Systematic Review and Meta-Analysis of the Impact of Hypoxia on Infarcted Myocardium: Better or Worse?

Abstract

Background/Aims: Patients with myocardial infarction and hypoxemia require supplemental oxygen. However, the current therapeutic paradigm is contradicted by several recent studies in which the post-infarcted heart appears to benefit from systemic hypoxia. With this systematic review and meta-analysis, we aimed to discover whether systemic hypoxia is beneficial or detrimental to the infarcted myocardium. Methods: We conducted an electronic search of the PubMed, EMBASE, and Web of Science databases and extracted the outcomes of cardiac function, geometry, and hemodynamics. A random-effect model was applied when the I² value of greater than 50%. The sensitivity analysis was performed by omitting one study at a time, and publication bias was assessed using Egger’s test. In addition, the quality of studies was evaluated using the risk of bias tool devised by the Systematic Review Centre for Laboratory Animal Experimentation. Results: Six reports comprising 14 experiments were ultimately screened from among 10,323 initially identified preclinical studies. Few studies reported the method of randomization and none described allocation concealment, random outcome assessment or blinding. Overall, chronic hypoxia was found to have a beneficial effect on the ejection fraction (standard mean difference [SMD] = 5.39; 95% confidence interval [CI], 3.83 to 6.95; P < 0.001) of the infarcted heart, whereas acute hypoxia significantly improved hemodynamics, as indicated by an increase in the maximal rate of rise of left ventricular pressure (SMD = 1.27; 95% CI, 0.27 to 2.28; P = 0.013) and cardiac output (SMD = 1.26; 95% CI, 0.34 to 2.18; P = 0.007) and a decrease in total systematic vascular resistance (SMD = –0.89; 95% CI, –1.24 to –0.53; P < 0.001). Furthermore, a reduced oxygen content increased the stroke volume (P = 0.010). However, hypoxia reduced the end-systolic (SMD = –2.67; 95% CI, –4.09 to –1.26; P < 0.001) and end-diastolic (SMD = –3.61; 95% CI, –4.65 to –2.57; P < 0.001) left ventricular diameters and increased the total pulmonary resistance (SMD = 0.76; 95% CI, 0.20 to 1.33; P = 0.008), pulmonary arterial mean pressure (SMD = 2.02; 95% CI, 0.23 to 3.81; P = 0.027), and left atrial pressure (SMD = 1.20; 95% CI, 0.57 to 1.82; P < 0.001). Conclusion: Hypoxia significantly improved heart function after infarction, with particular beneficial effects on systolic function and hemodynamics. However, it had slightly adverse effects on pulmonary circulation and left ventricular geometry. A lower inspired oxygen concentration may improve cardiac function, although further research is needed to determine the optimum level of hypoxia. Finally, more studies of hypoxia and myocardial infarction in larger species are required before these findings can be incorporated into therapeutic guidelines.

p66Shc is an apoptotic rheostat whose targeted ROS inhibition improves MI outcomes

“…Identifying p66Shc's ROS product as O2is consistent with reports where MI was associated with increased post-ischemic [O2 -], ischemia severity, and O2 --dependent negative PMI remodeling (Kramer et al, 1987;Siwik et al, 1999;van Deel et al, 2008). These results may also explain, in part, why hypoxia is beneficial in diseases where decreased p66Shcmediated ROS improves outcomes (e.g., Leigh syndrome, MI) (Jain et al, 2019;Pang et al, 2018;Wojtala et al, 2017).…”

“…These results may also explain, in part, why hypoxia is beneficial in diseases where decreased p66Shc-mediated ROS improves outcomes ( e . g ., Leigh syndrome, MI) (Jain et al, 2019; Pang et al, 2018; Wojtala et al, 2017).…”

Hypoxia and the phenomenon of immune exclusion

“…Hypoxia normally occurs during development: mammalian embryogenesis occurs at low oxygen concentrations (1-5%) and the gradient of oxygen itself functions as morphogen in many developmental systems [42,43]. Hypoxia is also linked to many medical conditions including myocardial infarction, ischemic or hemorrhagic brain stroke, transient ischemic attack and late stages of some neurodegenerative diseases [43][44][45][46][47].…”

Re-enforcing hypoxia-induced polyploid cardiomyocytes enter cytokinesis through activation of β-catenin

“…In their study, adult mice were exposed to a gradual (1% per day) decrease and were kept at 7% oxygen for 2 weeks. Our previous study showed different oxygen concentration affect cardiac function 47 , suggesting that distinct hypoxic environment may activate the G1-S phase or ana-telophase of M phase of CMs, leading to polyploidization or regeneration. Further research needs to find the molecular mechanism in different effect of hypoxic condition on the cycle activity of CMs.…”