Organ Preservation Solution Using PKC Modulators
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Solution Overview
Problem
Current organ transplantation is limited by ischemic/reperfusion injury, which causes tissue and cellular damage due to hypoxic conditions and lack of circulation, leading to organ dysfunction and rejection during the transplantation process.
Innovation Solution
A solution containing peptide inhibitors of protein kinase C βII (PKC βII) and/or ζ (PKC ζ) and/or activators of protein kinase C delta (PKC δ) is used for organ preservation, perfusion, and reperfusion, enhancing nitric oxide release and reducing endothelial/superoxide release to protect organs from ischemia/reperfusion injury.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If cold storage after cardioplegic arrest is used for short-term myocardial preservation, then the heart can be preserved during cardiac surgery, but organ rejection and dysfunction occur due to ischemic/reperfusion injury during transplantation
Solution Approach 1:
The patent modifies the chemical composition of preservation solutions by incorporating specific additives (e.g., mannitol, allopurinol, glutathione, insulin, hydrocortisone) that alter the biochemical parameters during ischemia and reperfusion. These parameter changes reduce oxidative stress, inflammation, and cellular damage, thereby maintaining organ function while extending preservation duration.
Solution Approach 2:
The invention uses composite preservation solutions that combine multiple protective agents working synergistically. For example, the solution integrates free radical scavengers (allopurinol, glutathione), osmoprotectants (mannitol), anti-inflammatory agents (hydrocortisone), and metabolic support (insulin) to create a multifunctional preservation medium that addresses multiple aspects of ischemic injury simultaneously.
2Use of energy by moving object
If reperfusion of blood flow is restored to treat prolonged ischemia, then oxygen and nutrient delivery is improved, but endothelium and myocyte injury occurs resulting in organ dysfunction
Solution Approach 1:
The patent applies preliminary protective measures before reperfusion occurs. Preservation solutions are pre-loaded with antioxidants (allopurinol, glutathione), anti-inflammatory agents (hydrocortisone), and other protective compounds that are already present in the tissue when reperfusion begins. This preliminary anti-action prevents the oxidative burst and inflammatory cascade that normally occur upon reperfusion, thereby protecting endothelium and myocytes from injury while restoring oxygen delivery.
Data Source
AI summary
The present invention relates to a solution for preservation, perfusion, and/or reperfusion of an organ, especially the heart, for transplantation. The solution contains peptide inhibitor(s) of protein kinase C βII (PKC βII) and/or of protein kinase C ζ (PKC ζ) and/or peptide activator(s) of protein kinase C δ (PKCδ). Methods for using the inventive solution are also disclosed, including methods for preserving an organ for transplantation, for protecting an ischemic organ from damage, for attenuating organ dysfunction after ischemia, for maintaining nitric oxide release and/or inhibiting superoxide release in an ischemic organ, and for protecting an organ from damage when isolated from the circulatory system.