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)     

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 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.     

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 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.     

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.     

Effects of theophylline and enprofylline on diaphragmatic contractility

Experimental data suggest that theophylline (T) enhances diaphragmatic contractility by increasing the influx of calcium at the cell membrane level through an inhibition of adenosine receptors (Aubier et al., J. Appl. Physiol. 54: 460-4, 1983). Enprofylline (E) is a xanthine drug that has poor ability to antagonize physiological actions of adenosine. The aim of this study was to compare the effects on diaphragmatic contractility of T and E in order to determine whether antagonism of adenosine receptors was the underlying mechanism of the inotropic effect of T on diaphragmatic contractility. Ten normal subjects were studied in the sitting position. The contractile properties of the diaphragm were assessed by measuring the transdiaphragmatic pressure (Pdi) generated at functional residual capacity during bilateral electrical stimulation of the phrenic nerves. The subjects were randomized, and after control measurements were performed, they received T or E. This was a double-blind crossover study, the measurements being repeated with the second drug after one week. Both drugs were administered intravenously with a loading dose of 6 and 2 mg/kg administered in 30 min for T and E and a maintenance dose of 0.9 and 0.075 mg.kg-1 X h-1 for T and E, respectively. Measurements were performed before and 60 min after T or E administration. Plasmatic levels of both drugs were also analyzed. In all the subjects, therapeutic levels of T or E were reached (14.8 +/- 0.6 and 3.9 +/- 0.42 mg/l for T and E, respectively, at 30 min).(ABSTRACT TRUNCATED AT 250 WORDS)     

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 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.     

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.     

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)     

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.     

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.     

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)     

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.     

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 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)     

Diaphragmatic O2 and lactate extraction during submaximal and maximal exertion in ponies

Diaphragmatic O2 and lactate extraction were studied in 10 healthy ponies at rest and during treadmill exercise. The phrenic vein was aseptically catheterized via a lateral thoracotomy 8-35 days before the study. Arterial and phrenic venous blood samples were obtained simultaneously at rest and at 30-s intervals during 4 min of exertion. Three levels of exertion were studied (moderate, 10 mi/h; heavy, 15 mi/h; maximal, 20 mi/h), and a rest period of at least 90 min was allowed between them. Each pony was studied twice at least 2-3 days apart. At rest the diaphragmatic venous PO2, O2 saturation, arteriovenous O2 content difference, and O2 extraction were 43.2 +/- 2.0 Torr, 76.1 +/- 3.2%, 3.14 +/- 0.43 ml/dl, and 23.60 +/- 3.61%, respectively. Significant decrease in phrenic venous PO2 and O2 saturation occurred within 30 s of exercise. Phrenic venous PO2 decreased to 20.3 +/- 1.0, 18.9 +/- 1.1, and 15.4 +/- 0.9 Torr at 120 s of moderate, heavy, and maximal exercise, respectively. Corresponding values of phrenic venous O2 saturation were 33.6 +/- 2.2, 25.8 +/- 2.1, and 17.9 +/- 0.5%, respectively. Diaphragmatic arteriovenous O2 content difference expanded to 13.11 +/- 0.49, 15.00 +/- 0.60, and 16.90 +/- 0.60 ml/dl at 120 s of moderate, heavy, and maximal exercise, respectively, as O2 extraction rose to 65.93 +/- 1.98, 73.90 +/- 1.99, and 80.95 +/- 0.47%, respectively. During heavy and maximal exercise, the diaphragmatic venous lactate concentration remained similar to the arterial concentration.(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.     

Effects of Ca2+ withdrawal on diaphragmatic fiber tension generation

The effects of extracellular Ca2+ withdrawal were studied on isolated diaphragmatic muscle fibers and compared with the effects on the papillary, soleus, and extensor digitorum longus (EDL) contractility, using the same in vitro model. Diaphragmatic fibers were obtained from 15 rats, and papillary muscles, soleus, and EDL were obtained from 10 animals. Isometric force generated in response to 1-Hz supramaximal electrical stimulation was measured with a highly sensitive photoelectric transducer. After control measurements, perfusion with a Krebs solution depleted of calcium (0 Ca2+) was started while the fibers were continuously stimulated (4 times/min) and twitches recorded. For the papillary fibers, perfusion with zero Ca2+ was followed by an immediate decrease in twitch tension, complete twitch abolition occurring within 3 +/- 1 min after zero-Ca2+ exposure. Diaphragmatic fibers behaved similarly, although twitch abolition was delayed (10 +/- 3 min after 0-Ca2+ exposure). For the soleus fibers, the twitch amplitude amounted to 38 +/- 10% of control (62% decrease on the average) after 30 min of zero-Ca2+ exposure, no twitch abolition being noted even after 1 h of Ca2+-free exposure. The twitch amplitude of the EDL fibers amounted to 75 +/- 7% of control (25% decrease) after 30 min of zero-Ca2+ exposure. The recovery kinetics for the four fiber types after reexposure to Ca2+-containing solution were also different, with papillary and diaphragmatic fibers recovering completely within 2.5 +/- 0.5 and 4 +/- 0.5 min, respectively. By contrast, neither the soleus nor the EDL showed complete recovery after 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)