Compartmental analysis of extracorporeal liver perfusion systems
OwnerGregory Thomas EVERSON, Michael P. MCRAEinventors
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Abstract
Methods are provided for effectively distinguishing the abilities of a human liver and an extracorporeal liver in an extracorporeal liver perfusion system to extract cholate and, thus, measure relative liver function.
Claims26
A method of determining hepatic clearance in a system comprising (i) a human patient comprising a native liver supported on (ii) an extracorporeal liver perfusion system (ECS) comprising an (iii) extracorporeal liver, the method comprising
- determining compartment volumes (L) of the patient systemic circulation(S), the extracorporeal liver perfusion system (E), the extracorporeal liver (X), and the human patient native liver (H);
- deriving or measuring blood flow rates q (L/min) between the compartments;
- obtaining blood or serum samples collected at one or more or two or more time points within 180 minutes of intravenous administration of a dose of a first distinguishable cholate compound (DIV) to the systemic circulation of the patient (S), and optional simultaneous oral or nasogastric (NG) tube administration of a dose of a second distinguishable cholate compound (Doral) to the patient;
- wherein the blood or serum samples were simultaneously collected from each of the patient systemic circulation (BS);
- the extracorporeal liver perfusion system (BE);
- and inferior vena cava (IVC) outflow of the EC liver (BX);
- measuring the first distinguishable cholate concentration and optionally the second distinguishable cholate concentration in each of the blood or serum samples;
- and
- calculating the simultaneous systemic clearance of the intravenously administered first distinguishable cholate of the patient liver (ClH) and of the extracorporeal liver (Clx) in the extracorporeal liver perfusion system (ECS).
A method of determining hepatic clearance in a system comprising (i) a human patient without a native liver supported on (ii) an extracorporeal liver perfusion system (ECS) comprising an (iii) extracorporeal liver, the method comprising
- determining compartment volumes (L) of the patient systemic circulation(S), the extracorporeal liver perfusion system (E), and the extracorporeal liver (X);
- deriving or measuring blood flow rates q (L/min) between the compartments;
- obtaining blood or serum samples collected at one or more or two or more time points within 180 minutes of intravenous administration of a dose of a first distinguishable cholate compound (DIV) to the systemic circulation of the patient (S), and optional simultaneous oral or nasogastric (NG) tube administration of a dose of a second distinguishable cholate compound (Doral) to the patient;
- wherein the blood or serum samples were simultaneously collected from each of the patient systemic circulation (BS);
- the extracorporeal liver perfusion system (BE);
- and inferior vena cava (IVC) outflow of the EC liver (BX);
- measuring the first distinguishable cholate concentration and optionally the second distinguishable cholate concentration in each of the blood or serum samples;
- and
- calculating the systemic clearance of the intravenously administered first distinguishable cholate of the extracorporeal liver (Clx) in the extracorporeal liver perfusion system (ECS).
A method of determining total systemic clearance (ClTot) in a system comprising an extracorporeal liver perfusion system (ECS), a human patient having a native liver, and an extracorporeal (EC) liver, the method comprising:
- receiving blood or serum samples collected from one or more of the ECS, the patient systemic circulation, and inferior vena cava (IVC) outflow of the EC liver at one or more, or two or more, time points within 180 minutes of intravenous administration to the patient of a first distinguishable cholate compound, and optional simultaneous oral or nasogastric administration to the patient of a second distinguishable cholate compound;
- measuring distinguishable cholate concentrations (C) of the first distinguishable cholate compound and optionally the second distinguishable cholate compound in each of the blood or serum samples;
- optionally measuring blood flow rates (q, L/min) in one or more of the ECS (E), the human patient systemic circulation(S), and the extracorporeal liver (X) in at least one of the time points;
- and
- calculating total systemic clearance (ClTot) as the intravenous clearance of first distinguishable cholate compound of the system.
Dependencies are inferred from the claim text.