Diaphragm metabolism during supramaximal phrenic nerve stimulation

The metabolic changes accompanying diaphragm fatigue caused by supramaximal stimulation of the phrenic nerves are incompletely described. In particular, we wished to determine whether the occurrence of anaerobic metabolism correlated with fatigue as defined by decline in force generation. In 10 anesthetized mechanically ventilated mongrel dogs we measured arterial pressure, transdiaphragmatic pressure (Pdi), phrenic arterial flow (Qdi-Doppler flow probe), arterial and phrenic venous blood gases, and lactate levels. From these we derived indexes of diaphragm O2 consumption (VO2) and lactate production. Bilateral phrenic nerve pacing was carried out (50 Hz, duty cycle 0.4, 24 contractions/min) for two 15-min pacing periods separated by a 45-min rest period. Over each pacing period Pdi decreased from approximately 16 to approximately 10 cmH2O (P less than 0.01, no significant difference between periods). Initially, during pacing, Qdi and VO2 each increased fivefold over prepacing base line. Qdi remained elevated at this level whereas VO2 decreased over the pacing period by approximately 25%. Hence, the change in VO2 over the pacing period was due primarily to changes in O2 extraction. During the first pacing period lactate production was observed early and declined throughout the pacing period. No lactate production was observed during the second pacing period, although Pdi, VO2, and Qdi responses were the same for both pacing periods. Phrenic venous PO2 remained greater than 30 Torr throughout both pacing periods.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of digoxin on diaphragmatic strength generation

Contrary to hindlimb muscle, extracellular calcium plays an important role in diaphragmatic strength generation (J. Appl. Physiol. 58: 2054-61, 1985). Since the inotropic effect of digitalis appears to be related to cell membrane transport of calcium, we studied the effect of digoxin on diaphragmatic contractility in 20 anesthetized dogs. The diaphragm was electrically stimulated with intramuscular electrodes. The transdiaphragmatic pressure (Pdi) during supramaximal (50 V) 2-s stimulations applied over a frequency range of 10-100 Hz was measured with balloon catheters at functional residual capacity. Cardiac output was measured with a Swan-Ganz catheter and diaphragmatic blood flow (Qdi) by timed volume collections of left inferior venous effluent. The force generated by the sartorius muscle during electrical stimulations was studied concomitantly to Pdi. In 10 dogs (group A) 0.04 mg/kg of digoxin was infused in 10 min. In 10 other dogs (group B) 0.2 mg/kg was administered. All measurements were performed during control and 30, 60, 90, and 120 min after digoxin administration. In group A, digoxin plasmatic level at 60 min reached a therapeutic range in all dogs (1.8 +/- 0.3 ng/ml), whereas in group B, digoxin plasmatic level was higher (8 +/- 1.3 ng/ml). No significant change in cardiac output and Qdi was noted after administration of digoxin, either in the dogs of group A or those of group B.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hypocalcemia on diaphragmatic strength generation

We studied the effects of hypocalcemia on diaphragmatic force and diaphragm blood flow (Qdi) in 12 anesthetized dogs. The diaphragm was electrically stimulated with intramuscular electrodes surgically implanted in the ventral surface of each hemidiaphragm. The transdiaphragmatic pressure (Pdi) during supramaximal (50 V) 2-s stimulations applied over a frequency range of 10-100 Hz was measured with balloon catheters during tracheal occlusion at functional residual capacity. A catheter was placed via the femoral vein into the left inferior phrenic vein, and Qdi was measured by timed volume collections of left inferior venous effluent. A catheter was introduced in a femoral artery to monitor blood pressure (BP). In five additional dogs, the force generated by the sartorius muscle during electrical stimulation was also studied concomitantly to diaphragmatic force. The animals were mechanically ventilated throughout the experiment, and the arterial blood gases and pH were maintained constant. Hypocalcemia was induced by a continuous infusion of EGTA (70 mg X kg-1 X h-1), which led to a progressive decrease (P less than 0.0001) of ionized calcium plasmatic level from 2.21 +/- 0.4 meq/1 during control to 1.69 +/- 0.06, 1.25 +/- 0.5, and 1.07 +/- 0.5 meq/1 after 30, 60, and 120 min, respectively. Hypocalcemia decreased progressively Pdi, which amounted to 84 +/- 3 (P less than 0.001) and 98 +/- 2% of control values for the low frequencies (10 and 20 Hz) and the high frequencies (50 and 100 Hz), respectively, after 30 min of EGTA infusion and to 74 +/- 5 and 79 +/- 6% for the low and high frequencies, respectively, after 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diaphragmatic blood flow in the dog

In anesthetized mongrel dogs we measured the blood flow in the left phrenic artery (Qdi), using an electromagnetic flow probe, before and during supramaximal phrenic nerve stimulation (pacing). This was done at constant respiratory rate (24/min) but at three different stimulation frequencies at a duty cycle of 0.4 (20, 50, and 100 Hz) and at three different duty cycles at a stimulation frequency of 50 Hz (duty cycle = 0.2, 0.4, and 0.8). Qdi was unchanged during diaphragm contraction until transdiaphragmatic pressure (Pdi) was greater than approximately 11 cmH2O, whereafter it began to decrease, reaching zero at Pdi approximately 20 cmH2O. Thus, when Pdi was greater than 21 cmH2O, all flow occurred during relaxation. Qdi averaged over the entire respiratory cycle (Qt) was less at duty cycle = 0.8 than under the other conditions. This was because of decreasing length of relaxation phase rather than a difference of relaxation phase flow (Qr), which was maximal during all conditions of phrenic stimulation. During pacing-induced fatigue, Qt actually rose slightly as Pdi fell. This was due to an increase in contraction phase flow while Qr remained constant. The relationship between Qt and tension-time index was not unique but varied according to the different combinations of duty cycle and stimulus frequency.     

Bilateral phrenic stimulation: a simple technique to assess diaphragmatic fatigue in humans

Transdiaphragmatic pressure (Pdi) and the rate of relaxation of the diaphragm (tau) were measured at functional residual capacity (FRC) in six normal seated subjects during single-twitch stimulation of both phrenic nerves. The latter were stimulated supramaximally with needle electrodes with square-wave impulses of 0.1-ms duration at 1 Hz before and after diaphragmatic fatigue produced by resistive loaded breathing. Constancy of chest wall configuration was achieved by monitoring the diameter of the abdomen and the rib cage with a respiratory inductive plethysmograph system. During control the peak Pdi generated during the phrenic stimulation amounted to 34.4 +/- 4.2 (SE) cmH2O and represented in each subject a fixed fraction (17%) of its maximal transdiaphragmatic pressure. After diaphragmatic fatigue the peak Pdi decreased by an average of 45%, amounting to 18.1 +/- 2.7 cmH2O 5 min after the fatigue run, and tau increased from 55.2 +/- 9 ms during control to 77 +/- 8 ms 5 min after the fatigue run. The decrease in peak Pdi and the increase in tau observed after the fatigue run persisted throughout the 30 min of the recovery period studied, the peak Pdi amounting to 18.4 +/- 2.8 and 18.9 +/- 3.3 cmH2O and tau to 81.3 +/- 5.7 and 88.7 +/- 10 ms at 15 and 30 min after the end of the fatigue run, respectively. It is concluded that diaphragmatic fatigue can be detected in man by bilateral phrenic stimulation with needle electrodes without any discomfort for the subject and that the decrease in diaphragmatic strength after fatigue is long lasting.     

Relationship of changes in diaphragmatic muscle blood flow to muscle contractile activity

The effect of increases in diaphragmatic muscle contractile activity on diaphragm blood flow remains unclear. The present study examined the effect of electrically induced isometric diaphragmatic muscle contractions on diaphragmatic blood flow. Studies were performed on diaphragmatic muscle strips prepared in anesthetized mechanically ventilated dogs. Diaphragmatic contractile activity was quantitated as the tension-time index (TTI) (i.e., the product of tension magnitude and duration). Blood flow to the strip (Qdi) was measured from the volume of the phrenic venous effluent using a drop counter. The separate effects on Qdi of 30-s periods of continuous and rhythmic contractions were examined. Qdi increased with increases in TTI and peaked at a TTI of 20-30% of maximum after which Qdi fell progressively with further increases in TTI. At levels of TTI greater than 30%, the pattern of muscle contraction significantly affected blood flow. Qdi was significantly lower during activity and the postcontraction hyperemia significantly greater at a given TTI when contractions were continuous than when contractions were intermittent. Above a TTI of 30%, Qdi during contraction decreased linearly with increases in duty cycle and curvilinearly with increases in tension. We conclude that during isometric diaphragmatic contractions, diaphragmatic blood flow may become mechanically impeded, and the magnitude of the impediment in blood flow depends on the pattern of diaphragmatic contractions. With increases in contractile activity above a critical level, changes in duty cycle exert progressively greater effects on diaphragmatic blood flow than changes in muscle tension.     

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.     

Effects and mechanism of action of terbutaline on diaphragmatic contractility and fatigue

We studied the effects of intravenously administered terbutaline on diaphragmatic force and fatigue during electrical stimulation of the diaphragm in 17 anesthetized dogs. The diaphragm was stimulated indirectly through the phrenic nerves with electrodes placed around the fifth roots and directly with electrodes surgically implanted in the abdominal side of each hemidiaphragm. Transdiaphragmatic pressure (Pdi) during direct or indirect supramaximal 2-s stimulation applied over a frequency range of 10-100 Hz was measured with balloon catheters during tracheal occlusion at functional residual capacity. In seven dogs the administration of terbutaline (0.5 mg) had no effect on Pdi at any stimulation frequency applied directly or indirectly. The effect of terbutaline (0.5 mg) on diaphragmatic fatigue was then tested in 10 other dogs. Diaphragmatic fatigue was produced by continuous 20-Hz electrical supramaxial stimulation of the phrenic nerves during 30 min. At the end of the fatigue procedure Pdi decreased by 50 +/- 5 and 30 +/- 8% of control values at 10 and 100 Hz, respectively, for either direct or indirect stimulation. The decrease in Pdi for low frequencies of stimulation (10 and 20 Hz) lasted 100 +/- 18 min, whereas it lasted only 40 +/- 10 min for the high frequencies (50 and 100 Hz). When terbutaline (0.5 mg) was administered after the fatiguing procedure, Pdi increased within 15 min by 20 +/- 4% at 10 Hz and by 12 +/- 3% at 100 Hz for either direct or indirect stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of inspiratory resistive loaded breathing and hypoxemia on diaphragmatic function in the piglet.

The combined effects of inspiratory resistive loaded breathing (IRL) and hypoxemia on transdiaphragmatic pressure (Pdi) in nine 1-mo-old Yorkshire piglets were studied. IRL was adjusted to increase spontaneously generated Pdi five to six times above baseline but maintain arterial PCO2 < 70 Torr to prevent hypercapnic depression of diaphragmatic contractility. Measurements of ventilation, blood gases and pH, Pdi, diaphragmatic electromyogram, Pdi during phrenic nerve stimulation, diaphragmatic blood flow, and end-expiratory lung volume were obtained at baseline, after 2 h of IRL, and then after 1 h of hypoxemia (arterial PO2 approximately 40 Torr) combined with IRL. Diaphragmatic muscle samples were obtained after study completion and immediately frozen in liquid nitrogen for determination of tissue ATP, phosphocreatine, lactate, and glycogen levels. Ten 1-mo-old piglets were subjected to IRL alone and served as controls. IRL alone resulted in significant impairment of Pdi generation. The addition of hypoxemia for 1 h did not further compromise Pdi in comparison to control animals who were subjected to IRL alone. Blood flow to both the costal and crural segments of the diaphragm increased significantly during IRL; the addition of the hypoxemic stress resulted in further significant augmentation of blood flow to both segments of the diaphragm. No differences were noted in diaphragmatic muscle tissue ATP, phosphocreatine, or glycogen between control and IRL animals or between control and IRL plus hypoxemia animals. Muscle lactate levels increased significantly in the IRL plus hypoxemia animals only. The data from this study suggest that moderate hypoxemia during resistive-loaded breathing in the piglet does not accentuate diaphragmatic fatigue.     

Relationship among EMG and contractile responses of the diaphragm elicited by hypotension

In a canine model, we investigated the effects of severe hypotension on the indexes of diaphragmatic failure. We measured 1) the transdiaphragmatic pressure obtained in response to 20- and 100-Hz stimulation of phrenic nerves (Pdi20 and Pdi100), 2) the power spectrum of diaphragmatic electromyogram (EMG), 3) the ratio of integrated diaphragmatic EMG to Pdi (Edi/Pdi), and 4) the rate of relaxation of Pdi100 and Pdi20. Arterial blood pressure (Pa) was reduced to 40-50 mmHg by a balloon inflated in the inferior vena cava and was maintained at this level until Pdi100 declined to 75% of the control value (100% shock time, ST). A recovery period of 60 min at normal Pa was allowed. During hypotension, Pdi100 and Pdi20 declined only at 100% ST [95.0 +/- 13.0 (SE) min]; however, only Pdi100 recovered within 15 min. The power spectrum shifted to low frequencies early and progressively during shock period. Edi/Pdi rose significantly at 80 and 100% ST and recovered within 15 min. The relaxation rate of Pdi20 and Pdi100 increased significantly at 100% ST only. We conclude that 1) diaphragmatic contractility is depressed during severe hypotension, 2) changes in the power spectrum occurred first in the shock state, followed by alterations in Edi/Pdi, and subsequently both changes in the frequency-pressure curve and relaxation rate occurred last.     

Effect of endotoxin on diaphragm lymph contamination in unanesthetized sheep

The preparation for collecting lung lymph from sheep caudal mediastinal lymph node (CMN) efferent vessels is widely used to study the effects of endotoxin on lung microvascular permeability. However, there are nonpulmonary lymph vessels that drain into the CMN along with the afferent lymph vessels from the lung. Thus CMN lymph is a mixture of lymph from the lung and diaphragm lymph vessels as well as from other nonpulmonary lymph vessels. We studied the effect of 0.5-1.0 microgram/kg Escherichia coli endotoxin on the flow rates in diaphragm and CMN efferent lymph vessels (Qdi and QCMN, respectively) in unanesthetized sheep. For the time period between 2 and 5.5 h after endotoxin QCMN was increased from its base line of 7.2 +/- 4.4 (SD) to 17.3 +/- 10.6 ml/h and the lymph-to-plasma protein concentration ratio (L/PCMN) had increased from 0.68 +/- 0.11 to 0.81 +/- 0.06. During the same time period, Qdi was 4.5 +/- 3.1 ml/h compared with 1.0 +/- 0.8 ml/h at base line and the diaphragm lymph-to-plasma protein concentration ratio (L/Pdi) was 0.92 +/- 0.07 (base line = 0.74 +/- 0.15). The increases in flow rate and protein concentration were significant for each type of vessel (P less than 0.05). We conclude that the period of increased QCMN and L/PCMN after endotoxin is associated with an increase in Qdi and L/Pdi. Thus, it is difficult to determine how much of the CMN lymph response comes from the lungs and how much comes from diaphragm lymph vessels.     

Effect of abdominal compression on maximum transdiaphragmatic pressure

Transdiaphragmatic pressure (Pdi) is lower during maximum inspiratory effort with the diaphragm alone than when maximum inspiratory and expulsive efforts are combined. The increase in Pdi with expulsive effort has been attributed to increased neural activation of the diaphragm. Alternatively, the increase could be due to stretching of the contracted diaphragm. If this were so, Pdi measured during a combined maximum effort would overestimate the capacity of the diaphragm to generate inspiratory force. This study determined the likely contribution of stretching of the contracted diaphragm to estimates of maximum Pdi (Pdimax) obtained during combined inspiratory and expulsive effort. Three healthy trained subjects were studied standing. Diaphragmatic Mueller maneuvers were performed at functional residual capacity and sustained during subsequent abdominal compression by either abdominal muscle expulsive effort or externally applied pressure. Measurements were made of changes in abdominal (Pab) and pleural (Ppl) pressure, Pdi, rib cage and abdominal dimensions and respiratory electromyograms. Three reproducible performances of each maneuver from each subject were analyzed. When expulsive effort was added to maximum diaphragmatic inspiratory effort, Pdimax increased from 86 +/- 12 to 148 +/- 14 (SD) cmH2O within the 1st s and was 128 +/- 14 cmH2O 2 s later. When external compression was added to maximum diaphragmatic inspiratory effort, Pdimax increased from 87 +/- 16 to 171 +/- 19 cmH2O within the 1st s and was 152 +/- 16 cmH2O 2 s later.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in rate of relaxation of sniffs with diaphragmatic fatigue in humans

The rate of relaxation of the diaphragm after stimulated (4 subjects) and voluntary (8 subjects) contractions was compared in normal young men. Stimulated contractions were induced by supramaximal unilateral phrenic nerve stimulation and voluntary contractions by short, sharp sniffs of varying tensions against an occluded airway. The rate of relaxation of the diaphragm was calculated from the rate of decline of transdiaphragmatic pressure (Pdi). In both conditions the maximum relaxation rate (MRR) was proportional to the peak transdiaphragmatic pressure (Pdi), whereas the time constant (tau) of the later exponential decline in Pdi was independent of Pdi. The mean +/- SE rate constant of relaxation (MRR/Pdi) was 0.0078 +/- 0.0002 ms-1 and the mean tau was 57 +/- 3.8 ms for stimulated contractions. The rate of relaxation after sniffs was not different, and it was not affected by either the lung volume at which occluded sniffs were performed (in the range of residual volume to functional residual capacity + 1 liter) or by the relative contribution gastric pressure made to Pdi. After diaphragmatic fatigue was induced by inspiring against a high alinear resistance there was a decrease in relaxation rate. In the 1st min postfatigue MRR/Pdi decreased (0.0063 +/- 0.0003 ms-1; P less than 0.005) and tau increased (83 +/- 5 ms; P less than 0.005). Both values returned to prefatigue levels within 5 min of the end of the studies. We conclude that the sniff may prove to be clinically useful in the detection of diaphragmatic fatigue.     

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)     

O2 metabolism of the sheep diaphragm during flow resistive loaded breathing

To determine whether O2 availability limited diaphragmatic performance, we subjected unanesthetized sheep to severe (n = 11) and moderate (n = 3) inspiratory flow resistive loads and studied the phrenic venous effluent. We measured transdiaphragmatic pressure (Pdi), systemic arterial and phrenic venous blood gas tensions, and lactate and pyruvate concentrations. In four sheep with severe loads, we measured O2 saturation (SO2), O2 content, and hemoglobin. We found that with severe loads Pdi increased to 74.7 +/- 6.0 cmH2O by 40 min of loading, remained stable for 20-30 more min, then slowly decreased. In every sheep, arterial PCO2 increased when Pdi decreased. With moderate loads Pdi increased to and maintained levels of 40-55 cmH2O. With both loads, venous PO2, SO2, and O2 content decreased initially and then increased, so that the arteriovenous difference in O2 content decreased as loading continued. Hemoglobin increased slowly in three of four sheep. There were no appreciable changes in arterial or venous lactate and pyruvate during loading or recovery. We conclude that the changes in venous PO2, SO2, and O2 content may be the result of changes in hemoglobin, blood flow to the diaphragm, or limitation of O2 diffusion. Our data do not support the hypothesis that in sheep subjected to inspiratory flow resistive loads O2 availability limits diaphragmatic performance.     

Effects of phrenic nerve cooling on diaphragmatic function

The effects of phrenic nerve cooling at 0 degrees C on the nerve and diaphragmatic function were evaluated in dogs. Eleven dogs, anesthetized and mechanically ventilated, were studied. Left diaphragmatic function was assessed by recording the transdiaphragmatic pressure (Pdi) generated during electrical stimulation of the left phrenic nerve at different frequencies (0.5, 30, and 100 Hz). Phrenic nerve stimulations were achieved either directly by electrodes placed around the phrenic nerve above its pericardial course or by intramuscular electrodes placed close to the phrenic nerve endings. Electrical activity of the hemidiaphragm (Edi) was recorded and phrenic nerve conduction time (PNCT) was measured during direct phrenic stimulation. A transpericardial cooling of the nerve, at 0 degrees C, on a length of 1 cm, was performed during 30 min (group A, n = 7) or 5 min (group B, n = 4). After the cooling period, phrenic and diaphragmatic functions were assessed hourly for 4 h (H1-H4). Cooling the phrenic nerve produced a complete phrenic nerve conduction block in all dogs, 100 +/- 10 s after the onset of cold exposure. Conduction recovery time was longer in group A (11 +/- 7 min) than in group B (2 +/- 0.5 min) and PNCT remained increased throughout the study in group A. Furthermore, in group A, Pdi and Edi during direct phrenic stimulation were markedly depressed from H1 to H4. No change in these parameters was noted until H3 during intramuscular stimulation, time at which a significant decrease occurred. By contrast, Pdi and Edi from direct and intramuscular stimulations remained unchanged throughout the study in group B.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of lung inflation on diaphragmatic shortening

The effect of lung inflation on chest wall mechanics was studied in 11 vagotomized pentobarbital sodium-anesthetized dogs. Diaphragmatic shortening (percent change from initial length at functional residual capacity, %LFRC) and transdiaphragmatic pressure swings (delta Pdi) were compared with control values over a range of positive-pressure breathing that produced a maximum increase in lung volume to 40% of inspiratory capacity. There was no change in the electromyogram of the diaphragm or parasternal intercostals during positive-pressure breathing. delta Pdi and tidal volume (VT) fell to 52 +/- 3.3 and 42.5 +/- 5% (SE) of control. This was associated with a reduction in the initial resting length of 13 +/- 1.9 and 21 +/- 2.2%LFRC (SE) in the costal and crural diaphragms, respectively. Tidal diaphragmatic shortening, however, decreased to 66 +/- 7 and 57 +/- 7 and the mean velocity decreased to 78 +/- 10 and 63 +/- 8% (SE) of control for the costal and crural diaphragms, respectively. We conclude that the reduction in diaphragmatic shortening is the main determinant of the reduced delta Pdi and VT during lung inflation and relate this to what is currently known about diaphragmatic contractile properties.     

Effects of uncompensated and compensated metabolic acidosis on canine diaphragm

We investigated the effects of metabolic acidosis and compensated metabolic acidosis on force of contraction of the diaphragm in anesthetized dogs. Mechanically ventilated animals were prepared with an open thorax. A balloon was positioned beneath the diaphragm to measure transdiaphragmatic pressure (Pdi), and a plaster cast was placed around the abdomen to maintain length and geometry of the diaphragm. The force of contraction was evaluated by measuring Pdi during supramaximal phrenic stimulation at different frequencies and also during spontaneous inspiratory efforts. In 13 dogs with an arterial pH (pHa) of 7.38 and arterial PCO2 (PaCO2) of 36.5 Torr, metabolic acidosis was produced by infusion of HCl until pHa equaled 6.98 and PaCO2 equaled 36.4 Torr. Pdi at all frequencies greater than 10 Hz was significantly reduced (P less than 0.05). The dogs were then hyperventilated until pHa was 7.34 and PaCO2 was 12.8 Torr. Pdi was significantly reduced again at all frequencies (P less than 0.05) except 5 Hz. The percent reduction in Pdi by compensated acidosis was significantly greater at low-frequency stimulation than at high (P less than 0.05). Similar qualitative results were observed during spontaneous inspiratory efforts where Pdi was compared at constant magnitudes of diaphragmatic electromyograms. Twitch characteristics revealed that metabolic acidosis led to a significant shortening of twitch relaxation time (P less than 0.05), and compensated metabolic acidosis added to this effect a significant decrease in twitch amplitude (P less than 0.05).     

Central components of diaphragmatic fatigue assessed by phrenic nerve stimulation

The extent to which diaphragmatic fatigue results from failure of neural drive has been investigated using twitch occlusion. Fatigue was induced by repeatedly generating transdiaphragmatic pressures (Pdi) of either 50 or 75% maximum Pdi (Pdimax) until approximately 10 min after the target Pdi could no longer be reached (Tlim). Maximal bilateral shocks delivered periodically to the phrenic nerves elicited Pdi twitches between breaths (Tr) and superimposed on the voluntary contractions (Ts). The ratio [1 - Ts/Tr], which provides an index of the degree of central nervous system muscle activation, increased as fatigue developed. However, superimposed twitches were still detectable at and beyond Tlim when all contractions involved maximal efforts. They were not seen in maximal contractions of the unfatigued muscle. Initially, the diaphragm electromyogram increased, but then declined. No impairment of neuromuscular transmission was seen. We conclude that at and beyond Tlim about one-half of the reduction in Pdimax resulted from reduced central motor drive; the remainder resulted from peripheral muscle contractile failure. No fatigue was evident during 50% Pdimax dynamic contractions.     

Effects of endotoxic shock on diaphragmatic function in mechanically ventilated rats.

Diaphragmatic function was investigated in mechanically ventilated rats during endotoxic shock (group E, n = 18) and after saline solution injection (group C, n = 8). Endotoxic shock was produced by a 1-min injection of Escherichia coli endotoxin (10 mg/kg iv) suspended in saline. Diaphragmatic strength was assessed before (T0) and 15 (T15) and 60 (T60) min after injection by measuring transdiaphragmatic pressure (Pdi) generated during bilateral phrenic stimulation at 0.5, 10, 20, 30, 50, and 100 Hz. Diaphragmatic neuromuscular transmission was assessed by measuring the integrated electrical activity of the diaphragm. Diaphragmatic endurance was assessed 75 min after injection from the rate of Pdi decline after a 30-s continuous 10-Hz phrenic stimulation. In 16 additional animals, diaphragmatic glycogen content was determined 60 min after inoculation with endotoxin (n = 8) or 0.9% sodium chloride solution (n = 8). Diaphragmatic resting membrane potential (Em) was measured in 16 additional animals 60 min after endotoxin (n = 8) or saline injection (n = 8). Mean blood pressure decreased from 74 +/- 3 to 53 +/- 6 mmHg at T60 in group E, whereas it was maintained in group C. At T60 Pdi was decreased in group E for frequencies of 50 and 100 Hz and was associated with a decreased diaphragmatic electromyographic activity of 25.3 +/- 2.5 and 26.5 +/- 5.2% for 50- and 100-Hz stimulations, respectively, in comparison with T0 values.(ABSTRACT TRUNCATED AT 250 WORDS)