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Biomedical subjects

C L Gibbs

Publications and source records attributed to C L Gibbs.

At least 19 recordsLinked to original sources
PubMed2001

Effects of ageing on the activation metabolism of rat papillary muscles.

1. A myothermic technique has been used to investigate the mechanics and energetics of left ventricular papillary muscles from 6-, 15-, 22- and 27-32-month-old Sprague-Dawley rats. 2. There was a significant increase in the left ventricular mass to body mass (LVM:BM) ratio in the senescent. 27-32-month-old group of animals compared with the younger animals (P<0.05). 3. The maximum stress developed in the senescent groups was reduced by almost 40% in comparison with the stress developed by the 6-, 15- and 22-month-old groups (P<0.001). The mean rise time, half relaxation time and half width were increased significantly (P<0.05) in the 22-month-old group but, unexpectedly, this effect was not seen in the senescent group. 4. Heat production per beat versus total stress relationships were obtained in two different ways to determine the magnitude of the activation heat and the isometric economy (given by the slope of the relationship). The activation heat was not significantly different between groups with either method, but there was a significant increase (P<0.001) in the economy with which stress was developed in the senescent group in comparison with the 6- and 15-month-old groups. 5. A combination of forskolin (2.5-6.5 micromol/L) and high Ca2+ (7.5 mmol/L) was used to increase the energy usage per beat. In the 6- and 15-month-old groups, these agents caused a four-fold increase in the activation heat magnitude compared with a less than two-fold increase in the 22-month-old and senescent groups (P<0.001). There was no effect of forskolin/high calcium on the slope of the heat:total stress relationship. 6. The data suggest that, under conditions known to increase cardiac contractility, there is a reduced ability to cycle calcium in the 22-month-old and senescent groups relative to the young adult 6-month-old and adult 15-month-old groups.

Aging↗
PubMed2001

Increased dietary salt accelerates chronic allograft nephropathy in rats.

BACKGROUND: Chronic allograft nephropathy (CAN), a major problem in renal transplantation, is related to both alloantigen-dependent and -independent processes. Because dietary salt intake modulated glomerular production of transforming growth factor-beta, which has been shown to play an important role in CAN, we hypothesized that dietary salt would directly enhance renal injury in a rodent model of CAN. METHODS: Dietary NaCl was increased from 1.0% (normal) to 8.0% in a group of Fisher/Lewis rats 25 days following orthotopic renal transplantation and was continued until 16 weeks after transplantation. RESULTS: Blood pressure, which was recorded using radiotelemetry in the first eight-weeks post-transplantation, did not differ between the groups, but allograft recipients on the 8.0% NaCl diet rapidly demonstrated increased urinary albumin excretion. Renal function determined by dynamic functional imaging was worse in allograft recipients on the 8.0% NaCl diet by six weeks following transplantation. Histologic examination at 16 weeks confirmed a significant increase in allograft damage in the 8.0% NaCl group compared with allografts from rats on 1.0% NaCl diet. These findings included glomerulosclerosis and tubulointerstitial injury that consisted of fibrosis, tubular atrophy and dilation, intratubular casts, and tubular epithelial cell damage. Small arteries and arterioles did not show evidence of damage from hypertension or other abnormality. CONCLUSIONS: In this model of CAN, renal allograft dysfunction preceded hypertension and was accelerated significantly by an increase in dietary salt.

Albuminuria↗
PubMed2001

Comparison of the efficiency of rat papillary muscles during afterloaded isotonic contractions and contractions with sinusoidal length changes.

The results of previous studies suggest that the maximum mechanical efficiency of rat papillary muscles is lower during a contraction protocol involving sinusoidal length changes than during one involving afterloaded isotonic contractions. The aim of this study was to compare directly the efficiency of isolated rat papillary muscle preparations in isotonic and sinusoidal contraction protocols. Experiments were performed in vitro (27 degrees C) using left ventricular papillary muscles from adult rats. Each preparation performed three contraction protocols: (i) low-frequency afterloaded isotonic contractions (10 twitches at 0.2 Hz), (ii) sinusoidal length change contractions with phasic stimulation (40 twitches at 2 Hz) and (iii) high-frequency afterloaded isotonic contractions (40 twitches at 2 Hz). The first two protocols resembled those used in previous studies and the third combined the characteristics of the first two. The parameters for each protocol were adjusted to those that gave maximum efficiency. For the afterloaded isotonic protocols, the afterload was set to 0.3 of the maximum developed force. The sinusoidal length change protocol incorporated a cycle amplitude of +/-5% resting length and a stimulus phase of -10 degrees. Measurements of force output, muscle length change and muscle temperature change were used to calculate the work and heat produced during and after each protocol. Net mechanical efficiency was defined as the proportion of the energy (enthalpy) liberated by the muscle that appeared as work. The efficiency in the low-frequency, isotonic contraction protocol was 21.1+/-1.4% (mean +/- s.e.m., N=6) and that in the sinusoidal protocol was 13.2+/-0.7%, consistent with previous results. This difference was not due to the higher frequency or greater number of twitches because efficiency in the high-frequency, isotonic protocol was 21.5+/-1.0%. Although these results apparently confirm that efficiency is protocol-dependent, additional experiments designed to measure work output unambiguously indicated that the method used to calculate work output in isotonic contractions overestimated actual work output. When net work output, which excludes work done by parallel elastic elements, rather than total work output was used to determine efficiency in afterloaded isotonic contractions, efficiency was similar to that for sinusoidal contractions. The maximum net mechanical efficiency of rat papillary muscles performing afterloaded isotonic or sinusoidal length change contractions was between 10 and 15%.

Animals↗
PubMed2000

Effects of aging on the work output and efficiency of rat papillary muscle.

OBJECTIVES: This study aimed to investigate the effect of aging on the work output and efficiency of rat papillary muscle. METHODS: The mechanical and energetic properties of left ventricular papillary muscle preparations isolated from 6-, 15-, and 27- to 32-month-old Sprague-Dawley rats were measured in myothermic experiments at 27 degrees C at a stimulus frequency of 0.167 Hz. RESULTS: We found that the basal metabolism measured in quiescent papillary muscles was significantly reduced in the 27- to 32-month-old group (4.9 mWg(-1) compared to 7.7 and 7.0 mWg(-1) in the 6- and 15-month groups). In isotonic experiments, the work output (at a range of afterloads) was significantly depressed for the 27- to 32-month group being only 52% of the work output of the 6-month group. This outcome was due to a decrease in both the extent of muscle shortening only, 66% of 6- and 15-month data, and in the maximum force developed. The reduced work was accompanied by a parallel decrease in energy consumption (enthalpy) and hence, the net mechanical efficiency (work/active enthalpyx100%) was not altered. A force-length- area (FLA) analysis was applied to the isotonic data and an energy: FLA regression line was obtained for each preparation. We found that there were no significant differences in either the intercept or slope of the energy: FLA relation with age. Contractile efficiency (39+/-3%) in the 27- to 32-month group was not significantly different to that found in the 6-month (43+/-4%) or 15-month (40+/-3% group). CONCLUSION: There are no changes in the mechanical performance or efficiency of cardiac muscle from young (6-month-old) or adult (15-month-old) rats but in the aged and senescent rats (27-32-month-old) there is a pronounced decline in stress development and shortening ability leading to a fall in work output. Mechanical and contractile efficiency however remain unchanged in old age and the data resembles that obtained in pressure overload hypertrophy.

Aging↗
PubMed2000

Energetics of rat papillary muscle during contractions with sinusoidal length changes.

The mechanical efficiency of rat cardiac muscle was determined using a contraction protocol involving cyclical, sinusoidal length changes and phasic stimulation at physiological frequencies (1-4 Hz). Experiments were performed in vitro (27 degrees C) using rat left ventricular papillary muscles. Efficiency was determined from measurements of the net work performed and enthalpy produced by muscles during a series of 40 contractions. Net mechanical efficiency was defined as the percentage of the total, suprabasal enthalpy output that appeared as mechanical work. Maximum efficiency was approximately 15% at contraction frequencies between 2 and 2.5 Hz. At lower and higher frequencies, efficiency was approximately 10%. Enthalpy output per cycle was independent of cycle frequency at all but the highest frequency used. The basis of the high efficiency between 2 and 2.5 Hz was that work output was also greatest at these frequencies. At these frequencies, the duration of the applied length change was well matched to the kinetics of force generation, and active force generation occurred throughout the shortening period.

Animals↗
PubMed1998

Efficiency of skeletal and cardiac muscle.

In the human physiology literature values for skeletal and cardiac mechanical efficiency are being reported that seem to be much higher than are found in isolated tissue studies. We consider some of the different efficiency definitions and explore some possible reasons for low isolated tissue values, these include the experimental protocols used, the time at which measurements are made, afterloaded versus sinusoidal contractions, the effects of varying activation levels and recovery heat uncertainty. We examine some of the mechanical and energetic differences between cardiac and skeletal muscle--the absence of shortening heat, the linear relationship between energy per beat and pressure-volume area, constant contractile efficiency, and a larger crossbridge (CB) working stroke. Some observations are made on muscle energetics and loose and tight coupling CB models.

Biomechanical Phenomena↗
PubMed1997

Energetics of lengthening in mouse and toad skeletal muscles.

1. The energetics of lengthening were studied in amphibian and mammalian skeletal muscle. The aims were to determine whether energy absorption during stretch is a general property of skeletal muscle and to investigate the influence of lengthening velocity on energy absorption. 2. Experiments were performed in vitro (21 degrees C) using bundles of muscle fibres from fast-twitch extensor digitorum longus and slow-twitch soleus muscles of the mouse and tibialis anterior muscles of a toad, Bufo marinus. Initial heat production and mechanical work done on muscles were measured during isovelocity lengthening. Enthalpy output during lengthening was calculated as the difference between the amount of heat produced and the work done. 3. For all three muscle types, more energy was put into muscles as work than was produced as heat. Thus, part of the energy put into muscles to stretch them must have been absorbed. 4. For all three muscle types, the amount of energy absorbed was constant at velocities exceeding approximately 0.5 Vmax (Vmax is the maximum shortening velocity), but was significantly lower at slow velocities of lengthening. The same amount of energy was absorbed by all three muscles when lengthened at > or = 0.5 Vmax. 5. It was concluded that absorption of energy during lengthening occurs in mammalian as well as amphibian muscle and that lengthening velocity has only a small effect on the amount of energy absorbed.

Animals↗
PubMed1997

Age-related decline in murine macrophage production of nitric oxide.

Since certain functions mediated by nitric oxide (NO) decline with age, the age dependence of NO production by macrophages from BALB/c mice was investigated. Lipopolysaccharide-, peptidoglycan-polysaccharide-, or interferon-gamma-stimulated splenic and peritoneal macrophages from young (1 month old), middle-aged (4-5 months old), and old (6-20 months old) BALB/c mice showed a progressive and marked decline in NO production. This age-related decline in inducible NO extended to C57/BL6 and CB6F1 mice. mRNA for inducible NO synthase (iNOS), the enzyme responsible for inducible NO production by macrophages, also declined with age. Importantly, the reduced NO production by macrophages from old mice could be up-regulated by pretreating the mice with either cholera toxin or concanavalin A. These findings indicate that reduced production of NO by murine macrophages correlates directly with advancing age, likely due to deficient signals or signal transduction responsible for iNOS mRNA and protein generation.

Age Factors↗
PubMed1997

Skeletal muscle resting metabolism in cold-acclimated rats: effect of age, noradrenaline and hyperosmolarity.

1. A myothermic technique has been used to measure the resting metabolism of small bundles of a fast twitch muscle, extensor digitorum longus (EDL), and a slow twitch muscle, soleus (SOL), in 7-week-old rats. At 27 degrees C, mean (+/-SEM) resting heat rates were 2.33 +/- 0.41 and 2.09 +/- 0.37 mW/g in EDL and SOL, respectively (n = 16). 2. Seven-week-old rats were cold acclimatized at 4 degrees C for 1-4 weeks and the metabolic rates of the fast and slow twitch muscles were monitored and compared with 7- and 11-week-old controls. There was a 160% increase in metabolic rate from week 7 to week 11, but the increase also occurred in the control group. 3. In accordance with several literature reports, noradrenaline at concentrations of 10(-7) and 10(-6) mol/L had no effect on either the control or cold-acclimatized resting heat rate. 4. The osmolarity of the physiological solution bathing the muscle bundles was increased by 100 mosmol using sodium sulphate. Basal metabolism increased by similar amounts (approximately 250%) in both the fast and slow muscle bundles. Periods of cold exposure had no significant effect on the magnitude of the increment. 5. Bumetanide, a potent inhibitor of Na(+)-Cl- co-transport, produced only a slight reduction in the heat increments caused by hyperosmolar challenge.

Acclimatization↗
PubMed1996

Shortening heat in slow- and fast-twitch muscles of the rat.

Shortening heat has been reported in several amphibian skeletal muscles. In this investigation, shortening heat has been investigated in both soleus and extensor digitorum longus (EDL) muscles of young rats. The procedure involved shortening the muscles through two different distances, at near maximum velocity and at the onset of a summated twitch from different initial lengths. At the end of the shortening period, the muscle contracted isometrically, and the stress and associated heat production were recorded. These heat-stress data were compared with heat-stress data of isometric twitches at different initial lengths. There was a parallel upward shift in energy output when shortening occurred, indicating the presence of a shortening heat. Shortening heat increased with the distance shortened in soleus, but this was not the case for EDL. The values for the shortening heat coefficient for both muscle types are slightly higher than those reported for amphibian skeletal muscle and suggest that shortening heat is a significant component of the energy output of mammalian skeletal muscle.

Animals↗
PubMed1996

Mechanisms contributing to pulsus alternans in pressure-overload cardiac hypertrophy.

The mechanisms underlying pulsus alternans in pressure-over-load (POL) cardiac hypertrophy were investigated. Simultaneous measurements of force and intracellular Ca2+ (using fura 2) in right ventricular papillary muscles under conditions that produced mechanical alternans, revealed alternation of the amplitude of the Ca2+ transient together with alternation of force in some POL muscles. Instances when alternation of force occurred without any apparent alternation of the Ca2+ transient were also observed. Exposure of muscles to 5 microM ryanodine significantly attenuated mechanical alternans, thereby implicating a role for the sarcoplasmic reticulum (SR) in this process. The time course of restitution of force and the intracellular Ca2+ transient were, however, unchanged in POL hearts, indicating that SR Ca2+ cycling was not appreciably slowed. The fraction of Ca2+ recirculated intracellularly was derived from studies of postextrasystolic potentiation and was significantly reduced in the POL hearts, suggesting additional differences in cellular Ca2+ regulation. We conclude that changes in Ca2+ handling play an important role in the onset of mechanical alternans in POL hypertrophy, but that additional factors, most likely a slowing of crossbridge cycling rate, are also likely to be important.

Animals↗
PubMed1995

Fatigue and heat production in repeated contractions of mouse skeletal muscle.

1. This study tested the hypothesis that moderate fatigue of skeletal muscle arises from a mismatch between energy demand and energy supply. Fatigue was defined as the decline in isometric force. Energy supply and demand were assessed from measurements of muscle heat production. 2. Experiments were performed in vitro (21 degrees C) with bundles of muscle fibres from mouse fast-twitch extensor digitorum longus muscle and slow-twitch soleus muscle. Fibre bundles were fatigued using a series of thirty isometric tetani. Cycle duration (time between successive tetani) was 5 s. The amount of fatigue that occurred during a series of tetani was varied by varying contraction duty cycle (tetanus duration/cycle duration) by varying tetanus duration. 3. Peak isometric force and total heat production in each cycle were measured. For each cycle, the amounts of initial heat (H(i)) and recovery heat (Hr) produced were calculated and used as indices of energy use and supply, respectively. H(i) and Hr were used to estimate the net initial chemical breakdown (in energy units) in each cycle (H(i,net)). 4. The magnitude of H(i,net) was greatest in the early stages of the contraction protocol when Hr was still increasing towards a steady value. The magnitude of decline in force between successive tetani was proportional to H(i,net) for both muscles. 5. The results are consistent with the idea that the development of moderate levels of fatigue at the start of a series of contractions is due to the rate of energy supply being inadequate to match the rate of energy use.

Animals↗
PubMed1995

Mechanical determinants of myocardial oxygen consumption.

1. Recent developments which attempt to identify the mechanical determinants of myocardial oxygen consumption (mVO2) are considered, with emphasis being placed on the pressure-work and pressure-volume area (PVA) indices. 2. The difficulty of establishing a realistic in vivo basal mVO2 value is explained and the experimental reasons for the controversy over the magnitude of the activation metabolism are outlined. 3. The time varying elastance model of the heart is discussed including some current problems. The evidence for PVA as a satisfactory index of mVO2 under all physiological and pharmacological conditions is examined. Most pharmacological agents alter the intercept of the mVO2:PVA relationship but do not effect its slope: this result is interpreted to mean that the majority of current inotropic agents alter the energetic cost of calcium release/retrieval but not crossbridge efficiency. 4. An attempt is made to establish the likely cost of a cardiac contraction in man. The use of newer technology (i) to estimate mVO2 via positron emission tomography and (ii) to measure the work and potential energy output of the heart per beat with conductance catheters, is explained.

Animals↗
PubMed1995

Papillary muscles split in the presence of 2,3-butanedione monoxime have normal energetic and mechanical properties.

A number of studies have used 2,3-butanedione monoxime (BDM) to avoid myocardial damage when small muscle preparations were cut from large hearts. The present study investigates the mechanical and energetic effects of varying muscle cross-sectional area (CSA) by dissection in physiological saline containing BDM. By use of adult rat hearts, three muscle groups were obtained: whole left ventricular papillary muscles (Whole) and left ventricular papillary muscles split longitudinally in the presence of 30 mM BDM, with removal of approximately 10% (BDMSP1) or 40-50% (BDMSP2) of the muscle (5 animals in each group). The isolated muscle preparations were studied at 27 degrees C and stimulated at 0.167 Hz. The Whole and BDMSP1 preparations had comparable CSAs; in isotonically contracting muscles working against a range of afterloads, work, enthalpy (energy use), and mechanical efficiency (work/enthalpy x 100%) were similar for the two groups. In addition, isometric performance [e.g., developed stress (force/CSA), length-tension relationship, and contraction time course] was also similar for the two groups. The thinner BDMSP2 preparations showed an enhanced mechanical performance compared with the Whole and BDMSP1 groups. This outcome was in accordance with data in the literature documenting a negative correlation between stress and CSA. The results suggest that BDM-split and intact papillary muscles of similar CSA have comparable energetic and mechanical properties.

Animals↗
PubMed1993

Intracellular Ca2+, force and activation heat in rabbit papillary muscle: effects of 2,3-butanedione monoxime.

We have investigated the effects of 2,3-butanedione monoxime (BDM) and mannitol on Ca2+ metabolism in rabbit cardiac muscle. Simultaneous measurements of force and intracellular Ca2+ were made in right ventricular papillary muscles loaded with the fluorescent Ca2+ indicator fura-2. At a BDM concentration of 2 mM, peak isometric force was only 52% of control values and this was reduced to 18% at a concentration of 5 mM. The peak of the Ca2+ transient decreased by 8% at 2 mM BDM and by 18% at the higher concentration. In the presence of 362 mM mannitol peak isometric force decreased by 78% and there was a tendency for the peak of the Ca2+ transient to increase. A combination of 362 mM mannitol with 5 mM BDM completely inhibited force production despite peak Ca2+ levels that were no different from control values. In myothermic experiments under similar conditions the latency release protocol of Gibbs et al. (1988) and the BDM protocol of Alpert et al. (1989) were used to derive independent estimates of tension-independent (activation) heat in the same muscle. For both protocols the heat-stress relationship was well fitted by first-order linear regression. The activation heat estimate was significantly higher when measured with the latency release technique (2.31 mJ/g) compared with the BDM protocol (1.24 mJ/g). Our results confirm that in rabbit cardiac muscle low concentrations of BDM (2 mM) cause a marked inhibition of force development with little apparent effect on peak Ca2+ levels. Therefore, the lower activation heat estimates under these conditions may not be due to a reduced intracellular Ca2+ concentration. It is possible that the higher activation heat values obtained with protocols not involving chemical interventions may include the energy usage contributed by cellular processes that presumably do not occur in the presence of BDM and mannitol.

Analysis of Variance↗