Dimethyl malonate slows succinate accumulation and preserves cardiac function in a swine model of hemorrhagic shock.

ABSTRACT:

Background

Succinate (SI) is a citric acid cycle metabolite that accumulates in tissues during hemorrhagic shock (HS) due to electron transport chain uncoupling. Dimethyl malonate (DMM) is a competitive inhibitor of SI dehydrogenase, which has been shown to reduce SI accumulation and protect against reperfusion injury. Whether DMM can be therapeutic after severe HS is unknown. We hypothesized that DMM would prevent SI buildup during resuscitation (RES) in a swine model of HS, leading to better physiological recovery after RES.

Methods

The carotid arteries of Yorkshire pigs were cannulated with a 5-Fr catheter. After placement of a Swan-Ganz catheter and femoral arterial line, the carotid catheters were opened and the animals were exsanguinated to a mean arterial pressure (MA

SUBMITTER: Taghavi S 

PROVIDER: S-EPMC9232889 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature