Methane supplementation improves graft function in experimental heart transplantation

Area of Science:

• Cardiovascular Surgery
• Organ Transplantation
• Biomedical Engineering

Background:

• Cell viability during cold storage is critical for successful organ transplantation.
• Methane (CH4) exhibits bioactivity in ischemia/reperfusion, suggesting potential protective effects.

Purpose of the Study:

• To investigate if cold storage in methane (CH4)-enriched preservation solution enhances defense against organ dysfunction in experimental heart transplantation (HTX).

Main Methods:

• Rat hearts were cold-stored in standard Custodiol (CS) or CH4-saturated CS solution (CS-CH4).
• Standard heterotopic heart transplantation (HTX) was performed, followed by assessment of left ventricular (LV) pressure-volume relationships, coronary blood flow (CBF), and myocardial tissue analysis.
• Mitochondrial function, endoplasmic reticulum (ER) stress, and apoptosis markers were evaluated.

Main Results:

• CS-CH4 grafts showed significantly improved LV systolic pressure and systolic pressure increment compared to CS grafts.
• Diastolic function and coronary blood flow (CBF) were enhanced in the CS-CH4 group.
• Mitochondrial oxidative phosphorylation capacity was better preserved, with reduced cytochrome c release, ER stress, and proapoptotic protein transcription in CS-CH4 stored hearts.

Conclusions:

• Methane (CH4) addition during cold storage improves early in vitro heart graft function.
• CH4 reduces mitochondrial dysfunction, inflammation, and ER stress-linked proapoptotic signaling.
• CH4-enriched preservation offers a promising approach to mitigate organ dysfunction during cold storage for transplantation.