Protective effects of a magnesium magnetic isotope (Mg25)-exchanging nanoparticle (25MgPMC16) on mitochondrial functional disorders in esmolol-induced cardiac arrest in rats

Abstract

1 In cardiac surgery, agents are needed to produce temporary cardiac arrest (cardioplegia). One of these agents is esmolol (ESM) which is a short-acting selective beta-1 adrenergic receptor antagonist and its overdose causes diastolic ventricular arrest.

2 The ²⁵MgPMC₁₆ (porphyrin adducts of cyclohexil fullerene-C60) is known as a nanoparticle which has a cardioprotective effect when the heart is subjected to stressful conditions.

3 In this study, we aimed to confirm the deleterious effects of ESM overdose on cardiac mitochondria and identify any protective effects of ²⁵MgPMC₁₆ in male Wistar rats. Esmolol 100 mg kg⁻¹ (LD50 = 71 mg kg⁻¹) was injected intravenously (i.v.) into tail vein to induce cardiac arrest. This dose was obtained from an ESM dose–response curve which induces at least 80% arrest in rats.

4 ²⁵MgPMC₁₆ at three different doses (45, 90 and 224 mg kg⁻¹) was injected i.v. as pretreatment, eight hours before ESM injection. ²⁵MgCl₂ or ²⁴MgPMC₁₆ were used as controls. Following cardiac arrest, the heart was removed and the mitochondria extracted. Mitochondrial viability and the adenosine 5′-diphosphate sodium salt hydrate/Adenosine 5′-triphosphate disodium salt hydrate (ADP/ATP) ratio were measured as biomarkers of mitochondrial function.

5 Results indicate that ²⁵MgPMC₁₆ caused a significant increase in mitochondrial viability and decrease in ADP/ATP ratio. No significant changes were seen with ²⁴MgPMC₁₆ or ²⁵MgCl₂. It is concluded that cardiac arrest induced by ESM overdose leads to a significant decrease in mitochondrial viability and their ATP levels, whereas pretreatment by ²⁵MgPMC₁₆ can protect mitochondria by increasing ATP level through liberation of Mg into cells and the improvement of hypoxia.