Leading international institutions are designing and developing various types of ventricular assist devices (VAD) and total artificial hearts (TAH). Some of the commercially available pulsatile VADs are not readily implantable into the thoracic cavity of smaller size patients because of size limitation. The majority of the TAH dimensions requires the removal of the patients' native heart. A miniaturized artificial heart, the auxiliary total artificial heart (ATAH), is being developed in these authors' laboratories. This device is an electromechanically driven ATAH using a brushless direct current (DC) motor fixed in a center metallic piece. This pusher plate-type ATAH control is based on Frank-Starling's law. The beating frequency is regulated through the change of the left preload, assisting the native heart in obtaining adequate blood flow. With the miniaturization of this pump, the average sized patient can have the surgical implantation procedure in the right thoracic cavity without removing the native heart. The left and right stroke volumes are 35 and 32 ml, respectively. In vitro tests were conducted, and the performance curves demonstrate that the ATAH produces 5 L/min of cardiac output at 180 bpm (10 mmHg of left inlet mean pressure and 100 mm Hg of left outlet mean pressure). Taking into account that this ATAH is working along with the native heart, this output is more than satisfactory for such a device.
While a centrifugal pump is generally used for nonpulsatile blood flow, it can also produce a pulsatile flow by alternating the impeller rotational speed (rpm) periodically. However, there is concern that this centrifugal pump pulsatile mode may induce added hemolysis as a result of the repeated acceleration and deceleration of rpm. Thus, a hemolysis study of the pulsatile modes of the Gyro C1E3 centrifugal pump (Gyro-P) was conducted. The results were then compared with the nonpulsatile mode of the same Gyro pump (Gyro-N) and the nonpulsatile BioMedicus BP-80 (Bio-N) pump. Three different conditions were simulated: left ventricular assist device (LVAD), cardiopulmonary bypass (CPB), and percutaneous cardiopulmonary support (PCPS). The beating rate of the Gyro-P was set at 40 bprn, with repetition of 2 different impeller speeds (the lower rpm being 70% of the higher speed). The 2 impeller speeds were set to obtain the same average flow as that of the nonpulsatile mode. The hemolysis results of the Gyro-P were comparable to or better than those of the Bio-N, and no excessive hemolysis was observed, compared to the Gyro-N. In conclusion, the Gyro-P had an excellent hemolytic characteristic and generated no excessive hemolysis in most clinical usage conditions. With the concern of hemolysis eliminated, this pulsatile mode may have various possible advantages.
ABSTRACT:The metabolism of [ 14 C]pioglitazone was studied in vitro in incubations with freshly isolated human, rat, and monkey hepatocytes. Radioactivity detection high-performance liquid chromatography analysis of incubation extracts showed the detection of 13 metabolites (M1-M13) formed in incubations with human hepatocytes. An identical set of metabolites (M1-M13) was also detected in monkey hepatocytes. However, in rat hepatocytes, M1 through M3, M5 through M7, M9 through M11, and M13 were also detected, but M4, M8, and M12 were not detected. The structures of the metabolites were elucidated by liquid chromatography/tandem mass spectrometry using electrospray ionization. Novel metabolites of pioglitazone detected using these methods included thiazolidinedione ring-opened methyl sulfoxide amide (M1), thiazolidinedione ringopened N-glucuronide (M2), thiazolidinedione ring-opened methyl sulfone amide (M3), thiazolidinedione ring N-glucuronide (M7), thiazolidinedione ring-opened methylmercapto amide (M8), and thiazolidinedione ring-opened methylmercapto carboxylic acid (M11). In summary, based on the results from these studies, two novel metabolic pathways for pioglitazone in hepatocytes are proposed to be as follows: 1) N-glucuronidation of the thiazolidinedione ring of pioglitazone to form M7 followed by hydrolysis to M2, and methylation of the mercapto group of the thiazolidinedione ring-opened mercapto carboxylic acid to form M11; and 2) methylation of the mercapto group of the thiazolidinedione ring-opened mercapto amide to form M8, oxidation of M8 to form M1, and oxidation of M1 to form M3.
Giant hepatocellular adenomas are associated with a high incidence of rupture with intraabdominal hemorrhage and may also undergo malignant transformation. If resection is not technically feasible, liver transplantation should be a treatment option. The aim of this report is to describe the indications, feasibility, and outcome of liver transplantation for hepatocellular adenomas. A 66‐year‐old man with a 17‐cm hepatocellular adenoma originating in the left lobe but involving nearly the entire liver and a 35‐year‐old woman with a 20‐cm tumor involving the right lobe of the liver and compressing the left lobe underwent liver transplantation without complication. In both cases, a histological diagnosis was made by core needle biopsy preoperatively, and resection was technically not possible. Hepatocellular adenoma involving nearly all of the liver with no evidence of malignant change was confirmed in the explant liver from both cases. Giant hepatocellular adenomas may be unresectable and require liver transplantation for complete removal to prevent potential rupture with hemorrhage or malignant transformation Copyright © 1995 by the American Association for the Study of Liver Diseases.
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