Diaphragmatic function during hypercapnia: neonatal and developmental aspects

The effect of acute hypercapnia on diaphragmatic force output was studied in 6 young (4-8 days) and 6 older (16-20 days) anesthetized, spontaneously breathing piglets. Diaphragmatic force output was assessed by analysis of the transdiaphragmatic pressure (Pdi) generated during phrenic nerve stimulation. Pdi was measured under base-line conditions (50% O2-50% N2) and after 10 min of hypercapnia induced by breathing 5, 10, or 15% CO2 balanced with N2 and 50% O2. Pdi was significantly less than base line during the 10 and 15% hypercapnic conditions in the young (P less than 0.05) but not the older piglets. End-expiratory lung volume was noted to decrease during 15% CO2 hypercapnia. Force output augmentation occurred at this lower end-expiratory lung volume and was significantly greater in the older piglet compared with its younger counterpart (P less than 0.05). When the effects of lung volume on Pdi were corrected for, there was no age-related difference in the response to 15% CO2 hypercapnia. We conclude that severe hypercapnia has a depressant effect on diaphragmatic force output in both young and older piglets, and a differential augmentation in diaphragmatic force-output gain occurs at lower end-expiratory lung volume between young and older piglets, with the greater output occurring in the more mature animal.     

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.     

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 digitalis on the diaphragm in anesthetized dogs

We examined the effect of digitalis on diaphragmatic contractility and fatigability in 19 anesthetized mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. In a first group of five dogs, Pdi-stimulus frequency relationships were compared before and after administration of ouabain in doses of 0.01, 0.02, and 0.04 mg/kg. In a second group, diaphragmatic fatigue was produced by bilateral phrenic nerve stimulation at 30 Hz. Ten seconds of stimulation and 15 s of mechanical ventilation were repeated for 30 min. The rates of decrease in Pdi were compared between two groups, one of 0.05 mg/kg deslanoside-treated dogs (n = 7) and one of nontreated dogs (n = 7). After ouabain administration Pdi was significantly greater at each frequency in a dose-dependent manner. On the other hand, the rate of decrease in Pdi in the deslanoside group was significantly smaller than that in the nontreated group, whereas deslanoside did not greatly change the Pdi-frequency curves in fresh diaphragm. We conclude that ouabain improves contractility of the fresh diaphragm and that deslanoside has a protective effect against fatigability.     

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.     

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)     

Diaphragmatic pressures: transvenous vs. direct phrenic nerve stimulation

Diaphragmatic force, determined by stimulating the phrenic nerve while simultaneously measuring the pressures in a closed respiratory system, was assessed in five anesthetized dogs over a 5-h period to evaluate the inherent variability of this technique. Transdiaphragmatic pressure (Pdi) was measured at functional residual capacity during stimulation (120 Hz, 0.2-ms duration) of one phrenic nerve by either direct phrenic nerve stimulation (DPNS) or transvenous phrenic nerve stimulation (TPNS). An analysis of variance showed no significant (P greater than 0.50) change during the 5-h period. There was a significant correlation (r = 0.94, P less than 0.001) between Pdi obtained by TPNS and that obtained by DPNS. It is concluded that either DPNS or TPNS can be used to evaluate diaphragmatic strength over a 5-h period and that TPNS can be used in lieu of DPNS.     

Cervical magnetic stimulation: a new painless method for bilateral phrenic nerve stimulation in conscious humans

Assessing diaphragmatic contractility is a common goal in various situations. This assessment is mainly based on static or dynamic maximal voluntary maneuvers and twitch transdiaphragmatic pressures (Pdi) obtained by stimulation of the phrenic nerves (PS). PS eliminates the central components of diaphragmatic activation, but the available techniques of PS remain subject to some limitations. Transcutaneous PS is painful, and needle PS is potentially dangerous. Time-varying magnetic fields can stimulate nervous structures without pain and without adverse effects. In six subjects, we have studied cervical magnetic stimulation (CMS) as a method of PS. We have compared the stimulated Pdi (Pdistim) with the maximal Pdi obtained during static combined expulsive-Mueller maneuver (Pdimax) and with the Pdi generated during a sniff test (Pdisniff). CMS produced twitch Pdi averaging 33.4 +/- 9.7 cmH2O. Pdistim/Pdimax and Pdistim/Pdisniff were 24 +/- 6 and 41 +/- 14%, respectively. These values are comparable to those obtained in other studies with transcutaneous PS. They were highly reproducible in all the subjects. Electromyographic data provided evidence of bilateral maximal stimulation. CMS is a nonspecific method and may stimulate various nervous structures. However, diaphragmatic contraction was elicited by stimulation of the phrenic trunk, since the phrenicodiaphragmatic latencies (less than 7 ms) were in the range of values reported with direct stimulation of the trunk. Cocontraction of neck muscles, including the sternomastoid, was present, but its influence in the CMS-induced Pdi seems minimal. We conclude that magnetic stimulation is an easy, well-tolerated, reproducible safe, and valuable method to assess phrenic conduction and diaphragmatic twitch response.     

Effects of respiratory muscle unloading on exercise-induced diaphragm fatigue.

We previously compared the effects of increased respiratory muscle work during whole body exercise and at rest on diaphragmatic fatigue and showed that the amount of diaphragmatic force output required to cause fatigue was reduced significantly during exercise (Babcock et al., J Appl Physiol 78: 1710, 1995). In this study, we use positive-pressure proportional assist ventilation (PAV) to unload the respiratory muscles during exercise to determine the effects of respiratory muscle work, per se, on exercise-induced diaphragmatic fatigue. After 8-13 min of exercise to exhaustion under control conditions at 80-85% maximal oxygen consumption, bilateral phrenic nerve stimulation using single-twitch stimuli (1 Hz) and paired stimuli (10-100 Hz) showed that diaphragmatic pressure was reduced by 20-30% for up to 60 min after exercise. Usage of PAV during heavy exercise reduced the work of breathing by 40-50% and oxygen consumption by 10-15% below control. PAV prevented exercise-induced diaphragmatic fatigue as determined by bilateral phrenic nerve stimulation at all frequencies and times postexercise. Our study has confirmed that high- and low-frequency diaphragmatic fatigue result from heavy-intensity whole body exercise to exhaustion; furthermore, the data show that the workload endured by the respiratory muscles is a critical determinant of this exercise-induced diaphragmatic fatigue.     

Arterial CO2 partial pressure affects diaphragmatic function

The purpose of this study was to examine in an in vivo preparation acute variations of PCO2 on diaphragmatic contractility. Plaster casts were snugly fit around the abdomen of six open-chested dogs, moving the abdominal contents rostrally. Diaphragmatic contractions against this very fixed load in response to phrenic nerve stimulation (supramaximal voltage at 1, 20, 50, and 80 Hz) or during spontaneous inspiratory efforts were virtually isometric (quasi-isometric). Transdiaphragmatic pressure (Pdi) measured by an abdominal balloon was used as an index of diaphragmatic contractility. Arterial PCO2 (PaCO2) was reduced by hyperventilation and raised by increasing PICO2. Pdi values in response to stimulation at 1, 20, 50, and 80 Hz in ranges I (PaCO2 = 0-19 Torr) and II (PaCO2 = 20-34 Torr) did not differ statistically from the control Pdi values (range III; PaCO2 = 35-45 Torr). In range IV (PaCO2 = 46-70 Torr) Pdi values for stimulations of 20, 50, and 80 Hz were significantly lower than control. In range V (PaCO2 = 71-90 Torr), VI (PaCO2 = 91-101 Torr), and VII (PaCO2 greater than or equal to 102 Torr) Pdi values were significantly less than those in range IV at all frequencies of stimulation. In the four dogs measured during spontaneous inspiratory efforts the integrated diaphragmatic electromyogram (Edi) was correlated with the Pdi. As PaCO2 rose (range III to VII), the Pdi values observed at 25, 50, 75, 100% of the maximum Edi (of range III) were significantly lower than the Pdi value of range III.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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)     

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 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).     

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)     

Diaphragm fatigue induced by inspiratory resistive loading in spontaneously breathing rabbits

Diaphragmatic contractility was assessed in spontaneously breathing ketamine-anesthetized rabbits by measuring the strength of diaphragmatic contraction in response to bilateral supramaximal phrenic nerve stimulation at frequencies between 10 and 100 Hz. During 10-180 min of inspiratory resistive loading, contractility decreased by approximately 40%, and hypoxemia and both respiratory and lactic acidosis developed. After 10 min of recovery, both the response to high-frequency stimulation (100 Hz) and the arterial PO2 and PCO2 returned to base-line levels, whereas metabolic acidosis and reduced response to low-frequency stimulation (10-20 Hz) persisted. Similar levels of hypoxemia and respiratory acidosis in the absence of inspiratory resistive loading did not alter diaphragmatic contractility. We conclude that in anesthetized rabbits excessive inspiratory resistive loading results in partially reversible diaphragm fatigue of the high- and low-frequency types, accompanied by hypoventilation and lactic acidosis.     

Mechanics of the canine diaphragm in ascites: a CT study.

Ascites causes an increase in the elastance of the abdomen and impairs the lung-expanding action of the diaphragm, but its overall effects on the pressure-generating ability of the muscle remain unclear. In the present study, radiopaque markers were attached to muscle bundles in the midcostal region of the diaphragm in five dogs, and the three-dimensional locations of the markers during relaxation and during phrenic nerve stimulation in the presence of increasing amounts of ascites were determined using a computed tomographic scanner. From these data, accurate measurements of muscle length and quantitative estimates of diaphragm curvature were obtained, and the changes in transdiaphragmatic pressure (Pdi) were analyzed as functions of muscle length and curvature. With increasing ascites, the resting length of the diaphragm increased progressively. In addition, the amount of muscle shortening during phrenic nerve stimulation decreased gradually. When ascites was 100 ml/kg body wt, therefore, the muscle during contraction was longer, leading to a 20-25% increase in Pdi. As ascites increased further to 200 ml/kg, however, muscle length during contraction continued to increase, but Pdi did not. This absence of additional increase in Pdi was well explained by the increase in the diameter of the ring of insertion of the diaphragm to the rib cage and the concomitant increase in the radius of diaphragm curvature. These observations indicate that the pressure-generating ability of the diaphragm is determined not only by muscle length as conventionally thought but also by muscle shape.     

Diaphragmatic contractility after upper abdominal surgery

Postoperative dysfunction of the diaphragm has been reported after upper abdominal surgery. This study was designed to determine whether an impairment in diaphragmatic contractility was involved in the genesis of the diaphragmatic dysfunction observed after upper abdominal surgery. Five patients undergoing upper abdominal surgery were studied. The following measurements were performed before and 4 h after surgery: vital capacity (VC), functional residual capacity (FRC), and forced expiratory volume in 1 s. Diaphragmatic function was also assessed using the ratio of changes in gastric pressure (delta Pga) over changes in transdiaphragmatic pressure (delta Pdi). Finally contractility of the diaphragm was determined by measuring the change in delta Pdi generated during bilateral electrical stimulation of the phrenic nerves (Pdi stim). Diaphragmatic dysfunction occurred in all the patients after upper abdominal surgery as assessed by a marked decrease in delta Pga/delta Pdi from 0.480 +/- 0.040 to -0.097 +/- 0.152 (P less than 0.01) 4 h after surgery compared with preoperative values. VC also markedly decreased after upper abdominal surgery from 3,900 +/- 630 to 2,060 +/- 520 ml (P less than 0.01) 4 h after surgery. In contrast, no change in FRC and Pdi stim was observed 4 h after surgery. In contrast, no change in FRC and Pdi stim was observed 4 h after upper abdominal surgery compared with the preoperative values. We conclude that contractility of the diaphragm is not altered after upper abdominal surgery, and diaphragmatic dysfunction is secondary to other mechanisms such as possible reflexes arising from the periphery (chest wall and/or peritoneum), which could inhibit the phrenic nerve output.     

Dose effect of pentobarbital sodium on control of breathing in cats

The dose effect of pentobarbital sodium on integrated ("moving time average") phrenic activity (EPHR), transdiaphragmatic pressure (Pdi), gastric pressure (Pga), changes in lung volume (V), and mechanical properties of the respiratory system was studied in six cats breathing room air. Increased pentobarbital dose from an initial value of 35 mg/kg ip, had no substantial effect on the relationship between EPHR and Pdi during both unoccluded and occluded inspirations, indicating that the diaphragmatic excitation-contraction coupling was not affected. Similarly, increased anesthetic dose had no effect on the relationship between EPHR and delta Pga during both occluded and unoccluded breaths, suggesting that the contribution of the diaphragm to the breathing movements did not change with increasing depth of anesthesia. Although the time course of phrenic activity showed substantial interanimal differences, the shape of the phrenic neurogram did not change substantially with increased pentobarbital dose in any of the cats studied. Increased anesthetic dose depressed, in the same proportion, the rate of rise of EPHR, Pdi, and V, but the mechanical properties of the respiratory system remained unchanged. The depression of ventilation with increased anesthetic dose was not proportional to the drop in central inspiratory activity, as quantified in terms of rate of rise of EPHR.     

Effects of loaded breathing and hypoxia on diaphragm metabolism as measured by (31)P-NMR spectroscopy.

Diaphragm fatigue may contribute to respiratory failure. (31)P-nuclear magnetic resonance spectroscopy is a useful tool to assess energetic changes within the diaphragm during fatigue, as indicated by P(i) accumulation and phosphocreatine (PCr) depletion. We hypothesized that loaded breathing during hypoxia would lead to diaphragm fatigue and inadequate aerobic metabolism. Seven piglets were anesthetized by using halothane inhalation. Diaphragmatic contractility was assessed by transdiaphragmatic pressure (Pdi) at end expiration with the airway occluded. A nuclear magnetic resonance surface coil placed under the right hemidiaphragm measured P(i) and PCr during four conditions: control, inspiratory resistive breathing (IRB), IRB with hypoxia, and recovery (IRB without hypoxia). IRB alone resulted in hypercarbia (32 +/- 7 to 61 +/- 21 Torr) and respiratory acidosis but no change in diaphragm force output or aerobic metabolism. Combined IRB and hypoxia resulted in decreased force output (Pdi decreased by 40%; from 30 +/- 17 to 19 +/- 11 mmHg) and evidence of metabolic stress (ratio of P(i) to PCr increased by 290%; from 0.19 +/- 0.09 to 0.74 +/- 0.27). We conclude that diaphragm fatigue associated with inadequate aerobic oxidative metabolism occurs in the setting of loaded breathing and hypoxia. Conversely, aerobic metabolism and force output of the diaphragm remain unchanged from control during loaded normoxic or hyperoxic breathing despite the onset of respiratory failure.