An organ perfusion apparatus and method monitor, sustain and/or restore vability of organs and preserver organs for storage and/or transport. Other apparatus include an organ transporter, an organ cassette and an organ diagnostic device. The method includes perfusing the organ at hypothermic and/or normothermic temperatures, preferably after hypothermic organ flushing for organ transport and/or storage. The method can be practiced with prior or subsequent static or perfusion hypothermic exposure of the organ. Organ viability is restored by restoring high energy nucleotide (e.g., ATP) levels by perfusing the organ with a medical fluid, such as an oxygeneted cross-linked hemoglobin-based bicarbonate medical fluid, at normothermic temperatures. In perfusion, organ perfusion pressure is preferably controlled in response to a sensor disposed in an end of tubuing placed in the organ, by a pneumatically pressurized medical fluid reservoir, providing perfusion pressure fine tuning, overpressurization preventing and emergency flow cut-off. In the hypothermic mode, the organ is perfused with a medical fluid, preferably a simple crystalloid solution containing antioxidants, intermittently or in slow continuous flow. The medical fluid may be fed into the organ from an intermediary tank having a low pressure head to avoid organ overpressurization. Preventing overpressurization prevents or reduces damage to vascular endothelial lining and to organ tissue in general. Viability of the organ may be automatically monitored, preferably by monitoring characteristics of th emedical fluid perfusate. The perfusion process can be automatically controlled using a control program.

Apparatus and method for maintaining and/or restoring viability of organs

A photoplethysmographic (PPG) technique to assess blood flow in bone tissue has been developed and tested. The signal detected by the PPG consists of a constant-level (DC) component—which is related to the relative vascularization of the tissue—and a pul- satile (AC) component—which is synchronous with the pumping action of the heart. The PPG probe was ap- plied on the skin over the patella. The probe uses near- infrared (804 nm) and green (560 nm) light sources and the AC component of the PPG signals of the two wavelengths was used to monitor pulsatile blood flow in the patellar bone and the overlying skin, respec- tively. Twenty healthy subjects were studied and arte- rial occlusion resulted in elimination of PPG signals at both wavelengths, whereas occlusion of skin blood flow by local surface pressure eliminated only the PPG signal at 560 nm. In a parallel study on a physical model with a rigid tube we showed that the AC com- ponent of the PPG signal originates from pulsations of blood flow in a rigid structure and not necessarily from volume pulsations. We conclude that pulsatile blood flow in the patellar bone can be assessed with the present PPG technique.

Non-invasive continuous estimation of blood flow changes in human patellar bone

To assess local haemodynamic effects of raised tissue pressure per se and of arterial and venous pressure variations during raised tissue pressure, and to evaluate the vascular waterfall phenomenon. An isolated pump-perfused sympathectomised cat skeletal muscle enclosed in a plethysmograph. Hydrostatic capillary pressure (Pc), tissue volume alterations and blood flow wre recorded at various arterial (PA) or venous (PV) pressure levels at a raised tissue pressure (Ptissue). Total vascular resistance (Rtot) and its three consecutive sections, arterial resistance (Rart), venular resistance (Pvenule), and venous outflow orifice resistance (Rorifice), were recorded. Increase in Ptissue increased Pc due to a marked increase in Rorifice and unchanged Rart and, when Ptissue>PV by about 90% of the Ptissue increase. During the raised Ptissue, a PA increase (95 to 115 mmHg) increased Pc (by 3.1±1.1 mmHg) causing fluid filtration, and a PA decrease (95 to 75 mmHg) decreased Pc (by 2.4±0.5 mmHg) causing fluid absorption. Rart was unchanged, indicating impaired autoregulation. Increased PV had no haemodynamic effects when PV Ptissue blood flow and Pc increased gradually, causing fluid filtration. Tissue volume is increased by raised an decreased by lowered PA, the latter may be of use to decrease ICP in the injured brain. The results indicate that PEEP or head elevation will not influence ICP from the venous side if CVP<ICP. Finally, the “vascular waterfall phenomenon” was rejected as Rorifice is a normal variable fluid resistance.

Effects of arterial and venous pressure alterations on transcapillary fluid exchange during raised tissue pressure.

Background: Treatment of increased intracranial pressure often includes an active change in arterial and venous pressure, sometimes with draining of cerebrospinal fluid. We evaluated tissue and perfusion pressure during corresponding interventions in an organ enclosed in a rigid compartment with capillaries permeable for electrolytes and impaired autoregulation, conditions comparable to those present in the injured brain.



Method: An isolated cat skeletal muscle enclosed in a closed fluid-filled plethysmograph served as a model for the injured brain surrounded by cerebrospinal fluid and the cranium. Tissue pressure and blood flow were measured during variation in arterial and venous pressures and in intraplethysmographic fluid volume. Autoregulation was depressed by papaverine.



Results: 1) Tissue pressure was not influenced by the venous pressure when this was below the tissue pressure, hereby generating venous collapse and a venous outflow resistance. When venous pressure was higher than the tissue pressure (no venous outflow resistance), these two parameters changed in parallel. 2) A change in arterial pressure induced a similar large change in tissue pressure at steady state, whereas blood flow remained unchanged. 3) Variation in tissue pressure induced by a change in the intraplethysmographic fluid volume was transient.



Conclusions: If applicable to the injured brain, the results indicate that 1) a venous pressure change has a small influence on the intracranial pressure when a venous outflow resistance is present, 2) brain oedema can be reduced by lowering of the arterial inflow pressure, and blood flow will be maintained, 3) the decrease in intracranial pressure obtained by draining cerebrospinal fluid will be transient.

The role of arterial and venous pressure for volume regulation of an organ enclosed in a rigid compartment with application to the injured brain.

Surgery and traumatic injury are often followed by tissue oedema and a low plasma albumin concentration, indicating leakage of fluid and proteins from the intravascular to the interstitial space. Transcapillary leakage can be referred to as an increase in capillary hydraulic conductance and/or a decrease in the reflection coefficient for plasma macromolecules. This study evaluates if time-dependent variations in the reflection coefficient for albumin and capillary hydraulic conductance can be confirmed experimentally following a surgical trauma using a blood perfused cat skeletal muscle in vivo preparation. The hydraulic conductance was estimated by the capillary filtration coefficient, and was used to evaluate variation in capillary fluid permeability. According to the Starling fluid equilibrium, the ratio between the reflection coefficients for albumin on two occasions can be calculated from the maximum osmotic absorption rates induced by a fixed intravenous bolus infusion of albumin (0.5 g kg -1 ) and from the capillary filtration coefficients. We found a decrease in the reflection coefficient of about 30% up to 10 h after the preparation. The capillary filtration coefficient showed no significant change over time, but decreased by 5-10% following the albumin infusion. We conclude that: (1) the reflection coefficient for albumin is reduced after a trauma, whereas the effects on the capillary fluid permeability are small, (2) albumin in plasma contributes to preserve normal capillary fluid permeability and, (3) the model seems to be useful for evaluation of relative variations in the reflection coefficient for albumin.

Reflection coefficient for albumin and capillary fluid permeability in cat calf muscle after traumatic injury.

This paper describes the design of a servo-controlled precision roller pump applicable for constant blood flow or constant blood pressure perfusion in research on the peripheral circulation. The pump, and its feed-back control, can simulate normal cardiac induced autoperfusion by reproducing the arterial pulse pressure configuration with high fidelity. Its design is such as to minimize damage of the red blood cells and consequent release of vasoactive substances, a problem encountered with most conventional pumps. The present pump principle may also find a use in heart-lung machines and dialysis equipment and can be used as a precision infusion pump.

Lars‐Åke Clementz

Papers

A servo‐controlled roller pump for constant flow or constant pressure blood perfusion under normal pulsatile or non‐pulsatile conditions