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Biomedical subjects

F Bellemare

Publications and source records attributed to F Bellemare.

At least 55 records · Page 3Linked to original sources

Effect of lung volume on in vivo contraction characteristics of human diaphragm.

We performed transcutaneous bilateral phrenic nerve stimulation at varying lung volumes between residual volume (RV) and total lung capacity (TLC) in six normal male volunteers. Peak twitch transdiaphragmatic pressure declined from 49.1 +/- 9.1 (SD) cmH2O at RV to 19.6 +/- 5.97 (SD) cmH2O at TLC. Twitch contraction time fell from 91.8 +/- 11.3 (SD) ms at RV to 57.7 +/- 7.4 (SD) ms at TLC. There was a good correlation between changes in contraction time and transdiaphragmatic pressure (r = 0.7). The fall in transdiaphragmatic pressure was almost all due to a fall in pleural pressure, with little change in gastric pressure between RV and TLC. At TLC the pleural pressure in response to phrenic nerve stimulation was -0.58 cmH2O. We conclude that, as lung volume increases and the diaphragm shortens, it becomes less effective as a pressure generator and that pressure it generates is less well converted into useful inspiratory pressure. At a lung volume close to TLC, the diaphragm ceases to act as an inspiratory muscle.

Adult↗

Contractile properties of the human diaphragm in vivo.

The mechanical properties of the human diaphragm have been studied at fractional residual capacity in normal seated subjects with closed glottis. The transdiaphragmatic pressure (Pdi) developed in response to single shocks or to trains of stimuli at increasing frequency was approximately 3 times greater during bilateral than unilateral stimulation. During unilateral phrenic nerve stimulation the Pdi twitches increased as the interval (0-200 ms) of a preceding conditioning stimulus to the contralateral phrenic nerve was decreased suggesting that the two hemidiaphragms are mechanically coupled in series. The contraction time and half-relaxation time of single bilateral twitches as well as the Pdi-frequency relationship (5-35 Hz) during bilateral tetanic stimulation indicate that the contractile properties of the human diaphragm are intermediate between those of fast- and slow-twitch muscle fibers. The results suggest that the contractile properties of the human diaphragm are well illustrated by single bilateral twitches recorded from the relaxed muscle, but that the responses to unilateral stimulation are misleading due to distortion by abnormal changes in the muscle geometry.

Adult↗

Mixing of single-chain amphiphiles in two-chain lipid bilayers. 2. Characteristics of chlorophyll a and alpha-tocopherol incorporation in unilamellar phosphatidylcholine vesicles.

As a step toward the elucidation of the biological significance of the isoprenic chains found ubiquitously in single-chain lipids involved in electron and energy transfer of chloroplasts and mitochondria, we undertook a comparative study of the incorporation of chlorophyll a (Chl a) and alpha-tocopherol (alpha T) in unilamellar phosphatidylcholine (PC) vesicles. We observed that while Chl alpha is added to the PC bilayers in a simple, almost linear way, the inclusion of alpha T is a sigmoid-like function characterized first by a slow variation of alpha T incorporation followed by a rather steep increase till saturation occurs at initial mol% alpha T of approx. 5%. Owing to the likeness of the isoprenic chains of Chl a and alpha T the simplest interpretation of the data is that the different mixing behaviours of the two lipids in PC vesicles are due to the special arrangement of the tetrapyrrole macrocycle and the chromanol ring in the lipid bilayers. However, no satisfactory explanation of the mechanisms involved can be given as yet. One possibility is that the inclusion of Chl a and alpha T in the membranes results from adsorption differences brought about by the extent of penetration of the molecule into the monolayers of the unilamellar vesicles.

Chlorophyll↗

Assessment of human diaphragm strength and activation using phrenic nerve stimulation.

The phrenic nerves were stimulated bilaterally in human subjects with supermaximal shocks and the transdiaphragmatic pressure (Pdi) twitches recorded at end-expiratory lung volume with glottis closed. Stimulus maximality was monitored by the evoked muscle potentials. The highly reproducible twitch amplitudes elicited from the relaxed diaphragm were greater with bound (48 +/- 13 cm H2O) than unbound (34.6 +/- 10 cm H2O) abdomen in sitting position. With bound abdomen, the twitch amplitudes were similar in sitting and supine positions. When the same stimuli were applied during voluntary contractions the superimposed twitch amplitude declined almost linearly with the voluntary Pdi exerted, reflecting a progressively increasing activation by the CNS. From this relationship both the maximal Pdi (Pdimax) and the relative degree of diaphragm activation (% Pdimax) can be estimated for any type of breathing effort. Generally no twitch could be detected during maximal efforts (Pdimax: 218 +/- 34 cm H2O) indicating that all stimulated motor units were already fully activated. The Pditwitch/Pdimax ratio of 0.21 +/- 0.04 was similar to the twitch/tetanus ratios of isolated mammalian muscle, suggesting that bilateral stimulation can activate all phrenic motor neurons.

Adult↗

Respiratory muscle length measured by sonomicrometry.

The use of sonomicrometry to study the mechanical properties of the diaphragm in vivo is presented. This method consists of the implantation of piezoelectric transducers between muscle fibers to measure the fibers' changes in length. Ultrasonic bursts are produced by one transducer upon electrical excitation and sensed by a second transducer placed 1-2 cm away. The time elapsed between the generation of the ultrasound burst and its detection is used to calculate the intertransducer distance. Excitation and sampling are done at 1.5 kHz and the output is a DC signal proportional to the length change between the transducers. Neither irreversible injury to the diaphragm nor regional differences within an anatomical part or segment were noted. Measurements were stable within the physiological range of temperature. We measured costal and crural length and velocity of contraction in anesthetized dogs during spontaneous breathing, occluded inspirations, passive lung inflation, and supramaximal phrenic nerve stimulation. We found that shortening during spontaneous breathing was 11 and 6% for crural and costal, respectively. The crural leads the costal in velocity of shortening. Supramaximal stimulation results in a velocity of shortening of 5 resting lengths X s-1. During an occluded inspiration crural shortens as much as in the nonoccluded breath, whereas costal shortens less. During passive lung inflation there is a nearly linear relationship between lung volume and diaphragm length; however, the relationships of chest wall dimensions with diaphragm length are nonlinear and cannot be described by any simple function. Some of the implications of these data on the present understanding of diaphragmatic mechanics are discussed.

Animals↗

Toward a multistep mechanism of cytochrome c reactivity. Answer to a comment.

Koppenol's rejection (Biophys. Chem. 18 (1983) 203) of a model of polarity-dependent ferrocytochrome c oxidation (M. Fragata and F. Bellemare, Biophys. Chem. 15 (1982) 111) places emphasis on the role of the protein surface charges in reactivity but is at the same time too restrictive as it neglects largely the polarity (dielectric constant) of the aqueous and hydrophobic interfaces of the exposed heme edge and the inner cleft (heme crevice) of cytochrome c which appear to be the oxidation-reduction sites. It is suggested that a more general model should take into account (i) a recognition (or diffusion) step where the distance travelled by cytochrome c at the membrane surface and/or the Brownian displacements in the bulk solution are greatly influenced by ionic strength, and (ii) a redox step where low polarity effects prevail with concomitant weakening of ionic activity.

Animals↗

Changes in relaxation rate with diaphragmatic fatigue in humans.

Maximum relaxation rate (MRR) and the time constant of relaxation (tau) of transdiaphragmatic pressure (Pdi) was measured in four male subjects and compared with the high-to-low frequency ratio (H/L) of the diaphragmatic electromyogram (EMG) as a predictor of diaphragmatic fatigue. Pdi and inspiratory time-to-total breath duration ratios (TI/TT) were varied, and TT and tidal volume were held constant; inspiratory resistances were used to increase Pdi. Studies were performed at various tension-time indices (TTdi = Pdi/Pdimax X TI/TT). Base-line MRR/Pdi was 0.0100 +/- 0.0004 (SE) ms-1, and baseline tau was 53.2 +/- 3.2 ms. At TTdi greater than 0.20, MRR and H/L decreased and tau increased, with maximum changes at the highest TTdi. At TTdi less than 0.20, there was no change in H/L, MRR, or tau. The time course of changes in H/L correlated with those of MRR and tau under fatiguing conditions. In this experimental setting, change in relaxation rate was as useful a predictor of diaphragmatic fatigue as fall in H/L of the diaphragmatic EMG.

Adult↗

Effect of tension and timing of contraction on the blood flow of the diaphragm.

An open-chest animal model was developed to study the diaphragmatic blood flow (Qdi) during bilateral electrophrenic stimulation. Two patterns of stimulation were used, continuous and intermittent, and both patterns were held at various transdiaphragmatic pressures (Pdi). The contractions were nearly isometric and held at an initial length of supine functional residual capacity (FRC). Qdi was measured in six dogs by catheterizing a branch of the diaphragmatic vein and by counting the blood drops with an infrared cell. During continuous contractions Qdi increased as a function of Pdi up to 70 +/- 12 ml . 100 g-1 . min-1 at 20% Pdimax. At higher levels Qdi decreased progressively and approached zero at 75% of Pdimax. A postcontraction hyperemia occurred at Pdi values greater than 20% Pdimax and increased as a function of Pdi. During intermittent contractions Qdi was a unique function of the diaphragmatic tension-time index (TTdi), a product of Pdi times the duty cycle (contraction time/total cycle time). Qdi increased progressively up to a TTdi of 25% Pdimax and decreased above that point toward zero at TTdi of 80% Pdimax. The postcontraction hyperemia appeared at a TTdi of about 15% of Pdimax and increased as a function of TTdi. It is concluded that Qdi is limited beyond a TTdi of about 20% Pdimax, as indicated by the increase in postcontraction hyperamia, and that Qdi is a function of both Pdi and the timing of contraction.

Animals↗

Force reserve of the diaphragm in patients with chronic obstructive pulmonary disease.

The fatigue threshold of the human diaphragm in normal subjects corresponds to a transdiaphragmatic pressure (Pdi)-inspiratory time integral (TTdi) of about 15% of Pdimax. The TTdi of resting ventilation was measured in 20 patients with chronic obstructive pulmonary disease (COPD) and ranged between 1 and 12% of Pdimax (mean 5%). TTdi was significantly related to total airway resistance (Raw) (r = 0.57; P less than 0.05). Five of these patients were asked to voluntarily modify their TI/TT (ratio of inspiratory time to total cycle duration; from 0.33 to 0.49) so as to increase their TTdi from a control value of 8% to an imposed value of 17% of Pdimax. The imposed pattern induced a progressive decline in the high-frequency (150-350 Hz)/low-frequency (20-40 Hz) power ratio (H/L) of the diaphragm electromyogram (fatigue pattern), quantitatively similar to that seen in normal subjects breathing with similar TTdi levels. The decay in H/L was followed by a progressive fall in mean Pdi meanly due to decrease in gastric pressure swings. It is concluded that 1) the force reserve of the diaphragm in COPD patients is decreased because of a decrease in Pdimax; 2) the remaining force reserve of the diaphragm can be exhausted by even minor modifications in the breathing pattern; and 3) at a TI/TT of 0.40 our COPD patients can increase their mean Pdi 3-fold before reaching a fatiguing pattern of breathing compared with 8-fold in normal subjects.

Aged↗

Motor-unit discharge rates in maximal voluntary contractions of three human muscles.

Single motor-unit firing rates have been recorded during maximal voluntary contractions using tungsten microelectrodes. Over 300 units from four subjects were sampled from each of three muscles. These were the biceps brachii, adductor pollicis, and soleus, chosen because of known differences in their fiber-type composition and contractile properties. In all cases the contraction maximality was assured by delivering single supramaximal shocks during the voluntary contractions. All motor units were deemed to have already been fully activated if no additional force resulted. Thus for each muscle, the firing rates elicited by a maximal voluntary effort are sufficient to generate a fully fused tetanus in each motor unit. For the biceps brachii and adductor pollicis muscles, the mean firing rates (+/- SD) were 31.1 +/- 10.1 and 29.9 +/- 8.6 Hz, respectively, while for soleus they were only 10.7 +/- 2.9 HZ. For each muscle the firing rates distribution covered approximately a four-fold range about the mean value. The mean firing rates for each muscle varied roughly in proportion to their respective twitch contraction and half relaxation times. These contractile time measurements for both biceps brachii and adductor pollicis agreed well with the mean values reported for human fast-twitch motor units, while those for soleus fell in the range observed for human slow-twitch units. An argument is presented that suggests that, in response to voluntary effort, the range of discharge rates of each motor-unit pool is limited to those only just sufficient to produce maximum force in each motor unit. This suggestion is based on the relationship between the range of motor-unit firing frequencies observed during maximum voluntary contractions, their range of contraction times, and the stimulation frequencies required for maximum force generation. The implications of this hypothesis for motor control are discussed.

Adult↗

Dielectric constant dependence of biological oxidation-reduction. 1. A model of polarity-dependent ferrocytochrome c oxidation.

A theoretical model for the effect of the dielectric constant (c) of the solvent medium on ferrocytochrome c oxidation by ferricyanide is developed to account for the observed variations of the rate constant (k) of reactions in aqueous binary mixtures with alcohols (less than 5-10 mol% ethanol and propranolol). A correlation between k and c is found if ln k is expressed as a function of the Kirkwood parameter (c-1)(2c+1). The results of calculations indicate that the use of the 'overall dipole moment' of cytochrome c in oxidoreduction studies is likely to be unreliable. Instead, the decrease in k in alcohol/water mixtures is best explained--in conformity with Onsager's theory of the reaction field--by a polarity effect on the dipole moment of the cytochrome c heme upon diffusion of the polar solvent molecules into the low dielectric constant heme crevice.

Alcohols↗

Effect of pressure and timing of contraction on human diaphragm fatigue.

The relationship between the mean transdiaphragmatic pressure swing developed with each inspiration (Pdi) and the fraction of the breathing cycle time spent in inspiration (TI/Ttot) (Pdi X TI/Ttot) was related to the maximal time that such a run could be sustained (Tlim). Four normal subjects breathed with a constant breathing pattern for 45 min or until Pdi could no longer be sustained, whichever came first. The breathing patterns included Pdi of 0.15-0.90 of Pdimax and TI/Ttot of 0.15-1.0. Pdi was obtained by adjusting an inspiratory resistance, and the timing by monitoring tidal volume with time base from an oscilloscope. The Tlim of a run was found to be inversely related to both Pdi and TI/Ttot and hence inversely related to their product, following a quadratic hyperbole function. Pdi X TI/Ttot represents an index of the tension time of the diaphragm (TTdi). The breathing pattern that could be sustained more than 45 min was found to have a TTdi of about 0.15, which was termed critical TTdi. Above that value Tlim decreased as a function of TTdi. The results are consistent with Tlim being related to diaphragmatic blood flow limitation.

Diaphragm↗

Evaluation of human diaphragm fatigue.

The time course of the frequency content of the electromyogram (EMG) was studied in the diaphragm of five normal subjects breathing through high inspiratory resistance. The ratio between the power content of a high-frequency band (150-350 Hz) (H) and a low-frequency band (20-40 Hz) (L) was calculated for each breath and expressed as a fraction of the initial breath. The rate of decay (when existent) was exponential and was quantified by measuring the time constant of decay of H/L (TF). Runs were held sustaining the ratio of inspiratory time to total breath cycle duration (TI/Ttot) from 0.2 to 1 and transdiaphragmatic pressure (Pdi) of 0.1-0.8 of Pdimax. It was found that TF was monotonically related to Pdi X TI/Ttot, following a hyperbolic relationship. TF was compared with velocity of conduction of the myopotentials and with center frequency of the EMG power spectrum and found to follow similar trends showing, however, different absolute rate of change. The values of TF were found to be directly related to the time a given pattern could be sustained (Tlim). It is concluded that EMG changes and Tlim are related and are expressions of the metabolic changes induced by the contraction pattern.

Adult↗

Transmembrane distribution of alpha-tocopherol in single-lamellar mixed lipid vesicles.

A study of the molar ratio dependence of the incorporation of alpha-tocopherol into single-lamellar vesicles showed that the number of molecules which the bilayers can accommodate increased linearly with increasing alpha-tocopherol/phosphatidylcholine initial molar ratios till about 0.05, then approached a saturation limit. At 5 mol%, one alpha-tocopherol molecule per 60 phospholipids can be incorporated into the membranes. Up to this limit the distribution of alpha-tocopherol in the bilayers is uniform, while at initial molar ratios higher than 0.05 a disproportionation toward the inner monolayer of the vesicles is observed. The average outer/total ratio is found to be 0.27 +/- 0.03 at alpha-tocopherol/phosphatidylcholine molar ratios above 0.07 and is similar to asymmetrical distributions that have been reported in vesicles containing other one-chain amphiphiles (e.g., cholesterol). This large disproportionation is in contrast with the packing distribution of certain two-chain amphiphiles, and indicates that one of the driving forces for asymmetry formation in lipid bilayers might be dependent on the number of hydrocarbon chains per amphiphile molecule. A possible reason for the disproportionation effect observed in our experiments is the displacement of unsaturated phospholipids to the outer monolayer of the single-lamellar vesicles, by the more rigid isoprene units of alpha-tocopherol.

Lipid Bilayers↗

Effect of cholate on H(+)-ATPase and other proteins of dog renal brush-border membrane.

A short treatment of dog renal brush-border membrane vesicles (BBMV) with sodium cholate, followed by dialysis of the detergent, reorients the polarity of H(+)-ATPase in the membrane and exposes its ATP binding sites to the extravesicular space, as previously shown with pig BBMV. In cholate-pretreated vesicles, the H(+)-ATPase remains fully active, but is inserted under the reversed polarity in sealed vesicles. A large spontaneous N-ethylmaleimide-sensitive ATPase activity is thus observed, as well as a steep intravesicular acidification upon external ATP addition, two findings absent in native vesicles. The ability of nitrate plus ATP to dissociate the hydrolytic subunits ot the proton pump in cholate-pretreated vesicles, but not in native vesicles, demonstrates that most of the ATP binding subunits are accessible to ATP following cholate treatment. The sensitivity of the cytoplasmic domain of the H(+)-ATP activity to trypsin also confirms the reorientation of the enzyme in cholate-pretreated vesicles. The H(+)-ATPase and alkaline phosphatase remain largely associated with the membranes after the treatment with cholate, but gamma-glutamyltranspeptidase, aminopeptidase N, and neutral endopeptidase are largely solubilized. Upon dialysis of cholate, all these enzymes are in part reinserted in the membrane according to their original polarity. The reorientation process is however specific for the H(+)-ATPase. Cholate treatment does not increase the formation of inside-out vesicles. Thus the treatment with cholate really reorients the polarity of the H(+)-ATPase in vesicles and allows for study of the proton pumping capacity of vacuolar H(+)-ATPase of proximal tubules.

Adenosine Triphosphate↗