Fat emulsion and ARDS.
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Fat Emulsions, Intravenous↗
Biomedical subjects
C Roussos
Publications and source records attributed to C Roussos.
Electromyographic study of respiratory muscles during human diving at 46 ATA.
Electromyographic (EMG) recordings of the 6th to 7th intercostal space (thoracic EMG) and abdominal muscles, ventilatory pattern, and the work of breathing were studied in 4 human subjects exposed for 12 days to 46 ATA of helium-oxygen (density = 8.7 g.liter-1) then of nitrogen-helium-oxygen gas mixture (ternary mixture) (density = 11.1 g.liter-1). We found that the respiratory muscle work necessary for eupneic ventilation was multiplied by 4 at 46 ATA. During quiet breathing as well as during forced inspiratory maneuvers, the power spectrum of thoracic EMG shifted to the left in three individuals during the sojourn at maximal pressure, whichever gas mixture was inhaled. This was corroborated by the decreased ratio of EMG power in a high to that in a low band of frequencies. These alterations disappeared at the end of the decompression period, suggesting the existence of inspiratory muscle fatigue at high pressure. Hyperbaric tremor was recorded on the thoracic EMG and was maximal with He-O2 inhalation. It disappeared at the end of the period at 46 ATA (He-N2-O2).
Adult↗
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)
Animals↗
In situ isolated perfused and innervated left hemidiaphragm preparation.
We developed a vascularly isolated in situ preparation of the left hemidiaphragm in which arterial blood was only provided through the left phrenic artery and the venous blood only drained through the phrenic vein. The costal margins were secured and connected to three force transducers. Muscle shortening was measured by sonomicrometry. The presence of arterial collaterals between the left hemidiaphragm and the systemic circulation was excluded by the systemic injection of a vital dye (Lissamine Green), a neuromuscular blocking agent (succinylcholine), and by the injection of epinephrine. Left phrenic nerve stimulation produced homogeneous shortening and tension. The degree of shortening in the isolated and intact left diaphragm at the same resting length was similar. The preparation was stable for 2 h with less than 10% decline in maximum tension. Two advantages of this preparation are particularly important. 1) Diaphragmatic energetics can be studied independently of systemic factors, and 2) the role of phrenic nerve afferents in the control of breathing and systemic circulation can easily be assessed without activating nonphrenic nerve afferents.
Animals↗
Effects of furosemide on pulmonary shunts.
In 23 mechanically ventilated anuric (six) or oliguric (17) patients (less than 16 ml/h of urine output) with severe gas exchange abnormality, we investigated the effect of furosemide on intrapulmonary shunt (Qs/QT). Before and after 0.5, 1, and 2 h of IV administration of 200 mg of furosemide, we assessed the intrapulmonary shunt and PaO2 while patients' hemodynamic measurements were monitored. Ventilatory parameters remained constant throughout the study. While the urine output was minimal and no alteration in hemodynamic values was found, the Qs/QT decreased from 27.7 +/- 2.3 percent (mean +/- SEM) at control to 24.3 +/- 2.1 percent (p less than 0.01) at 0.5 h, 21.7 +/- 2.1 percent (p less than 0.001) at 1 h, and 18.1 +/- 1.8 percent (p less than 0.001) at 2 h. The PaO2 showed no significant difference at 0.5 h but rose significantly from 96 +/- 14 to 105 +/- 14 mm Hg (p less than 0.05) and 111 +/- 14 mm Hg (p less than 0.01) at 1 and 2 h, respectively. Since we observed no changes in hemodynamics, we speculate a direct effect of furosemide in the pulmonary vasculature affecting the ventilation-perfusion mismatch and, therefore, the Qs/QT and PaO2.
Acute Kidney Injury↗
Autoregulation of diaphragmatic blood flow in dogs.
In eight anesthetized spontaneously breathing dogs, we determined whether diaphragmatic blood flow is dependent on arterial blood pressure (Pa) or whether it is autoregulated. We also determined whether diaphragmatic muscular activity affects the degree of autoregulation. We measured blood flow through the left phrenic artery (Qphr) with an electromagnetic flow probe and decreased Pa in steps by controlled hemorrhage. Phrenic venous blood was sampled to allow the calculation of diaphragmatic O2 consumption (VO2phr). Diaphragmatic energy demands were varied by using three inspiratory resistances (R1, R2, and R3), which increased peak transdiaphragmatic pressure two-, three-, and fourfold, respectively. During quiet breathing, Qphr was independent of Pa between Pa of 90 and 120 mmHg (i.e., plateau of pressure-flow relation), but at lower Pa, Qphr was directly related to Pa. During inspiratory loading, the Qphr plateau ended at a higher Pa than with quiet breathing, but within the normal ranges of Pa there still was a plateau. VO2phr at a given work load was constant between Pa of 70 and 120 mmHg, but at Pa of 50-55 mmHg, VO2phr declined with all work loads. We conclude that in spontaneously breathing dogs 1) Qphr is autoregulated over the normal range of blood pressures and 2) VO2phr is maintained over wider ranges of Pa than Qphr.
Animals↗
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.
Animals↗
Diaphragmatic energetics and blood flow during pulmonary edema and hypotension.
We studied the role of O2 supply and demand factors for producing diaphragmatic failure in a canine model of cardiogenic shock with pulmonary edema. We produced pulmonary edema with oleic acid and then hypotension with cardiac tamponade and followed the animals until respiratory failure began, which was defined by a 50% fall in frequency of breathing and diaphragmatic pressure-time index (PTI; cmH2O.s-1.min-1) with no decrease in the diaphragmatic electromyogram. Regional blood flows were measured with radiolabeled microspheres. Diaphragmatic O2 consumption (VO2 di) (ml.min-1.100 g-1) was determined from the diaphragmatic blood flow (Qdi) and the arterial and phrenic venous O2 contents. With oleic acid-induced pulmonary edema, PTI Qdi, and VO2 di increased from control of 101.7 +/- 31.7, 17 +/- 1.8, and 0.81 +/- 0.11, respectively, to 187.2 +/- 27.6, 42.2 +/- 7.2, and 3.32 +/- 0.35 (P less than 0.05). With tamponade, PTI did not change (186.7 +/- 60.0), whereas VO2 di increased further to 3.98 +/- 0.98 (P less than 0.05) due to increased O2 extraction and no significant change in Qdi (32.8 +/- 4.0). As fatigue developed, VO2 di decreased to 2.30 +/- 0.23 due to the combined effects of small declines in Qdi and the arterial O2 content but remained higher than control even though the energy demands returned to control values. In conclusion, when cardiogenic shock is added to pulmonary edema VO2 di and energy output do not increase further and eventually fall.
Animals↗
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.
Animals↗
Metabolite changes in the loaded hypoperfused and failing diaphragm.
Metabolite changes in the costal diaphragm were determined in anesthetized dogs subjected to a moderate inspiratory elastic load and to reduced blood flow. Diaphragmatic blood flow was reduced by occlusion of the descending aorta and internal mammary arteries. The goal of this study was to demonstrate that the failing diaphragm under these conditions shows biochemical changes similar to that of skeletal muscle fatigue. Selected metabolite concentrations were determined 1) during mechanical ventilation and normal blood flow, 2) during blood flow reduction and inspiratory loading when the ratio of airway pressure to diaphragmatic electromyogram (Paw/Edi) had decreased by 50% (fatigue), and 3) at 1 h after restoration of blood flow and mechanical ventilation (recovery). During fatigue, glycogen, ATP, and phosphocreatine were 30, 50, and 50% of control levels, respectively. Glucose 6-phosphate and lactate were two- and fivefold higher, respectively, than control concentrations. During recovery, all metabolites, except ATP and lactate, returned to control concentrations. These changes were not seen in resting ischemic skeletal muscles or in the diaphragmatic samples of the mechanically ventilated animals with diaphragmatic blood flow limitation. We conclude that when the loaded and hypoperfused diaphragm fails, as indicated by lower than control Paw/Edi, metabolite changes similar to that observed in fatigued skeletal muscle occur.
Adenosine Triphosphate↗
Interposed abdominal compressions and carotid blood flow during cardiopulmonary resuscitation. Support for a thoracoabdominal unit.
To determine if the timing of interposed abdominal compressions (IAC) affects the augmented blood flow during this form of cardiopulmonary resuscitation (CPR), we performed early-onset or late-onset abdominal compressions at three vascular volumes in nine dogs. Early-onset IAC began immediately following chest compression; we predicted that this would act primarily by emptying the aorta and sustaining the elevated intrathoracic pressure. Late-onset IAC began one-fourth to one-third of the time into diastole; this would have primarily increased venous return. We measured carotid blood flow (electromagnetic flow probe) and right atrial (Pra), thoracic aortic (Pta), abdominal aortic (Paa), and intra-abdominal pressures. The IAC-CPR increased carotid blood flow compared with conventional CPR (22.8 +/- 13.1 percent vs 8.7 +/- 5.8 percent of control; p less than 0.003), but there was no difference between the early and late modes of IAC (22.7 +/- 11.6 percent vs 22.9 +/- 14.7 percent of control). The increase in carotid blood flow was present with the first abdominal compression and was constant over the 40 to 60 seconds of CPR. Peak Pra, Pta, and Paa were similar during abdominal compression (91.8 +/- 16.9 mm Hg, 96.1 +/- 16.0 mm Hg, and 102.4 +/- 15.2 mm Hg, respectively; p less than 0.001). The Pta-Pra diastolic gradient was 18.0 +/- 8.2 mm Hg for early-onset and 20.6 +/- 7.5 mm Hg for late-onset compression (not significant). We conclude that increased carotid blood flow in IAC-CPR in the dog is principally due to the increased pressure in a common thoracoabdominal unit.
Abdomen↗
Effects of norepinephrine and fluid administration on diaphragmatic O2 consumption in septic shock.
The effects of norepinephrine infusion and fluid administration on diaphragmatic O2 consumption during endotoxic shock were assessed in spontaneously breathing anesthetized dogs. Blood flow was measured with the microsphere technique, and diaphragmatic venous blood was obtained via a catheter inserted into the left inferior phrenic vein. One group of dogs (n = 6) received 10 mg/kg Escherichia coli endotoxin intravenously (E group). In the second and third groups, blood pressure after endotoxin injection was restored by continuous infusion of norepinephrine tartrate (N group) or by infusion of normal saline and dextran infusion (F group). The animals were observed for 2 h after endotoxin injection. Cardiac output fell significantly in the E and N group, whereas it was restored in the F group. Minute ventilation and diaphragmatic pressure-time index rose twofold in the three groups of dogs. Diaphragmatic O2 consumption (VO2 di) increased substantially in the E group to a mean value of 3.46 ml X 100 g-1 X min-1, which was achieved by higher blood flow and by an increase in O2 extraction. In the N group, VO2 di was higher than control but was lower than that of the E group (mean value of 1.43 ml X 100 g-1 X min-1), which was achieved solely by increasing O2 extraction. In the F group, VO2 di was also lower than that of the E group (mean value of 1.51 ml X 100 g-1 X min-1), which was achieved by high diaphragmatic blood flow. Thus, at any given diaphragmatic task, the diaphragm consumed less O2 in the N and F group than in the E group.
Animals↗
The effects of ischemia, lactic acid and hypertonic sodium chloride on phrenic afferent discharge during spontaneous diaphragmatic contraction.
In 9 sodium pentobarbital anaesthetized cats, 50 single-unit phrenic afferent recordings were determined during spontaneous ventilation, retrograde carotid arterial injection of lactic acid (LA, 0.1 N) and NaCl (5%), and a 2-min occlusion of the superior thoracic aorta. Fifty percent of the units had tonic low-frequency spontaneous discharge; 50% had phasic high-frequency discharge. Tonic fiber activity increased significantly with LA, NaCl and occlusion, while phasic fiber activity decreased in all 3 conditions. These results suggest that the diaphragm contains sensory endings sensitive to ischemia and extracellular metabolic changes.
Animals↗
Diaphragmatic fatigue and blood flow distribution in shock.
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Animals↗
Respiratory muscle energetics during endotoxic shock in dogs.
Respiratory muscle O2 consumption, lactate production, and endogenous substrate utilization during endotoxic shock were assessed in two groups of anesthetized spontaneously breathing dogs. In the endotoxin group (Escherichia coli endotoxin 10 mg/kg iv) and the sham group (saline iv), we sampled diaphragm, external intercostal, and gastrocnemius muscle tissue for glycogen and lactate concentrations before and after 3 h of the experimental period. Only in the endotoxin group did blood pressure and cardiac output decline significantly. Arterial O2 content did not change significantly during shock, whereas mixed venous, phrenic venous, and femoral venous O2 contents dropped to 8.0 +/- 1.1, 5.8 +/- 0.8, and 3.6 +/- 0.6 ml/dl at 60 min of shock, respectively, with little change thereafter. At 30 min of shock, femoral venous lactate rose higher than arterial values, whereas at 90 min of shock, onward, phrenic venous lactate was significantly higher than arterial concentrations. All muscle tissues showed significant lactate production and glycogen depletion after shock. In a second set of experiments we measured respiratory muscle blood flow during shock with radioactive microspheres. At 60 min of shock, diaphragmatic and intercostal blood flow rose by six- and twofold, respectively, whereas gastrocnemius blood flow declined significantly. We conclude that during endotoxin shock 1) the increased demands of the respiratory muscles are met by increasing blood flow and O2 extraction; 2) anaerobic metabolism and respiratory muscle substrate depletion, or both, may contribute to the observed fatigue.
Animals↗
Phrenic afferents and their role in inspiratory control.
In anesthetized cats, with vagi cut and the spinal cord severed at the C8 level, phrenic motor and/or sensory discharge was recorded. Small afferent phrenic fibers were identified through their activation by lactic acid, hyperosmotic NaCl solution, or phenyl diguanide. They exhibited a spontaneous but irregular low-frequency discharge. Block of their conduction by procaine had no effect on eupneic motor phrenic activity. Large afferent phrenic fibers showed a spontaneous rhythmic discharge, and cold block (6 degrees C) of these fibers significantly prolonged the phrenic discharge time (Tphr) and total breath duration (TT) during eupnea. The stimulation of all afferent phrenic fibers lowered the impulse frequency of phrenic motoneurons (f impulses) and shortened both Tphr and TT. When the stimulation was performed during cold block all of the effects on phrenic output persisted, but changes in timing were less pronounced. Under procaine block, only the effects of phrenic nerve stimulation on Tphr persisted. These results suggest that both large and small afferent phrenic fibers control the inspiratory activity with a prominent role of small fibers on phrenic motoneuron impulse frequency.
Afferent Pathways↗
Respiratory muscle blood flow in oleic acid-induced pulmonary edema.
If respiratory muscle blood flow (RMBF) demands in pulmonary edema are large enough, an imbalance between supply and demand could lead to respiratory muscle failure. Therefore, to determine the magnitude of RMBF in this condition we produced pulmonary edema by injecting oleic acid into the pulmonary circulation and measured RMBF with radiolabeled microspheres injected into the left atrium. We then related changes in muscle blood flow to changes in respiratory variables including frequency of breathing (fb, breaths/min), tidal volume (VT, ml), ventilation (VE, ml . kg-1 . min-1), pleural pressure-time index (PTI, cmH2O), and dynamic compliance (Cdyn, 1/cmH2O) at 0 (control), 30, 60, and 120 min. Cardiac output and blood pressure did not change throughout the experiment, but hypoxia became progressively more severe with a final PO2 of 37 +/- 10 Torr. With pulmonary edema, fb rose from a control value of 32 +/- 13 to 111 +/- 33 at peak, VE rose from 237 +/- 90 to 806 +/- 188, but VT did not change. PTI rose from 54 +/- 16 to 180 +/- 48, and Cdyn decreased from 0.06 +/- 0.02 to 2.02 +/- 0.01. Diaphragmatic blood flow (Qdi) rose from 16.0 +/- 6.26 to 120.1 +/- 54.5 ml . min-1 X 100 g-1 and accounted for 55% of the total RMBF of 217 +/- 100 ml/min. The RMBF accounted for 11.4 +/- 4.7% of the cardiac output at peak affect. The rise in Qdi was best predicted by PTI and to a smaller extent by PO2.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effects of aminophylline and salbutamol on diaphragmatic force during compensated metabolic acidosis.
We investigated the effects of aminophylline and salbutamol on tetanic force generated by the diaphragm during compensated metabolic acidosis in dogs. Anesthetized, mechanically ventilated animals were prepared with an open thorax. A cast was placed around the abdomen to maintain length and geometry of the diaphragm during contractions. A thin-walled latex balloon was positioned beneath the diaphragm to measure transdiaphragmatic pressure (Pdi). Pdi served as the index of diaphragmatic force of contraction. We measured Pdi during supramaximal phrenic stimulation at low and high frequencies and also during spontaneous inspiratory efforts for a constant diaphragmatic EMG activity. Compensated metabolic acidosis significantly reduced Pdi at all stimulation frequencies (p less than 0.05). The mean percent decrease at low frequencies was greater than at high (p less than 0.05). Pdi was decreased during spontaneous contractions as well (p less than 0.05). Administration of aminophylline significantly improved Pdi at all frequencies of phrenic stimulation (p less than 0.05) and during spontaneous inspiratory efforts (p less than 0.05). Infusion of salbutamol did not have a significant effect on Pdi at any frequency of stimulation but did produce a small potentiating effect during spontaneous contractions (p less than 0.05). We also recorded and analyzed the Pdi response to a single supramaximal impulse to the phrenic nerve, referred to as a twitch, to gain insight into possible cellular mechanisms underlying alterations in tetanic force of contraction. Compensated metabolic acidosis led to a significant reduction in peak twitch tension (PTT) (p less than 0.05) and half relaxation time (1/2RT) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Acidosis↗