Figure 5. Proposed mechanisms underlying LE-induced rescue of cardiac arrest as a result of bupivacaine-overdose.

Oxidation of LE contains long chain fatty acids occurs in the mitochondria. Fatty acids are transported into the mitochondria via carnitine shuttle, and go through β-oxidation to produce NADH and FADH₂. NADH and FADH₂ enter the electron transport chain (ETC). ETC couples electron transfer between an electron donor (NADH and FADH2) and an electron acceptor (such as O₂) to the transfer of H⁺ ions (protons) across a membrane. The resulting electrochemical proton gradient is used to generate energy in the form of adenosine triphosphate (ATP) in complex V. The release of H⁺ from complex I, III and IV lead to lowering PH in outer mitochondrial membrane which lead to inhibition of mPTP opening. Inhibition of β-oxidation pathway by CVT abolishes the production of NADH, FADH₂, as well as H⁺ ions, leading to generation of less ATP. The rise of Ca²⁺ ions in mitochondria through Ca²⁺ uniporter will trigger the opening of mPTP. LE enhances the homeostasis of cardiomyocytes to better regulate calcium overload and therefore delay the opening of mPTP. FACS; Fatty Acyl CoA Synthase, CPT1, Carnitine Acyl Transferase 1, CT; Carnitine Acylcarnitine Translocase, CPT2, Carnitine Acyl Transferase 2.