Methods to improve organ viability
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Publication Number
US-11950590-B2
Publication Date
2024-04-09
Expiration Date
Abstract
The present disclosure provides methods to improve the viability of an organ, or organs, by continuously administering a composition comprising NOx gas directly to the organ(s).
Core Innovation
The invention is a method to improve the viability of an organ intended for transplant or damaged by ischemia-reperfusion by continuously administering nitric oxide (NOx) gas directly to the organ. The NOx gas is administered via an organ perfusion system and/or ventilation so that the organ is maintained in direct contact with the NOx gas during the preservation or treatment period.
A central aspect is the delivery of nitric oxide (NO) gas in a defined initial dose range and subsequent dose increase or adjustment based on viability improvement and limiting conditions. The method starts with an initial dose of about 0.05 ppm to about 20 ppm of nitric oxide (NO) gas directly to the organ, with incremental increasing of the dose by increments of 0.1 ppm to 5 ppm until viability is increased, until the dose of NO gas exceeds 50 ppm, or until a methemoglobin level exceeds 5%.
The method is tied to explicit viability and mechanistic assessment indicators, including mitochondrial function measured by respiratory control ratio (RCR), mitochondrial reactive oxygen species (mtROS), and oxidative stress-related markers such as SOD2 (MnSOD) activity and nitrotyrosine inhibition. The preservation of mitochondrial function is further characterized in the document by mitochondrial complex I–IV activity preservation.
Claims Coverage
The document includes two independent methods. Across both independent claims, the core coverage is the direct administration of nitric oxide (NO) gas to an organ via an organ perfusion system or ventilation starting within 0.05 ppm to 20 ppm, followed by dose increase or adjustment until viability is increased or until dose or methemoglobin thresholds are reached.
Dose-increment NO administration to improve organ viability
administering to the organ an initial dose of about 0.05 ppm to about 20 ppm of nitric oxide (NO) gas directly to the organ via an organ perfusion system or ventilation; and incrementally increasing the dose of NO gas by increments of 0.1 ppm to 5 ppm until the viability of the organ is increased, the dose of NO gas exceeds 50 ppm, or a methemoglobin level exceeds 5%.
Threshold-controlled NO dose adjustment for organ viability improvement
administering to the organ an initial dose of about 0.05 ppm to about 20 ppm of nitric oxide (NO) gas directly to the organ via an organ perfusion system or ventilation; and adjusting the dose of NO gas until the viability of the organ is increased, the dose of NO gas exceeds 50 ppm, or a methemoglobin level exceeds 5%.
Both independent claims cover a direct NO gas administration strategy to improve organ viability using an initial NO dose in the 0.05 ppm to 20 ppm range delivered via an organ perfusion system or ventilation, with dose increase or adjustment governed by viability increase and stopping conditions tied to exceeding 50 ppm NO dose and exceeding 5% methemoglobin.
Stated Advantages
Improves the viability of an organ intended for transplant or damaged by ischemia-reperfusion.
Documented Applications
Improving viability in a lung transplant context, including an EVLP example.
Improving organ-related outcomes in a pediatric swine cardiac arrest iNO example, including improved cerebral mitochondrial readouts.
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