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Biomedical subjects

N Hamilton

Publications and source records attributed to N Hamilton.

At least 37 records · Page 2Linked to original sources
PubMed1992

Energy status of the rapidly paced canine myocardium in congestive heart failure.

Rapid ventricular pacing (RVP) is used as an experimental model of congestive heart failure (CHF). The purpose of this study was to determine the energy status of the dog myocardium after the development of CHF via chronic RVP. The myocardium had a significantly lower (P < 0.05) energy charge (EC) during CHF (0.63 +/- 0.01) than in sham-operated controls (0.82 +/- 0.02). This was due to significant differences in concentrations in ATP (-48%), ADP (29%), and AMP (275%) in the RVP group. However, the total adenine nucleotide pool was not different between groups. Myocardial lactate concentration was also similar. Glycogen was significantly lower (P < 0.05) by 20% at peak CHF. The adenine nucleotides were similar among the different myocardial layers (endo-, mid-, and epicardium). The administration of enalapril (an inhibitor of angiotension-converting enzyme) to decrease vascular resistance had no effect on the myocardial energy status of CHF dogs. These findings suggest that the lower EC in CHF animals is not the result of subendocardial ischemia. Also, lower EC is not associated with endogenous glycogen depletion or increased lactate concentration. The energy status of the myocardium in RVP-induced CHF is unlike that seen in ischemia-induced heart failure. This suggests that CHF in RVP is not vascular in origin.

Adenine Nucleotides↗
PubMed1991

Cell size of mammalian myocardia is not related to physiological demand.

Morphological characteristics of myocardial ventricular myocytes have been evaluated from 5 mammalian orders with resting heart rates ranging from 51 to 475 bpm. The purpose was to determine if morphological characteristics of the myocardia are related to the functional demand imposed on the cell as represented by the resting heart rate. Cell size is a constant among mammals of different sizes which have different physiological demands. In contrast, there is more mitochondrial area and less myofibrillar area per cell in animals with rapidly beating hearts than in animals with slower heart rates. Additionally, the mean cross sectional area of individual myofibrils is 30% larger in the cow as compared to the mouse. These findings combined with our previous studies indicate that the different functional requirements of myocardia from different mammalian orders are satisfied by intracellular adaptations of both a structural and biochemical nature.

Animals↗
PubMed1991

Contractile and calcium regulating capacities of myocardia of different sized mammals scale with resting heart rate.

The purpose of this study was to determine if selected biochemical parameters representing the contractile and calcium regulating systems of cardiac muscle scaled among mammals having inherently different resting heart rates (RHR). Eight mammalian species with RHR ranging from 51 to 475 beats per minute (bpm) were studied. The oxidative capacity of the myocardium is highly correlated with the RHR. The hypothesis of the present study was that the capacities of the energy utilizing processes of contraction and calcium regulation would also be correlated to the functional demand imposed on the muscle as represented by the RHR. Myosin (M) and myofibrillar (MF) ATPase activities, myosin isoenzyme distribution and sarcoplasmic reticulum (SR) ATPase activity were determined. Animals with RHR above 300 bpm express V1 myosin while animals with lower RHR express primarily V3. M and MF ATPase activities correlated with RHR, but the major difference in activities occurred at the 'threshold' RHR of about 300 bpm at which the switch from V3 to V1 appears to occur. SR ATPase activity per mg of microsomal protein was for the most part constant among different mammals, but the SR ATPase activity per g of heart tissue was significantly correlated with RHR as slower beating hearts tended to yield less SR protein per unit mass. We conclude that both the contractile and calcium regulating systems are scaled to the functional parameter of RHR among different mammals. The contractile system uses a slow myosin ATPase isoform at low resting heart rates whereas above the postulated threshold RHR of about 300 bpm a switch in gene expression to a fast myosin ATPase isoform occurs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1991

Effects of different rates of cardiac pacing on rat myocardial energy status.

The energy status of mammalian cells is a finely regulated phenomenon. This is especially true in cardiac muscle cells in which energy requirements are high and the system must provide rapid turnover of the adenine nucleotides and instant response to changes in energetic demands. We have examined the acute response of the rat myocardium to ventricular pacing up to 2.5 times the resting heart rate. The purpose of this study was to determine at what level of pacing the normal energy status could be maintained and at what point it was compromised. Myocardial energy charge (EC = (ATP + 0.5 ADP)/(ATP + ADP + AMP] was maintained at 1, 1.5 and 2 times the resting heart rate but declined significantly at 2.5 times. In contrast, phosphorylation potential (PP = ATP/ADPf x Pi) was drastically altered in hearts paced at 1.5, 2 and 2.5 times the resting rate. Tissue lactate increased and glycogen decreased in a linear fashion as pacing rate increased, indicating that the metabolic challenge was proportional to the pacing rate. EC seems to reflect the overall status of the cell and its ability to maintain a dynamic equilibrium. PP may reflect the immediate and necessary driving force for mitochondrial respiration in times of increased demand. These data suggest that the myocardium may meet the increased energy demands of acute ventricular pacing by shifting the molar ratio of ATP to ADP times Pi in favour of driving phosphorylation.

Adenosine Triphosphate↗
PubMed1991

The remodelling of skeletal muscle for indefatigable hemodynamic work.

Skeletal muscle possesses inherent plasticity of gene expression. Low frequency pulse-train stimulation can remodel the biochemical machinery that confers physiological expression and fatigue resistance approaching that of the myocardium. This fatigue-resistant muscle can generate sufficient force to meet the power requirements for useful cardiac work. This ultimate goal is currently being pursued in models of cardiomyoplasty and muscle-powered cardiac assist devices. In this article, we review the three major subcellular systems subserving canine skeletal muscle transformation and compare them to those of cardiac muscle. The magnitude of the problem of clinical heart failure and the feasibility of fatigue-resistant skeletal muscle joining the therapeutic armamentarium are addressed. The adaptation and transformation of fast-twitch skeletal muscle in response to chronic electrical stimulation augers therapeutic potential as an endogenous, readily available power source for myocardial assistance. The basis mechanisms of skeletal muscle fatigue require elucidation to gain a complete and thorough understanding of how to manipulate this property to provide continuous hemodynamic work.

Animals↗
PubMed1991

Competitive control of myosin expression: hypertrophy vs. hyperthyroidism.

The competition between two opposing influences on the phenotypic expression of skeletal muscle myosin were studied to determine which was the dominant regulator. Experimental hyperthyroidism, which induces fast myosin expression, was produced by subcutaneous implantation of a 40-day constant-time-release triiodothyronine pellet. Compensatory hypertrophy, which induces slow myosin expression, was produced by surgical removal of a synergistic hindlimb muscle. Hyperthyroidism increased the percentage of type II fibers and the fast myosin isoforms in both the plantaris and soleus muscles. Hypertrophy significantly increased the percentage of type I fibers and the slow myosin type in the plantaris and soleus muscles. However, with the simultaneous introduction of hyperthyroidism and hypertrophy, only the hyperthyroid effects were observed. Hyperthyroidism and not physiological demand was found to be the dominant regulator of skeletal muscle myosin expression.

Adaptation, Physiological↗
PubMed1991

Biochemical characterization of exercise-trained porcine myocardium.

The purpose of this study was to determine whether cardiac biochemical adaptations are induced by chronic exercise training (ET) of miniature swine. Female Yucatan miniature swine were trained on a treadmill or were cage confined (C) for 16-22 wk. After training, the ET pigs had increased exercise tolerance, lower heart rates during exercise at submaximal intensities, moderate cardiac hypertrophy, increased coronary blood flow capacity, and increased oxidative capacity of skeletal muscle. Myosin from both the C and ET hearts was 100% of the V3 isozyme, and there were no differences between the myosin adenosine triphosphatase (ATPase) or myofibrillar ATPase activities of C and ET hearts. Also, the sarcoplasmic reticulum Ca(2+)-ATPase activity and Na(+)-Ca2+ exchange activity of sarcolemmal vesicles were the same in cardiac muscle of C and ET hearts. Finally, the glycolytic and oxidative capacity of ET cardiac muscle was not different from control, since phosphofructokinase, citrate synthase, and 3-hydroxyacyl-CoA dehydrogenase activities were the same in cardiac tissue from ET and C pigs. We conclude that endurance exercise training does not provide sufficient stress on the heart of a large mammal to induce changes in any of the three major cardiac biochemical systems of the porcine myocardium: the contractile system, the Ca2+ regulatory systems, or the metabolic system.

Aging↗
PubMed1990

Histochemical and biochemical plasticity of muscle fibers in the little brown bat (Myotis lucifugus).

Fiber composition, and glycolytic and oxidative capacities of the pectoralis, gastrocnemius, and cardiac muscles from active and hibernating little brown bats (Myotis lucifugus) was studied. The data were used to test two hypotheses: First, since hibernating bats maintain the capability of flight and make use of leg muscles to maintain a roosting position all winter, the fiber composition of the pectoralis and gastrocnemius muscles should not change with season. Second, we tested the hypothesis of Ianuzzo et al. (in press), who propose that the oxidative potential of mammalian cardiac muscle should increase with increasing heart rate while glycolytic potential should not. Our results indicate that the fiber composition of the pectoralis muscle was uniformly fast-twitch oxidative (FO) regardless of the time of year, as predicted. However, the gastrocnemius muscle exhibited a change in FO composition from 83% in active to 61% in hibernating animals. Contrary to the variable change in histochemical properties with metabolic state, a trend of reduced maximal oxidative (CS) and glycolytic (PFK) potential during hibernation in both flight and leg muscles was apparent. The oxidative potential of flight and leg muscles decreased by 15.2% and 56.5%, respectively, while the glycolytic potential of the same muscles decreased by 23.5% and 60.5%, respectively. As predicted, the glycolytic potential of cardiac muscle remained constant between active and hibernating bats, although there was a significant decrease (22.0%) in oxidative potential during hibernation.

Animals↗
PubMed1990

Role of cardiac work in regulating myocardial biochemical characteristics.

The purpose of this study was to determine the extent to which functional demand regulates the biochemical character and enzyme capacities of the rat myocardium. Hearts from donor rats were heterotopically transplanted onto the abdominal aorta and inferior vena cava of isogenic recipients. The procedure results in a perfused but nonpumping heart that has a reduced heart rate (HR) and performs essentially no stroke work (SW). After 30 days, metabolic enzyme activities (phosphorylase, 6-phosphofructokinase, citrate synthase, and 3-hydroxyacyl-CoA dehydrogenase) were significantly lower (40-60%) in the nonworking heart. Specific sarcoplasmic reticulum Ca2(+)-adenosinetriphosphatase (ATPase) activity was unchanged, but activity per gram of heart was 41% lower. Myosin isozymes were 58% V1, 21% V2, and 21% V3 in the nonworking heart compared with 100% V1 in the working heart. Myosin and myofibrillar ATPase activities each decreased by 28%. These findings suggest that both HR and SW play major and specific roles in regulating myocardial biochemical capacities and determining the myosin phenotype.

Animals↗
PubMed1990

Biochemical transformation of canine skeletal muscle for use in cardiac-assist devices.

Skeletal muscle has an inherent biochemical phenotypic plasticity that provides the possibility for it to be remodeled into a "heart-like" muscle for use in cardiac-assist devices. The purpose of this study was to chronically stimulate skeletal muscle electrically to transform the biochemical capacities of the three major subcellular systems (i.e., metabolic, calcium regulating, and contractile) to resemble those of heart muscle. The latissimus dorsi muscle (LDM) of mongrel dogs weighing 22-27 kg was stimulated via the thoracodorsal nerve at 2 Hz for 6-8 wk. This stimulation protocol reduced the phosphorylase (glycogenolytic) and phosphofructokinase (glycolytic) activities by 70%. The aerobic (citrate synthase activity) and fatty acid oxidative (3-hydroxyacyl-CoA dehydrogenase activity) capacities were not significantly increased by chronic stimulation and remained at about one-fourth those in the canine heart. The calcium-dependent sarcoplasmic reticulum adenosinetriphosphatase (ATPase) activity in the microsomal fraction, which was sixfold greater in the nonstimulated LDM than in the heart, was reduced by electrical stimulation to a level similar to that of the dog heart. The contractile capacity was evaluated by determining the percentage of types I and II fibers, the myofibrillar ATPase activity, and the proportion of myosin isoforms. The transformed muscle was comprised of 93 +/- 2% type I fibers, a myofibrillar ATPase activity similar to that in heart with primarily a slow-twitch muscle myosin isoform. In conclusion, electrical stimulation of canine LDM at 2 Hz for 6-8 wk resulted in two of the three biochemical systems, which confer physiological expression and fatigue resistance to muscle being transformed to resemble those of the myocardium.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1989

Effect of hindlimb immobilization and recovery on compensatory hypertrophied rat plantaris muscle.

Compensatory hypertrophy of the rat plantaris muscle (PLT) was induced by ipsilateral gastrocnemius muscle ablation. Following 8 weeks (wks) of hypertrophy, hindlimbs were cast immobilized (HI) for 4 weeks after which weight bearing was unrestricted for 8 wks (recovery). Compensatory hypertrophy increased PLT wet weight/body weight ratio (83%), muscle fiber cross-sectional areas (1.5 to 2 fold), and the percent of slow oxidative (%SO) fibers (2 fold) in the experimental compared to the contralateral sham control muscle. PLT protein content and maximal activities of phosphofructokinase (PFK), mitochondrial glycerol phosphate dehydrogenase, and succinate dehydrogenase were unaltered with muscle hypertrophy. HI produced significant decreases in PFK activity (50%) and muscle fiber cross-sectional areas (50%) but did not significantly change the histochemical myofibrillar ATPase profile. Following remobilization, muscle weight/body weight ratio and maximal enzyme activities recovered to that of aged matched controls. Muscle fiber areas returned to pre-immobilization sizes but were approximately 25% smaller than aged matched control hypertrophy muscles. The %SO fibers in the hypertrophied muscle remained higher than controls but did not return to pre-immobilization values. These results indicate that biochemical and histochemical characteristics of hypertrophied rat PLT recover from HI during 8 wks of normal weight bearing similar to that of normal control muscle. However, the recovery time period was insufficient to allow complete compensation of fiber size to that of the age-matched control animals.

Animals↗
PubMed1989

Biochemical characteristics of mammalian myocardia.

Selected biochemical parameters of the ventricular myocardium were compared among several orders of adult mammals with established differences in resting heart rate (cattle, 51 beats/min; swine, 68; canine, 107; rabbit, 256; guinea-pig, 273; rat, 355; mouse, 475). It was hypothesized that the biochemical character of mammalian myocardia is associated with the chronic functional demand on the muscle. Therefore, differences observed in the myocardial biochemical potential among the species could reflect differences in resting heart rate. Myocardia from smaller mammals with higher resting heart rate had significantly (P less than 0.05) higher maximal activities of citrate synthase, 3-hydroxyacyl-CoA dehydrogenase, lactate dehydrogenase (muscle/total), hexokinase and oxidation rates of glucose and palmitate than did larger mammals with lower resting heart rate. Maximal activities of phosphorylase and phosphofructokinase were more uniform across the animals. Correlation coefficients determined among average values of measured biochemical parameters and resting heart rate indicated that resting heart rate was closely associated with: citrate synthase (r = 0.86), 3-hydroxyacyl-CoA dehydrogenase (r = 0.93), ratio muscle/total lactate dehydrogenase (r = 0.89), hexokinase (r = 0.89), glucose oxidation (r = 0.88), and palmitate oxidation (r = 0.93). Significant correlations were observed among all of these parameters with the exception of citrate synthase vs. 3-hydroxyacyl-CoA dehydrogenase, and glucose oxidation vs. muscle/total lactate dehydrogenase. It was concluded that the oxidative capacity of mammalian myocardia was closely associated with resting heart rate, whereas the glycolytic potential of the myocardia was more uniform among the species.

Animals↗
PubMed1988

Postmortem biochemical indices of antemortem hemorrhagic shock.

The purpose of this study was to determine if the perturbations in two glycolytic metabolites that occur during hemorrhagic shock can be used as discriminatory postmortem indicators of death resulting from severe hemorrhagic shock. Two groups of male albino Sprague-Dawley rats were hemorrhaged by withdrawing either 40% (Group I) or 45% (Group II) of the total blood volume. Glycogen and lactate concentrations were determined at 0 and 48 hr postmortem in the following tissues and organs: diaphragm, heart, liver, kidney cortex, and kidney medulla. The differences in lactate and glycogen in Group I at 0 hr were not significantly different from the nonhemorrhaged controls, with the exception of the lower liver glycogen concentration (58% of control). In Group II glycogen concentration was significantly reduced at 0 hr in the diaphragm (70% of control), liver (37%), and kidney medulla (55%). Lactate concentration was higher in all tissues examined by 270-640%; within 48 hr all tissues for both control and hemorrhaged animals had declined to baseline levels of glycogen concentration, whereas lactate levels had increased as much as 34-fold. There were no highly significant differences in glycogen at 48 hr between the control and hemorrhaged groups. In Group II the lactates were similar for both the control and hemorrhaged animals with the exception of the higher concentrations in the kidney cortex (54%) and medulla (41%). It was concluded from these findings that although significant metabolic perturbations are present at the time of death due to hemorrhage these differences do not persist up to 48 hr postmortem, with the possible exception of the kidney lactate concentrations.

Animals↗
PubMed1987

Effect of head-neck position on elbow flexor muscle torque production.

The purpose of this study was to investigate whether the tonic neck reflex affects elbow flexor muscle torque production in healthy, young adults and which head-neck (H-N) positions have the greatest influence. Forty-eight male and female students between the ages of 18 and 35 years volunteered as subjects. Head-neck positions involving the sagittal and horizontal planes and combinations of these were tested. The nondominant hand was used to apply tension to the lever of an isokinetic analyzer under both isometric (static) and isotonic (dynamic) conditions. Peak torque was determined for each H-N position under each condition. Differences in peak torque were elicited more easily from the female subjects than from the male subjects. Head-neck rotation (horizontal plane) appeared to have a greater influence on elbow flexor muscle torque production than movements in the sagittal plane, particularly when movements in the two planes were combined. We concluded, therefore, that H-N position must be considered during rehabilitation of the upper extremity.

Adolescent↗
PubMed1984

Glycogen repletion in different skeletal muscles from diabetic rats.

It was hypothesized that chronically untreated streptozotocin-diabetic rats may compensate for the detrimental effect of insulin deficiency on glycogen restoration following muscular work. Glycogen concentration ([GLY]) was reduced by in situ stimulation of the sciatic nerve of anesthetized normal (N) and diabetic (D) Sprague-Dawley albino rats. Glycogen repletion occurred most rapidly within 30 min after stimulation. By 2 h all N muscles returned to basal [GLY]. D muscles repleted glycogen at a rate 45-75% of normal and not all of the D muscle returned to basal [GLY] by 8 h poststimulation. Neither the partial reduction in diabetic hyperglycemia by using phlorizin nor the acute further lowering of diabetic hypoinsulinemia by using insulin antibody affected glycogen restoration in D muscles. Acute insulin replenishment resulted in restoration of normal [GLY] in D muscles within 2 h poststimulation. These findings are not consistent with the proposed hypothesis and indicate insulin is necessary to have normal rates of glycogen restoration following muscular activity.

Animals↗
PubMed1982

Effects of streptozotocin diabetes, insulin treatment, and training on the diaphragm.

The adaptive capability of the diaphragm, the only skeletal muscle considered a vital organ, has received little investigative attention compared with the limb muscles. Since it is chronically active, we asked whether it will adapt to exercise training and if so to what extent. Metabolic adaptations of the diaphragm to exercise training were studied under three conditions: normal, streptozotocin-diabetic, and diabetic receiving insulin treatment. The activities of hexokinase (HK), phosphorylase, and phosphofructokinase (PFK) in the diaphragm of sedentary diabetic Sprague-Dawley albino rats were 22-36% lower than in normal animals. Insulin treatment returned PFK and HK to normal and above normal, respectively. Tricarboxylic acid cycle marker enzymes were not affected by the diabetic condition or insulin treatment. beta-Oxidation enzyme 3-hydroxyacyl-CoA dehydrogenase (HADH) was 60% higher than normal in the diabetic diaphragm and returned to normal with insulin treatment. Training resulted in increases in the glycolytic and aerobic capacities of all groups. The aerobic changes were similar to those of limb muscles. HADH activity was increased in the normal and diabetic insulin-treated trained groups, but because of its already high activity in the diabetic diaphragm, it did not require an adaptation.

Animals↗