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Caiozzo, V. J.

Publications and source records attributed to Caiozzo, V. J..

The Artificial Gravity Bed Rest Pilot Project: Effects on Knee Extensor and Plantar Flexor Muscle Groups

The goal of this project was to examine the effects of artificial gravity (2.5 g) on skeletal muscle strength and key anabolic/catabolic markers known to regulate muscle mass. Two groups of subjects were selected for study: 1) a 21 day-bed rest (BR) control (C) group (N=7); and 2) an AG group (N=8), which was exposed to 21 days of bed-rest plus daily 1 hr exposures to AG (2.5 g). This particular experiment was part of an integrated AG Pilot Project sponsored by NASA/Johnson Space Center. The in vivo torque-velocity relationships of the knee extensors and plantar flexors of the ankle were determined pre and post treatment. Also, pre- and post treatment biopsy samples were obtained from both the vastus lateralis and soleus muscles and were used, in part, for a series of analyses on gene expression (mRNA abundance) of key factors implicated in the anabolic versus catabolic state of the muscle. Post/Pre toque-velocity determinations revealed greater decrements in knee extensor performance in the C versus AG group (P less than 0.04). The plantar flexor muscle group of the AG subjects actually demonstrated a net gain in torque-velocity relationship; whereas, in the C group the overall post/pre responses declined (AG vs C; P less than 0.001). Measurements of muscle fiber cross-sectional area (for both muscles) demonstrated a loss of approx. 20% in the C group while no losses were evident in the AG group. RT-PCR analyses of muscle biopsy specimens demonstrated that markers of growth and cytoskeletal integrity (IGF-1, IGF-1 BP4, mechano growth factor, total RNA, and pro-collagen 3a) were higher in the AG group, whereas catabolic markers (myostatin and atrogen) were elevated in the C group. Importantly, these patterns were seen in both muscles. Based on these observations we conclude that paradigms of AG have the potential to maintain the functional, biochemical, and structural homeostasis of skeletal muscle in the face of chronic unloading states. These findings also warrant further studies since it is likely that other robust paradigms of AG that employ various exercise strategies may be more effective in counteracting long duration unloading states as anticipated on the platforms of the Moon and Mars.

Caiozzo, V. J.↗

Single-fiber myosin heavy chain polymorphism during postnatal development: modulation by hypothyroidism

The primary objective of this study was to follow the developmental time course of myosin heavy chain (MHC) isoform transitions in single fibers of the rodent plantaris muscle. Hypothyroidism was used in conjunction with single-fiber analyses to better describe a possible linkage between the neonatal and fast type IIB MHC isoforms during development. In contrast to the general concept that developmental MHC isoform transitions give rise to muscle fibers that express only a single MHC isoform, the single-fiber analyses revealed a very high degree of MHC polymorphism throughout postnatal development. In the adult state, MHC polymorphism was so pervasive that the rodent plantaris muscles contained approximately 12-15 different pools of fibers (i.e., fiber types). The degree of polymorphism observed at the single-fiber level made it difficult to determine specific developmental schemes analogous to those observed previously for the rodent soleus muscle. However, hypothyroidism was useful in that it confirmed a possible link between the developmental regulation of the neonatal and fast type IIB MHC isoforms.

NASA Program Biomedical Research and Countermeasur↗

The effects of space flight on the contractile apparatus of antigravity muscles: implications for aging and deconditioning

Previous studies have shown that the unloading of skeletal muscle, as occurring during exposure to space flight, exerts a profound effect on both the mass (cross sectional area) of skeletal muscle fibers and the relative expression of protein isoforms comprising the contractile system. Available information suggests that slow (type I) fibers, comprising chiefly the antigravity muscles of experimental animals, in addition to atrophying, undergo alterations in the type of myosin heavy chain (MHC) expressed such that faster isoforms become concomitantly expressed in a sub-population of slow fibers when insufficient force-bearing activity is maintained on the muscle. Consequently, these transformations in both mass and myosin heavy chain phenotype could exert a significant impact on the functional properties of skeletal muscle as manifest in the strength, contractile speed, and endurance scope of the muscle. To further explore these issues, a study was performed in which young adult male rats were exposed to zero gravity for six days, following which, the antigravity soleus muscle was examined for a) contractile properties, determined in situ and b) isomyosin expression, as studied using biochemical, molecular biology, and histochemical/immunohistochemical techniques.

Flight Experiment↗

A new animal model for modulating myosin isoform expression by altered mechanical activity

The purpose of this study was to develop a new rodent model that is capable of delineating the importance of mechanical loading on myosin heavy chain (MHC) isoform expression of the plantar and dorsi flexor muscles of the ankle. The essential components of this system include 1) stimulating electrodes that are chronically implanted into a muscle, allowing for the control of the activation pattern of the target muscle(s); 2) a training apparatus that translates the moment of the ankle into a linear force; and 3) a computer-controlled Cambridge 310 ergometer. The isovelocity profile of the ergometer ensured that the medial gastrocnemius (MG) produced forces that were > 90% of maximal isometric force (Po), and the eccentric contractions of the tibialis anterior (TA) were typically 120% of Po. Both the concentric and eccentric training programs produced statistically significant increases in the muscle mass of the MG (approximately 15%) and TA (approximately 7%) as well as a decrease in myofibrillar adenosinetriphosphatase activity. Both the white and red regions of the MG and TA exhibited significant increases in the relative content of the type IIa MHC and concomitant decreases in type IIb MHC expression. Although the red regions of the MG and red TA contained approximately 10% type I MHC, the training programs did not affect this isoform. It appears that when a fast-twitch muscle is stimulated at a high frequency (100 Hz) and required to contract either concentrically or eccentrically under high loading conditions, the expression of the type IIa MHC isoform will be upregulated, whereas that of the type IIb MHC will be concomitantly downregulated.

NASA Discipline Musculoskeletal↗

Response of slow and fast muscle to hypothyroidism: maximal shortening velocity and myosin isoforms

This study examined both the shortening velocity and myosin isoform distribution of slow- (soleus) and fast-twitch (plantaris) skeletal muscles under hypothyroid conditions. Adult female Sprague-Dawley rats were randomly assigned to one of two groups: control (n = 7) or hypothyroid (n = 7). In both muscles, the relative contents of native slow myosin (SM) and type I myosin heavy chain (MHC) increased in response to the hypothyroid treatment. The effects were such that the hypothyroid soleus muscle expressed only the native SM and type I MHC isoforms while repressing native intermediate myosin and type IIA MHC. In the plantaris, the relative content of native SM and type I MHC isoforms increased from 5 to 13% and from 4 to 10% of the total myosin pool, respectively. Maximal shortening velocity of the soleus and plantaris as measured by the slack test decreased by 32 and 19%, respectively, in response to hypothyroidism. In contrast, maximal shortening velocity as estimated by force-velocity data decreased only in the soleus (-19%). No significant change was observed for the plantaris.

Non-NASA Center↗