Removal of mercaptans from a gas stream using continuous adsorption-regeneration.

The removal of the mercaptan, 1-methyl-1-propanethiol, from aqueous solutions using a non-porous, electrically conducting carbon-based adsorbent (Nyex 1000) was investigated. The adsorption process was found to be rapid (equilibrium capacity achieved within 5 minutes) with low adsorptive capacity (of the order of 0.4 mg g(-1)) when compared with activated carbon. Electrochemical regeneration of the Nyex 1000 in a simple divided electrochemical cell within a sequential batch treatment unit restored 100% of the adsorbent's adsorptive capacity using treatment times as low as 20 minutes by passing a current of 0.5 A. The sorptive characteristics of a Nyex-water slurry were also modelled and investigated both in a bubble column and in a continuous adsorption-regeneration treatment system. It was demonstrated that the continuous removal-destruction system could achieve a step reduction in challenge gas concentration of approximately 75% for a period of 35 minutes with a current of 5 Amps. This was attributed to mass transfer enhanced by a combination of adsorption and chemical reaction with free chlorine species generated in the electrochemical process.

Oxidised proteins and superoxide anion production in the diaphragm of severe COPD patients.

In the diaphragms of chronic obstructive pulmonary disease (COPD) patients, the nature of oxidatively modified proteins and superoxide anion production were explored. Diaphragm specimens were obtained through thoracotomy because of localised lung lesions in COPD patients (16 severe and eight moderate) and 10 control subjects. Lung and respiratory muscle functions were evaluated. Oxidised proteins were identified using immunoblotting and mass spectrometry. Protein and activity levels of the identified proteins were determined using immunoblotting and activity assays. Lucigenin-derived chemiluminescence signals in a luminometer were used to determine superoxide anion levels in muscle compartments (mitochondria, membrane and cytosol) using selective inhibitors. In severe COPD patients compared with controls, respiratory muscle function was impaired; creatine kinase, carbonic anhydrase III, actin and myosin were oxidised; myosin carbonylation levels were increased five-fold; creatine kinase content and activity and myosin protein were reduced; superoxide anion levels were increased in both mitochondria and membrane compartments; and the percentage of superoxide anion inhibition achieved by rotenone was significantly greater. In severe COPD patients, oxidation of diaphragm proteins involved in energy production and contractile performance is likely to partially contribute to the documented respiratory muscle dysfunction. Furthermore, generation of the superoxide anion was increased in the diaphragms of these patients.

Transcriptome of angiopoietin 1-activated human umbilical vein endothelial cells.

Angiopoietin 1 (Ang-1) is the main ligand for endothelial cell-specific tyrosine kinase (Tie-2) receptors and it promotes migration and proliferation and inhibits apoptosis and vascular leakage. The exact mechanisms through which the Ang-1 exerts these effects remain unclear. The authors exposed human umbilical vein endothelial cells (HUVECs) to Ang-1 (300 ng/mL) for 4 h and conducted gene expression profiling using oligonucleotide microarrays. Real-time polymerase chain reaction (PCR) was also conducted to verify several of the genes that were regulated by Ang-1. Exposure to Ang-1 resulted in induction of 86 genes that are involved in endothelial cell (EC) proliferation, differentiation, migration, and survival. Thirty-six of these genes, including stanniocalcin, cyclin D1, vascular endothelial growth factor C, fms-related tyrosine kinase 1, interleukin 8, and CXCR4 have previously been shown to be induced by vascular endothelial growth factor (VEGF), suggesting significant similarities between VEGF and Ang-1 pathways. Ang-1 exposure also inhibited mRNA expressions of 49 genes, most of which are involved in cell cycle arrest, apoptosis, and suppression of transcription. These results indicate that Ang-1 triggers coordinated responses in endothelial cells designed to inhibit the expression of proapoptotic and antiproliferative genes and up-regulate proproliferative, proangiogenic, and antiapoptotic pathways. Moreover, we also found that the Erk1/2, phosphatidylinositol (PI) 3-kinase, and the mTOR pathways are involved in Ang-1-induced gene expression in HUVECs.

Respiratory loading intensity and diaphragm oxidative stress: N-acetyl-cysteine effects.

We hypothesized that resistive breathing of moderate to high intensity might increase diaphragm oxidative stress, which could be partially attenuated by antioxidants. Our objective was to assess the levels of oxidative stress in the dog diaphragm after respiratory muscle training of a wide range of intensities and whether N-acetyl-cysteine (NAC) might act as an antioxidant. Twelve Beagle dogs were anesthetized with 1% propophol, tracheostomized, and subjected to continuous inspiratory resistive breathing (IRB) (2 h/day for 2 wk). They were further divided into two groups (n = 6): NAC group (oral NAC administration/24 h for 14 days) and control group (placebo). Diaphragm biopsies were obtained before (baseline biopsy) and after (contralateral hemidiaphragm) IRB and NAC vs. placebo treatment. Oxidative stress was evaluated in all diaphragm biopsies through determination of 3-nitrotyrosine immunoreactivity, protein carbonylation, hydroxynoneal protein adducts, Mn-SOD, and catalase, using immunoblotting and immunohistochemistry. Both protein tyrosine nitration and protein carbonylation were directly related to the amount of the respiratory loads, and NAC treatment abrogated this proportional rise in these two indexes of oxidative stress in response to increasing inspiratory loads. A post hoc analysis revealed that only the diaphragms of dogs subjected to high-intensity loads showed a significant increase in both protein tyrosine nitration and carbonylation, which were also significantly reduced by NAC treatment. These results suggest that high-intensity respiratory loading-induced oxidative stress may be neutralized by NAC treatment during IRB in the canine diaphragm.

Regulation of baseline vascular resistance in the canine diaphragm by nitric oxide.

1. The role played by nitric oxide (NO) in the regulation of blood flow to the canine isolated hemidiaphragm was evaluated by determining (a) the effects of the L-arginine analogues NG-nitro-L-arginine methyl ester (L-NAME), NG-nitro-L-arginine (L-NOARG), and argininosuccinic acid (ArgSA) on baseline vascular resistance and of the latter two agents on endothelium-dependent (acetylcholine, ACh) and endothelium independent (sodium nitroprusside, SNP) vasodilatation; (b) the effects of L- and D-arginine on baseline vascular resistance; and (c) the effects of L-glutamine, an inhibitor of intracellular recycling of L-citrulline to L-arginine, on baseline resistance and on the response to ACh and SNP. 2. L-NAME, L-NOARG and ArgSA (6 x 10(-4) M final concentration) increased baseline diaphragmatic vascular resistance to a similar extent (28.6 +/- 4.2%, 26.7 +/- 4.3% and 32.8 +/- 4.6% respectively). L-NOARG and ArgSA reversed the vasodilator effect of ACh but not of SNP. 3. L- and D-arginine had no effect on vascular resistance. 4. L-Glutamine (10(-3) M) increased baseline vascular resistance by 10 +/- 1.9% (P < 0.05) but did not alter responses to either ACh or SNP. 5. Basal NO release plays a role in the regulation of baseline diaphragmatic vascular resistance. L-Arginine analogues tested potently and specifically inhibited this process. Moreover, extracellular L-arginine appears to have no effect on baseline diaphragmatic vascular resistance.

Intrathoracic and extrathoracic sources of exhaled nitric oxide in porcine endotoxemic shock.

OBJECTIVES: Nitric oxide (NO), a highly reactive species produced by the activity of NO synthases (NOS), is normally present in the exhaled air of humans and animals. Exhaled NO concentration increases significantly in humans with sepsis and animals, but neither the source nor NOS isoforms responsible for this rise in pulmonary NO production are known. The main objective of this study is to determine the sites and the mechanisms of enhanced NO production in the exhaled air of endotoxemic pigs. DESIGN: Randomized, controlled, animal study. SETTING: University-based animal research facility. SUBJECTS: Thirteen pathogen-free adult female pigs (22 to 27 kg). INTERVENTIONS: Anesthetized pigs were divided into two groups: control and lipopolysaccharides (LPS) (septic) groups. In both groups, extrathoracic (upper airways, nasal, and paranasal) and intrathoracic (bronchi, bronchioles, and alveoli) compartments were ventilated equally with two separate ventilators connected to two tracheal tubes. The LPS group received slow infusion (over 2 h) of Escherichia coli endotoxin (10 microg/kg/h), whereas saline solution was infused into the control group. Expired air of the two compartments was collected throughout the 2-h observation period. The animals were then killed and the lungs were quickly excised and frozen. MEASUREMENTS: Hemodynamic variables were measured in both groups. NO concentration in the exhaled air of both compartments was measured with a chemiluminescence analyser. Pulmonary NOS activity was evaluated by measuring the conversion of L-[2,3H]-arginine to L-[2,3H]-citrulline, and pulmonary expression of NOS was evaluated by immunoblotting. RESULTS: Baseline NO concentration in both groups was significantly higher in the extrathoracic vs intrathoracic compartment (average of 5.2 vs 3.4 parts per billion). Endotoxin infusion elicited a significant and early (after 45 min) rise in exhaled NO concentration in the extrathoracic compartment. Exhaled NO in the intrathoracic compartment also rose significantly but after 90 min of endotoxin infusion. Measurement of lung NOS activity showed a substantial rise in Ca++/calmodulin-dependent activity in the LPS group with no rise in Ca++/calmodulin-independent activity. Immunoblotting of lung tissue samples indicated the absence of the inducible isoform in both groups of animals. Moreover, LPS injection elicited no significant alterations in the pulmonary expression of the endothelial and the neuronal isoforms. CONCLUSIONS: Both extrathoracic and intrathoracic compartments contribute to the rise in exhaled NO production in experimental septic shock. The rise in exhaled NO production is due to increased activity of constitutive NOS isoforms as a result of increased cofactor availability and/or downregulation of the endogenous inhibitors of NOS.

Relationship of resting lung mechanics and exercise pattern of breathing in patients with chronic obstructive lung disease.

To investigate the influence of resting pulmonary mechanics on the pattern of breathing during exercise in chronic obstructive pulmonary disease (COPD), we studied 29 patients with moderate to severe COPD (FEV1 50 +/- 20 percent predicted), and 10 normal subjects. Lung mechanics were studied using esophageal balloon technique and body-box. Incremental exercise testing was performed to exhaustion. As minute ventilation (VE) increases, COPD patients with the highest pulmonary resistance (RI) or lowest elastic recoil pressure (PL), used a greater tidal volume/vital capacity ratio (VT/VC) than the COPD patients with more normal RL or lowest PL. To describe the breathing pattern during exercise, an exponential constant (K) describes the rates of increase in VT/VC ratio with increasing VE, calculated according to the equation VT = VC(1-e-KVE). The K values achieved by COPD patients were higher than in normal subjects. In addition, K value correlated negatively with the resting FEV1 and FVC of COPD patients. When COPD patients were grouped according to their K values, it was revealed that patients with high K values generated greater VT/VC ratio and also have the most abnormal resting lung mechanics. These results suggest that the exercise breathing pattern in COPD patients is significantly influenced by the degree of impairment of resting lung mechanics.

Regulation of ventilatory muscle blood flow.

The ventilatory muscles perform various functions such as ventilation of the lungs, postural stabilization, and expulsive maneuvers (e.g., coughing). They are classified in functional terms as inspiratory muscles, which include the diaphragm, parasternal intercostal, external intercostal, scalene, and sternocleidomastoid muscles; and expiratory muscles, which include the abdominal muscles, internal intercostal, and triangularis sterni. The ventilatory muscles require high-energy phosphate compounds such as ATP to fuel the biochemical and physical processes of contraction and relaxation. Maintaining adequate intracellular concentrations of these compounds depends on adequate intracellular substrate levels and delivery of these substrates by arterial blood flow. In addition to the delivery of substrates, blood flow influences muscle function through the removal of metabolic by-products, which, if accumulated, could exert negative effects on several excitatory and contractile processes. Skeletal muscle substrate utilization is also dependent on the ability to extract substrates from arterial blood, which, in turn, is accomplished by increasing the total number of perfused capillaries. It follows that matching perfusion to metabolic demands is critical for the maintenance of normal muscle contractile function. In this article, I review the factors that influence ventilatory muscle blood flow. Major emphasis is placed on the diaphragm because a large number of published reports deal with diaphragmatic blood flow. The second reason for focusing on the diaphragm is because it is the largest and most important inspiratory muscle.

Inspiratory muscle function with restrictive chest wall loading during exercise in normal humans.

The effects of selective restriction of rib cage (Res,rc) and abdominal wall (Res,ab) movements on endurance of short-term constant-load heavy exercise and on diaphragmatic function during such exercise were examined in five normal young men. An inelastic surgical corset was used to achieve Res,rc and Res,ab. Subjects exercised on a cycle ergometer at 80% of their maximum power output to exhaustion on three occasions: with Res,rc, with Res,ab, and without restriction of chest wall movements (control). Transdiaphragmatic (Pdi), esophageal, and gastric pressures were measured. Electromyogram of the diaphragm was recorded by an esophageal electrode, and the ratio of the power content of a high-frequency to low-frequency band (H/L ratio) was measured. In addition, maximum Pdi (Pdimax) pre- and immediately postexercise was recorded. Res,rc was associated with a shorter endurance time, a progressive decline of the H/L ratio, and a significant reduction of Pdimax postexercise, whereas no such changes were found with Res,ab. We conclude that diaphragmatic function was well defended with abdominal wall loading, whereas limitation of rib cage expansion reduced diaphragmatic endurance during exercise. The diaphragmatic tension-time index (TTdi) in exercise was always less than the critical value of 0.15 found by Bellemare and Grassino (J. Appl. Physiol. 53: 1190-1195, 1982) when subjects inspired against large resistive loads at normal minute ventilations. We suggest that the higher inspiratory flow rate (P less than 0.05) and breathing frequency (P less than 0.05) account for the occurrence of diaphragmatic fatigue in exercise with Res,rc when the TTdi was 0.06 +/- 0.02.

Diaphragmatic intramuscular pressure in relation to tension, shortening, and blood flow.

We used an in situ isolated diaphragmatic preparation in anesthetized dogs to relate intramuscular pressure (IMP) to the blood flow, tension, and shortening of the diaphragm. In this preparation, the diaphragm shortens in a fashion similar to the intact diaphragm. Tension was measured by transducers attached to the left costal margin, which was detached from the rib cage and abdomen; IMP was measured by a miniature transducer placed between muscle fibers; length was measured by sonomicrometry; and diaphragmatic blood flow was monitored by measuring left phrenic arterial flow. In protocol 1, the relationships between tension, shortening, and IMP were assessed by stimulating the diaphragm for 2 s at various frequencies. Tension and shortening increased with increasing stimulation frequency up to 50 Hz with no change thereafter. Tension was linearly related to IMP. Similarly, there was a linear relationship between the degree of shortening and IMP; however, the slopes varied considerably between dogs. In protocol 2, the diaphragm was paced intermittently (12 trains/min, duty cycle of 0.5) with a gradual increase in stimulation frequency. Blood flow during contraction phase rose slightly at low tension and then declined significantly when tension exceeded 30% of maximum, whereas relaxation-phase flow increased with the increase in tension. IMP rose linearly with the increase in tension, and the IMP, at the point where contraction-phase flow became severely limited, was 50 +/- 14 mmHg (mean +/- SE). We conclude the following. 1) IMP is linearly related to tension and shortening; however, because tension and shortening changed simultaneously during contractions, the independent relationship of either tension or shortening and IMP remained untested.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of respiratory muscle and organ blood flow during endotoxic shock in dogs.

Respiratory muscle blood flow and organ blood flow during endotoxic shock were studied in spontaneously breathing dogs (SB, n = 6) and mechanically ventilated dogs (MV, n = 5) with radiolabeled microspheres. Shock was produced by a 5-min intravenous injection of Escherichia coli endotoxin (0.55:B5, Difco, 10 mg/kg) suspended in saline. Mean arterial blood pressure and cardiac output in the SB group dropped to 59 and 45% of control values, respectively. There was a similar reduction in arterial blood pressure and cardiac output in the MV group. Total respiratory muscle blood flow in the SB group increased significantly from the control value of 51 +/- 4 ml/min (mean +/- SE) to 101 +/- 22 ml/min at 60 min of shock. In the MV group, respiratory muscle perfusion fell from control values of 43 +/- 12 ml/min to 25 +/- 3 ml/min at 60 min of shock. In the SB group, 8.8% of the cardiac output was received by the respiratory muscle during shock in comparison with 1.9% in the MV group. In both groups of dogs, blood flow to most organs was compromised during shock; however, blood flow to the brain, gut, and skeletal muscles was higher in the MV group than in the SB group. Thus by mechanical ventilation a fraction of the cardiac output used by the working respiratory muscles can be made available for perfusion of other organs during endotoxic shock.

Diaphragmatic pressure-flow relationship during hemorrhagic shock: role of nitric oxide.

In the vascularly isolated resting and contracting (3 Hz) canine hemidiaphragm, we studied the effect of intra-arterial infusion of the nitric oxide (NO) inhibitor NG-nitro-L-arginine (LNA) on the relationship between phrenic arterial perfusion pressure (Pphr) and blood flow (Qphr). In separate groups of animals, either saline or LNA (final concn 6 x 10(-4) M) was infused into the phrenic artery over 20 min. The diaphragm was then autoperfused by diverting flow from the left femoral artery. Arterial blood pressure was reduced in stages by controlled hemorrhage. The Pphr-to-Qphr relationship was plotted for each animal, and the third-order polynomial of best fit was determined by least squares regression. The inflection point of this relationship was determined for each animal. In the contracting and resting diaphragms, the inflection point corresponded to Pphr values of 83.6 +/- 4.7 and 72.5 +/- 6.8 mmHg, respectively, in the saline-treated group compared with 86.2 +/- 2.7 and 76.8 +/- 5.1 mmHg, respectively, in the LNA-treated group. In the contracting diaphragm, LNA reduced Qphr uniformly across the entire range of perfusion pressures. In the resting diaphragm, the effect of LNA was not uniform. At perfusion pressures below the inflection point, the flow was reduced in proportion to the reduction in inflection point flow. At higher perfusion pressures, Qphr was decreased to a greater extent than could be accounted for by the change in inflection point flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoregulation of diaphragmatic blood flow in dogs.

In eight anesthetized spontaneously breathing dogs, we determined whether diaphragmatic blood flow is dependent on arterial blood pressure (Pa) or whether it is autoregulated. We also determined whether diaphragmatic muscular activity affects the degree of autoregulation. We measured blood flow through the left phrenic artery (Qphr) with an electromagnetic flow probe and decreased Pa in steps by controlled hemorrhage. Phrenic venous blood was sampled to allow the calculation of diaphragmatic O2 consumption (VO2phr). Diaphragmatic energy demands were varied by using three inspiratory resistances (R1, R2, and R3), which increased peak transdiaphragmatic pressure two-, three-, and fourfold, respectively. During quiet breathing, Qphr was independent of Pa between Pa of 90 and 120 mmHg (i.e., plateau of pressure-flow relation), but at lower Pa, Qphr was directly related to Pa. During inspiratory loading, the Qphr plateau ended at a higher Pa than with quiet breathing, but within the normal ranges of Pa there still was a plateau. VO2phr at a given work load was constant between Pa of 70 and 120 mmHg, but at Pa of 50-55 mmHg, VO2phr declined with all work loads. We conclude that in spontaneously breathing dogs 1) Qphr is autoregulated over the normal range of blood pressures and 2) VO2phr is maintained over wider ranges of Pa than Qphr.

In situ isolated perfused and innervated left hemidiaphragm preparation.

We developed a vascularly isolated in situ preparation of the left hemidiaphragm in which arterial blood was only provided through the left phrenic artery and the venous blood only drained through the phrenic vein. The costal margins were secured and connected to three force transducers. Muscle shortening was measured by sonomicrometry. The presence of arterial collaterals between the left hemidiaphragm and the systemic circulation was excluded by the systemic injection of a vital dye (Lissamine Green), a neuromuscular blocking agent (succinylcholine), and by the injection of epinephrine. Left phrenic nerve stimulation produced homogeneous shortening and tension. The degree of shortening in the isolated and intact left diaphragm at the same resting length was similar. The preparation was stable for 2 h with less than 10% decline in maximum tension. Two advantages of this preparation are particularly important. 1) Diaphragmatic energetics can be studied independently of systemic factors, and 2) the role of phrenic nerve afferents in the control of breathing and systemic circulation can easily be assessed without activating nonphrenic nerve afferents.

Respiratory muscle fatigue: a cause of ventilatory failure in septic shock.

The effect of endotoxic shock on the respiratory muscle performance was studied in spontaneously breathing dogs given Escherichia coli endotoxin (Difco Laboratories, 10 mg/kg). Diaphragmatic (Edi) and parasternal intercostal (Eic) electromyograms were recorded using fishhook electrodes. The recorded signals were then rectified and electrically integrated. Pleural, abdominal, and transdiaphragmatic (Pdi) pressures were recorded by a balloon-catheter system. After a short control period, the endotoxin was administered slowly intravenously (within 5 min). Death was secondary to respiratory arrest in all animals. All animals died within 150-270 min after the onset of endotoxic shock. Within 45-80 min of the endotoxin administration, mean blood pressure and cardiac output dropped to 42.1 +/- 4.1 and 40.1 +/- 6.0% (mean +/- SE) of control values, respectively, with little change afterward. Mean inspiratory flow rate and Pdi increased from control values of 0.27 +/- 0.03 l X s-1 and 5.75 +/- 0.7 cmH2O to mean values of 0.44 +/- 0.3 l X s-1 and 8.70 +/- 1.05 cmH2O and then decreased to 0.17 +/- 0.03 l X s-1 and 3.90 +/- 0.30 cmH2O before the death of the animals. There were no major changes in the mechanics of the respiratory system. Edi and Eic increased progressively to mean values of 360 +/- 21 and 263 +/- 22% of control, respectively, before the death of the animals. None of the dogs were hypoxic. Arterial PCO2 decreased from a control value of 42.9 +/- 1.7 Torr to a mean value of 29.9 +/- 2.8 Torr and then increased to 51 +/- 4.3 Torr before the death of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of nitric oxide production in response to skeletal muscle activation.

Nitric oxide (NO) is synthesized in normal muscle fibers by the neuronal (nNOS) and the endothelial (ecNOS) isoforms of nitric oxide synthase (NOS). NO contributes to the regulation of several processes such as excitation-contraction coupling and mitochondrial respiration. We assessed in this study whether NO production is regulated in response to an acute increase in muscle activation. Three groups of anesthetized, tracheostomized, spontaneously breathing rats were examined after an experimental period of 3 h. Group 1 served as a control (no loading), whereas groups 2 and 3 were exposed to moderate and severe inspiratory resistive loads, respectively, which elicited tracheal pressures of 30 and 70% of maximum, respectively. Ventilatory (diaphragm, intercostal, and transverse abdominis) and limb (gastrocnemius) muscles were excised at the end of the experimental period and examined for NOS activity and NOS protein expression. Neither submaximal nor maximum tracheal pressures were altered after 3 h of resistive loading. Diaphragmatic and intercostal muscle NOS activities declined significantly in response to moderate and severe loading, whereas those of transverse abdominis and gastrocnemius muscles remained unchanged. On the other hand, resistive loading had no significant effect on ventilatory and limb muscle NOS isoform expression. We propose that a contraction-induced decline in muscle NOS activity represents a compensatory mechanism through which muscle contractility and mitochondrial function are protected from the inhibitory influence of NO.

Effects of tension, duty cycle, and arterial pressure on diaphragmatic blood flow in dogs.

We investigated the selective effects of changes in transdiaphragmatic pressure (Pdi) and duty cycle on diaphragmatic blood flow in supine dogs at normal arterial pressure (N), moderate hypotension (MH), and severe hypotension (SH) [mean arterial pressure (Part) of 116, 75, and 50 mmHg, respectively]. The diaphragm was paced at a rate of 12/min by bilateral phrenic nerve stimulation. Left phrenic (Qphr-T) and left internal mammary (Qim-T) arterial flows were measured by electromagnetic flow probes. Changes in Pdi and duty cycle were achieved by changing the stimulation frequencies and the duration of contraction, whereas Part changes were produced by bleeding. With N and at a duty cycle of 0.5, incremental increases in Pdi produced peaks in Qphr-T and Qim-T at 30% maximum diaphragmatic pressure (Pdimax) with a gradual decline at higher Pdi. With MH and SH, blood flow peaked at 10% Pdimax. At any given Pdi, blood flow was lower with MH and SH in comparison to N. The effect of duty cycle was tested at two levels of Pdi. With N and at low Pdi (25% Pdimax), blood flow rose progressively with increases in duty cycle, whereas at moderate Pdi level (50% Pdimax) blood flow peaked at a duty cycle of 0.3, with no increase thereafter. With MH, blood flow at low Pdi rose linearly with increasing duty cycle but to a lesser extent than with N, and at a moderate Pdi flow peaked at a duty cycle of 0.3. With SH, blood flow at low and moderate Pdi was limited at duty cycles greater than 0.3 and 0.1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Diaphragmatic energetics and blood flow during pulmonary edema and hypotension.

We studied the role of O2 supply and demand factors for producing diaphragmatic failure in a canine model of cardiogenic shock with pulmonary edema. We produced pulmonary edema with oleic acid and then hypotension with cardiac tamponade and followed the animals until respiratory failure began, which was defined by a 50% fall in frequency of breathing and diaphragmatic pressure-time index (PTI; cmH2O.s-1.min-1) with no decrease in the diaphragmatic electromyogram. Regional blood flows were measured with radiolabeled microspheres. Diaphragmatic O2 consumption (VO2 di) (ml.min-1.100 g-1) was determined from the diaphragmatic blood flow (Qdi) and the arterial and phrenic venous O2 contents. With oleic acid-induced pulmonary edema, PTI Qdi, and VO2 di increased from control of 101.7 +/- 31.7, 17 +/- 1.8, and 0.81 +/- 0.11, respectively, to 187.2 +/- 27.6, 42.2 +/- 7.2, and 3.32 +/- 0.35 (P less than 0.05). With tamponade, PTI did not change (186.7 +/- 60.0), whereas VO2 di increased further to 3.98 +/- 0.98 (P less than 0.05) due to increased O2 extraction and no significant change in Qdi (32.8 +/- 4.0). As fatigue developed, VO2 di decreased to 2.30 +/- 0.23 due to the combined effects of small declines in Qdi and the arterial O2 content but remained higher than control even though the energy demands returned to control values. In conclusion, when cardiogenic shock is added to pulmonary edema VO2 di and energy output do not increase further and eventually fall.

Mechanical impedance as determinant of inspiratory neural drive during exercise in humans.

Five healthy males exercised progressively with small 2-min increments in work load. We measured inspiratory drive (occlusion pressure, P0.1), pulmonary resistance (RL), dynamic pulmonary compliance (Cdyn), transdiaphragmatic pressure (Pdi), and diaphragmatic electromyogram (EMGdi). Minute ventilation (VE), mean inspiratory flow rate (VT/TI), and P0.1 all increased exponentially with increased work load, but P0.1 increased at a faster rate than did VT/TI or VE. Thus effective impedance (P0.1/VT/TI) rose throughout exercise. The increasing P0.1 was mostly due to augmented Pdi and coincided with increased EMGdi during this initial portion of inspiration. We found no consistent change in RL or Cdyn throughout exercise. With He breathing (80% He-20% O2), RL was reduced at all work loads; P0.1 fell in comparison with air-breathing values and VE, VT, and VT/TI rose in moderate and heavy work; and P0.1/VT/TI was unchanged with increasing exercise loads. Step reductions in gas density at a constant work load of any intensity showed an immediate reduction in the rate of rise of EMGdi and Pdi followed by increased VT/TI, breathing frequency, and hypocapnia. These changes were maintained during prolonged periods of unloading and were immediately reversible on return to air breathing. These data are consistent with the existence of a reflex effect on the magnitude of inspiratory neural drive during exercise that is sensitive to the load presented by the normal mechanical time constant of the respiratory system. This "load" is a significant determinant of the hyperpneic response and thus of the maintenance of normocapnia during exercise.

Effects of diaphragmatic ischemia on the inspiratory motor drive.

To assess the effect of diaphragmatic ischemia on the inspiratory motor drive, we studied the in situ isolated and innervated left diaphragm in anesthetized, vagotomized, and mechanically ventilated dogs. The arterial and venous vessels of the left diaphragm were catheterized and isolated from the systemic circulation. Inspiratory muscle activation was assessed by recording the integrated electromyographic (EMG) activity of the left and right costal diaphragms and parasternal intercostal and alae nasi muscles. Tension generated by the left diaphragm during spontaneous breathing attempts was also measured. In eight animals, left diaphragmatic ischemia was induced by occluding the phrenic artery for 20 min, followed by 10 min of reperfusion. This elicited a progressive increase in EMG activity of the left and right diaphragms and parasternal and alae nasi muscles to 170, 157, 152, and 128% of baseline values, respectively, an increase in the frequency of breathing efforts, and no change in left diaphragmatic spontaneous tension. Thus the ratio of left diaphragmatic EMG to tension rose progressively during ischemia. During reperfusion, only the frequency of breathing efforts and alae nasi EMG recovered completely. In four additional animals, left diaphragmatic ischemia was induced after the left phrenic nerve was sectioned. Neither EMG activity of inspiratory muscles nor respiratory timing changed significantly during ischemia. In conclusion, diaphragmatic ischemia increases inspiratory motor drive through activation of phrenic afferents. The changes in alae nasi activity and respiratory timing indicate that this influence is achieved through supraspinal pathways.