Key result
Dexmedetomidine pretreatment cuts apoptosis by ~44% in cardiomyocytes exposed to hypoxia and reoxygenation.
Why the study?
Clinical outcomes in myocardial ischemia-reperfusion injury remain inconsistent with experimental findings because underlying mechanisms are not fully elucidated, prompting investigation into whether dexmedetomidine protects injured cardiomyocytes and ameliorates endoplasmic reticulum stress.
Does dexmedetomidine prevent hypoxia/reoxygenation injury in H9c2 embryonic rat cardiomyocytes?
Does dexmedetomidine prevent hypoxia/reoxygenation injury in H9c2 embryonic rat cardiomyocytes?
Absolute Event Rate: 9% vs 16%
p-value: p=<0.05
In an in vitro model, dexmedetomidine attenuated hypoxia/reoxygenation-induced injury and apoptosis in H9c2 cardiomyocytes by inhibiting endoplasmic reticulum stress.
DEX may attenuate MIRI via ERS modulation; leaves open clinical translation pending human trials.
Myocardial ischemia‑reperfusion injury (MIRI) has been confirmed to induce endoplasmic reticulum stress (ERS) during downstream cascade reactions after the sufficient deterioration of cardiomyocyte function. However, clinically outcomes have been inconsistent with experimental findings because the mechanism has not been entirely elucidated. Dexmedetomidine (DEX), an α2 adrenergic receptor agonist with anti‑inflammatory and organ‑protective activity, has been shown to attenuate IRI in the heart. The present study aimed to determine whether DEX is able to protect injured cardiomyocytes under in vitro hypoxia/reoxygenation (H/R) conditions and evaluate the conditions under which ERS is efficiently ameliorated. The cytotoxicity of DEX in H9c2 cells was evaluated 24 h after treatment with several different concentrations of DEX. The most appropriate H/R model parameters were determined by the assessment of cell viability and injury with Cell Counting Kit‑8 and lactate dehydrogenase (LDH) release assays after incubation under hypoxic conditions for 3 h and reoxygenation conditions for 3, 6, 12 and 24 h. Additionally, the aforementioned methods were used to assess cardiomyocytes cultured with various concentrations of DEX under H/R conditions. Furthermore, the degree of apoptosis and the mRNA and protein expression levels of glucose‑regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and caspase‑12 were evaluated in all groups. The addition of 1, 5 and 10 µM DEX to the cell culture significantly increased the proliferation of H9c2 cells by >80% under normal culture conditions. In the H/R model assessment, following 3 h of anoxia exposure, H9c2 cell viability decreased to 62.67% with 3 h of reoxygenation and to 36% with 6 h of reoxygenation compared with the control. The viability of H9c2 cells subjected to hypoxia for 3 h and reoxygenation for 3 h increased by 61.3% when pretreated with 1 µM DEX, and the LDH concentration in the supernatant was effectively decreased by 13.7%. H/R significantly increased the percentage of apoptotic cells, as detected by flow cytometry, and increased the expression levels of GRP78, CHOP and caspase‑12, while treatment with either DEX or 4‑phenylbutyric acid (4‑PBA) significantly attenuated these effects. Additionally, despite the protective effect of DEX against H/R injury, 4‑PBA attenuated the changes induced by DEX and H/R. In conclusion, treatment with 1 µM DEX alleviated cell injury, apoptosis and the increases in GRP78, CHOP and caspase‑12 expression levels in H9c2 cells induced by 3 h of hypoxia and 3 h of reoxygenation.
No takes yet. Share an insight, caveat, or question.
Zhu et al. (2020) studied Myocardial ischemia-reperfusion injury. Dexmedetomidine vs. Hypoxia/reoxygenation without dexmedetomidine was evaluated on Apoptosis rate (p=<0.05). Pretreatment with 1 µM dexmedetomidine significantly reduced the apoptosis rate from 16% to 9% and decreased lactate dehydrogenase release by 13.7% in H9c2 cardiomyocytes subjected to 3 hours of hypoxia and 3 hours of reoxygenation.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: