Protective effect of MitoTEMPO against cardiac dysfunction caused by ischemia-reperfusion: MCAO stroke model study

Int J Neurosci. 2023 Oct 20:1-12. doi: 10.1080/00207454.2023.2273768. Online ahead of print.

Abstract

Purpose: Neurological impairments are the leading cause of post-stroke mortality, while stroke-related cardiovascular diseases rank second in significance. This study investigates the potential protective effects of MitoTEMPO (2,2,6,6-tetramethyl-4-[[2-(triphenylphosphonio) acetyl] amino]-1-piperidinyloxy, monochloride, monohydrate), a mitochondria-specific antioxidant, against cardiac and neurological complications following stroke. The objective is to assess whether MitoTEMPO can be utilized as a protective agent for individuals with a high risk of stroke.

Materials and methods: Seventeen-week-old male Wistar Albino rats were randomly assigned to three groups: SHAM, ischemia-reperfusion and MitoTEMPO + ischemia-reperfusion (MitoTEMPO injection 0.7 mg/kg/day for 14 days). The SHAM group underwent a sham operation, while the ischemia-reperfusion group underwent 1-h middle cerebral artery occlusion followed by three days of reperfusion. Afterwards, noninvasive thoracic electrical bioimpedance and electrocardiography measurements were taken, and sample collection was performed for histological and biochemical examinations.

Results: Our thoracic electrical bioimpedance and electrocardiography findings demonstrated that MitoTEMPO exhibited a protective effect on most parameters affected by ischemia-reperfusion compared to the SHAM group. Furthermore, our biochemical and histological data revealed a significant protective effect of MitoTEMPO against oxidative damage.

Conclusions: The findings suggest that both ischemia-reperfusion-induced cardiovascular abnormalities and the protective effect of MitoTEMPO may involve G-protein coupled receptor-mediated signaling mechanisms. This study was conducted with limitations including a single gender, a uniform age group, a specific stroke model limited to middle cerebral artery, and pre-scheduled only one ischemia-reperfusion period. In future studies, addressing these limitations may enable the implementation of preventive measures for individuals at high risk of stroke.

Keywords: Cardiovascular disease; ischemic stroke; middle cerebral artery occlusion.