Normobaric, intermittent hypoxia conditioning is cardio- and vasoprotective in rats

Манухина, Е. Б.; Belkina, L. M.; Terekhina, O. L.; Abramochkin, Denis V.; Смирнова, Е. А.; Буданова, О.П.; Mallet, Robert T.; Downey, H. Fred

doi:10.1177/1535370213508718

Cited by 39 publications

(44 citation statements)

References 59 publications

(122 reference statements)

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“…These clinical studies in patients are substantiated by relevant preclinical studies showing antiarrhythmic and myocardial protective effects of IHT in animals. 96,97,100,193,194 Further information on the cardioprotective effects of IHT are available in the recent reviews by Zhang and Zhou 195 and by Serebrovska and Shatilo. 196 Various antistress effects of IHT have been described by IHT pioneer Felix Meerson.…”

Section: Iht Reduces Vrfsmentioning

confidence: 99%

“…Thus, it was not surprising that rats treated for 21 consecutive days with IHT had no right ventricular hypertrophy. 100 IHT improves cerebral blood flow and prevents cerebrovascular rarefaction in AD In a rat model of experimental AD induced by bilateral injection of a fragment of Ab (Ab 25-35) into the basal magnocellular nuclei, cerebral blood flow in the parietal cortex Figure 2 The vicious cycle of dementation and cerebral underperfusion. Decreased activity lowers energy consumption and, thus, demand for blood flow in that brain region.…”

Section: Intermittent Hypoxic Training (Iht) Improves Cerebrovascularmentioning

confidence: 99%

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Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Манухина

Downey

Shi

et al. 2016

Exp Biol Med (Maywood)

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Alzheimer's disease (AD) is a leading cause of death and disability among older adults. Modifiable vascular risk factors for AD (VRF) include obesity, hypertension, type 2 diabetes mellitus, sleep apnea, and metabolic syndrome. Here, interactions between cerebrovascular function and development of AD are reviewed, as are interventions to improve cerebral blood flow and reduce VRF. Atherosclerosis and small vessel cerebral disease impair metabolic regulation of cerebral blood flow and, along with microvascular rarefaction and altered trans-capillary exchange, create conditions favoring AD development. Although currently there are no definitive therapies for treatment or prevention of AD, reduction of VRFs lowers the risk for cognitive decline. There is increasing evidence that brief repeated exposures to moderate hypoxia, i.e. intermittent hypoxic training (IHT), improve cerebral vascular function and reduce VRFs including systemic hypertension, cardiac arrhythmias, and mental stress. In experimental AD, IHT nearly prevented endothelial dysfunction of both cerebral and extra-cerebral blood vessels, rarefaction of the brain vascular network, and the loss of neurons in the brain cortex. Associated with these vasoprotective effects, IHT improved memory and lessened AD pathology. IHT increases endothelial production of nitric oxide (NO), thereby increasing regional cerebral blood flow and augmenting the vaso-and neuroprotective effects of endothelial NO. On the other hand, in AD excessive production of NO in microglia, astrocytes, and cortical neurons generates neurotoxic peroxynitrite. IHT enhances storage of excessive NO in the form of S-nitrosothiols and dinitrosyl iron complexes. Oxidative stress plays a pivotal role in the pathogenesis of AD, and IHT reduces oxidative stress in a number of experimental pathologies. Beneficial effects of IHT in experimental neuropathologies other than AD, including dyscirculatory encephalopathy, ischemic stroke injury, audiogenic epilepsy, spinal cord injury, and alcohol withdrawal stress have also been reported. Further research on the potential benefits of IHT in AD and other brain pathologies is warranted.

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Section: Iht Reduces Vrfsmentioning

confidence: 99%

Section: Intermittent Hypoxic Training (Iht) Improves Cerebrovascularmentioning

confidence: 99%

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Манухина

Downey

Shi

et al. 2016

Exp Biol Med (Maywood)

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“…IH can protect the heart against ischemia-reperfusion injury (197) by improving against ischemia-induced contractile dysfunction (31, 127), endothelial dysfunction (110,111), arrhythmias (110,116,209), and cell death (45, 89). Also, IH treatment can promote higher resistance to arrhythmias during acute myocardial ischemia and prevent the development of atherosclerosis in rabbits (88).…”

Section: Whenmentioning

confidence: 99%

The polymorphic and contradictory aspects of intermittent hypoxia

Almendros

Wang

Gozal

2014

American Journal of Physiology-Lung Cellular and Molecular Phys

153

131

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Intermittent hypoxia (IH) has been extensively studied during the last decade, primarily as a surrogate model of sleep apnea. However, IH is a much more pervasive phenomenon in human disease, is viewed as a potential therapeutic approach, and has also been used in other disciplines, such as in competitive sports. In this context, adverse outcomes involving cardiovascular, cognitive, metabolic, and cancer problems have emerged in obstructive sleep apnea-based studies, whereas beneficial effects of IH have also been identified. Those a priori contradictory findings may not be as contradictory as initially thought. Indeed, the opposite outcomes triggered by IH can be explained by the specific characteristics of the large diversity of IH patterns applied in each study. The balance between benefits and injury appears to primarily depend on the ability of the organism to respond and activate adaptive mechanisms to IH. In this context, the adaptive or maladaptive responses can be generally predicted by the frequency, severity, and duration of IH. However, the presence of underlying conditions such as hypertension or obesity, as well as age, sex, or genotypic variance, may be important factors tilting the balance between an appropriate homeostatic response and decompensation. Here, the two possible facets of IH as derived from human and experimental animal settings will be reviewed.

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“…IHT also dramatically increases myocardial resistance to ischemia-reperfusion injury and arrythmogenesis in dogs [Zong et al, 2004; Mallet et al, 2006; Estrada et al, 2016] and rats [Manukhina et al, 2013], and preserves post-infarct vascular endothelial responses and coronary blood flow in rats [Manukhina et al, 2013]. This gradually evolving, IHT mediated cardioprotection is abrogated by antioxidants or antagonists of β 1 -adrenergic (β 1 -AR) or δ-opioid (δ-OR) receptors [Mallet et al, 2006; Estrada et al, 2016].…”

Section: Introductionmentioning

confidence: 99%

δ-Opioid receptors: Pivotal role in intermittent hypoxia-augmentation of cardiac parasympathetic control and plasticity

Estrada

Barlow

Yoshishige

et al. 2016

Autonomic Neuroscience

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Background Intermittent hypoxia training (IHT) produces robust myocardial protection against ischemia-reperfusion induced infarction and arrhythmias. Blockade of this cardioprotection by antagonism of either β1-adrenergic or δ-opioid receptors (δ-OR) suggests autonomic and/or opioidergic adaptations. Purpose To test the hypothesis that IHT shifts cardiac autonomic balance toward greater cholinergic and opioidergic influence. Methods Mongrel dogs completed 20 d IHT, non-hypoxic sham training, or IHT with the δ-OR antagonist naltrindole (200 μg/kg sc). The vagolytic effect of the δ-OR agonist met-enkephalin-arg-phe delivered by sinoatrial microdialysis was evaluated following IHT. Sinoatrial, atrial and left ventricular biopsies were analyzed for changes in δ-OR, the neurotrophic monosialoganglioside, GM-1, and cholinergic and adrenergic markers. Results IHT enhanced vagal bradycardia vs. sham dogs (P<0.05), and blunted the δ2-OR mediated vagolytic effect of met-enkephalin-arg-phe. The GM- 1 labeled fibers overlapped strongly with cholinergic markers, and IHT increased the intensity of both signals (P<0.05). IHT increased low and high intensity vesicular acetylcholine transporter labeling of sinoatrial nodal fibers (P<0.05) suggesting an increase in parasympathetic arborization. IHT reduced select δ-OR labeled fibers in both the atria and sinoatrial node (P<0.05) consistent with moderation of the vagolytic δ2-OR signaling described above. Furthermore, blockade of δ-OR signaling with naltrindole during IHT increased the protein content of δ-OR (atria and ventricle) and vesicular acetylcholine transporter (atria) vs. sham and untreated IHT groups. IHT also reduced the sympathetic marker, tyrosine hydroxylase in ventricle (P<0.05). Summary IHT shifts cardiac autonomic balance in favor of parasympathetic control via adaptations in opioidergic, ganglioside, and adrenergic systems.

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Normobaric, intermittent hypoxia conditioning is cardio- and vasoprotective in rats

Cited by 39 publications

References 59 publications

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease

The polymorphic and contradictory aspects of intermittent hypoxia

δ-Opioid receptors: Pivotal role in intermittent hypoxia-augmentation of cardiac parasympathetic control and plasticity

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