Conditioning of skeletal muscles in adult and old mice for protection from contraction-induced injury.

The purpose of this study was to design a conditioning program that protected muscles in both adult and old mice from a protocol of contractions that previously caused a significant number of damaged fibers and a deficit in force. Hind-limb dorsiflexor muscles of adult (7 months) and old (22 months) female B6D2F1 mice were exposed once a week to a protocol of repeated forced stretches while maximally activated in vivo. By week 4, muscles of adult, but not old, mice showed no force deficit. Conditioning was continued for 6 weeks, when both age groups showed no force deficit for two consecutive weeks. Three days after the sixth contraction protocol, when morphological damage and force deficits are most severe, the numbers of damaged fibers in muscles of adult and old mice were not different from those in uninjured control muscles and the force deficits were reduced dramatically compared with unconditioned muscles. We conclude that muscles of both adult and old mice conditioned successfully, but muscles of old mice conditioned more slowly than those of adult mice.

Age effects on the adaptive response of the female rat heart following aortic constriction.

Aging is associated with adaptations in the hearts of mammals that diminish the reserve capacity to meet hemodynamic loading challenges. To evaluate potential mechanisms of this phenomenon, the following hypotheses were tested: compared with hearts of adult rats, hearts of aged rats undergoing aortic constriction will exhibit (a) a lower concentration of myofibrillar proteins, (b) a reduced sensitivity to extracellular calcium, and (c) a reduced coronary perfusion. Female Fischer 344 rats aged 9 months (adult) and 27 months (aged) were assigned to control (C) or aortic-constriction (AC) groups and studied at 7 and 28 days post-AC, yielding six groups of rats. Analysis of variance was used to examine the effects of age and AC. The left ventricular (LV) mass/body mass ratio expressed a percentage of age-matched control value averaged AC-7adult, 111%; AC-28adult, 120%; AC-7aged, 106%; AC-28aged, 123% (AC, p < .01). As a percentage of adult rats values, the pressure-generating capacity of the LV averaged Caged, 99%; AC-7aged, 92%; AC-28aged, 92% (age, p < .05). There were no differences attributable to age or AC in either myofibrillar protein concentration or calcium sensitivity. There was, however, a significantly lower concentration of nonmyofibrillar protein (approximately 10%) in the hearts of all three groups of aged rats compared with the adult rats that was unaltered by AC. The percentages of LV myosin heavy chain in the alpha-isoform were Cadult, 77%; AC-7adult, 66%; AC-28adult, 66%; Caged, 45%; AC-7aged, 41%; AC-28aged, 32% (age, p < .01; AC,p < .01). Coronary flow per gram of tissue averaged 9% lower in all three of the aged groups compared with the adult rats and was not significantly affected by AC (age, p < .05). The data suggest that a reduction in nonmyofibrillar protein and a reduced coronary flow, rather than changes in calcium sensitivity or myofibrillar protein, are associated with an impairment in the adaptive response of the aged heart.

Regional variation in cardiac myosin isoforms of female F344 rats during aging.

Myosin heavy chain (MHC) is a major contractile protein of heart muscle consisting of two isoforms in the rat, alpha-MHC that predominates in the hearts of young rats, and beta-MHC that progressively replaces it as the rats age. It was hypothesized that the magnitude of the age-associated decrease in the proportion of cardiac alpha-MHC would be similar in regions of the heart that differed in their initial MHC isoform pattern. MHCs from hearts of female Fischer 344 rats 3, 9, 15, 18, 24, and 27 months of age were separated by gradient gel electrophoresis. Hypertrophy was assessed by indexing regional heart mass to tibial length From 9 through 27 months of age, hypertrophy was 19% and 77% in the left ventricle and left atrial appendage, respectively. There was no significant hypertrophy in either the right ventricular free wall or the right atrial appendage. The proportion of alpha-myosin heavy chain ranged from 86 +/- 1.3% (mean +/- SE) in the right ventricular free wall to 62 +/- 5.8% in left ventricular papillary muscle of 9-month-old rats. In 27-month-old rats, it ranged from 59 +/- 2.7% in the right ventricular free wall to 20 +/- 3.1% in the left ventricular papillary muscle. There was a marked age-associated decrease in the proportion of alpha-myosin heavy chain overall (p <.001) that did not differ significantly among the regions studied (p = .109). These results suggest that the effects of advancing age on the cardiac MHC pattern are independent of age-associated hypertrophy.

Functional evaluation at the medial gastrocnemius donor site in rats.

The transfer of a skeletal muscle from a donor to a recipient site creates an initial deficit in the structure and function of the muscle group from which it originates. Removal of the donor muscle induces hypertrophy of the remaining synergistic muscles, which compensate for part of the deficit at the donor site. The medial gastrocnemius (MGN) muscle is a frequently utilized donor muscle. Compared with the mass and force production of the control four-muscle plantar flexor group in rats, removal of the MGN muscle creates an initial deficit of approximately 36 percent. At 60, 90, and 120 days after removal of the MGN muscle, the degree of compensation of the remaining three-muscle plantar flexor group (lateral gastrocnemius, soleus, and plantaris muscles) was evaluated. The mass of the three-muscle group increased 13 percent over the time course studied, but was still 28 percent less than the mass of the control four-muscle group. Similarly, the maximum force of the three-muscle group increased 27 percent, but was 21 percent lower than the control four-muscle group. The authors propose a model that illustrates the function restored at a donor site in terms of the percentage of the total muscle group comprised by the donor muscle and the ability of the remaining muscle group to compensate for its removal.

Injury to skeletal muscle fibers during contractions: conditions of occurrence and prevention.

Contraction-induced injury results in the degeneration and regeneration of muscle fibers. Of the three types of contractions--shortening (concentric), isometric, and lengthening (eccentric)--injury is most likely to occur and the severity of the injury is greatest during lengthening contractions. The magnitude of the injury to muscle fibers may be assessed by direct measures of cellular and ultrastructural damage; by indirect measures of changes in enzyme efflux, calcium influx, ratio of oxidized to reduced glutathione, and force development; and, in human beings, by reports of muscle soreness. The sequence of events includes an initial injury that is primarily mechanical and a secondary metabolic, or biochemical, injury that peaks 1 to 3 days after the injurious contractions. The recovery from contraction-induced injury is usually complete within 30 days. Repeated exposures to protocols of lengthening contractions result in "trained" muscles that are not injured by the protocol that previously caused injury.

Injury to skeletal muscle during altitude training: induction and prevention.

A contracting skeletal muscle will shorten, remain isometric, or lengthen depending on the interaction between external load and the force developed by the muscle. Most physical activities involve shortening, isometric and lengthening contractions. The fluctuations in terrain encountered at altitude, increase both the likelihood that lengthening contractions will occur and the severity of the stretches. When performing a given amount of work, muscles lengthened during contractions expend less energy and fatigue less rapidly than muscles that shorten. Conversely, with equal activation, displacement, and velocity, the work done on a muscle during lengthening contractions is greater than the work performed by a muscle during shortening contractions, but force decreases more rapidly during lengthening. Furthermore, muscles are more likely to be injured during lengthening contractions than during shortening or isometric contractions. The occurrence of contraction-induced injury can be eliminated, or minimized, by prior training specific for the performance of lengthening contractions.

Cardiac adaptations to aortic constriction in adult and aged rats.

Myocardial function in vitro and myosin heavy chains (MHCs) were studied in control and hypertrophied hearts of adult (9-10 mo) and aged (25-28 mo) female Fischer 344 rats 7 days after aortic constriction. Aortic constriction increased left ventricular mass to 110 and 112% of the control values of 484 +/- 12 and 617 +/- 18 (SE) mg in adult and aged rats, respectively. After aortic constriction, there was a significant age-related difference in the adaptation of peak pressure development in vitro, as peak left ventricular systolic pressure increased and decreased in hearts of adult and aged rats. The maximum rate of pressure development in control hearts of aged rats was 79% of the adult value of 11,264 +/- 1,527 mmHg/s; hypertrophy did not alter values of either age group. alpha-MHC accounted for 82 +/- 1 and 48 +/- 3% of the total left ventricular MHC for the adult and aged control groups, respectively, and values were not altered by aortic constriction. With hypertrophy 7 days after aortic constriction, there is an impairment in the adaptation of left ventricular function in hearts of aged compared with adult rats. This impairment is not explained by alterations in MHC isoform.