Abstract

The high-pressure gas (HPG) method with carbon monoxide (CO) and oxygen (O2) mixture maintains the preserved rat heart function. The metabolites of rat hearts preserved using the HPG method (HPG group) and cold storage (CS) method (CS group) by immersion in a stock solution for 24 h were assessed to confirm CO and O2 effects. Lactic acid was significantly lower and citric acid was significantly higher in the HPG group than in the CS group. Moreover, adenosine triphosphate (ATP) levels as well as some pentose phosphate pathway (PPP) metabolites and reduced nicotinamide adenine dinucleotide phosphate (NADPH) were significantly higher in the HPG group than in the CS group. Additionally, reduced glutathione (GSH), which protects cells from oxidative stress, was also significantly higher in the HPG group than in the CS group. These results indicated that each gas, CO and O2, induced the shift from anaerobic to aerobic metabolism, maintaining the energy of ischemic preserved organs, shifting the glucose utilization from glycolysis toward PPP, and reducing oxidative stress. Both CO and O2 in the HPG method have important effects on the ATP supply and decrease oxidative stress for preventing ischemic injury. The HPG method may be useful for clinical application.

Highlights

  • Transplantation is an important treatment approach for end-stage diseases

  • Six heart samples each of the control group group (CT), cold storage (CS), and high-pressure gas (HPG) groups were used for the metabolomic analysis by gas chromatography/tandem mass spectrometry (GC–MS/MS), and 172 metabolites were detected

  • The heart functions and mitochondrial activities in rat hearts are better maintained using the HPG method, which includes a mixture of carbon monoxide (CO) and O2, than using the CS method

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Summary

Introduction

Transplantation is an important treatment approach for end-stage diseases. As the organ must be removed from the body and preserved for a certain period of time, an ischemic injury is an inevitable event during the organ transplant procedure. The preservation time for clinically extracted hearts before transplantation is 4–6 h [1]. O2 concentration has been to be related to increased oxidative stress by and increased reactive cytochrome oxygen species while decreasing the activity of the normal cellular altering the responsible chain(ROS). The resulting oxidative stress in the organ transplant procedure initiates increased reactive oxygen species (ROS) while decreasing the activity of the normal cellular antioxidant cellular injury. The balance between oxidative and antioxidant systems is one of the important factors for maintaining transplantation. The rat heart function after h of HPG preservation using a mixture of 2 gases was HPG preservation using a mixture of CO and O2 gases was found to be almostand theOsame as that foundhearts to be almost thetransplanted same as that immediately in control hearts were transplanted immediately after in control that were afterthat extraction [9].

Comparison
Assessment cardiacmorphology morphology and activities after
Selection of Important Differential Metabolites
Alternations in Metabolic Pathway
Discussion
Animals
HPG Preservation Method and Experimental Design
Light Microscopy
Mitochondrial Activity Estimation
ATP Luciferase Assay
GSH and GSSG Assay
Sample Preparation
Instrumental Analysis
Multivariate Data Analysis
Statistical Analysis
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