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Biomedical subjects

E M Scarpelli

Publications and source records attributed to E M Scarpelli.

At least 37 records · Page 2Linked to original sources
PubMed1987

Ventilation and pulmonary mechanics during high-frequency oscillation of immature lungs at birth.

Ventilation was initiated and maintained by high-frequency oscillation (HFO) in nine immature lambs not expected to survive for more than a few minutes out of the uterus. They were delivered to HFO (18 to 20 Hz) and ventilated only with air at the setting that yielded optimal blood gases and pH. Once removed from HFO, cardiorespiratory arrest occurred within minutes despite the return of previously inhibited natural inspiratory efforts. At autopsy, the lungs were liquid-filled (i.e., fetal). Thus, HFO had maintained viability without promoting either lung stability or fetal pulmonary fluid (FPF) absorption. Additional experiments on excised immature lungs showed that aeration is determined by distending pressure, which is regulated by the flow through the oscillator circuit and monitored most accurately as transpulmonary pressure (TPP). Once air-entry has begun, alveolar recruitment and negative compliance establish the limits of tolerable lung expansion via TPP. Within these limits, the immature lung can be ventilated effectively with air. However, since these lungs do not produce intrapulmonary foam, lung stability and FPF absorption are not effected. Complications of HFO (including pneumothorax, decreased arterial pressure and heart rate, and metabolic acidemia) can be related to overdistention of the lungs.

Animals↗
PubMed1986

CO2 responsivity in the mouse measured by rebreathing.

We have modified the rebreathing method to study CO2 responsivity in very small mammals. Tidal volume (VT) and frequency (f) of pentobarbital-anesthetized mice were measured during rebreathing from a closed circuit, primed with 95% O2, 5% CO2, through which the gas was constantly circulated at 0.5 l X min-1. The circuit consisted of T-tube from a plethysmograph, Tygon tubing with compliant element, CO2 analyzer and pump, in series. Circuit PCO2 (PctCO2), which was recorded continuously during spontaneous breathing, rapidly equilibrated with end-tidal PCO2. CO2 response curves were constructed from extrapolated minute ventilation (V), VT, f and parameters of breath-to-breath timing, respectively, on PctCO2. Analyses of slopes of the response curves, change from onset of rebreathing to peak response, and PctCO2 at which the response peaked revealed that CO2 stimulates V by increasing f and VT and that this is effected by facilitation of central inspiratory-expiratory phase switching and inspiratory drive mechanisms. However, the stimulatory effect of CO2 on phase switching was not sustained, with maximal effect occurring before peak V. The advantages and facility of the modified rebreathing method make it suitable for studies of other small mammals, including neonates.

Animals↗
PubMed1985

Acute responses to phosgene inhalation and selected corrective measures (including surfactant).

We exposed 22 mongrel dogs to 94 ppm phosgene for 20 min from a non-rebreathing system. We expressed exposure to phosgene as ppm X VI X min X kg 1, i.e., the amount of gas containing a known phosgene concentration that was actually inhaled per min standardized to body weight, the "exposure index" (EI). In contrast, the conventional expression of exposure, i.e., ppm X min, fails to take volume inhaled (VI) and body weight into account. Five dogs received no intervention and served as controls. Fourteen dogs received basic therapy of oral cortisone (40 mg/kg) and NaHCO3 (3 mEq/kg) plus 100% O2 (FiO2 = 1.0) for 30 min after the exposure period. These animals were further divided according to the following selected additional therapies, which were started 30 min after exposure: Theophylline, 5 mg/kg iv for 20 min followed by 1 mg/kg/hr for 70 min (n = 5). Three dogs of this group were given a trial of 5 cm H2O expiratory resistance during the period of basic therapy. Because of the untoward response, expiratory resistance was discontinued and not used in other experiments. PGE2-hi, [1 microgram/kg/min] iv for 90 min (n = 3). PGE1-lo, [0.04 microgram/kg/min] iv for 90 min (n = 3). Atropine, 0.5 mg/kg iv at 30 and 50 min after exposure (n = 3). Three dogs [group 5] received oral cortisone and NaHCO3 plus inhaled supplementary surfactant, 2.7 mg/min ultrasonically nebulized (FiO2 = 0.5; phosphate buffer), for 30 min after exposure. All treated dogs, groups [1] through [4] and the surfactant group [5], received cortisone (40 mg/kg/hr iv), NaHCO3 to correct base deficit, and O2 to correct hypoxemia from 30 min to 120 min after exposure. Because of its clearly beneficial effect in group [1], theophylline was also given to all other treatment groups during this period. At the end of the study, all lungs were excised, examined and prepared for light microscopy. We found that EI, which varied among subjects because of spontaneous variations of VI during exposure, correlated significantly with the changes in base deficit induced by phosgene inhalation. We also found that the change in minute ventilation, delta VI X kg-1, correlated significantly with changes in lung compliance, peak flow and base deficit. Evaluation of the various therapeutic modalities revealed the following: Immediate therapy with O2 is vital and and FiO2 of 0.4 to 0.5 is sufficient.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Intranasal↗
PubMed1984

Intrasaccular bubbles of near-zero surface tension stabilize neonatal lungs.

Mature rabbit fetuses produce intrapulmonary foam at the onset of breathing at birth. Bubbles establish a minimal volume immediately and require relatively little distending pressure for their formation. Stability of bubbles that are formed during both rapid spontaneous breathing in vivo and slow inflation-deflation of excised lungs is determined by the surfactant content of fetal pulmonary fluid (FPF). Mature bubbles can be delivered at atmospheric pressure from all aerated saccules by microdissection. When observed in air-equilibrated normal saline solution (NSS), their stability with time indicates that film surface tension (gamma) is very low, i.e., near-zero. When mature FPF is replaced with NSS, stable bubble production is absent. Conversely, supplementation of immature FPF with a surfactant dispersion prior to aeration induces bubbles that are as stable (near-zero gamma) as those from mature lungs. Proper mixing of the supplement, e.g., by repeated inflation-deflation, is required for proper distribution of foam in the immature fetal saccules. From these findings, it may be concluded that bubbles establish the condition for production of near-zero gamma in situ. The latter stabilizes the lung by sustaining normal liquid transfers (Pattle theory). In addition, bubble films promote mechanical stability by providing a saccular infrastructure that resists collapse and retards surface spreading.

Animals↗
PubMed1984

CO2 and naloxone modify sleep/wake state and activate breathing in the acute fetal lamb preparation.

We studied locally anesthetized lamb fetuses (140-144 days' gestation) in utero on the day of surgical preparation (the acute preparation) to correlate sleep/wake (S/W) states with fetal breathing movements (FBM) activated by CO2 with and without endorphin displacement by naloxone. We placed electrodes for definition of S/W states, a carotid arterial catheter for injections and measurements of pressure, pHa, PaCO2 and PaO2, and intratracheal and intraesophageal catheters for measurement of FBM and esophageal motility. We recorded the onset, pattern and cessation of breathing and estimated fetal respiratory responsivity to CO2 rebreathing by the ewe using our fetal CO2 test (Moss, I.R. and Scarpelli , E.M., 1979, J. Appl. Physiol. 47: 527-531). Activation of breathing by CO2 either accompanied or followed wakefulness (W). FBM and W were sustained throughout CO2 stimulation. Cessation of breathing after the CO2 test was temporally associated with the resumption of sleep. When the test was started in active sleep (AS) and W, breathing threshold to CO2 was lower than when it was started in quiet sleep (QS). Naloxone treatment (1) resulted in activation of FBM in association with W, (2) lowered CO2 threshold as compared to that of CO2 tests entered in QS without naloxone, and (3) caused greater FBM responses to CO2 than without naloxone. These results extend previous reports from our laboratory in that they demonstrate the importance of W to normal respiratory responsivity to CO2 in the acute fetal preparation and the possible role of endorphins in respiratory control.

Animals↗
PubMed1984

Indomethacin and the cardiopulmonary adaptations of transition.

The present investigation examines the biochemical and physiologic changes produced in fetal rabbit lungs by adding a prostaglandin synthetase inhibitor, sodium indomethacin trihydrate, to the pulmonary perfusate. A control group was similarly perfused without adding indomethacin. The ductus arteriosus was ligated and perfusion was then continued for 2 h while pulmonary artery pressures were monitored. At the end of this period, with perfusion continuing, the lungs were inflated with air at 5 cm H2O increments. Volume changes were recorded. After deflation, the lungs were lavaged with normal saline. Phospholipids were extracted from lung homogenates and lavage. Total lipid phosphorus was determined. Pulmonary vascular resistances in both groups manifested a sharp increase in pressure with ligation of the ductus. After 2 h of perfusion, pulmonary pressures in the control groups had returned very nearly to preligation levels, while in the indomethacin-treated group, pulmonary pressures remained significantly elevated. The first full inflation produced a slight fall in pulmonary vascular resistance in all control animals and a slight rise in all the treated rabbits. Perfused but untreated lungs had higher volumes during inflation as compared to both indomethacin-perfused lungs and unperfused untreated lungs. In this model, prostaglandins appear to have a significant role at two key points in transition: 1) the gradual accommodation to mechanically or hemodynamically mediated increases in pulmonary vascular resistance and 2) the drop in pulmonary vascular resistance which occurs with the first inflation of the lungs. No direct effect of prostaglandin inhibition on surfactant production was documented.

Animals↗
PubMed1983

Time-dependency and static mechanics of immature airways and saccules.

Immature rabbit lungs were inflated, then deflated from the fetal pulmonary fluid (FPF)-filled state. Stereomicroscopic observation and measurement of volume change (delta V) during each pressure step and after 15 and 120 sec at each pressure revealed the following: (1) Only airways inflate from atmospheric pressure (P0) to P25. Significant time-dependency here is due to FPF flow through the narrowest airways, airways dilation and recruitment as functions of tissue and surface forces, and, perhaps, interfacial adsorption of surfactants. (2) Saccular recruitment and distention are the principal transformations from P30 to P35. Time-dependency here is the result of FPF flow and labile bubble production. (3) Time-dependency during deflation from P25 to P10 is due to diminishing influence of inflation processes and to decreasing radii of curvature at air/liquid interfaces as FPF refills the saccular air-spaces. Redistribution of air and hypophase liquid probably also play a role. (4) Deflation from P10 to P0 is determined by FPF flow through the smallest airways, interfacial forces, and recoil of previously distended airways as liquid locks are formed. Some implications are that FPF flow through the smallest airways is a gate to saccular ventilation; time-dependent processes place airspaces at risk to rupture; and different time constants of saccules and airways renders 120 sec pressure steps adequate for evaluation of the latter but not the former.

Animals↗
PubMed1981

The progressive onset of spontaneous and induced fetal breathing.

Intratracheal pressure (ITPmax) and respiratory drive (dITP/dt) from the occluded, liquid-filled trachea of term fetal lambs in utero were measured for each breath at the onset of fetal breathing (1) during spontaneous breathing, (2) during sciatic nerve stimulation, (3) during induced hypercapnia, and (4) following naloxone administration. These responses were characterized by linear increase of ITPmax and dITP/dt following which these parameters became stable. The rate of rise of ITPmax and dITP/dt was lowest and similar during spontaneous breathing and sciatic stimulation, but increased incrementally with hypercapnia and naloxone. Mechanical factors could not account for these responses in the liquid-filled lung, nor did appreciable chemical changes occur during this period. These results suggest that progressive breathing responses at the onset of fetal breathing may stem from gradual recruitment of central respiratory neurons, and that the rate of rise of such recruitment depends on facilitation by natural arousal, somatosensory stimulation and hypercapnia as well as on release from natural endorphin inhibition.

Animals↗
PubMed1981

Functional anatomy and volume-pressure characteristics of immature lungs.

The mechanical behavior of immature rabbit fetal lungs in situ was assessed by air and saline volume-pressure diagrams. All lungs were in their natural fetal state, i.e., filled with fetal pulmonary fluid, prior to inflation. Anatomic correlates were determined by continuous stereomicroscopic monitoring of the lungs. We found the following to be characteristic of immature lungs: (1) Tissue retractive forces are similar to adults. (2) Fetal lungs are not 'plastic' above functional residual capacity. (3) Initial aeration is by 'axial filling' in which airways are distended several times their resting size. (4) Invariably, peripheral rather than central saccules are the first to be aerated and saccules are recruited by both pressure- and time-dependent processes. (5) Pressure-dependence is related to surface forces and terminal orifice size, while time-dependent processes include orifice enlargement, liquid flow through terminal conduits, and the formation of very short-lived, labile bubbles. (6) 'Opening pressure' inflection in the VP diagram is not coincidental with, but follows the onset of saccular aeration. (7) Negative compliance at the onset of deflation is due to saccular enlargement and recruitment. (8) Hysteresis is due to tissue conformational characteristics at high pressures and air entrapment at low pressures. (9) Surface tension cannot be measured reliably from the saline and air VP diagrams.

Animals↗
PubMed1981

beta-Endorphin central depression of respiration and circulation.

Beta-Endorphin was injected into cerebrospinal fluid of lightly anesthetized dogs. Its effects on ventilation (V), tidal volume (VT), respiratory frequency (f), preinspiratory occlusion pressure (P500), and respiratory timing of unoccluded and occluded breaths were studied during CO2 rebreathing. Blood pressure and heart rate (HR) were monitored throughout the study. beta-Endorphin produced 1) early (approximately 15 min) but temporary depression of VT-PCO2 and P500-PCO2 responses; 2) progressive hypoventilation during spontaneous breathing and progressive depression of V-PCO2 and f-PCO2 responses, which were maximal at about 75 min, followed by gradual recovery; 3) progressive hypotension and bradycardia starting at about 15 min and reaching maximal effect at about 105 min. Increased expiratory time (TE) accounted for the changes in f. TE increased in unoccluded breaths and during both preinspiratory and inflation occlusion. After vagotomy, beta-endorphin produced insignificant effect on f, TE, and HR. Naloxone itself increased P500-PCO2 response; when given during beta-endorphin effect, it reversed the hypotension, bradycardia, V-PCO2, and f-PCO2 responses and facilitated the P500-PCO2 and VT-PCO2 responses. We conclude that beta-endorphin effect is produced by both depression of specific central cardiovascular and respiratory control units and facilitation of central vagal projections.

Animals↗
PubMed1981

Stimulatory effect of theophylline on regulation of fetal breathing movements.

We have performed the fetal CO2 response test on eight mature lambs in utero and have found that theophylline is a respiratory stimulant over a wide range of PaO2 and pHa. Theophylline produces significant increase in slope of P100, Pmax, and VEq response curves and significant increase in P100, Pmax, f, and VEq responses at PaCO2, 65 torr. It also produces significant lowering of the naturally high fetal absolute threshold to CO2, i.e., PaCO2 at which breathing starts during the CO2 test. "Offset" threshold, i.e., PaCO2 when breathing stops after the test, is the same with and without theophylline and equal to absolute threshold with theophylline. Our studies indicate that: (1) theophylline lowers fetal threshold and increases sensitivity to CO2; (2) increased sensitivity is expressed mainly by heightened Pmax (i.e., the equivalent of tidal volume) with some contribution of f particularly at high PaCO2; (3) decreased CO2 threshold is best assessed by determination of absolute threshold rather than the conventional x-axis intercept method; (4) the low offset threshold is consistent with our understanding that arousal is a requisite for generation and maintenance of fetal breathing; (5) theophylline is as effective a respiratory stimulant during fetal acidemia and hypoxemia as it is under normal conditions; and (6) a number of serious reservations must be held regarding use of theophylline during low pHa, low PaO2 states.

Animals↗
PubMed1979

Arterial pH, airway caliber and response to acetylcholine and catecholamines in vivo.

Direct assessment of tracheal circumference, which permits evaluation of constriction and dilatation in vivo, was made continuously in intact, pentobarbital-anesthetized, spontaneously breathing dogs. Immediate response to induction of hypercapnia included tracheal constriction and cessation of normal, vagus-dependent rhythmicity of airway tone. The characteristic constrictor response to acetylcholine was exaggerated significantly during hypercapnic acidosis and returned to normal when arterial pH, but not CSF pH, was corrected by NaHCO3 infusion. Epinephrine produced significant tracheal dilatation (infrequently followed by constriction) and isoproterenol produced only dilatation at normal pH. The catecholamine-induced dilatation was decreased significantly during hypercapnic acidosis, but improved after NaHCO3 infusion. Responses to acetylcholine and epinephrine were the the same as control during alkalemia, whereas the response to isoproterenol was unexplainedly diminished. Thus alkalemia may inhibit the action of isoproterenol; acidemia enhances parasympathomimetic constriction and reduces sympathomimetic dilatation; and correction of arterial pH returns these responses to normal, even if hypercapnia and CSF acidosis persist.

Acetylcholine↗