherapy. Cancer Lett 1997 118 29-35. 

The liver is unusual in that it receives blood from two sources, the hepatic artery and the hepatic portal vein. The two supplies eventually join at the central vein, hence hepatocytes are of two types those which are exposed to blood derived largely from the hepatic artery, known as the perivenons cells, and those that are exposed to blood largely from the portal vein which are known as periportal cells (see Chapter 8). The periportal hepatocytes contain the enzymes of the ornithine cycle. In contrast, the... 

Classically the liver has been divided into hexagonal lobules centred around the terminal hepatic venules. Blood enters the liver through the portal tracts that are situated at the corners of the hexagon. The portal tracts are triads of a portal vein, an hepatic artery, and a common hepatic bile duct. The vast expanse of hepatic tissue, mostly consisting of parenchymal cells (PC) or hepatocytes, is serviced via terminal branches of the portal vein and hepatic artery, which enters the tissue at intervals. The hepatocytes are organized into cords of cells radially disposed about the central hepatic venule. Between these cords are vascular sinusoids that transport the blood to the central hepatic venules. The blood is collected through the hepatic venules into the hepatic vein which exits the liver into the inferior vena cava (Figure 4.1). 

Figure 4.1. Schematic representation of the architecture of the liver. Blood enters the liver through the portal vein (PV) and hepatic arteries (HA), flows through the sinusoids, and leaves the liver again via the central vein (CV). KC, Kupffer cells SEC, sinusoidal endothelial cells HSC, hepatic stellate cells BD, bile duct. Modified from reference 98.

The liver is the central organ that filters, stores, and detoxifies blood and its constituents. Thus, it is highly susceptible to a host of injuries because of its portal location and physiologic function. Blood distribution gradient exists within the liver and this heterogeneity results in differential exposure of various parts of the organ to injury. Hepatocytes closest to the portal vein and hepatic artery receive oxygen- and nutrient-rich blood supply, which makes them less susceptible to injury than those distal to blood supply [2]. 

Nakuma K, Uemura K, Konno T, Yanaka N, Yokoyama I (1979) Studies on anticancer treatment with an anti-cancer drug injected into the ligated hepatic artery for liver cancer. Nichidoki Iho 24 675... 

The 3 10 cells in the liver—particularly the hepatocytes, which make up 90% of the cell mass—are the central location for the body s intermediary metabolism. They are in close contact with the blood, which enters the liver from the portal vein and the hepatic arteries, flows through capillary vessels known as sinusoids, and is collected again in the central veins of the hepatic lobes. Hepatocytes are particularly rich in endoplasmic reticulum, as they carry out intensive protein and lipid synthesis. The cytoplasm contains granules of insoluble glycogen. Between the hepatocytes, there are bile capillaries through which bile components are excreted. 

Fluoxuridine is administered by infusive introduction into the hepatic artery for metastases in the liver. Synonyms of this drug are FUDR and others. 

Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use sirolimus. Manage patients receiving the drug in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information needed for the follow-up of the patient. Liver transplantation-excess mortality, graft loss, and hepatic artery thrombosis (HAT) The use of sirolimus in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo liver transplant recipients. Many of these patients had evidence of infection at or near the time of death. 

Hepatic artery thrombosis In de novo liver transplant recipients, the use of sirolimus in combination with cyclosporine or tacrolimus was associated with an increase in P.1153... 

Fig. 1. Floxuridine radiosensitization—long-term freedom from liver progression for patients with nondiffuse primary hepatobiliary cancer treated with combined radiation therapy and hepatic artery infusion of floxuridine.

Primary hepatobiliary cancer University of Michigan Radiation + hepatic arterial floxuridine 16 mo... 

Ensminger WD, Rosowsky A, Raso V, et al. A clinical pharmacological evaluation of hepatic arterial infusions of 5-fluoro-2 -deoxyuridine and 5-fluorouracil. Cancer Res 1978 38 3784—3792. 

Lignocaine s clearance by the liver is flow dependent. In heart failure cardiac output may be very low and therefore hepatic blood flow through both the hepatic artery and the portal venous system is also low. This meant a lower extraction of the drug from the blood and accumulation of lignocaine until the high plasma concentration produced the central nervous system toxicity. 

In addition to the usual intravenous or oral routes, some anticancer agents have been administered by regional intraarterial perfusion to increase drug delivery to the tumor itself and at the same time diminish systemic toxicity. Thus, patients with metastatic carcinomas of the liver and little or no disease elsewhere (a common occurrence in colorectal cancer) can be treated with a continuous infusion of fluorouracil or floxuridine through a catheter implanted in the hepatic artery. 

Floxuridine (FUDR) is the nucleoside of 5-fluo-rouracil that is readily converted into 5-fluorouracil in vivo. It has similar pharmacological effects but is preferred to 5-fluorouracil for hepatic arterial infusions because it is more extensively metabolized in the liver than 5-fluorouracil, with less systemic toxicity. 

The other program involves systemic administration of the gene-laden adenovirus via a hepatic artery catheter to treat hepatocellular carcinoma (HCC). The hepatic artery supplies the normal liver with 25% of its blood supply. However, it is the sole blood supply for the carcinoma. Preclinical results demonstrated efficacy in a rat HCC model. In a small, open-label clinical trial of patients positive for HCC, but also having post-hepatitis cirrhosis, patient response was marginal [22]. 

Diseases that directly affect hepatic integrity include cirrhosis, viral infections, and collagen vascular diseases. Diseases that indirectly affect function include metabolic disorders (e.g., azotemia secondary to renal insufficiency) and cardiac disease. Although decreased left ventricular output can result in a decrease in hepatic arterial flow, right ventricular failure causes hepatic congestion, reducing the first-pass effect and delaying biotransformation. 

Thus, the patient with a toxic TCA concentration (see the case at the start of the Metabolism section) developed excessively high amitriptyline plasma levels due to the additive effects of diminished left ventricular function leading to decreased hepatic arterial blood flow alcohol and age-related decline in liver function and, finally. 

In animal studies, volatile anaesthetics reduce portal venous blood flow. However, the hepatic arterial buffer effect is preserved during isoflurane anaesthesia (unlike halothane) with the net effect being no overall change in hepatic blood flow. 

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