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Biomedical subjects

G Supinski

Publications and source records attributed to G Supinski.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effect of upper respiratory tract infection in patients with neuromuscular disease.

Respiratory muscle strength during acute upper respiratory tract infection (URI) was assessed in patients with various forms of neuromuscular disease. Vital capacity (VC), oxygen saturation, end-tidal PCO2, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were determined in 25 stable patients with various forms of neuromuscular disease. Thirteen episodes of URI developed in 10 patients. Respiratory parameters were reassessed within 24-36 h following the onset of symptoms in each patient. In patients with URI, mean baseline VC, MIP, and MEP were 1.16 L +/- 0.14, 49.2 cm H2O +/- 6.8, and 35.5 cm H2O +/- 3.8 and fell to 1.01 L +/- 0.15, 37.1 cm H2O +/- 6.2, and 25.5 cm H2O +/- 3.0 during URI (p < 0.05 for each), respectively. Mean baseline PCO2 and oxygen saturation were 39.1 mm Hg +/- 1.1 and 95.1% +/- 1.0, and during URI, 43.9 mm Hg +/- 2.1 (p < 0.05) and 95.0% +/- 1.0 (NS), respectively. Five episodes of significant hypercapnia were observed in 4 patients. All parameters returned to near baseline values following recovery. We conclude that patients with various forms of neuromuscular disease develop reductions in respiratory muscle strength in association with URI. Unlike normal subjects, however, these decrements in respiratory muscle function may result in symptoms of shortness of breath, reductions in vital capacity, and acute hypercapnia in this patient population.

Acute Disease↗
PubMed1996

Glutathione metabolic responses to loaded breathing: variation among respiratory muscles.

Several studies have shown that loaded breathing elicits an oxidation of reduced glutathione (GSH) to oxidized glutathione (GSSG) within the diaphragm, but the effects of loaded breathing on GSH and GSSG levels in other respiratory muscles have not been examined. The present experiment examined this issue by using decerebrate unanesthetized rats in which a large inspiratory resistive load was applied until respiratory arrest. Subsequently, muscle samples from the triangularis sterni, diaphragm (Dia), parasternal intercostal (PI), upper rib cage lateral intercostal, lower rib cage lateral intercostal, and soleus were assayed for GSH and GSSG. Glutathione levels were also measured on samples from unloaded control animals. We found that the Dia from loaded animals had a lower GSH level than did control animals (i.e., 653 +/- 99 and 928 +/- 40 nmol/gm for loaded and control groups, respectively; P < 0.05), higher GSSG level (68 +/- 14 and 32 &/- 7 nmol/gm for loaded and control groups, respectively; P < 0.05), and higher GSSG-to-GSH ratios (GSSG/GSH; 17.0 +/- 6.0 and 3.7 +/- 0.9% for loaded and control groups, respectively; (P <0.05). Of the other muscles examined, only the PI muscles had comparable alterations in glutathione levels in response to loading. Specifically, for the PI muscles of loaded and control groups, GSH was 427 +/- 75 and 618 +/- 40 nmol/g, (P < 0.05), GSSG was 71 +/- 16 and 20 +/- 5 nmol/g (P < 0.01), and GSSG/GSH was 22 +/- 8 and 3.6 +/- 1.2%, respectively (P < 0.05). No other muscle demonstrated a significant increase in GSSG or GSSG/GSH with loading, and only the lower rib cage lateral intercostal had a significant reduction in GSH. These findings indicate variation in the degree of glutathione oxidation elicited by inspiratory loading among the different respiratory muscles. The fact that quantitatively similar glutathione alterations were observed in the Dia and PI muscles suggests that these muscle groups may share a similar propensity to generate free radicals during inspiratory loading.

Animals↗
PubMed1996

Comparison of the effects of endotoxin on limb, respiratory, and cardiac muscles.

Recent work has shown that endotoxin administration produces reductions in respiratory muscle contractility and an increase in indexes of free radical-mediated lipid peroxidation within these muscles. It is not known, however, whether endotoxin-induced lipid peroxidation occurs only in the respiratory muscles or is a widespread phenomenon affecting all striated muscles. We therefore examined the effects of administration of a range of doses of endotoxin on the isometric force-generating ability and lipid peroxidation of three muscles: the diaphragm (Dia), a leg muscle [i.e., the flexor halluces longus (FHL)], and papillary cardiac muscle (Card). Studies were performed on hamsters divided into groups injected over 2 days with either saline or low, medium, or high doses of endotoxin. The animals were killed on the third study day, force generation by the three muscles was examined in vitro, and the muscles were assayed for 8-isoprostane, an index of lipid peroxidation. We found that endotoxin produced significant reductions in both FHL and Dia force generation, but Card force generation was unaffected. Changes in 8-isoprostane largely paralleled alterations in force, with endotoxin eliciting marked increases in Dia and FHL 8-isoprostane levels but no change in Card 8-isoprostane. These findings suggest that 1) lipid peroxidation and muscle dysfunction in response to endotoxin administration are not limited to the respiratory muscles but also occur in limb skeletal muscle and 2) cardiac muscle appear to be resistant to this particular mechanism of endotoxin-induced dysfunction.

Animals↗
PubMed1995

Effect of varying load magnitude on diaphragmatic glutathione metabolism during loaded breathing.

Some studies have suggested that protective mechanisms downregulate diaphragm activity during loaded breathing so as to prevent respiratory-muscle fatigue. Other work has indicated, however, that loading can sometimes elicit significant diaphragmatic fatigue, and that the development of fatigue may be related to alterations in diaphragmatic glutathione concentrations. One potential explanation for these discrepant observations is that the mechanism of respiratory failure may vary as a function of load magnitude, and that some loads evoke little fatigue whereas others produce substantial fatigue and glutathione alterations. The purpose of this study was to examine this issue by determining the diaphragmatic fatigue and alterations in glutathione concentrations produced by a range of inspiratory resistive loads. Experiments were performed on decerebrate rats divided into a control, unloaded group and a group loaded with small, medium, and large inspiratory resistive loads that were applied until respiratory failure occurred. After respiratory arrest, the animals' diaphragms were excised, an in vitro determination was done of diaphragm contractility characteristics, and samples of muscle were assayed for GSH (reduced glutathione) and GSSG (oxidized glutathione). We found that in vitro diaphragm force generation was severely reduced for loaded breathing, and surprisingly, that the magnitude of the low-frequency fatigue present was similar in the three loaded groups. Reductions in diaphragmatic GSH levels and increases in GSSG levels were found in all three loaded groups. Reductions in diaphragmatic GSH levels and increases in GSSG levels were found in all three loaded groups, but again, the magnitude of these changes were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Alterations in diaphragm strength and fatiguability in congestive heart failure.

Recent reports suggested that exercise intolerance associated with congestive heart failure (CHF) may be due to changes in peripheral limb muscle function. Our purpose was to determine whether CHF also elicits alterations in diaphragmatic function. CHF was induced in dogs by rapid ventricular pacing for a period of 4-6 wk. After signs of CHF developed, dogs were anesthetized and an acute study was performed to assess diaphragm function. Diaphragm strips were dissected in situ in the left costal diaphragm, the phrenic artery supplying these strips was cannulated, and strips were perfused with arterial blood at arteriovenous pressure gradient of 90 mmHg. Diaphragm strength and fatiguability were then determined, and phrenic flow response to transient arterial occlusion was assessed. A group of nonpaced normal dogs was similarly studied and served as controls. We found that CHF dogs had a significant reduction in diaphragm strength. For example, tetanic force in response to 100 Hz of stimulation was 25.5 +/- 1.0 N/cm2 in control dogs but only 19.6 +/- 1.9 kg/cm2 in CHF dogs (P < 0.02). In addition, CHF dogs had increased diaphragm fatiguability. Diaphragm force fell to 27 +/- 3% of its baseline value during a 30-min fatigue trial in CHF dogs but only to 44 +/- 4% in control dogs (P < 0.01). CHF dogs also had a altered phrenic arterial hyperemic response to arterial occlusion and a reduction in phrenic arterial blood flow achieved during the fatigue trial. We conclude that development of CHF is associated with significant alterations in diaphragmatic function, causing a marked increase in fatiguability.

Animals↗
PubMed1993

Effect of ischemia-reperfusion on diaphragm strength and fatigability.

Although episodes of prolonged limb skeletal muscle ischemia followed by periods of reperfusion and reoxygenation are known to elicit free radical-mediated injury, the susceptibility of the diaphragm to this form of injury is not known. The purpose of the present study was to determine the effects of a period of severe partial ischemia, followed by reperfusion, on diaphragm contractile function. We also examined the effect of administration of a free radical scavenger, dimethyl sulfoxide (DMSO), on the diaphragmatic response to ischemia-reperfusion. Experiments were performed on three groups of anesthetized dogs in which a vascularly isolated strip of diaphragm was dissected in situ: 1) a control group in which the diaphragm was perfused at the ambient systemic pressure, 2) a group in which the diaphragm was made ischemic for 3 h and reperfused for 1 h, and 3) a group given DMSO before periods of ischemia and reperfusion. In all groups, we measured diaphragm strip strength and fatigability; we also assessed diaphragm blood flow at several levels of contractile activity. Periods of ischemia, followed by reperfusion, were found to produce a downward shift of the diaphragm force-frequency relationship and also to markedly increase diaphragm fatigability. Diaphragm blood flow at rest and at low levels of contractile activity was unaffected by ischemia-reperfusion, but the flow achieved during fatiguing contractions was appreciably lower than that in nonischemic control animals. DMSO administration protected the diaphragm from the effects of ischemia-reperfusion, preventing alterations in fatigability and strength. Diaphragm flow in DMSO-treated animals was similar to that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects produced by infusion of a free radical-generating solution into the diaphragm.

Although studies have examined the susceptibility and pattern of injury induced by infusion of free radical-generating solutions into a number of vital organs, no such investigation has been performed for the diaphragm. The purpose of the present study was to examine the susceptibility of the diaphragm to damage by a free radical-generating solution (iron-ADP complexes). Studies were performed using an in situ canine diaphragmatic strip preparation in which the phrenic artery supplying the strip was cannulated and perfused with blood from the ipsilateral femoral artery. Four groups of studies were performed: (1) a group in which saline was infused into the arterial supply of the diaphragm for 15 min; (2) a group in which a solution of iron-ADP was infused; (3) a group in which both iron-ADP and superoxide dismutase (SOD), a free radical scavenger, were infused; and (4) a group given iron-ADP and denatured SOD. Strip tension and blood flow were monitored during electrically induced diaphragmatic contractions for 15 min before intraphrenic infusions, during the period of infusions, and for 90 min after cessation of infusions. We found that diaphragm tension did not change over time in saline-treated control animals but fell significantly in animals in which iron-ADP was infused. The effects of iron-ADP were largely prevented by concomitant administration of active SOD, but not by denatured SOD. On average, at 90 min after cessation of infusions, tension had fallen to 82 +/- 6, 41 +/- 8, 63 +/- 4, and 28 +/- 9% of its initial value in saline, iron-ADP, iron-ADP/SOD, and iron-ADP/denatured SOD groups, respectively (p < 0.001 for comparison of the four groups, with saline and iron-ADP/SOD groups different from the other two groups). Diaphragm blood flow did not change significantly in any group. These data suggest that free radical-mediated diaphragmatic injury can result in a marked reduction in diaphragm contractility.

Adenosine Diphosphate↗
PubMed1993

Effect of free radical scavengers on endotoxin-induced respiratory muscle dysfunction.

Recent studies have suggested that free radicals contribute to the diaphragmatic dysfunction observed in sepsis. However, previous work has not determined which species of free radicals are responsible for producing these effects or whether the intercostal muscles are affected similarly during sepsis. The purpose of this study was to examine these issues using a hamster model of endotoxin-mediated sepsis in which diaphragm and intercostal muscle function was assessed on muscle strips excised from these animals after killing. Several groups of animals were studied, including animals injected with (1) saline, (2) endotoxin, (3) endotoxin plus active PEG-SOD, a superoxide scavenger, (4) endotoxin plus active PEG-catalase, a hydrogen peroxide scavenger, (5) endotoxin plus DMSO, a hydroxyl scavenger, and (6) endotoxin plus denatured PEG-SOD. We found that endotoxin administration elicited significant reductions in diaphragm and intercostal muscle contractility. In each of the three groups of animals to which active free radical scavengers were administered, the effects of endotoxin were attenuated. Denatured PEG-SOD did not protect the respiratory muscles from endotoxin-mediated dysfunction, however. These data indicate that both the diaphragm and intercostal muscles are affected similarly by sepsis; moreover, several free radical species (superoxide ions, hydrogen peroxide, and hydroxyl ions) play a role in mediating this type of injury.

Animals↗
PubMed1992

Analysis of the contraction of series and parallel muscles working against elastic loads.

The purpose of the present study was to analyze the manner in which series and parallel arrangements of respiratory muscles, contracting together, augment the forces and displacements applied to external elastic loads over those produced by a single muscle contracting alone. We first developed a series of mathematical expressions to describe the behavior of various arrangements of muscles contracting against elastic loads. We then compared the predictions of these equations with the results from experiments in which the forces and displacements produced by simple arrangements of muscles were measured. Both theoretical and experimental results indicate that, against high elastic loads, parallel arrangements of muscle strips produce greater forces and greater displacements than do single muscles; parallel arrangements do not, however, significantly increase the displacement or force applied to low elastic loads. Conversely, series arrangements result in greater forces and greater displacement of low loads, but are no better than single muscles when contracting against high loads. Against moderate loads parallel and series arrangements of muscles appear to be equivalent in generating forces and displacements during contraction. This analysis suggests that a major determinant of the effects of contraction of various networks of inspiratory muscles is the magnitude and character of the respiratory impedance against which these muscles must work. The primary difference between series and parallel arrangements of muscles is that muscles arranged in series are most effective against low elastic loads and muscles in parallel act most effectively against high loads.

Animals↗
PubMed1992

Relationship between parasternal and external intercostal muscle length and load compensatory responses in dogs.

1. The effects of tracheal occlusion on peak parasternal (PA) and external intercostal (EI) (3rd interspace) EMG activities were examined at different end-expiratory lung volumes both above and below functional reserve capacity (FCR) in anaesthetized, vagotomized and spontaneously breathing dogs. 2. Parasternal (PA) and external intercostal (EI) muscle lengths were monitored in situ. The difference in peak EMG activity between free and occluded breaths (test breaths) was related to the coincident peak change in intercostal muscle length (delta L) for each muscle, respectively. 3. At FRC, tracheal occlusion resulted in compensatory augmentation of peak EI, but little change in peak PA EMG activities. At lung volumes below FRC, airway occlusion resulted in augmentation of both PA and EI activities. Responses to airway occlusion at lung volumes above FRC were variable. The magnitude and duration of these changes in EMG, however, could be linearly related to the value of delta L. With delta L = 0, there was no change in peak EI or PA EMG; for values of delta L less than 0, there was attenuation of EI and PA EMG; for delta L greater than 0, there was enhancement of EI and PA EMG activation. 4. The magnitude of the changes in EMG activity in response to tracheal occlusion was more prominent for the EI muscle compared to the PA, the latter of which are known to have much fewer muscle spindles than EI muscle. 5. Our results suggest that a difference in end-inspiratory muscle length between the control and occluded breaths is a stimulus for the intercostal response to applied loads implicating muscle spindles as the predominant receptor moderating these responses. We hypothesize that when delta L = 0, no change in EMG occurs since the spindles sense no change in muscle length. When delta L less than 0 (i.e. peak muscle length during the occluded breath is shorter than control) muscle spindles would be disengaged, resulting in a disfacilitation of EMG activity. Where delta L greater than 0 (i.e. peak muscle length during the occluded breath is longer than control), muscle spindles are stimulated, resulting in enhancement of EMG activity. 6. Additional doses of Nembutal (20 mg), which produced significant changes in breathing pattern, did not affect the magnitude of the load compensatory responses.

Animals↗
PubMed1992

Effect of PEG-superoxide dismutase on the diaphragmatic response to endotoxin.

Although it is known that endotoxin can induce diaphragmatic dysfunction, the mechanism of this effect is not fully understood. However, because the effects of endotoxin on other tissues appear to be mediated in part by free radicals, the present study sought to determine if free radicals may also contribute to the diaphragmatic dysfunction induced by endotoxin administration. Studies were performed on four groups of hamsters. One group of animals received intraperitoneal injections of endotoxin on the first and second days of study (i.e., 10 and 20 mg/kg, respectively). The second group received saline rather than endotoxin, the third group received both endotoxin and a free radical scavenger, PEG-SOD (2,000 U/kg given intraperitoneally every 12 h on Days 1 and 2), and the fourth group received PEG-SOD alone. All groups were killed on the third study day (i.e., 48 h after the initial injections). Diaphragmatic contractile function was assessed in vitro using muscle strips excised from the costal diaphragms of freshly killed animals; diaphragm samples were also assayed for malondialdehyde (MDA), a commonly used index of free-radical-mediated lipid peroxidation. MDA levels were higher in diaphragms from endotoxin-treated animals than from saline-treated control animals, and the contractility of diaphragm strips from endotoxin-treated animals was reduced when compared with strips from saline-treated control animals. Administration of PEG-SOD prevented MDA formation and contractile dysfunction in endotoxin-treated animals. Diaphragm contractility and MDA levels for animals given PEG-SOD alone were similar to those for saline-treated control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of acute fasting on diaphragm strength and endurance.

The effects of short periods of fasting on diaphragm contractile function remain unclear. The purpose of the present study was (1) to examine the relationship between duration of acute fasting and diaphragm contractile performance, and (2) to assess the effects of fasting on diaphragm glycogen stores and the relationship between changes in diaphragm function and alterations in muscle glycogen stores. Studies were performed on four groups of Syrian hamsters (nine animals in each group). One group served as a control and was allowed to feed normally, whereas the other three groups were fasted for either 1, 2, or 3 days. Diaphragm strips from animals were studied in vitro by measuring tension during electrically induced contractions. Two strips from each animal were studied; one strip was examined with a bath glucose equal to the prevailing blood glucose, and the second was preincubated in a high glucose solution (170 mg/dl) for 20 min. Fasting resulted in reductions in body weight, blood glucose concentrations, diaphragm strength, and diaphragm endurance in strips tested at the prevailing blood glucose levels. These effects were pronounced in animals fasted for 3 days, with little or no change in diaphragm contractility observed in animals fasted for shorter periods. Diaphragm weight, thickness, and glycogen content were unchanged in the fasted animals, as was the weight of the soleus muscle. Preincubation of strips from 3-day-fasted animals in a high glucose medium resulted in a significant increase in diaphragm strip strength and endurance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of N-acetylcysteine on diaphragm fatigue.

It has recently been postulated that diaphragm fatigue may be due, at least in part, to a form of low-grade injury to subcellular organelles. Moreover, several studies have shown that thiol-containing compounds can protect cardiac and striated skeletal muscle organelles from the deleterious effects of a number of physiological stresses. The purpose of the present study was to determine whether pretreatment with N-acetylcysteine (NAC), a thiol-containing compound, would attenuate the rate of development of diaphragmatic fatigue. Studies were performed with the use of an in situ rabbit diaphragm strip preparation that permitted direct and continuous measurement of diaphragm tension development. Diaphragm fatigue was induced by rhythmically stimulating strips to contract at 30/min (20-Hz trains) for 20 min. The diaphragm force-frequency relationship (10-, 20-, 50-, and 100-Hz stimuli) was assessed immediately before and after fatigue trials and then again 20 min into the period of recovery. Half the animals were treated with intravenous NAC before fatigue, whereas the remaining animals were given intravenous saline. The rate of development of fatigue was markedly greater in saline-treated control than in NAC-treated animals, with reductions in tension of 55 +/- 3 and 34 +/- 3%, respectively, in these two groups of animals over 20 min (P less than 0.001). Although rhythmic stimulation resulted in a downward shift in the force-frequency relationship in both NAC- and saline-treated animals, the magnitude of this shift was substantially greater in saline-treated animals (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗
PubMed1990

Effect of codeine on the sensations elicited by loaded breathing.

The present study examined the effect of codeine, a centrally acting opiate, on the respiratory sensations elicited in normal subjects by breathing to exhaustion against externally applied inspiratory threshold loads. Subjects were tested on two separate days following the double-blind, randomized administration of either placebo or codeine (90 mg). The intensity of the sensations of effort and discomfort experienced during two loaded breathing trials (a "high" load that was 73% of the maximum inspiratory pressure (MIP) and a "low" load that was 63% of the MIP) was evaluated using category (Borg) scores on each day of study. To verify that the dosage of codeine administered was sufficient to produce analgesia, we also determined the effect of this dosage on the time that subjects could tolerate immersion of one hand in ice water. Codeine altered neither the perceived effort nor the sense of discomfort associated with breathing against external loads and had no appreciable effect on the time to exhaustion during loaded breathing trials. This dose of codeine did, however, increase the time that ice water immersion could be tolerated and reduced the rate at which the sense of discomfort increased over time during ice water trials. These results indicate that, provided the pressure-time index of respiratory muscle contraction remains constant, analgesic doses of codeine alter neither the sensations elicited by loaded breathing nor the total time that breathing against a fatiguing inspiratory load can be tolerated.

Adult↗
PubMed1989

Inspiratory action of separate external and parasternal intercostal muscle contraction.

We have previously shown that electrical stimulation of the thoracic spinal cord produces near maximal activation of the inspiratory intercostal muscles. In the present investigation, we used this technique to evaluate the relative capacity of separate external (EI) and parasternal intercostal (PA) muscle contraction to produce changes in airway pressure and inspired volume. Studies were performed in 23 anesthetized phrenicotomized dogs. Electrical stimuli were applied to the spinal cord after hyperventilation-induced apnea, before and after sequentially severing either the PA or EI muscles from the first through sixth intercostal spaces. During spinal cord stimulation (SCS), measurements were made of inspired volume (delta V) with the airway open and negative airway pressure (delta P) during tracheal occlusion. Compared with control values, sectioning of the PA muscles resulted in a 40.9% reduction in delta P and 35.7% reduction in delta V during SCS. In other animals, initial sectioning of the EI muscles produced reductions in delta P and delta V of 67.4 and 63.0, respectively, during SCS. After subsequent section of the PA muscles, SCS produced only negligible inspired volumes and changes in airway pressure. We conclude that 1) the EI and PA muscles are each capable of generating substantial changes in airway pressure and large inspired volumes and 2) the ventilatory capacity of the EI muscles exceeds that of the PA muscles.

Animals↗
PubMed1988

Reversibility of diaphragm fatigue by mechanical hyperperfusion.

Diaphragm function is thought to depend on the balance between diaphragm blood flow and metabolic demand. If blood flow is inadequate, fatigue should ensue. Likewise, in the presence of fatigue, function should improve when blood flow is increased. To test this hypothesis, we evaluated the effect of increasing blood flow to the fatigued diaphragm. Studies were performed on anesthetized, mechanically ventilated dogs in which strips of costal diaphragm were developed in situ. Strip tension was measured with an isometric tension transducer. The inferior phrenic artery supplying the strip was cannulated and pump perfused at a pressure of 92 +/- 3 mm Hg; phrenic artery flow and pressure were continuously monitored with in-line doppler flow probes and pressure transducers, respectively. Fatigue was produced by electrically stimulating strips to contract 15 times/min (initial tension 80% of maximum, duty cycle 50%). Rhythmic contraction resulted in a downward shift in the diaphragm force-frequency relationship in all strips. In eight strips, stepwise increments in phrenic artery perfusion pressure to 161 +/- 8 and 281 +/- 17 mm Hg were produced by increasing pump speed at 6 and 8 min into rhythmic stimulation; in four strips, phrenic artery perfusion pressure was increased to 152 +/- 20 and 257 +/- 32 mm Hg at 20 and 25 min into rhythmic stimulation, respectively. Each increase in phrenic artery pressure resulted in increases in phrenic artery flow and diaphragm tension and produced an upshift in the diaphragm force-frequency relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effect of hypoxia on diaphragm blood flow, oxygen uptake, and contractility.

Recent studies examining the effects of hypoxia on diaphragm function have reached conflicting conclusions, with some reports suggesting an adverse effect of even mild hypoxemia while others indicate that the diaphragm may be extremely resistant to hypoxic stress. Diaphragm tension was not, however, directly measured nor was diaphragm length controlled in these previous reports, and it seems possible that methodologic limitations may have been responsible for these discrepant results. The purpose of the present study was to examine the effects of graded, steady-state hypoxia on diaphragm blood flow, oxygen extraction, oxygen consumption, and contractility using an in situ canine diaphragm strip preparation that permitted direct and continuous measurement of diaphragm length, tension, and blood flow. Measurements were made with the diaphragm at rest, during normoxia (PaO2, 90 to 160 mm Hg), mild hypoxia (PaO2, 45 to 60 mm Hg), and severe hypoxia (PaO2, 25 to 35 mm Hg); measurements were made with the diaphragm at rest, during rhythmic contractions at a tension time index (TTI) of 0.05, and with contractions at a TTI of 0.15. Decreases in arterial oxygenation resulted in progressive increases in blood flow and in the fractional extraction of oxygen in both resting and contracting diaphragm strips. At all levels of activity tested, blood flow and fractional extraction increased sufficiently to keep diaphragm oxygen consumption constant despite reductions in arterial oxygen content. Diaphragm contractility, as assessed from the tension generated in response to a range of electrical stimuli (1 to 80 Hz), was unaffected by hypoxia for trials performed with the diaphragm at rest and contracting at a TTI of 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗