Effect of sustained hypobaric hypoxia during maturation and aging on rat myocardium. I. Mechanical activity

Abstract

. Effect of sustained hypobaric hypoxia during maturation and aging on rat myocardium. I. Mechanical activity. J Appl Physiol 98: 2363-2369, 2005. First published February 10, 2005 doi:10.1152/japplphysiol.00988.2004.-Long-lasting cardioprotection may be attained by chronic hypoxia. The basal parameters of contractile function and their response to hypoxia/reoxygenation were measured under isometric conditions, in papillary muscles isolated from left ventricle of rats that were submitted to 53.8 kPa in a hypobaric chamber from 7 wk of age and for their lifetime and of their siblings kept at 101.3 kPa. During acclimatization, hematocrit increased, body weight gain decreased, and heart weight increased with right ventricle hypertrophy. Papillary muscle cross-sectional area was similar in both control and hypoxic groups up to 45 wk of exposure. Developed tension (DT) was 34 -64% higher in rats exposed to hypoxia for 10, 26, and 45 wk than in their age-matched controls, whereas resting tension was unchanged. Maximal rates of contraction and relaxation showed a similar pattern of changes as DT. Recovery of DT and maximal rates of contraction and relaxation after 60-min hypoxia and 30-min reoxygenation was also improved in adult hypoxic rats to values similar to those of young rats. Heart acclimatization was lost after 74 wk of exposure. Results are consistent with the development of cardioprotection during high-altitude acclimatization and provide an experimental model to study the mechanisms involved, which are addressed in the accompanying paper. high altitude; acclimatization; heart contractility; hypoxia/reoxygenation TOLERANCE OF THE MYOCARDIUM to oxygen deprivation may be increased by pharmacological intervention, ischemic preconditioning, or systemic hypoxia (37). Chronic normobaric hypoxia (inspired O 2 fraction ϭ 0.12) from birth increases the resistance of the isolated neonatal rabbit heart to ischemia (2, 3). Adaptation of rats to intermittent hypobaric hypoxia (53.8 kPa) protects the heart against acute ischemia-reperfusion injury and ischemia-induced arrhythmias and infarction (1, 30). More recently, short episodes of intermittent or continuous hypoxia were shown to induce delayed cardioprotection (11,47). Although the mechanisms underlying increased resistance to O 2 deprivation remain largely unknown, activation of mitochondrial ATP-sensitive K ϩ channels and increased cellular nitric oxide (NO) steady-state levels, by their effects on the regulation of mitochondrial bioenergetics, appear to be involved in both long-lasting (adaptation to chronic hypoxia) and shortlasting (acute systemic hypoxia and ischemia preconditioning) forms of hypoxic cardioprotection (1,3,4,7,18,22,24,30,31,34,35,44,45,47).Hypoxic states of the cardiovascular system are undoubtedly associated with the most frequent diseases of modern times. Myocardial hypoxia is the result of a disproportion between O 2 supply and demand. Among the most common causes for a reduced O 2 supply to the myocardium, hypoxic hypoxia (often described ...

Effects of a single bout of isometric neuromuscular electrical stimulation on rat gastrocnemius muscle: A combined functional, biochemical and MRI investigation

“…Given that rat body weight reached a plateau at $10 months (La Padula and Costa, 2005) and considering that the rate of protein synthesis declined with age (Garlick et al, 1989;Kelly et al, 1984), the use of older rats could have minimized the influence of high protein synthesis rate on muscle injury and could therefore be viewed as a better model to investigate muscle damage. However, previous experiments conducted in mature animals have failed to demonstrate any muscle damage after a single bout of electrically-induced isometric contractions (Geronilla et al, 2003;Peters et al, 2003).…”

Strategic localization of heart mitochondrial NOS: a review of the evidence

“…Rats submitted to simulated chronic hypoxia using a hypobaric chamber showed right ventricle hypertrophy, increased hematocrit values (78), and about 60% enhanced activity of heart mtNOS (141). This upregulation was associated with a preservation of the papillary muscle contractile parameters upon aging and improved tolerance to postischemic contractile dysfunction.…”

Chronic Intermittent Hypobaric Hypoxia Ameliorates Ischemia/Reperfusion-Induced Calcium Overload in Heart via Na+/Ca2+Exchanger in Developing Rats

“…Since age is an important factor in the tolerance of the heart to ischemia, an animal's age significanly affects the cardiac protective effect induced by hypoxia adaptation [27,28]. For calcium homeostasis, the basal myocardium [Ca 2+ ] i in developing animals is low and increases along with the cardiac maturation [29].…”