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)     

Relationship of diaphragmatic contractility to diaphragmatic blood flow in newborn lambs

We determined the relationship of diaphragmatic contraction rate to diaphragmatic blood flow (Qdi), metabolism, and contractility in nine open-chested mechanically ventilated newborn lambs. The diaphragm was paced for 15 min at slow (20/min) and fast (100/min) contraction rates each followed by a 30-min rest period. There was a mild reduction in transdiaphragmatic pressure (Pdi) during the slow contraction period accompanied by a shift to the right of the curve relating stimulation frequency (10-100 Hz) to Pdi. Pdi returned to control at the start of the fast contraction period, but then fell by 30% within 2 min with continued fast contraction rates. The frequency-Pdi curve was significantly shifted to the right. Qdi, O2 transport, and O2 consumption increased during slow contraction and to an even greater extent during fast contraction. Fractional O2 extraction reached an apparent maximum during slow contraction. Lactate efflux from the right phrenic vein during slow contraction remained unchanged from control. During fast contraction lactate efflux rose proportionately more than did O2 consumption. We conclude that the energy demands at fast rates of diaphragmatic contraction in newborn lambs cannot be met by aerobic metabolism alone despite increasing O2 transport to the diaphragm.     

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)     

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.     

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.     

Aminophylline and human diaphragm strength in vivo

The transdiaphragmatic pressure (Pdi) twitch response to single shocks from supramaximal bilateral phrenic nerve stimulation was studied before and after acute intravenous infusions of aminophylline [14.9 +/- 3.1 (SD) micrograms/ml] in nine normal subjects. Stimulation was performed with subjects in the sitting position against an occluded airway from end expiration. Baseline gastric pressure and abdominal and rib cage configuration were kept constant. There was no significant difference in peak twitch Pdi from the relaxed diaphragm between control (38.8 +/- 3.3 cmH2O) and aminophylline (40.2 +/- 5.2 cmH2O) experiments. Other twitch characteristics including contraction time, half-relaxation time, and maximum relaxation rate were also unchanged. The Pdi-twitch amplitude at different levels of voluntary Pdi was measured with the twitch occlusion technique, and this relationship was found to be similar under control conditions and after aminophylline. With this technique, maximum Pdi (Pdimax) was calculated as the Pdi at which stimulation would result in no Pdi twitch because all motor units are already maximally activated. No significant change was found in mean calculated Pdimax between control (146.9 +/- 27.0 cmH2O) and aminophylline (149.2 +/- 26.0 cmH2O) experiments. We conclude from this study that the acute administration of aminophylline at therapeutic concentrations does not significantly affect contractility or maximum strength of the normal human diaphragm in vivo.     

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.     

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)     

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).     

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.     

Twitch transdiaphragmatic pressure depends critically on thoracoabdominal configuration.

We measured the effect of thoracoabdominal configuration on twitch transdiaphragmatic pressure (Pdi, t) in response to supramaximal, transcutaneous, bilateral phrenic nerve shocks in three thin normal men. Pdi, t was measured as a function of lung volume (VL) in the relaxation configuration, at functional residual capacity (FRC), and at the same end-tidal VL 1) during relaxation; 2) with the abdomen (Ab) expanded and the rib cage (RC) in its relaxed FRC configuration; 3) with RC expanded and Ab in its relaxed FRC configuration; and 4) in configuration 3 with an active transdiaphragmatic pressure similar to that required to produce configuration 2. In increasing VL from FRC to configuration 1, Pdi, t decreased by 3.6 cmH(2)O; to configuration 2 by 14.8 cmH(2)O; to configuration 3 by 3.7 cmH(2)O; and to configuration 4 by 2.7 cmH(2)O. We argue that changes in velocity of shortening and radius of curvature are unlikely to account for these effects and suggest that changes in diaphragmatic fiber length (L(di)) are primarily responsible. If so, equivolume displacements of Ab and RC change L(di) in a ratio of approximately 4:1. We conclude that Pdi, t is exquisitely sensitive to abdominal displacements that must be rigorously controlled if Pdi, t is to be used to assess diaphragmatic contractility.     

Functional adaptation of diaphragm to chronic hyperinflation in emphysematous hamsters

Costal strips of diaphragmatic muscle obtained from animals with elastase-induced emphysema generate maximum tension at significantly shorter muscle fiber lengths than muscle strips from control animals. The present study examined the consequences of alterations in the length-tension relationship assessed in vitro on the pressure generated by the diaphragm in vivo. Transdiaphragmatic pressure (Pdi) and functional residual capacity (FRC) were measured in 22 emphysematous and 22 control hamsters 4-5 mo after intratracheal injection of pancreatic elastase or saline, respectively. In 12 emphysematous and 12 control hamsters Pdi was also measured during spontaneous contractions against an occluded airway. To allow greater control over muscle excitation, Pdi was measured during bilateral tetanic (50 Hz) electrical stimulation of the phrenic nerves in 10 emphysematous and 10 control hamsters. Mean FRC in the emphysematous hamsters was 183% of the value in control hamsters (P less than 0.01). During spontaneous inspiratory efforts against a closed airway the highest Pdi generated at FRC tended to be greater in control than emphysematous hamsters. When control hamsters were inflated to a lung volume approximating the FRC of emphysematous animals, however, peak Pdi was significantly greater in emphysematous animals (70 +/- 6 and 41 +/- 8 cmH2O; P less than 0.05). With electrophrenic stimulation, the Pdi-lung volume curve was shifted toward higher lung volumes in emphysematous hamsters. Pdi at all absolute lung volumes at and above the FRC of emphysematous hamsters was significantly greater in emphysematous compared with control animals. Moreover, Pdi continued to be generated by emphysematous hamsters at levels of lung volume where Pdi of control subjects was zero.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of contraction frequency and duty cycle on diaphragmatic blood flow

The effects of diaphragmatic contraction frequency (no. of intermittent tetanic contractions/min) at a given tension-time index and of duty cycle (contraction time/total cycle time) on diaphragmatic blood flow were measured in anesthetized mongrel dogs during bilateral supramaximal phrenic nerve stimulation. Diaphragmatic blood flow was measured by the radionuclide-labeled microsphere method. Contraction frequency was varied between 10 and 160/min at duty cycles of 0.25 and 0.75. Diaphragmatic blood flow increased with contraction frequency from 1.47 +/- 0.13 ml X min-1 X g-1 (mean +/- SE) at an average of 18/min to 2.65 +/- 0.16 ml X min-1 X g-1 at 74/min (P less than 0.01) with a duty cycle of 0.25 and from 1.32 +/- 0.19 ml X min-1 X g-1 at an average of 15/min to 1.96 +/- 0.15 ml X min-1 X g-1 at 80/min (P less than 0.02) with a duty cycle of 0.75. At higher contraction frequencies diaphragmatic blood flow did not increase further at both duty cycles. In addition, diaphragmatic blood flow was higher with a duty cycle of 0.25 than 0.75 at all contraction frequencies. We conclude that frequency of contraction is a major determinant of diaphragmatic blood flow and that high duty cycle impedes diaphragmatic blood flow.     

Pleural pressure increases during inspiration in the zone of apposition of diaphragm to rib cage

The zone of apposition of diaphragm to rib cage provides a theoretical mechanism that may, in part, contribute to rib cage expansion during inspiration. Increases in intra-abdominal pressure (Pab) that are generated by diaphragmatic contraction are indirectly applied to the inner rib cage wall in the zone of apposition. We explored this mechanism, with the expectation that pleural pressure in this zone (Pap) would increase during inspiration and that local transdiaphragmatic pressure in this zone (Pdiap) must be different from conventionally determined transdiaphragmatic pressure (Pdi) during inspiration. Direct measurements of Pap, as well as measurements of pleural pressure (Ppl) cephalad to the zone of apposition, were made during tidal inspiration, during phrenic stimulation, and during inspiratory efforts in anesthetized dogs. Pab and esophageal pressure (Pes) were measured simultaneously. By measuring Ppl's with cannulas placed through ribs, we found that Pap consistently increased during both maneuvers, whereas Ppl and Pes decreased. Whereas changes in Pdi of up to -19 cmH2O were measured, Pdiap never departed from zero by greater than -4.5 cmH2O. We conclude that there can be marked regional differences in Ppl and Pdi between the zone of apposition and regions cephalad to the zone. Our results support the concept of the zone of apposition as an anatomic region where Pab is transmitted to the interior surface of the lower rib cage.     

Effect of separate hemidiaphragm contraction on left phrenic artery flow and O2 consumption

Phrenic arterial blood flow has been shown to increase during bilateral phrenic nerve stimulation (BPNS). However, the role of unilateral phrenic nerve stimulation [left (LPNS) or right (RPNS)] on the blood flow and O2 consumption of the contralateral hemidiaphragm is not known and is explored here. In six anesthetized, mechanically hyperventilated dogs, left phrenic arterial blood flow (Qlpha) was measured (Doppler technique). Supramaximal (10 V, 30 Hz, 0.25-ms duration) LPNS, RPNS, and BPNS at a pacing frequency 15/min and duty cycle of 0.50 were delivered in separate runs. Left hemidiaphragmatic blood samples for gas analyses were obtained by left phrenic venous cannulation. During RPNS, Qlpha and left hemidiaphragmatic O2 consumption (VO2ldi) did not change significantly compared with control. During LPNS and BPNS, there was a significant increase in Qlpha and VO2ldi (P less than 0.01). There was no significant difference in Qlpha and VO2ldi between LPNS and BPNS (P greater than 0.05). We conclude 1) that there is a complete independence of left-right hemidiaphragmatic circulation both at rest and during diaphragm pacing and 2) that during unilateral stimulation transdiaphragmatic pressure is not related to diaphragmatic blood flow.     

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 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)     

Interaction of fatigue and hypercapnia in the canine diaphragm

We studied 10 open-chest dogs and measured the pressure across the diaphragm (Pdi) in each period of the protocol during stimulation at frequencies of 1, 20, 50, and 80 Hz. Three ranges of arterial PCO2 (PaCO2) were examined: less than or equal to 26, 36-50, and greater than or equal to 89 Torr. The diaphragm was fatigued with repetitive phrenic stimulation (30 Hz). During the fatiguing activity, five of the animals were subjected to hypercapnia and the other five to hypocapnia. A frequency-Pdi curve was generated for each period in the protocol. The data show that 1) fatiguing to 50% of the initial Pdi value during hypercapnia was significantly more rapid than during hypocapnia; 2) both the prefatigue and postfatigue mean Pdi values over all interactions of frequency, fatigue, and PaCO2 were unaffected by the fatiguing environment (hypercapnia vs. hypocapnia); 3) the percent reduction of Pdi by hypercapnia was the same at all four frequencies; 4) hypocapnia did not alter either the pre- or postfatigue frequency-Pdi curve; and 5) one-half relaxation time, unaffected by PaCO2, was prolonged by fatigue. We conclude that the hypercapnic diaphragm has less endurance than the hypocapnic diaphragm and that although both fatigue and hypercapnia decrease Pdi, they appear to be separate entities working through different mechanisms.     

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.     

Diaphragmatic function during hypoxemia: neonatal and developmental aspects

The effect of acute hypoxemia on diaphragmatic force output was studied in five young (age 4-8 days, wt 1.3-2.2 kg) and five older (age 16-19 days, wt 2.8-3.3 kg), anesthetized, spontaneously breathing piglets. Diaphragmatic force output was assessed by analysis of the transdiaphragmatic pressure (Pdi) generated during an occluded inspiratory effort, at end-expiratory lung volume, triggered by supramaximal transvenous stimulation of both phrenic nerves at frequencies of 20, 30, 50, and 100 Hz. During pressure measurements, the piglets were fitted with a rigid plaster cast covering the abdomen and lower third of the chest to ensure a consistency in diaphragmatic shortening during phrenic nerve stimulation. Pdi was measured under base-line conditions [inspired O2 fractional concentration (FIO2) = 0.50] and after 10 min of hypoxemia induced by breathing 12-14% FIO2. Pdi was significantly less than base line during acute hypoxemia at all frequencies of stimulation in both young and older piglets. The decline in the older piglets' Pdi during hypoxemia was significantly greater than that seen in younger piglets. We conclude that acute hypoxemia impairs the capacity of the developing piglet diaphragm to generate force. Furthermore, our data suggest that the young piglet is more resistant to the depressant effects of hypoxemia when compared to its older counterpart.