Reversal of hypoxia-induced decrease in human cardiac response to isoproterenol infusion

Richalet, Jean‐Paul; Le-Trong, J. L.; Rathat, C; Merlet, Pascal; Bouissou, P.; Keromes, A; Veyrac, P

doi:10.1152/jappl.1989.67.2.523

Cited by 34 publications

(27 citation statements)

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“…Gi protein is upregulated mainly in RV, while functional activity of Gs protein is decreased in both RV and LV [ 10 ]. These changes fully explain the decrease in chronotropic response to adrenergic activation at high altitude [ 11 ], as well as the reduction in maximal heart rate at exercise [ 12 ]. Moreover, this desensitization of heart response to adrenergic activation is a remarkable protecting mechanism of the heart against a possible unbalance of oxygen availability to cardiac tissue in conditions of severe environment hypoxic conditions.…”

Section: The Effects Of Hypoxia On the Heart Experimental Studiesmentioning

confidence: 77%

Right Ventricle and High Altitude

Richalet

Pichon

2014

The Right Heart

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At high altitude, as hypoxia induces pulmonary vasoconstriction and increases ipulmonary arterial pressure, right ventricular (RV) function will be affected. The right ventricular function may be affected directly by the hypoxaemic challenge or indirectly through a pressure overload due, in turn to changes in the pulmonary circulation. Both animal and human studies show that moderate or transient hypoxia results in adaptive changes in right ventricle that are reversible with re-exposure to normoxic conditions and RV dysfunction is mainly due to mechanical overload from the pulmonary circulation. When hypoxia is more severe or more prolonged, it may directly impact ventricular diastolic or systolic function through mechanisms that remain to be unraveled. Chronic exposure to hypoxia in high-altitude natives suffering from Monge's disease may lead to RV hypertrophy, RV failure and overall cardiac failure. The adrenergic system may be involved, as well as HIF, PKC or phospholamban. More studies using the latest imaging technology should give us a better understanding of RV systolic and diastolic function in humans exposed to altitude hypoxia including acute, chronic or chronic intermittent hypoxia.

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Section: The Effects Of Hypoxia On the Heart Experimental Studiesmentioning

confidence: 77%

Right Ventricle and High Altitude

Richalet

Pichon

2014

The Right Heart

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“…From Richalet [ 32 ] in humans [ 34 , 35 ] or in dogs [ 25 ]. This blunted response to adrenergic activation is partly rapidly reversible with reoxygenation [ 35 ].…”

Section: Desensitization Of the β-Adrenergic System In Prolonged Hypoxiamentioning

confidence: 99%

Physiological and Clinical Implications of Adrenergic Pathways at High Altitude

Richalet

2016

Advances in Experimental Medicine and Biology

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The adrenergic system is part of a full array of mechanisms allowing the human body to adapt to the hypoxic environment. Triggered by the stimulation of peripheral chemoreceptors, the adrenergic centers in the medulla are activated in acute hypoxia and augment the adrenergic drive to the organs, especially to the heart, leading to tachycardia. With prolonged exposure to altitude hypoxia, the adrenergic drive persists, as witnessed by elevated blood concentrations of catecholamines and nerve activity in adrenergic fibers. In response to this persistent stimulation, the pathways leading to the activation of adenylate cyclase are modified. A downregulation of β-adrenergic and adenosinergic receptors is observed, while muscarinic receptors are upregulated. The expression and activity of Gi and Gs proteins are modified, leading to a decreased response of adenylate cyclase activity to adrenergic stimulation. The clinical consequences of these cellular and molecular changes are of importance, especially for exercise performance and protection of heart function. The decrease in maximal exercise heart rate in prolonged hypoxia is fully accounted for the observed changes in adrenergic and muscarinic pathways. The decreased heart rate response to isoproterenol infusion is another marker of the desensitization of adrenergic pathways. These changes can be considered as mechanisms protecting the heart from a too high oxygen consumption in conditions where the oxygen availability is severely reduced. Similarly, intermittent exposure to hypoxia has been shown to protect the heart from an ischemic insult with similar mechanisms involving G proteins and downregulation of β receptors. Other pathways with G proteins are concerned in adaptation to hypoxia, such as lactate release by the muscles and renal handling of calcium. Altogether, the activation of the adrenergic system is useful for the acute physiological response to hypoxia. With prolonged exposure to hypoxia, the autonomous nervous system adapts to protect vital organs, especially the heart, against a too high energetic state, via a purely local autoregulation mechanism necessary for the preservation of overall homeostasis.

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“…At nearmaximal and maximal workloads, however, there is a decrease in heart rate with increasing altitude and time spent in altitude [1][2][3][4][5]. The maximal heart rate at a simulated altitude equivalent to the summit of Mount Everest (8848 m) was found to be only 118 beats:min −" [1].…”

Section: Introductionmentioning

confidence: 98%

“…On exposure to hypoxia, heart rate is increased both at rest and during submaximal exercise [1,2]. At nearmaximal and maximal workloads, however, there is a decrease in heart rate with increasing altitude and time spent in altitude [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Heart rate response to hypoxic exercise: role of dopamine D2-receptors and effect of oxygen supplementation

et al. 2001

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This study examined the effects of dopamine D(2)-receptor blockade on the early decrease in maximal heart rate at high altitude (4559 m). We also attempted to clarify the time-dependent component of this reduction and the extent to which it is reversed by oxygen breathing. Twelve subjects performed two consecutive maximal exercise tests, without and with oxygen supplementation respectively, at sea level and after 1, 3 and 5 days at altitude. On each study day, domperidone (30 mg; n=6) or no medication (n=6) was given 1 h before the first exercise session. Compared with sea level, hypoxia progressively decreased the maximal heart rate from day 1 and onwards; also, hypoxia by itself increased plasma noradrenaline levels after maximal exercise. Domperidone further increased maximal noradrenaline concentrations, but had no effect on maximal heart rate. On each study day at altitude, oxygen breathing completely reversed the decrease in maximal heart rate to values not different from those at sea level. In conclusion, dopamine D(2)-receptor blockade with domperidone demonstrates that hypoxic exercise in humans activates D(2)-receptors, resulting in a decrease in circulating levels of noradrenaline. However, dopamine D(2)-receptors are not involved in the hypoxia-induced decrease in the maximal heart rate. These data suggest that receptor uncoupling, and not down-regulation, of cardiac adrenoreceptors, is responsible for the early decrease in heart rate at maximal hypoxic exercise.

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Reversal of hypoxia-induced decrease in human cardiac response to isoproterenol infusion

Cited by 34 publications

References 0 publications

Right Ventricle and High Altitude

Right Ventricle and High Altitude

Physiological and Clinical Implications of Adrenergic Pathways at High Altitude

Heart rate response to hypoxic exercise: role of dopamine D2-receptors and effect of oxygen supplementation

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