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Biomedical subjects

A E Grassino

Publications and source records attributed to A E Grassino.

At least 19 recordsLinked to original sources
PubMed2005

Time-based gene expression programme following diaphragm injury in a rat model.

It was hypothesised that diaphragm injury activates a time-based programme of gene expression in muscle repair. Gene expression of different substances, such as proteases (calpain 94 (p94)), transcription factors (myogenin and cFos), growth factors (both basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF)-II), and structural proteins (myosin heavy chain (MHC) and titin), was quantified by RT-PCR in rat diaphragms exposed to caffeine-induced injury. Injured and noninjured (control) rat hemidiaphragms were excised at different time points (1-240 h). In injured hemidiaphragms, in comparison with control muscles, p94 expression levels peaked at 1 h post-injury (PI), cFos mRNA levels began to rise, after an initial dip, and peaked at 96 h PI, while myogenin mRNA levels started to increase as early as 12 h PI, IGF-II mRNA levels initially decreased until 48 h PI and increased thereafter, peaking at 72 h PI, bFGF mRNA levels rose to a maximum at 96 h PI, and MHC and titin mRNA levels were significantly elevated at 72 h PI. Caffeine-induced diaphragm injury is followed by a time-based expression programme of different genes tailored to meet muscle repair needs.

Animals↗
PubMed2001

Morphological and functional recovery from diaphragm injury: an in vivo rat diaphragm injury model.

Our objective was to develop an in vivo model to study the timing and mechanisms underlying diaphragm injury and repair. Diaphragm injury was induced in anesthetized rats by the application of a 100 mM caffeine solution for a 10-min period to the right abdominal diaphragm surface. Diaphragms were removed 1, 4, 6, 12, 24, 48, 72, and 96 h and 10 days after the injury, with contractile function being assessed in strips in vitro by force-frequency curves. The extent of caffeine-induced membrane injury was indicated by the percentage of fibers with a fluorescent cytoplasm revealed by inward leakage of the procion orange dye. One hour after caffeine exposure, 32.9 +/- 3.1 (SE) % of fibers showed membrane injury that resulted in 70% loss of muscle force. Within 72-96 h, the percentage of fluorescent cells decreased to control values. Muscle force, however, was still reduced by 30%. Complete muscle strength recovery was observed 10 days after the injury. Whereas diaphragmatic fiber repair occurred within 4 days after injury induction, force recovery took up to 10 days. We suggest that the caffeine-damaged rat diaphragm is a useful model to study the timing and mechanisms of muscle injury and repair.

Animals↗
PubMed2000

Influence of tension time on muscle fiber sarcolemmal injury in rat diaphragm.

We hypothesized that the amount of sarcolemmal injury is directly related to the total tension time (TT(tot)), calculated as mean tension x total stimulation time. Diaphragm strips from Sprague-Dawley rats were superfused at optimal muscle length with Krebs containing procion orange to identify sarcolemmal injury. TT(tot) was induced by stimulation with 100 Hz for 3 min at duty cycles of 0.02, 0.15, 0.3, and 0.6, or with continuous contractions at 0.2, 0.4, 0.6, and 1.0 of maximal tension. A significant positive correlation between TT(tot) and the percentage of fibers with injured sarcolemma (r(2) = 0.63, P < 0.05) is seen. Stimulation (at 100 Hz, duty cycle = 1) resulted in fast fatigue with low injury, likely caused by altered membrane conductivity. Stimulations inducing the largest injury are those showing progressive force loss and high TT(tot), where injury may be due to activation of membrane degradative enzymes. The maximal tension measured at 20 min poststimulation was inversely related to the number of fibers injured, suggesting loss of force is caused by cellular injury.

Animals↗
PubMed1997

Enhancement of signal quality in esophageal recordings of diaphragm EMG.

The crural diaphragm electromyogram (EMGdi) is recorded from a sheet of muscle, the fiber direction of which is mostly perpendicular to an esophageal bipolar electrode. The region from which the action potentials are elicited, the electrically active region of the diaphragm (EAR(di)) and the center of this region (EAR(di ctr)) may vary during voluntary contractions in terms of their position with respect to an esophageal electrode. Depending on the bipolar electrode's position with respect to the EAR(di ctr), the EMGdi is filtered to different degrees. The objectives of the present study were to reduce these filtering effects on the EMGdi by developing an analysis algorithm referred to as the "double-subtraction technique." The results showed that changes in the position of the EAR(di ctr) by +/- 5 mm with respect to the electrode pairs located 10 mm caudal and 10 mm cephalad provided a systematic variation in the EMG power spectrum center-frequency values by +/- 10%. The double-subtraction technique reduced the influence of movement of the EAR(di ctr) relative to the electrode array on EMG power spectrum center frequency and root mean square values, increased the signal-to-noise ratio by 2 dB, and increased the number of EMG samples that were accepted by the signal quality indexes by 50%.

Action Potentials↗
PubMed1997

Diaphragm muscle fiber injury after inspiratory resistive breathing.

Five awake previously tracheotomized mongrel dogs were challenged with inspiratory resistive breathing (IRB). The mean peak tracheal pressure = -35.4 +/- 1.1 cmH2O, ETCO2 = 39.8 +/- 1.5 mmHg was sustained for 2 h/d over 4 consecutive d. On the fourth day, following IRB, the dogs were placed under general anaesthesia, and the diaphragm was perfused via the internal mammary artery with a low molecular weight fluorescent tracer (Procion orange, FW = 631), to which normal muscle fibers are impermeable. Muscle fiber membrane damage was identified on tissue sections by using fluorescent microscopy showing the presence of the tracer in the cytoplasm. Four dogs undergoing the same protocol (except IRB) served as control. The dye was seen in 7.6 +/- 2.6% and in 0.3 +/- 0.1% of fibers in the IRB and control groups, respectively (p < 0.05). Via ATPase staining, it was found that fibers of type I were predominantly affected as compared to type II (p < 0.05). In addition, an increased area fraction of fibers demonstrating sarcomere disruption was found after IRB (2.4 +/- 0.5%) compared to pre-IRB (0.4 +/- 0.1%; p < 0.05). We conclude that resistive breathing of a magnitude similar to that seen in some respiratory diseases, or used in respiratory muscle training programs induces muscle membrane and sarcomere injury.

Animals↗
PubMed1996

Effects of diaphragm shortening on the mean action potential conduction velocity in canines.

1. The present study was designed to test if the mean muscle fibre action potential conduction velocity (VAPC) in the costal diaphragm changes with muscle length, in spontaneously breathing mongrel dogs. 2. VAPC was determined by the electromyogram (EMG) power spectrum 'dip' method, which is based on the bipolar electrode transfer function. A bipolar EMG electrode with a 20 mm fixed interelectrode distance was sutured to the costal diaphragm in the fibre direction, and in a region with a low density of motor endplates. Diaphragm length was measured with piezoelectric crystals positioned next to the EMG electrode. Seven dogs were vagotomized and spinally anaesthetized in order to increase diaphragmatic shortening, reduce velocity of shortening and abolish possible cross-talk signals from adjacent muscles. 3. Our results showed that VAPC in the canine costal diaphragm was 3.4 m s-1 and was not significantly related to diaphragmatic shortening.

Action Potentials↗
PubMed1996

Influence of the bipolar electrode transfer function on the electromyogram power spectrum.

This study demonstrates the impact of the bipolar electrode transfer function on the canine diaphragm electromyogram (EMG) power spectrum, as evaluated with a new electrode design and implantation technique. The results show that: (a) changes in interelectrode distance transformed single-peaked power spectrums into double-peaked spectrums; (b) the mean action potential conduction velocity (APCV), and power spectrum center frequency (CF) and median frequency (MF), are related for interelectrode distances of 5 and 10 mm, but not for 15 and 20 mm; and (C) CF, MF, -3-dB, and -6-dB bandwith values depend on interelectrode distance. We conclude that bipolar electrodes, with a nonfixed interelectrode distance, cannot be used for physiological interpretations of the EMG power spectrum. Nonetheless, power spectrums obtained with fixed and appropriate interelectrode distances can be trusted, if the electrodes are positioned in the direction of the muscle fibers and in regions with low densities of motor endplates.

Action Potentials↗
PubMed1995

Activity of costal and crural diaphragm during progressive hypoxia or hypercapnia.

Because costal and crural diaphragm segments have different functional characteristics, ventilatory stimulation with hypoxia or hypercapnia may elicit differential segmental function. We report measurements of diaphragm segmental length, shortening, and electromyogram (EMG) activity from 11 canines that were chronically implanted with sonomicrometry transducers and EMG electrodes and then studied a mean of 18 days postimplantation while awake and breathing spontaneously during CO2 rebreathing and progressive isocapnic hypoxia. Ventilatory responses to hypercapnia and progressive hypoxia were moderate at 1.13 +/- 0.31 (SD) 1. min-1. mm-1 arterial Pco2 and -0.98 +/- 0.51 l. min-1.%arterial O2 saturation-1. When tidal values for breathing pattern and segmental function were compared at matching tidal volumes that correspond to mean CO2 of 49.4 arterial Pco2 and 77% arterial O2 saturation, there was no significant difference in resting length, tidal shortening, or tidal EMG of costal or crural segments. Intrabreath profiles of flow, shortening, and EMG activity at matched tidal volumes showed that 1) inspiratory flow during hypoxia was significantly greater during early inspiration, 2) crural EMG activity preceded costal EMG activity in early inspiration during both hypercapnia and hypoxia, 3) both segments showed increased postinspiratory inspiratory activity with stimulated ventilation, and 4) postinspiratory shortening and EMG were greatest for the crural segment during hypoxia. These results suggest that costal and crural diaphragm segments exhibit differential function during chemical stimulation, especially during postinspiration.

Algorithms↗
PubMed1995

Automatic assessment of electromyogram quality.

Power spectrum analysis of the diaphragm electromyogram (EMGdi) is time consuming, and no criteria have been developed to objectively quantify contamination of the signal. The present work describes a set of computer algorithms that automatically select EMGdi free of the electrocardiogram and numerically quantify the common artifacts that affect the EMGdi. The algorithms were tested 1) on human EMGdi (n = 5) obtained with esophageal electrodes positioned at the level of the gastroesophageal junction, 2) on EMGdi obtained in mongrel dogs (n = 5) with intramuscular electrodes in the costal diaphragm, and 3) on computer-simulated power spectra. For authentic and simulated power spectra, indexes were obtained by the algorithms and were able to quantify signal disturbances induced by noise, electrode motion, esophageal peristalsis (in humans), and non-QRS complex-related electrocardiogram activity. With the index inclusion thresholds set to levels that allowed for a high signal acceptance rate with relatively small artifact-induced fluctuations (10-15%) of the EMGdi center frequency, the computer algorithms were found to be as reliable as or more reliable than other methods, including careful visual selection of the time domain signals by experienced analysts. In conclusion, the frequency domain application of computer algorithms offers a reliable and reproducible means to objectively quantify the sources that contaminate the interference pattern EMG.

Algorithms↗
PubMed1995

History of diaphragm physiology: the achievements of Galen.

Galen (129-200 AD) produced a large written output which was to remain one of the major basis of clinical medicine for centuries. His contribution to respiration, reported in his own books and in those of Oribasius, was that of a chest physician and of an experimental physiologist. He described in minute details how to perform a remarkable series of experiments by which he demonstrated the anatomy and function of the respiratory muscles. He described the actions of the diaphragm and how it moves the rib cage, in a series of spinal chord sections and muscle denervations. He investigated the passive or active nature of expiration and made fine observations of lung movements through the exposed pleural space. He described the interaction between the lungs and chest wall and developed the concept of interaction between ribcage and abdominal muscles in maintaining the position of the diaphragm, showing a clear understanding of the principle that the diaphragm can move upward during an isovolume manoeuvre as long as the ribcage is allowed to expand. A skillful clinician, Galen applied his theories of the analysis of problems at the bedside, particularly in patients affected with dyspnoea which he attributed to respiratory muscle dysfunction.

Animals↗
PubMed1994

Costal and crural diaphragm function during panting in awake canines.

During natural panting for thermal regulation, the pattern of activation of the major respiratory muscles, including costal and crural diaphragm segments, is not known. We measured diaphragm segmental length, shortening, and electromyographic (EMG) activity in five chronically implanted canines awake and breathing spontaneously at rest and during a mild dry heat stress. During panting, minute ventilation increased fourfold from 5.07 l/min and respiratory rate increased from 16.9 to 192.8 breaths/min or 3.2 Hz. During panting, end-expiratory length of both costal and crural segments decreased, concurrent with significant increases in end-expiratory EMG. With the onset of panting, tidal costal shortening decreased significantly from 6.29% of end-expiratory length to 3.54%, whereas crural shortening decreased from 6.04 to 2.46%. Meanwhile, segmental EMG tended to increase during panting. During panting, intrabreath costal and crural segmental function revealed differential activation; the costal segment shortened in concert with inspiratory flow, whereas peak crural shortening occurred in expiration, almost 180 degrees out of phase with costal. The divergence in segmental shortening during panting was accompanied by a lesser shift in timing of segmental EMG. In the awake spontaneously panting canine, asynchronous costal and crural shortening may enhance gas mixing in a manner analogous to high-frequency ventilation.

Animals↗
PubMed1994

The earliest history of diaphragm physiology.

The diaphragm was recognized as a distinct anatomical structure in the earliest Greek writings. However, the precise description of wounds suffered by warriors during the Trojan war by Homer was not tied to any particular function. The diaphragm was assimilated to the region that harbours thought. The first physiologic explanations of respiration by Empedocles in the 5th century BC and the concepts introduced by Plato and Hippocrates did not include a significant participation of the diaphragm. Aristole was the first to link respiration to a particular organ and a specific movement of the thorax. However, he considered that it was the heart which caused the lungs to expand by heating them, and the lungs in turn forced the thorax to dilate, a concept which was to survive until the 17th century. As in Aristole's theory the diaphragm played no role in respiration and was just a fence separating the thorax from the abdomen. A major break through occurred in Alexandria in the 4th and 3rd century BC: Herophilus was the first to recognize that muscles were the agents of movement and Erasistratus performed animal experiments which showed that the respiratory muscles were the agents of respiratory movements, thus opening the way to the later discoveries of Galen.

Anatomy↗
PubMed1993

Costal and crural diaphragm function during CO2 rebreathing in awake dogs.

If costal and crural diaphragm segments can perform as separate muscles, then CO2-stimulated ventilation may elicit differential segmental function. We studied diaphragm segmental length, shortening, and electromyogram (EMG) activity in 10 awake dogs chronically implanted with sonomicrometer transducers and EMG electrodes. During CO2 rebreathing, segmental shortening and EMG activity per whole tidal breath progressively increased, but segmental responses could not be differentiated at any level of CO2. With increasing CO2, resting end-expiratory length of both diaphragm segments increased. During the complete intrabreath inspiratory-expiratory cycle, costal and crural diaphragm revealed distinctive segmental function. At rest, crural shortening exceeded costal shortening in earliest inspiration, costal and especially crural shortening persisted into early expiration, and EMG activity of the crural segment was greater than that of the costal segment in earliest inspiration and showed more end-inspiratory/early expiratory [post-inspiratory inspiratory activity (PIIA)] activity. During CO2-stimulated breathing, neither segment shortened during the inspiratory flow of earliest inspiration. During CO2 rebreathing, shortening of the crural segment exceeded that of the costal segment during early inspiration and outlasted costal shortening during expiration; for both segments, shortening persisted after termination of inspiratory airflow. With increased CO2, EMG activity of the crural segment preceded that of the costal segment in earliest inspiration and was dominant into expiration, whereas costal EMG activity terminated abruptly with inspiratory flow. Thus, costal EMG PIIA was not evident during hypercapnia, whereas crural EMG PIIA was significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Mechanisms of muscle fatigue.

The concept of muscle fatigue as a factor limiting muscle performance has evolved into one in which fatigue is avoided in order to protect the muscle from injury induced by over stimulation. No one mechanism accounts for all the changes in muscle performance occurring during fatigue. Research on pathophysiological factors limiting force production or shortening capacity during the fatigue process has widened to detailed electrophysiologic, metabolic and molecular aspects. All are extensively reviewed in the present paper. The known mechanisms are likely to be interdependent, synergistic, and integrated. A careful interpretation of individual research is implied, particularly when data from experimental animal models are translated to human beings.

Action Potentials↗
PubMed1992

Optimal diaphragmatic blood perfusion.

The intrabreath time course of phrenic artery blood perfusion (Qpha) was studied in five anesthetized dogs. The diaphragm was paced with submaximal levels of stimulation at various duty cycles (DC) to achieve tension-time index below and above the fatigue threshold (0.03-0.60). Left Qpha was measured via Doppler technique during control (inactive diaphragm) and during two submaximal levels of bilateral phrenic nerve stimulation sustained for 1 min. Measurements were done when Qpha reached steady state in each run. The frequency of pacing of each run was 10/min, and the DC ranged from 0.1 to 0.9 in 0.1 increments. Shortening of costal and crural segments was measured by sonomicrometry. It was found that Qpha during the diaphragmatic contraction phase (QphaC) was a sigmoidal function of DC and was not affected by the levels of transdiaphragmatic pressure (Pdi) explored (34-64% of maximal Pdi). Qpha during the diaphragmatic relaxation phase (QphaR) was a parabolic function of the DC, reaching an optimal value at DC of approximately 0.3 at any given Pdi. QphaR increased significantly with the preceding level of Pdi. QphaT (the sum of QphaC and QphaR) was a parabolic function of DC, reaching peak values at DC of 0.4-0.6 and then decreasing. This function was similar at two levels of Pdi. Post-pacing hyperemia was directly related to tension-time index greater than 0.20.

Animals↗
PubMed1990

Contraction-dependent modulations in regional diaphragmatic blood flow.

Blood flow (Q) of the diaphragm was measured simultaneously with Doppler probes placed on diaphragmatic veins and an artery and by direct volumetric measurements obtained from cannulation of diaphragmatic blood vessels. The Doppler converting coefficients obtained were 6.27, 7.25, 4.21, and 41.07 ml.min-1.kHz-1 for left phrenic artery flow (Qpha), phrenic vein flow (Qphv), internal mammary vein flow (Qimv), and azygos vein flow (Qazv), respectively. The time course of Qpha, Qphv, Qimv, and Qazv after imposed patterns of diaphragmatic contraction was measured in nine anesthetized dogs. Each pattern consisted of various combinations of transdiaphragmatic pressure (Pdi), frequency of pacing (f), and duty cycle obtained by bilateral phrenic nerve stimulation. The dogs were prepared with chests open and loosely casted abdomens. Qpha, Qphv, Qimv, and Qazv were measured at rest (control, passive diaphragm, mechanical ventilation) and at two submaximal levels of stimulation (30 and 60% of Pdimax). The f was 10 or 30 cycles/min and the duty cycle was 0.25, 0.50, and 0.75. The results show 1) Qpha, Qphv, Qimv, and Qazv reached stable values (equilibration) after 30-36 s of pacing; 2) the steady Qpha, Qphv, and Qimv were linearly related to Pdi, and they were related by a parabolic function to duty cycle, whereas Qazv was not significantly affected by Pdi and increased linearly as a function of the duty cycle; 3) the diaphragmatic blood drainage was approximately 60% through the intercostal veins leading into the azygos trunk, 25% through the phrenic vein, and 15% through the internal mammary vein during pacing of the diaphragm at a duty cycle of 0.50 and 60% Pdimax; and 4) for a given pacing pattern, Qpha and Qphv increased with f, but Qimv and Qazv did not.

Animals↗
PubMed1990

Intrinsic PEEP and arterial PCO2 in stable patients with chronic obstructive pulmonary disease.

Dynamic pulmonary hyperinflation and intrinsic PEEP (PEEPi) are known to play an important role in causing acute respiratory failure in COPD patients. In the present study, we have explored (1) the prevalence and magnitude of PEEPi in stable COPD patients, and (2) the correlation of PEEPi with respiratory mechanics and PaCO2. In 96 stable COPD patients with varying degrees of airway obstruction, we measured pulmonary flow resistance (RL), dynamic lung compliance (CLdyn), breathing pattern, arterial blood gases, and dynamic PEEPi. Dynamic PEEPi was determined as a negative deflection in esophageal pressure from the start of inspiratory effort to the onset of inspiratory flow. A significant correlation was found between dynamic PEEPi and FEVi (% predicted; r = -0.56, p less than 0.001), between PEEPi and RL (r = 0.69, p less than 0.001), and between PaCO2 and PEEPi (r = 0.6, p less than 0.001). These results indicate that increased severity of airway obstruction promotes PEEPi and concomitant dynamic hyperinflation. This implies increased inspiratory work in the face of decreased effectiveness of the inspiratory muscles as pressure generators. The present results suggest that dynamic hyperinflation may play a role in causing chronic hypoventilation in COPD patients.

Aged↗