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Systems and Methods for Pseudo In Vivo Organ Preservation Disclosure Number: IPCOM000242027D
Publication Date: 2015-Jun-15
Document File: 5 page(s) / 29K

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Systems and Methods for Pseudo In Vivo Organ Preservation

Current organ preservation techniques based on stasis should try to achieve homeostasis, which can be termed pseudo in vivo (PIV) organ preservation. This approach would duplicate all systems interacting with the organ in vivo in an external device, designed to ensure functionally, nutritionally, thermodynamically, mechanically, and hygienically equivalent conditions. The last two conditions necessitate innovative methods designed to maintain realistic shear stress due to flows within the organ and to clean and filter fluids that are recirculated to serve the organ.

The invention generally relates to systems, methods, and devices for ex vivo organ care. More particularly, in various embodiments, the invention relates to caring for an organ ex vivo at physiologic or near-physiologic conditions.

Ischemia and reperfusion–elicited tissue injury contributes to morbidity and mortality in a wide range of pathologies and is a major challenge during organ transplantation. An imbalance in metabolic supply and demand within the ischemic organ results in profound tissue hypoxia and microvascular dysfunction. Subsequent reperfusion further enhances the activation of innate and adaptive immune responses and cell death programs. Recent advances in understanding the molecular and immunological consequences of ischemia and reperfusion may lead to innovative therapeutic strategies for treating patients with ischemia and reperfusion–associated tissue inflammation and organ dysfunction (Eltzschig and Eckle, 2011).

As Perrille et al. (2011) explain, reperfusion therapy must be applied as soon as possible to attenuate the ischemic insult of acute myocardial infarction (AMI). However reperfusion is responsible for additional myocardial damage, which likely involves opening of the mitochondrial permeability transition pore (mPTP). In reperfusion injury, mitochondrial damage is a determining factor in causing loss of cardiomyocyte function and viability. Major mechanisms of mitochondrial dysfunction include the long lasting opening of mPTPs and the oxidative stress resulting from formation of reactive oxygen species (ROS). Several signaling cardioprotective pathways are activated by stimuli such as preconditioning and postconditioning, obtained with brief intermittent ischemia or with pharmacological agents. These pathways converge on a common target, the mitochondria, to preserve their function after ischemia/reperfusion. The present review discusses the role of mitochondria in cardioprotection, especially the involvement of adenosine triphosphate-dependent potassium channels, ROS signaling, and the mPTP. Ischemic postconditioning has emerged as a new way to target the mitochondria, and to drastically reduce lethal reperfusion injury. Several clinical studies using ischemic postconditioning during angioplasty now support its protective effects, and an interesting alternative is pharmacological postconditi...