Myocardial Metabolic Changes in Chronic Hypoxia

Moret, Pierre

doi:10.1159/000169358

Cited by 10 publications

(7 citation statements)

References 12 publications

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“…Data on actual myocardial fuel substrate preferences in humans in response to high altitude and matched to appropriate control subjects are limited. However, Moret (1971/72) reported higher cardiac lactate and lower fatty acid utilization in South American individuals residing at high altitude. In agreement, lowland subjects exposed to acute altitude simulation, and rats to hypobaric hypoxia, both displayed increased glucose uptake (Hurford et al 1990; Roberts et al 1996).…”

Section: Chronic Hypoxia and Cardiac Fuel Substrate Switchingmentioning

confidence: 89%

Cardiac metabolic adaptations in response to chronic hypoxia

Essop

2007

The Journal of Physiology

106

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Since a constant supply of oxygen is essential to sustain life, organisms have evolved multiple defence mechanisms to ensure maintenance of the delicate balance between oxygen supply and demand. However, this homeostatic balance is perturbed in response to a severe impairment of oxygen supply, thereby activating maladaptive signalling cascades that result in cardiac damage. Past research efforts have largely focused on determining the pathophysiological effects of severe lack of oxygen. By contrast, and as reviewed here, exposure to moderate chronic hypoxia may induce cardioprotective properties. The hypothesis put forward is that chronic hypoxia triggers regulatory pathways that mediate long-term cardiac metabolic remodelling, particularly at the transcriptional level. The novel proposal is that exposure to chronic hypoxia triggers (a) oxygen-sensitive transcriptional modulators that induce a switch to increased carbohydrate metabolism (fetal gene programme) and (b) enhanced mitochondrial respiratory capacity to sustain and increase efficiency of mitochondrial energy production. These compensatory protective mechanisms preserve contractile function despite hypoxia.

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Section: Chronic Hypoxia and Cardiac Fuel Substrate Switchingmentioning

confidence: 89%

Cardiac metabolic adaptations in response to chronic hypoxia

Essop

2007

The Journal of Physiology

106

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“…Therefore, the findings would suggest that during hypoxia the same apparent cardiac power output could be maintained with a smaller aerobic energy release than during air breathing. Moret (1971) studied subjects, acclimatized to high altitude at their native altitude. He observed a lower myocardial oxygen uptake than in subjects studied at sea level and interpreted this as a sign of higher mechanical efficiency of the heart.…”

Section: Discussionmentioning

confidence: 99%

“…supply capacity of the coronary vasculature (Hartley et al 1974). Early studies of healthy humans living at altitudes of 3600-4750 m above sea level showed a more complete myocardial oxygen extraction, smaller coronary blood flow and lower myocardial oxygen consumption than in sea level residents (Moret 1971). Changes in a similar direction were found in sea level residents after 10 days ofacclimatization at 3100 m (Grover & Alexander 1976, Moret 1971/72, Grover et al 1976).…”

mentioning

confidence: 92%

Myocardial oxygen supply and lactate metabolism during marked arterial hypoxaemia

Grubbström

Berglund

Kaijser

1993

Acta Physiologica Scandinavica

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Myocardial O2 delivery and changes in myocardial lactate metabolism during marked hypoxaemia (PaO2 5-5.4 kPa, Sa O2 70-75%) produced by 12% O2 breathing were studied in 12 healthy subjects at rest and during supine exercise up to maximal intensity. Blood for O2 and lactate analyses was sampled from catheters in an artery (a) and the coronary sinus (cs) and coronary sinus blood flow (CSBF) was measured by thermodilution. Lactate metabolism was evaluated in a subgroup of the subjects using i.v. infusion of [14C]lactate. At rest and during submaximal exercise up to heart rate 156 beats min-1 myocardial O2 uptake (MQO2) was maintained at the same level during hypoxaemia as during normoxaemia. This was achieved at rest mainly by a more complete O2 extraction, during exercise entirely by greater CSBF. During maximal exercise CSBF was 35% greater during hypoxaemia than normoxaemia, while there was no difference in cs O2 saturation. Maximal MQO2 was smaller during hypoxaemia than normoxaemia in spite of no difference in rate pressure product. The a-cs difference of lactate was reduced during hypoxaemia and there was a significant myocardial release of lactate, as calculated from [14C]lactate data, during hypoxaemic exercise, but not during hypoxaemic rest or normoxaemic rest and exercise. It is concluded that the heart has a coronary flow reserve of about 35%, which can be utilised under hypoxaemia. When this reserve is insufficient to supply the myocardium with oxygen lactate is produced to cover part of the myocardial ATP regeneration.

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“…At the same time an elevation was noted in ADP (p<0.02) and AMP content (p<0.001). Such a reduction in ATP production brings into play some substitute pathways on the one hand, and some increased efficiency of the respiratory processes at the mitochondria level on the other hand [10,11,20], We may assess that during this period the tissue is temporarily in a situation of energetic disequilibrium.…”

Section: Immediate Stage Of Adaptation (Assays Performed During the Fmentioning

confidence: 99%

“…According to these authors, this modification enters into the adaptation process concerning the glycolytic pathways among the animals exposed to an intense energy consumption. Thus during adaptation to high altitude, the cardiac muscle has to effect a considerable strain because of rapid changing of circulatory dynamics [10].…”

Section: Immediate Stage Of Adaptation (Assays Performed During the Fmentioning

confidence: 99%

Changes in Energetic Metabolism of Rat Myocardium during Acclimation to High Altitude

Vergnes¹,

Pr²

1976

Enzyme

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The results reported in this paper refer to the modifications of energetic equilibrium in the myocardium tissue, involved by altitude chronic hypoxia. Experiments have been done on adult rats (males and females) placed in the Jungfraujoch station, in the Alps, at 3,500 m. The obtained data were compared to control animals, bred in Geneva. On the first days of stay at high altitude, a significant fall of tissue energy charge, due to the non-modified enzyme levels in comparison with the controls, was observed. After several weeks of stay in chronic hypoxia, the metabolic modifications leading to the improvement of energy production and to the achievement of a new equilibrium state, take place. In acclimatized animals some good correlation, between the energy charge and the activity of glycolytic enzymes (PGK and PK) ensuring the ATP regeneration, is established.

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Myocardial Metabolic Changes in Chronic Hypoxia

Cited by 10 publications

References 12 publications

Cardiac metabolic adaptations in response to chronic hypoxia

Cardiac metabolic adaptations in response to chronic hypoxia

Myocardial oxygen supply and lactate metabolism during marked arterial hypoxaemia

Changes in Energetic Metabolism of Rat Myocardium during Acclimation to High Altitude

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