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Biomedical subjects

C A Carrington

Publications and source records attributed to C A Carrington.

At least 19 recordsLinked to original sources
PubMed2003

Interaction between muscle metaboreflex and mechanoreflex modulation of arterial baroreflex sensitivity in exercise.

The effect of external calf compression on baroreflex sensitivity (BRS) during electrically evoked plantar flexion and postexercise circulatory occlusion (PECO) was studied. Subjects took part in two experimental trials: control and compression. In both trials, electrically evoked isometric plantarflexion (Stim) was performed at 30% maximum voluntary contraction force for 2 min. During compression, a cuff (inflated to 250 mmHg) was applied to the active calf during exercise and PECO. Sequence analysis carried out on the systolic blood pressure responses, and R-wave-R-wave intervals revealed a rightward shift of the regression line along the pressure axis during Stim in both trials. In the control experiment, BRS was significantly (P < 0.01) increased from 10.37 +/- 1.87 ms/mmHg during Stim to 12.79 +/- 1.62 ms/mmHg during PECO. With external compression, BRS was unaltered between Stim (10.84 +/- 1.86 ms/mmHg) and PECO (11.40 +/- 1.54 ms/mmHg). Because the metabolic conditions were the same in both experiments, the results may best be explained by reactivation of muscle mechanoreceptor activity by external compression during PECO.

Adult↗
PubMed2001

Exercise-induced muscle chemoreflex modulation of spontaneous baroreflex sensitivity in man.

1. The goal of this study was to determine the effect of exercise-induced muscle chemoreflex activation on baroreflex sensitivity (BRS). This is a retrospective study using data obtained during two prior studies. 2. Twenty-three subjects with a mean (S.E.M.) age of 28 (1.5) years took part in the study. Sequence analysis was performed on the systolic blood pressure (SBP) responses, measured by a Finapres, and R-R intervals, measured from the ECG. 3. Electrically evoked isometric exercise (Stim) of the triceps surae was performed for 2 min at 30 % maximum voluntary contraction force. During exercise and for a further 2 min thereafter, circulation to the lower leg was occluded by inflation of a thigh cuff to above 200 mmHg. 4. Prior to exercise mean (+/- S.E.M.) BRS was 10.92 +/- 6.3 ms mmHg(-1), and BRS remained at this level during evoked exercise (10.90 +/- 7.1 ms mmHg(-1)). BRS increased to 12.34 +/- 6.0 ms mmHg(-1) during post-exercise circulatory occlusion (PECO) (P < 0.05, MANOVA, post hoc Student's paired t test vs. Stim) and fell to 9.27 +/- 4.4 ms mmHg(-1) during recovery (P < 0.01 vs. PECO value, P = 0.059 vs. resting value). 5. These data indicate that during PECO following electrically evoked plantar flexion, where only muscle chemosensitive afferents were likely to be stimulated, BRS was increased.

Adult↗
PubMed2001

Is there a relationship between muscle fatigue resistance and cardiovascular responses to isometric exercise in mild chronic heart failure?

BACKGROUND: Exercise intolerance in chronic heart failure (CHF) may be due to altered fatigue resistance and muscle afferent input to the cardiovascular system from dysfunctional skeletal muscle. AIM: To determine whether calf muscle fatigue resistance was associated with the magnitude of a muscle afferent driven cardiovascular response to isometric exercise. METHODS AND RESULTS: Cardiovascular responses were recorded in eight stable CHF patients (ejection fraction 20-40%) and nine healthy, age-matched controls during voluntary and electrically evoked isometric plantar flexion and post-exercise circulatory occlusion. The force developed by the plantar flexors during a 2-min submaximal electrically evoked fatigue test was measured. There was no relationship between ischaemic muscle fatigue and cardiovascular changes during and after voluntary contraction in either group nor evoked contraction in the CHF group. In the control group, the change in diastolic blood pressure (DBP) at the end of evoked contraction was related to the severity of fatigue at 90 s and 120 s (FI=0.01DeltaDBP+0.3, r=0.81, P<0.05 and FI=0.02DeltaDBP+0.8, r=0.84, P<0.01, respectively). CONCLUSION: Muscle fatigue resistance did not relate to the magnitude of the cardiovascular stress generated by isometric exercise of the same muscle in these patients.

Blood Pressure↗
PubMed2001

Effect of cell surface concentration of human DAF on transgenic pig aortic endothelial cells on the degree of protection afforded against human complement deposition.

Cultures of hDAF transgenic porcine aortic endothelial cells (TPAEs) with levels of cell surface hDAF expression between 2000 and 300 000 molecules per cell have been used to determine the relationship between expression of hDAF and protection from human complement deposition in an in vitro model. At concentrations below 45 000 molecules per cell, the relationship between hDAF expression and degree of protection conferred is linear. Concentrations of 123 000 molecules per cell and higher give maximal protection (60% reduction of susceptibility to neat human serum) in this model. It is concluded that increasing hDAF expression above that displayed by the A74 line of hDAF transgenic pigs (240 000 +/- 15 000 molecules per cell) would not confer any additional benefit.

Animals↗
PubMed2001

Muscle afferent and central command contributions to the cardiovascular response to isometric exercise of postural muscle in patients with mild chronic heart failure.

The roles of muscle afferent activity and central drive in controlling the compromised cardiovascular system of patients with mild chronic heart failure (CHF) during isometric exercise were examined. Blood pressure and heart rate responses were recorded in eight stable CHF patients (ejection fraction 20-40%; age 62+/-11 years) and in nine healthy age-matched controls during voluntary and electrically evoked isometric plantar flexion and subsequent post-exercise circulatory occlusion (PECO). During voluntary contraction, control subjects had a greater mean increase in systolic blood pressure than patients (42.4+/-19.2 and 23.0+/-10.9 mmHg respectively; P<0.01), but this was not the case during PECO. During electrically evoked contraction, but not during PECO, the CHF group had smaller (P<0.05) mean increases in both systolic and diastolic blood pressure than controls (13.0+/-5.3 compared with 25.4+/-14.0 mmHg and 7.6+/-3.0 compared with 12.9+/-7.2 mmHg respectively). Intra-group comparison between responses to voluntary and electrically evoked contractions revealed greater (P<0.05) mean increases in systolic and diastolic blood pressure during the voluntary contraction in both the patients and the control subjects. These data suggest that muscle afferent drive to the pressor response from the triceps surae is low in this age group, both in control subjects and in CHF patients. Additionally, the patients may have a relatively desensitized muscle mechanoreceptor reflex.

Aged↗
PubMed1999

The effects of athletic training and muscle contractile character on the pressor response to isometric exercise of the human triceps surae.

In this study, the influence of athletic training status and the contractile character of the active muscle on the magnitude of the pressor response (PR) to voluntary and electrically evoked isometric plantar flexion was investigated. Subjects were 10 sprint-trained athletes (sprint) (100-m, 200-m and 400-m) [mean (SD) age, 21 (2) years], 14 endurance trained athletes (distance) [22 (2) years] and 8 untrained men (control) [23 (3) years]. Twitch time to peak tension (TPT) in the sprint group [108 (7) ms] was significantly less (P<0.001) than that of the distance group [124 (10) ms]. During voluntary contraction, the mean change in systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (fc) was not significantly different between groups. During electrically evoked contractions, mean changes in SBP, DBP and fc were not significantly different between the sprint, distance and control groups. However, division of the sprint group into 400-m (sprint I) and 100/200-m athletes (sprint II) showed that an increase in DBP of 1.6 kPa (12 mm Hg) in sprint I was significantly less (P<0.05) than the 2.5 kPa (19 mm Hg) increase observed for both the distance and control groups. Prediction of the DBP response from our previously published relationship between TPT and DBP showed close agreement in all subject groups except sprint I; in these subjects the observed DBP response was only 55% of that predicted. Attenuation of the PR in the involuntary experiment suggests that some aspect of sprint training, but not endurance training, modifies the muscle afferent input to the PR in man.

Adult↗
PubMed1995

The relationship between the pressor response to involuntary isometric exercise and the contractile protein profile of the active muscle in man.

The present investigation examined the relationship between the pressor response during electrically evoked isometric ankle plantar flexion and the contractile protein profile of the active muscle in seven young men [mean (SD) age, 26 (6) years] and five older men [70 (4) years]. Muscle biopsy samples were taken from lateral gastrocnemius (LG) and soleus (SOL) of each subject. These were analysed for isomyosin composition using non-denaturing pyrophosphate polyacrylamide gel electrophoresis. The degree of association was examined between the cardiovascular changes and the fast isomyosin content of LG and SOL individually and in combination (SOL/LG). In the total subject group there was no association between the heart rate response or the change in systolic blood pressure (BP) and the fast isomyosin composition. However, the change in diastolic BP was significantly associated with the fast isomyosin composition of SOL/LG (delta diastolicBP = 0.31 + 0.045% FM SOL/LG, r = 0.65, P = 0.029). These findings suggest that the magnitude of the peripheral reflex mediated pressor response to isometric exercise and the fast isomyosin content of the active muscle are related.

Adult↗
PubMed1995

Electrically evoked torque-velocity characteristics and isomyosin composition of the triceps surae in young and elderly men.

The electrically evoked isokinetic torque-velocity relationship of the triceps surae of eight elderly and four non-trained young men was examined in relation to the isomyosin composition of the soleus and the gastrocnemius muscles, determined under non-denaturing conditions using pyrophosphate gel electrophoresis. The angle specific torque-velocity properties of the triceps surae were measured using maximal percutaneous electrical stimulation at 50 Hz and a release technique. The elderly subjects generated significantly (P < 0.05) less absolute torque at all angular velocities when compared with the young subjects. When the isokinetic data were normalized to the isometric torque, the lower normalized torques generated by the elderly subjects were not statistically different from the young. The total fast isomyosin (FM) content of the soleus and gastrocnemius in the elderly subjects was 22 +/- 13 and 35+/- 18%, respectively. This compared with 29 +/- 8 (n.s) and 44 +/- 8% (n.s.) in the young subjects. When the gastrocnemius and soleus muscles were given an equal weighting and considered together to represent the whole triceps surae, the normalized torque at the fixed angular velocity of 5 rads s-1 was significantly associated with %FM (r = 0.90, P < 0.01), and the isomyosin bands %FM1 (r = 0.90, P < 0.01) and %FM2 (r = 0.93, P < 0.001) when only the elderly subjects were considered. No relationships were observed between contractile characteristics and contractile protein profile when only the young subjects were considered. This was despite the inclusion of a further two sprint and three endurance trained athletes to increase the range of contractile characteristics and differences in muscle composition.

Adult↗
PubMed1993

The pressor response to involuntary isometric exercise of young and elderly human muscle with reference to muscle contractile characteristics.

Changes in heart rate (fc) and blood pressure (BP) were observed in eight healthy young men aged [mean (SD)] 20 (1) years and ten healthy elderly men aged 65 (5) years, during electrically evoked contractions of the ankle plantar flexors and elbow flexors which were sustained for 2 min. There was no significant difference in the fc response to evoked contraction of the ankle plantar flexors or elbow flexors between young and elderly subjects. During contraction of the elbow flexors, elderly subjects produced an unexpectedly large rise in systolic BP which was significantly greater than that of the young subjects. The exaggerated response seen in the elderly group may be due to a more rigid arterial tree which is thought to occur with advancing age. Electrically evoked contraction of the slower contracting elderly ankle plantar flexors resulted in a significantly diminished diastolic BP response when compared with that of the young subjects. In contrast, during electrically evoked contraction of the elbow flexors, which showed a similar twitch time course in young and elderly subjects, the diastolic BP response was not significantly different between groups. This may reflect differences in the peripheral reflex input to the pressor response in elderly arm and leg muscles which, in turn, may be influenced by relative fast twitch fibre area.

Adult↗
PubMed1989

Sensitive and specific two-site immunoradiometric assays for human insulin, proinsulin, 65-66 split and 32-33 split proinsulins.

Monoclonal antibody-based two-site immunoradiometric assays are described for human insulin, proinsulin, 65-66 split and 32-33 split proinsulin. The detection limits of the assays lie in the range 0.8-2.5 pM. The assays for 65-66 and 32-33 split proinsulins do not distinguish between these substances and their respective C-terminal di-desamino derivatives. The assay of 65-66 split proinsulin does not cross-react with insulin, proinsulin or 32-33 split proinsulin. This material was undetectable (less than 1.0 pM) in plasma taken after an overnight fast in eight normal male subjects and the maximum individual concentration reached in plasma taken during an oral glucose tolerance test of these subjects was 3.8 pM. The proinsulin assay cross-reacted 66% with 65-66 split proinsulin but not with insulin or 32-33 split proinsulin. The 32-33 split proinsulin assay cross-reacted 84 and 60% with proinsulin and 65-66 split proinsulin respectively. The insulin assay cross-reacted 5.3, 62 and 5.0% with intact proinsulin, 65-66 split proinsulin and 32-33 split proinsulin respectively. The very low concentration of 65-66 split proinsulin meant that this derivative did not interfere significantly with the specificity of the assays of proinsulin and insulin. The concentration of 32-33 split proinsulin could be calculated by subtracting the cross-reactivity of the measured proinsulin. The mean concentrations of insulin, proinsulin and 32-33 split proinsulin in eight young male subjects in the fasting state were (pM +/- S.E.M.) 20 +/- 0.3, 2.3 +/- 0.3 and 2.1 +/- 0.7 and at the maximum reached during an oral glucose tolerance test, 150 +/- 26, 9.9 +/- 1.4 and 19.7 +/- 6.0 respectively.

Adult↗
PubMed1989

Insulin deficiency in non-insulin-dependent diabetes.

A highly specific two-site immunoradiometric assay for insulin was used to measure the plasma insulin response to 75 g glucose administered orally to 49 patients with non-insulin-dependent diabetes (NIDDM). The plasma insulin concentration 30 min after glucose ingestion was lower in the diabetic patients than in matched controls for both non-obese (11-83 pmol/l vs 136-297 pmol/l, p less than 0.01) and obese subjects (23-119 pmol/l vs 137-378 pmol/l, p less than 0.01). By means of another two-site immunoradiometric assay, the basal intact proinsulin level was found to be higher in the NIDDM patients than in the controls for both non-obese (7.1 [SEM 1.2] pmol/l vs 2.4 [0.4] pmol/l, p less than 0.01) and obese subjects (14.4 [2.2] pmol/l vs 5.9 [1.9] pmol/l, p less than 0.01). The basal level of 32-33 split proinsulin was also raised in NIDDM. Previous failure to show clear separation between normal and NIDDM insulin responses was probably due to the high concentrations of proinsulin-like molecules in the plasma of NIDDM patients. These substances cross-react as insulin in most, if not all, insulin radioimmunoassays but have very little biological insulin-like activity. It is therefore now possible and necessary to designate most NIDDM patients as insulin deficient.

Diabetes Mellitus, Type 2↗
PubMed1988

Effects of sulphonylureas and diazoxide on insulin secretion and nucleotide-sensitive channels in an insulin-secreting cell line.

1. The effects of various sulphonylureas and diazoxide on insulin secretion and the activity of various channels have been studied using tissue culture and patch-clamp methods in an insulin-secreting cell line derived from a rat islet cell tumour. 2. Tolbutamide, glibenclamide and HB699 increased the rate of insulin release by 2-5 fold. The concentrations of tolbutamide and glibenclamide giving half-maximum effects on insulin secretion were approximately 40 microM and 0.2 microM, respectively. 3. Diazoxide (0.6-1.0 mM) per se, had either no effect or produced a small increase in insulin secretion, whereas when secretion was maximally stimulated by the combination of glucose (3 mM) and leucine (20 mM), it produced inhibition. Tolbutamide-induced release was also inhibited by diazoxide. 4. Tolbutamide, glibenclamide, HB699 and HB985 reduced the open-state probability of the ATP-K+ channel in a dose-dependent manner. Tolbutamide and glibenclamide were shown to be effective regardless of which side of the membrane they were applied. 5. In whole cell recording, in which the total ATP-sensitive K+ conductance of the cell could be measured, dose-inhibition curves for tolbutamide and glibenclamide were constructed, resulting in Ki values of 17 microM and 27 nM, respectively. The value of Ki for tolbutamide was unchanged when ATP (0.1 mM) was present in the electrode. 6. Diazoxide (0.6 mM) activated the ATP-K+ channels only when they had first been inhibited by intracellular ATP (0.1 mM) or bath applied tolbutamide (3-30 microM). The inhibition produced by glibenclamide could not be reversed by diazoxide. 7. Neither tolbutamide (1.0 mM) nor glibenclamide (10 microM) altered the open-state probability of the Ca2+-activated K+ channel or the Ca2+-activated non-selective cation channel which are present in this cell line. 8. It is concluded that the sulphonylureas and related hypoglycaemic drugs and diazoxide regulate insulin secretion by direct effects on the ATP-K+ channel or a protein closely associated with this channel.

Adenosine Triphosphate↗
PubMed1987

Nucleotide-sensitive ion channels in human insulin producing tumour cells.

Cells from a human insulin producing tumour have been studied and single channel currents recorded. We have observed three main cation-selective channels in excised patch experiments. An ATP-sensitive potassium channel is present the activity of which can be inhibited by the oral hypoglycaemic drug, tolbutamide. A calcium-activated non-selective cation channel, which is inhibited by AMP could also be seen. In addition a large conductance potassium selective channel, possibly the "maxi" calcium-activated potassium channel is present in these cells.

Adenoma↗