Recovery of damaged skeletal muscle in mdx mice through low-intensity endurance exercise.

The lack of dystrophin in mdx mice leads to cycles of muscle degeneration and regeneration processes. Various strategies have been proposed in order to reduce the muscle-wasting component of muscular dystrophy, including implementation of an exercise programme. The aim of this study was to examine how low-intensity endurance exercise affects the degeneration-regeneration process in dystrophic muscle of male mdx mice. Mice were subjected to low-intensity endurance exercise by running on a motorized Rota-Rod for 5 days/week for 6 weeks. Histomorphological analysis showed a significant reduction of measured inflammatory-necrotic areas in both gastrocnemius and quadriceps muscle of exercised mdx mice as compared to matched sedentary mdx mice. The degenerative-regenerative process was also evaluated by examining the protein levels of connexin 39 (Cx39), a specific gene expressed in injured muscles. Cx39 was not detected in sedentary wild type mice, whereas it was found markedly increased in sedentary mdx mice, revealing active muscle degeneration-regeneration process. These Cx39 protein levels were significantly reduced in muscles of mdx mice exercised for 30 and 40 days, revealing together with histomorphological analysis a strong reduction of degeneration process in mice subjected to low-intensity endurance exercise. Muscles of exercised mdx mice did not show significant changes in force and fatigue resistance as compared to sedentary mdx mice. Overall in this study we found that specific low-intensity endurance exercise induces a beneficial effect probably by reducing the degeneration of dystrophic muscle.

Plasma leptin and vascular endothelial growth factor (VEGF) in normal subjects at high altitude (5050 m).

CONTEXT: High altitude (HA) is a model of severe hypoxia exposure in humans. We hypothesized that nocturnal hypoxemia or acute maximal exercise at HA might affect plasma leptin and VEGF levels. OBJECTIVES: Plasma leptin, VEGF and other metabolic variables were studied after nocturnal pulse oximetry and after maximal exercise in healthy lowlanders on the 3rd-4th day of stay in Lobuche (5050 m, HA) and after return to sea level (SL). RESULTS: Leptin was similar at SL or HA in both pre- and post-exercise conditions. Pre-exercise VEGF at HA was lower, and cortisol was higher, than at SL, suggesting that nocturnal intermittent hypoxia associated with periodic breathing at HA might affect these variables. CONCLUSIONS: Leptin levels appear unaffected at HA, whereas nocturnal hypoxic stress may affect plasma VEGF. Future HA studies should investigate the possible role of nocturnal intermittent hypoxemia on metabolism.

O2 transport in hypoxic albino rats of first and second generation.

The generations of rats raised in normobaric hypoxia (10% O2 in N2) were observed for changes in their oxygen-hemoglobin affinity, hemoglobin content (Hb) blood O2 capacity and pO2-O2 content curves: the first generation (H1) and the second generation (H2). H1 rats possessed a lower O2-Hb affinity while H2 rats had a higher O2-Hb affinity than normoxic control rats. Hb was greater in both hypoxic groups, however, H2 rats showed a Hb lower than that of H1 rats. Both hypoxic groups showed a leftward shift of the pO2-O2 content curve. In pO2 range between 25 and 50 mmHg, H2 rats showed a shift greater than H1 rats. So in hypoxic conditions the H1 rat's ability to supply enough O2 to the tissues is smaller than that of H2 rats. In the rat's adaptation to hypoxia the Hb increase plays only a minor role while O2-Hb affinity increase constitutes a physiologically meaningful adaptation.

Oxygen-haemoglobin dissociation curve in hypoxic rats of first or second generation.

1. Albino Wistar rats were raised in a normobaric hypoxic environment (10% O2 in N2). Two generations of hypoxic rats were observed for changes in their haemoglobin-oxygen (Hb-O2) dissociation curves (ODC), 2,3-diphosphoglycerate (2,3-DPG), haemoglobin (Hb), and Hill co-efficients at P50 (n50). The first generation were called (H1) and the second generation (H2). The control group (N) had a normoxic environment. 2. Thirty-five rats (13 N rats, 12 H1 rats and 10 H2 rats) were used. The 2,3-DPG was significantly higher in both hypoxic groups when compared with N rats (2.02 +/- 0.51 mmol/L) but 2,3-DPG of H2 rats was significantly lower than that of H1 rats (H1 = 3.48 +/- 0.58 mmol/L and H2 = 2.76 +/- 0.54 mmol/L). The haemoglobin values were N = 2.00 +/- 0.26, H1 = 2.65 +/- 0.32 and H2 = 2.36 +/- 0.30 mmol/L, respectively. 3. We observed considerable differences in Hb-O2 affinity between the three groups of rats. In standard conditions (pH = 7.400; pCO2 = 40 mmHg at 37 degrees C) the H1 rats showed a significantly decreased Hb-O2 affinity (P50,st = 37.0 +/- 1.3 mmHg) when compared with both H2 and N rats; the H2 rats showed a significantly increased Hb-O2 affinity (P50,st = 31.1 +/- 1.5 mmHg) when compared with controls N (P50,st = 34.7 +/- 2.1 mmHg). There were no significant differences in n50 values: N = 2.88 +/- 0.44; H1 = 2.88 +/- 0.77; and H2 = 2.94 +/- 0.67.(ABSTRACT TRUNCATED AT 400 WORDS)

P50 values in hypoxic albino rats of first and second generation.

We determined the "in vivo" (arterial pH and PCO2) and standard (pH = 7.4, PCO2 = 40 mm Hg) PO2 at 50% O2 saturation of hemoglobin (P50, vv and P50, st) in Wistar albino rats when living in a normobaric hypoxic environment. Two generations of hypoxic rats were observed for changes in their P50, vv, P50, st, (n50) 2,3-diphosphoglycerate (2,3-DPG), hemoglobin (Hb) and DPG-Hb ratio: the first generation (H1) and the second generation (H2). A few hours after birth, the H1 rats were placed and raised in a normobaric hypoxic environment (10% O2 in N2). The H2 rats were born from hypoxic parents of first generation and were raised in the same hypoxic environment. The control group had a normoxic environment. The P50, st was significantly higher in H1 rats than both H2 and controls. P50, st was similar in H2 and control rats. The P50, vv was significantly higher in H1 rats than both H2 and controls but it was significantly lower in H2 when compared with both controls and H1. Hb and 2,3-DPG had values significantly greater for both H1 and H2 when compared with their controls. However, the values of H2 were significantly lower than H1. The effectiveness of an increase in Hb-O2 affinity as an adaptive mechanism in H2 rats is discussed.

[Behavior of various enzyme activities during high blood lactate and pyruvate levels in albino rats reared in a normobaric hypoxic atmosphere for 1 or 2 generations]. / Andamento di alcune attivita' enzimatiche, della lattatemia e piruvatemia in ratti albini allevati in ambiente ipossico normobarico da una o due generazioni.

Albino rats Wistar family raised in normobaric hypoxic environment (10% O2 in N2) since one or two generations showed an increase in arterial blood creatine-kinase, glutamate-dehydrogenase, lactic-dehydrogenase, lactate and pyruvate when compared with normoxic controls. Moreover the values found in hypoxic rats of second generation were intermediate between those found in hypoxic rats of first generation and normoxic controls. These differences are probably due to an improved efficiency of the processes of cellular adaptation to the hypoxic environment when named species remain in hypoxic environment for more than one generation.

Body growth and polycythaemia in hypoxic albino rats of first and second generation.

1. In our study we followed the growth rate and the haematologic changes occurring in albino rats of Wistar strain when living in a hypoxic environment. Two generations of hypoxic rats were observed for changes in their erythrocytes (RBC), haematocrit (Hct) and haemoglobin (Hb): the first generation (H1) and the second generation (H2). A few hours after birth, the H1 rats were placed and raised in a normobaric hypoxic environment (10% O2 in N2). The H2 rats were born and raised in the environment previously described. The control group had a normoxic environment. The H1 and H2 rats had inferior growth rates in respect to their controls, but H2 were found to have a larger growth rate than the H1 group. The RBC, Hct and Hb had values significantly greater for both H1 and H2 when compared with their controls. However, we did find that the values of H2 were significantly lower than H1. We believe that these results are in relation to the degree of development of the adaptive processes to the hypoxic environment of the H2 rats.

[Effects of acute hypoxia and hyperoxia on respiratory rate in albino rats chronically exposed to hypoxia]. / Effetti dell'ipossia acuta e dell'iperossia sulla frequenza respiratoria nel ratto albino cronicamente esposto all'ipossia.

Changes in respiratory frequencies with hypoxic or hyperoxic exposure were studied in: 12 normoxic control rats (N) born and raised in normoxic environment at sea level; 12 rats (A) born and raised in normoxic environment at sea level exposed to normobaric hypoxia (10% O2 in N2) as adults; 12 rats of first generation (G1) raised in the above mentioned hypoxic environment since a few hours after birth; 12 rats of third generation (G3) conceived and born in the hypoxic environment of hypoxic parents of second generation and maintained continuously under hypoxic conditions until their utilization. The response of A rats to 10% O2 and 7% O2 breathing was elevated (57% and 86% over air breathing). The mean respiratory frequency of A rats exposed to 7% O2 rose to a greater extent than did that of N rats. The G1 and G3 rats were less responsive to 7% O2 (64% and 37% over air breathing, respectively) than N and A rats; however, in G1 rats the exposure to 7% O2 produced a greater rise of frequency than in G3 rats. Furthermore A rats, G1 rats and G3 rats were less responsive to 97% O2 breathing (19%, 19% and 11% below air breathing, respectively). Comparing these data with previous findings we suggest that, with chronic exposure to hypoxia, changes in ventilatory response to hypoxia and hyperoxia occur in the following manner: I) loss of response to hypoxia if chronic exposure is begun in the immediate postnatal period; 2) degree of response to hypoxia or hyperoxia influenced by duration of chronic exposure.

Acid-base balance and lactatemia in acute hypoxia in normoxic or hypoxic albino rats.

Albino rats Wistar family were raised since birth in normobaric hypoxic environment (10% O2 in N2). This hypoxic animal group and a normoxic control group were subjected to acute hypoxia in two spaced tests. The rats were exposed for 15 minutes to 7% O2 and later to 5% O2 gas mixture. At the end of the test with 7% O2 the hypoxic animals since birth showed a smaller quantity of blood lactate and their acid-base balance was more acid when compared to control animals. These differences were significant. In the considered metabolic parameters the differences between the 2 groups became not significant at the end of the test with 5% O2. We believe that the found differences in mentioned parameters between hypoxic and normoxic animals, also according to cellular adaptative processes, occurred during the rearing in hypoxic environment. In the test with 5% O2 the seriousness of the hypoxia overcomes the effects of adaptative mechanisms in hypoxic animals since birth. We believe that hypoxic rats since birth represent, limitedly to some aspects, different metabolic models compared to normoxic animals.

Arterial LDH, 2,3-DPG, lactate, pyruvate and acid-base balance in hypoxic albino rats of first or second generation.

Arterial acid-base balance, lactate, pyruvate, lactate dehydrogenase activity (LDH), 2,3-diphosphoglycerate content (2,3-DPG) of normoxic control rats were compared with those of rats exposed to a hypoxic normobaric environment (10% O2 in N2) within a few hours after birth (hypoxic animals of first generation or H1), and with those of rats of second generation (H2) conceived and born in the above mentioned hypoxic environment of H1 parents and maintained always in the same place since their utilization. The H1 rats showed a displacement of acid-base balance towards acidosis and an increase of lactate, pyruvate, LDH and 2,3-DPG in comparison with normoxic controls. The H2 rats showed a significant attenuation of acidosis in comparison with H1 rats; the values of lactate, pyruvate, LDH and 2,3-DPG were intermediate between those found in H1 and normoxic control rats. We believe that these results are in relation with the evolution of adaptative processes to hypoxic environment in hypoxic animals of second generation.

[Acid-base balance, blood lactate, blood pyruvate, and L/P ratio in albino rats raised in normobaric, hypoxic hypoxia for one or two generations]. / Equilibrio acido-base, lattatemia, piruvatemia, rapporto L/P in ratti albini allevati in ipossia ippossica normobarica da una o due generazioni.

Albino rats Wistar family raised in normobaric hypoxic environment (10% O2 in N2) since one or two generations showed a displacement of the acid-base balance of the arterial blood towards acidosis and an increase of blood lactate and pyruvate when compared with normoxic controls. Found differences were significant in all considered parameters except for lactate-pyruvate ratio. Moreover in hypoxic animals of second generation these differences were quantitatively less strong. In effect when we compared the two groups of hypoxic animals between them, they showed significant differences-estimated with Duncan's test - in the pH, B.E., S.B., lactate and pyruvate values. All the above mentioned differences pointed out less blood acidification and less increase of lactate and pyruvate in hypoxic animals of second generation. The results seem to indicate the beginning of adaptative processes to the extraordinary hypoxic normobaric environment in albino rat and the evolution of these processes when named species remain in hypoxic environment for more than one generation.

Acid-base balance and blood lactate and pyruvate levels in albino rats bred under normobaric hypoxia or normoxia, after muscular work in a hypoxic or hypoxic-hypercapnic environment.

Albino rats, Wistar family, have been raised since birth in normobaric hypoxic environment (10-12% O2). This hypoxic animal group and a normoxic animal group were subjected to muscular fatigue by forced march within revolving room. Normoxic animals were subjected to 3 spaced trials: in normoxic environment; in hypoxic normobaric environment; in the same hypoxic normobaric environment with about 2% CO2 added. Hypoxic animals were subjected to 2 spaced trials: in hypoxic normobaric environment; in the same hypoxic environment with about 2% CO2 added. At the end of every single trial, lactatemia, blood pyruvate, acid-base balance and the erythrocytic number were examined. Albino rats raised in hypoxic environment since birth, subjected to muscular work in hypoxic environment showed a smaller increase of lactatemia and a moderate variation of the acid-base balance, compared to normoxic animals in the same conditions. CO2 added to the respired hypoxic mixture during muscular work, attenuated in both animal groups, the observed modifications. Finally we found that the erythrocytes per mm3 of blood increased from the second drawing of blood.

[Acid-base equilibrium, blood lactic acid and pyruvic acid in albino rats after muscular exertion under conditions of normal oxygen, hypoxia and hypoxia-hypercapnia]. / Equilibrio acido-base, lattacidemia, piruvicemia, in ratti albini al termine di lavoro muscolare effettuato in normossia, ipossia, ipossia-ipercapnia.

Albino rats of the Wistar family were subjected at three subsequent equal trials of muscular work: the first in normoxyc conditions; the second in hypoxic normobaric conditions; the third in hypoxic-hypercapnic normobaric conditions. The modifications of the lactacidemia, pyruvicemia and acid-base balance were greatest at the end of hypoxic trial. Added CO2 (2%) sensitively reduced the acidificant effects of the muscular work on the acid-base balance.

[Effects of muscular exertion in a hypoxic and hypoxic-hypercapnic respiratory environment on acid-base equilibrium and blood lactic acid in the albino rat raised in hypoxic hypoxia from birth]. / Effetti del lavoro muscolare in ambiente respiratorio ipossico ed ipossico-ipercapnico, sull'equilibrio acido-base e lattacidemia, nel ratto albino allevato in ipossia ipossica sin dalla nascita.

Albino rats of the Wistar family were raised from the time of birth in the normobaric hypoxic environment. They were subjected at two subsequent equal trials of muscular work: the first in hypoxic normobaric conditions; the second in hypoxic hypercapnic conditions (CO2 = 2%). The modifications of the lactacidemia and acid-base balance at the end of the first trial are modest, lower than these observed in previous studies in normoxic rats. Added CO2 sensitively reduced the effects of the muscular work on the examined parameters.

[Initial observations on lipid metabolism in the albino rat raised under normobaric hypoxic hypoxia]. / Prime osservazioni sul metabolismo dei lipidi nel ratto albino allevato in ipossia ipossica normobarica.

The researches of Chiodi, Altland et Al. have shown fatty liver degeneration in hypoxic suckling rats. These alterations produced death within 30 days of life. In order to better understand the relationships between the fatty metabolism and hypoxia, we have studied total plasmatic lipids and cholesterol, glutamic-oxaloacetic and glutamic-pyruvic transaminase in the albino rats raised under normobaric hypoxia to avoid effects linked to barometric modifications. Total plasmatic lipids are reduced in hypoxic animals. In the others parameters we have not shown significant changes.

[Raising albino rats in a normobaric hypoxic environment]. / Allevamento di ratti albini in ambiente ipossico normobarico.

In the previous researches we found that the albino rats of Wistar stock, raised from the time of birth under hypoxia at simulated altitude, showed a displacement of the acid-base balance of blood towards the acid side and an increase in the 2,3-DPG, in Hb concentration and in the number of erythrocytes for mm3 of blood. In the same animals the body growth was slower in comparison to the control normoxic group. In order to separate the eventual effects of hypobaria from those of hypoxia "per se" we have repeated our research in normobaric hypoxic environment for 51 days as minimum period and 86 as maximum period of observation. The samples of blood were collected with heart drawing. The acid-base balance was determined by a hemogas-analyzer IL 213, the lactacidemia with the Boehringer enzyme tests. The animals showed again a displacement of the acid-base balance of blood towards the acid side. Nevertheless this phenomenon was less accentuated than in hypobaric conditions. The Weight curve of hypoxic animals superimposed to normoxic controls until 35 degree days. Thereafter the two curves turned apart within 20%.