Biomedical subjects

L Oppenheimer

Publications and source records attributed to L Oppenheimer.

At least 37 records · Page 2Linked to original sources

PubMed1989

Do transvascular forces in isolated lobe preparations equilibrate?

We used the stepwise pressure elevation technique to study the relationship between rate of constant weight gain (Qf) and microvascular pressure (Pc) in eight isolated canine left lower lobes. The slope of this relationship, which is assumed to represent lobar conductance to filtration (Kf) was 0.0022 +/- 0.003 ml.min-1.cmH2O-1.g dry wt-1. The intercept when Qf = 0, Pcrit, commonly interpreted as the Pc at which the balance of forces across the microvasculature is overwhelmed, was 9.53 +/- 1.18 cmH2O, a lower Pc than commonly used in weight transient experiments. Consequently, at Pc greater than 9.53 cmH2O, isogravimetric conditions were never achieved. In 12 additional experiments, the perfusate's colloid osmotic pressure (II) was increased from 12 to 37 mmHg with albumin. On average, Pcrit increased from 12.2 to 23 cmH2O. Using the changes in Pcrit and II, we estimated the microvascular drag reflection coefficient for albumin (sigma d) to be 0.67. After the addition of albumin, Pc less than Pcrit induced constant weight loss along the same Qf-to-Pc relationship. To control for time, five additional lobes were observed at constant Pc for 100-180 min. Slight acceleration of the rate of weight gain occurred after they increased their weight by 30-40%. The low Kf and high sigma d, as well as the stability of the preparation, suggest a well-preserved microvasculature. Qf at Pc between 12 and 24 cmH2O did not influence measurements of Kf using the weight transient method. The low Pcrit may reflect obliteration of lymphatic channels.

Animals↗

PubMed1989

Heterogeneity of maximal lobar emptying rates in dogs with compensatory lung growth.

Five dogs underwent left pneumonectomy at 10 wk of age, whereas four littermates underwent a sham operation. At 26 wk of age the postpneumonectomy dogs had total lung vital capacity (VC) and lung weight similar to controls, but maximum expiratory flow was reduced. Pressure capsules were glued to right lower (RLL) and right cardiac (RCL) lobes, and alveolar pressures (PA) were measured during forced expiration. In postpneumonectomy dogs RLL and RCL both emptied more slowly than in control dogs, and emptying was especially delayed in RCL, which underwent the most growth. When both lobes deflated together, PA in RCL and RLL were similar in control dogs, but in postpneumonectomy dogs PA in RCL exceeded that in RLL by approximately 3 cmH2O from 80 to 20% VC. Because the higher driving pressure in RCL compensated for the relatively high resistance of RCL, the pattern of lobar emptying was relatively uniform over these lung volumes. This result was compatible with interdependence of lobar maximum expiratory flows. In addition, at PA of 6-10 cmH2O in postpneumonectomy dogs, maximum emptying rates of RCL were less when RCL deflated alone than when RCL and RLL emptied together, again demonstrating interdependence of lobar maximum expiratory flow.

Animals↗

PubMed1987

Measurement of cardiac output in anesthetized rats by dye dilution using a fiberoptic catheter.

A method is described for the measurement of cardiac output and oxygen saturation in closed-chest rats using a small (2.4 F) commercially available fiberoptic catheter and a reflection-spectral-photometer. Positioned in the aortic arch, the catheter functions as an oxymeter for oxygen saturation and as a densitometer for measurement of indocyanine green, obviating the need for blood removal and passage through a densitometer. The sensitivity and reproducibility of this method were characterized in 90 rats by thermodilution, radiolabeled microspheres, and electromagnetic flow methods as standard references. Basal cardiac output as well as changes in cardiac output during isoproterenol infusion and blood removal and replacement were measured. In addition, multiple measurements of cardiac output over 1 min were used to document the method's suitability in constructing a ventricular function curve. With the fiberoptic catheter, cardiac output varied predictably with anesthesia, with rats on dial-urethane (n = 23) having values of 150 +/- 39 (SD) ml/min/kg and 2 and 1% enflurane (18-35 rats per group) yielding cardiac outputs of 190 +/- 60 and 236 +/- 77 ml/min/kg, respectively. Pentobarbital produced the least cardiovascular depression (n = 15) with an average cardiac output of 322 +/- 22 ml/min/kg. The average cardiac output with this method in 90 rats (regardless of anesthesia) was 214 +/- 91 (SD). This value was comparable to cardiac output values determined in paired experiments from radiolabeled microspheres (9 rats) 220 +/- 43, electromagnetic flow (11 rats) 177 +/- 33, and a subset of rats with thermodilution (231 +/- 45 ml/min/kg). The within measurement (repeat measurements) variability with the fiberoptic method was consistently less than the rat-to-rat variability when compared to the thermal and radiolabeled microsphere methods, but it was comparable to electromagnetic flow. The method can be used when rapid measurements (4 measurements within 60 s) of cardiac output are required, as in constructing a ventricular function curve, and can readily detect small changes in cardiac output during controlled hemorrhage and isoproterenol infusion. In summary, this method gives measurement of oxygen saturation and cardiac output by dye dilution without blood removal. There is less surgical preparation than required for electromagnetic cardiac output, and it is an alternative to the thermodilution method.

Animals↗

PubMed1987

Colorimetric device for measurement of transvascular fluid flux in blood-perfused organs.

The aim of this study was to develop a device capable of measuring transvascular fluid flux in blood-perfused organs. For any given blood flow through the organ (QT), transvascular flux (QF) can be considered as the fraction of QT exchange. Presumably, QF would change the background concentration of an impermeable tracer residing in the perfusate. Thus QF could be calculated from the relative changes in tracer concentration for any given QT. We have used Blue Dextran (1 g/l of blood) as the reference tracer. Because the minimum molecular weight of Blue Dextran is 2 X 10(6), we anticipated it to behave as an impermeable tracer in most organs. QF was simulated with continuous infusions of plasma, normal saline solution, and a 50% mixture of both. Changes in Blue Dextran concentration were continuously followed colorimetrically by changes in transmission of specific light at a wavelength of 632 nm. Because 632-nm light is affected by hematocrit and O2 saturation changes, two additional wavelengths were used: 815-nm, which is not affected by saturation or Blue Dextran concentration changes, was used to account for changes in hematocrit, and 887-nm specific light, which is not affected by Blue Dextran, served to correct for saturation changes. Red cells could not be used as the reference tracer because of the possibility of hematocrit changes independent of fluid flux (Fahraeus effect). The device so constructed proved capable of measuring rates of fluid infusion in the order of 0.1% of QT with a variability of 10% around the mean.

Animals↗

PubMed1987

Fast-phase transvascular fluid flux and the Fahraeus effect.

Transvascular fluid flux was induced in six isolated blood-perfused canine lobes by increasing and decreasing hydrostatic inflow pressure (Pi). Fluid flux was followed against the change in concentration of an impermeable tracer (Blue Dextran) measured directly with a colorimetric device. The time course of fluid flux was biphasic with an initial fast transient followed by a slow phase. Hematocrit changes unrelated to fluid flux occurred due to the Fahraeus effect, and their contribution to the total color signal was subtracted to determine the rate of fast fluid flux (Qf). Qf was related to Pi to derive fast-phase conductance (Kf). Slow-phase Kf was calculated from the constant rate of change of lobe weight. For a mean change in Pi of 7 cmH2O, 40% of the color signal was due to fluid flux. Fast- and slow-phase Kf's were 0.86 +/- 0.15 and 0.27 +/- 0.05 ml X min-1. cmH2O-1 X 100 g dry wt-1. The fast-phase Kf is smaller than that reported for plasma-perfused lobes. Possible explanations discussed are the nature of the perfusate, the mechanical properties of the interstitium, and the slow rate of rise of the driving pressure at the filtration site on the basis of a distributed model of pulmonary vascular compliance.

Animals↗

PubMed1987

Delayed resolution of high-pressure pulmonary edema or capillary leak.

Both clinical and experimental evidence suggest that the time course of edema formation is different from that of edema resolution. To better describe and quantify this difference, we followed the accumulation of high-pressure pulmonary edema in live dogs with the thermal-green dye (TGD) double-indicator technique at steady-state levels of lung liquid. We raised left atrial pressure (PLa) in steps of 5 to 10 mm Hg as high as 25 mm Hg and followed edema to steady-state levels. Lung water was then measured as PLa was lowered to initial values. By plotting steady-state edema against PLa, pressure-volume relationships were constructed. There was little change in edema until PLa reached approximately 15 mm Hg, at which point further changes in PLa were associated with large increases in lung liquid. At PLa = 25 mm/kg, the average lung water had increased by 10 ml/kg. In each animal there was slow resolution of edema with decreases in PLa from its peak back to its initial value, but in no animal was edema fully reabsorbed even though PLa was maintained at about 5 mm Hg for as long as 10 hours. Several possible explanations account for these observations. Water could be trapped in alveolar and central interstitial spaces. In addition, vessel closure in edematous lung units could further influence water reabsorption. These observations raise the possibility that pulmonary edema in the presence of normal filling pressures may represent resolution of a transient high-pressure edema as opposed to a capillary leak syndrome.

Animals↗

PubMed1986

Association between adverse maternal and embryo-fetal effects in norfloxacin-treated and food-deprived rabbits.

Norfloxacin is a new antibiotic which caused embryo-fetal toxicity in association with maternotoxicity when given orally to rabbits at 100 mg/kg/day. The intestinal flora of rabbits is unusually sensitive to many antibiotics and it was suspected that the maternotoxicity and embryo-fetal toxicity caused by oral norfloxacin were secondary to an effect on the intestinal flora. To test this idea, a teratologic study was conducted in which rabbits were dosed on Days 6 to 18 of gestation with norfloxacin given orally at 100 mg/kg/day or subcutaneously at 20 mg/kg/day. The oral treatment caused decreased food consumption (to less than 15 g/day in some animals), body weight loss, an increased resorption rate, and decreased fetal weight. Among the females in the orally dosed group, there was a significant correlation (p less than or equal to 0.005) between the effects on maternal body weight and the resorption rate. The subcutaneous treatment caused little intestinal exposure (biliary excretion = only 2-4% of dose) and no maternotoxicity or embryo-fetal toxicity, even though blood levels of drug were at least as high as those in the oral group. Since the maternotoxicity and embryo-fetal toxicity were specific to the oral route and not correlated with the level of systemic exposure, the maternotoxicity may have been secondary to an effect on the intestinal flora and the embryo-fetal toxicity may have been secondary to the maternotoxicity. The decreased food consumption observed in the oral group may have contributed to the embryo-fetal toxicity since, in a separate study, it was found that lowering the amount of food provided to rabbits on Days 6 to 18 of gestation from 150 g/day to 50 or 15 g/day also caused adverse maternal and fetal effects including, at 15 g/day, fetal malformations.

Animals↗

PubMed1986

Aortic valve orifice equation independent of valvular flow intervals: application to aortic valve area computation in aortic stenosis and comparison with the Gorlin formula.

An orifice equation is derived relating the effective aortic valve area, A, the average aortic valve pressure gradient, dP, the stroke volume, SV, and the heart frequency, FH, through considerations of momentum conservation across the aortic valve. This leads to a formula consistent with Newton's second law of motion. The form of the new equation is A = (7.5 X 10(-5)) SV FH2/Pd, where A, VS, FH and Pd are expressed in cm2, ml, s-1 and mmHg, respectively. Aortic valve areas computed with the new orifice equation are found to correlate with those computed by the Gorlin formula in conditions of resting haemodynamic states at a level of r = 0.86, SE = 0.25 cm2, N = 120. The results suggest that the new formula may be considered as an independent orifice equation having a similar domain of validity as the Gorlin formula. The new equation offers the possibility of deriving additional useful haemodynamic relationships through combination with established cardiological formulas and applying it in a noninvasive Doppler ultrasonic or echocardiographic context.

Aged↗

PubMed1986

Mechanism of reduced maximum expiratory flow in dogs with compensatory lung growth.

We examined the mechanism of the reduced maximum expiratory flow rates (Vmax) in a dog model of postpneumonectomy compensatory lung growth. During forced expiration, a Pitot-static tube was used to locate the airway site of flow limitation, or choke point, and to measure dynamic intrabronchial pressures. The factors determining Vmax were calculated and the results analyzed in terms of the wave-speed theory of flow limitation. Measurements were made at multiple lung volumes and during ventilation both with air and with HeO2. Five of the puppies had undergone a left pneumonectomy at 10 wk of age, and 5 littermate controls had undergone a sham operation. All dogs were studied at 26 wk of age, at which time compensatory lung growth had occurred in the postpneumonectomy group. Vmax was markedly decreased in the postpneumonectomy group compared with control, averaging 42% of the control flow rates from 58 to 35% of the vital capacity (VC). At 23% of the VC, Vmax was 15% less than control. Choke points were more peripheral in the postpneumonectomy dogs compared with controls at all volumes. The total airway pressure was the same at the choke-point airway in the postpneumonectomy dogs as that in the same airway in the control dogs, suggesting that the airways of the postpneumonectomy dogs displayed different bronchial area-pressure behavior from the control dogs. Despite the decreased Vmax on both air and HeO2, the density dependence of flow was high in the postpneumonectomy dogs and the same as controls at all lung volumes examined.

Airway Resistance↗

PubMed1985

Increased cardiac output increases shunt: role of pulmonary edema and perfusion.

In low-pressure pulmonary edema increased cardiac output (QT) increases shunt (Qs/QT); we tested whether the mechanism is an increase in extravascular lung water in turn mediated by the accompanying increase in microvascular pressure. In six pentobarbital sodium-anesthetized dogs ventilated with O2 we administered oleic acid into the right atrium. From base line to 2 h post-oleic acid we measured concurrent significant increases in Qs/QT (6-29%, O2 technique) and extravascular thermal volume (ETV, 2.6-7.1 ml/g dry intravascular blood-free lung wt, thermal-green dye indicator technique) that were stable by 90 min. Then, bilateral femoral arteriovenous fistulas were opened and closed in 30-min periods to cause reversible increases in QT and associated Qs/QT. When fistulas were open the time-averaged QT increased from 5.1 to 6.9 min (P less than 0.05), the simultaneous Qs/QT rose from 30.7 to 38.4% (P less than 0.05), but ETV did not increase. We conclude that increasing lung edema does not account for our rise in Qs/QT when QT increased.

Animals↗

PubMed1985

Vascular and interstitial mechanics in canine pulmonary emphysema.

We examined the changes in vascular and interstitial mechanics in pulmonary emphysema (PE) using a canine lobar model. PE was produced in the left lower lobe (LLL) of five dogs (group E) by six weekly intrabronchial instillations of the enzyme papain. In five control dogs (group C), a normal saline solution was used. In our in vivo preparation, vascular flow (Q) to the LLL was measured. Inflow (Ppa) and outlow (Pv) pressures to the LLL could be varied independently. The relationship of Ppa to Q was examined in zones 2 and 3 of West. The slope of the Ppa-Q relationship was used to determine vascular conductance, whereas the extrapolation to zero flow in zone 2 conditions represented the mean pressure required for vascular recruitment (Pi). Lobar weight gain was measured continuously. Following step increases in Ppa, the rapid increase in wet weight measured when Q to the LLL was zero was used to obtain vascular compliance (C). Subsequent slow increases in wet weight were used to determine the rate of fluid exchange with the interstitium (Qf). The slope of the Qf-Ppa relationship represented fluid conductance (Kf). The extrapolation to zero Qf gave the minimal pressure required for continuous edema formation (Pm). Compared with group C, vascular conductance (G) decreased and Pi increased in group E, whereas fluid conductance (Kf) and Pm increased. The decrease in G most likely resulted from the loss of vascular cross-sectional area in emphysematous lungs, whereas the increase in Pi was possibly due to mechanical changes in the lung interstitium which increased vessel closure. We propose that the increase in Kf in group E reflected an increase in interstitial conductance, such that due to structural changes in the interstitium in emphysematous lungs, tissue resistance to fluid flux decreased.

Airway Resistance↗

PubMed1985

Manipulation of tissue forces in treating the adult respiratory distress syndrome.

In 16 anesthetized dogs, low-pressure pulmonary edema was induced by the intravenous infusion of oleic acid (0.02 mL/kg). One group of four animals served as controls. In the remaining 12 animals, the pulmonary capillary wedge pressure (Pcwp) was lowered in an effort to decrease the accumulation of extravascular lung water (EVLW). In eight dogs, the EVLW value decreased as measured by the thermal green dye, double-indicator method. The low Pcwp was maintained until the EVLW reached a minimum. In four dogs, reduction of the Pcwp did not decrease the accumulation of EVLW but did reduce the rate of accumulation. In animals in which the EVLW reached a minimum, restoration of Pcwp to baseline values did not increase edema, while the control animals continued to deteriorate. Presumably, changes in tissue and lymphatic dynamics compensated for the increased capillary permeability.

Animals↗

PubMed1984

Pulmonary interstitial compartments and tissue resistance to fluid flux.

We have produced interstitial fluid exchange in six isolated plasma-perfused canine lobes by introducing small increases in microvascular hydrostatic pressure. We measured early fast fluid exchange with a colorimetric technique and used weight changes to follow slow exchange. The observed biphasic time course suggested fluid flux across the microvascular membrane into two interstitial compartments in series (perimicrovascular and central). We related the initial rate of fluid flux into each compartment to the applied hydrostatic pressure change to obtain membrane (Kf1) and tissue conductances (Kf2) and to the exchanged volume to determine perimicrovascular (C1) and central (C2) interstitial compliances. C2 (0.25 +/- 0.193) was twice C1 (0.10 +/- 0.031 ml X cmH2O-1 X g DW-1, where DW represents dry weight. C2 increased significantly with hydration (C2 = 0.06 X WW/DW - 0.15) ml X cmH2O-1 X g DW-1 (WW/DW, wet-to-dry weight ratio), whereas C1 did not. Kf1 (0.26 +/- 0.17) was one order of magnitude larger than Kf2 (0.027 +/- 0.014 ml X min-1 X cmH2O-1 X g DW-1). Kf2 increased with hydration (Kf2 = 0.005 X WW/DW - 0.007) ml X min-1 X cmH2O-1 X g DW-1, whereas Kf1 did not. Our data point to the tissues and not the microvascular membranes as the major rate-limiting structure. Our data suggest an interstitium composed of a smaller rigid perimicrovascular space which communicates to a larger looser downstream space by a high-resistance pathway. As hydration increases, fluid accumulation becomes easier because tissue resistance to fluid flux drops and the compliance of the downstream compartment doubles.

Animals↗

PubMed1984

Dynamic lung function in dogs with compensatory lung growth.

Nine puppies underwent left pneumonectomy at 10 wk of age while nine sex-matched littermates had a sham operation, and all animals were studied at 25 wk of age. Postpneumonectomy dogs demonstrated compensatory growth in that lung weight and total lung capacity (TLC) were the same as those of control animals when normalized for body weight. In postpneumonectomy dogs all lobes of the remaining right lung increased in weight, but this was most notable in the cardiac lobe which grew across the mediastinum. Subdivisions of lung volume were normal in postpneumonectomy animals except for residual volume (RV): RV/TLC was increased when compared with control animals. In intact dogs static pressure-volume curves of the lung and respiratory system did not differ between groups, and the static pressure-volume curves of excised lungs were closely similar. Maximum expiratory flow was sharply reduced in postpneumonectomy dogs, averaging 40% of flow in control dogs over the lower 50% of the vital capacity. In both groups the fractional increase in maximal expiratory flow during HeO2 breathing was substantial and similar. Regional compliances, resistances, and perfusion distribution were examined using 133Xe. Regional compliance and perfusion were reduced in the left hemithorax of postpneumonectomy dogs while regional resistances were increased.

Animals↗

PubMed1983

Model-independent procedure for area estimation and intergroup comparisons.

A method is provided for estimating the area under a response-time curve for an experimental situation where independent observations are made at each time point. The procedure utilizes least-squares spline functions and the jackknife technique to provide area estimates, standard errors, and a statistical test for intergroup comparisons. The method is based on an empirical model and provides a means of analysis when no prior model can be specified or if the incorrect specification of a model will produce invalid results. The method is illustrated using data from a study comparing the pharmacokinetic behavior of a fasciolicide in rats having either a young or old parasitic infestation. The results obtained are comparable with those generated by a model-dependent approach.

Animals↗

PubMed1983

Transvascular fluid flux measured from intravascular water concentration changes.

We have measured transvascular water flux in eight canine left lower lobes perfused in a zone 3 of West with indocyanine green-stained plasma. Transvascular flux of water was induced by a step change in the inflow pressure. Assuming the indocyanine green-labeled protein did not significantly cross the capillary membrane in one pass, the rate of transvascular fluid flux could be calculated from the change in outflow-to-inflow concentration of water. The method was validated against gravimetric measurements of water exchange. By comparing our direct measurements of transvascular flux with the time course of lobar weight change, we conclude that following changes in inflow pressure, vascular volume changes occur rapidly and slow changes in lung mass can be accounted for exclusively by water exchange. Our method shows transvascular flux follows a biphasic course, suggesting both a membrane and an interstitial resistance to fluid transudation.

Animals↗

PubMed1983

Dopamine, dobutamine, and phentolamine effects on pulmonary vascular mechanics.

The pressure-flow (P-Q) relationship of the pulmonary vasculature, in an isolated canine lobe perfused under classical zone II conditions, can be characterized by a rectilinear segment at high flow, a curvilinear segment at low flow, and a pulmonary arterial pressure (Ppa) that exceeds alveolar pressure at zero flow. This demonstrates the presence of critical closure in the pulmonary vascular bed. Effects of drugs on pulmonary vascular resistance (PVR) must take the normal P-Q relationship into account. We examined the effect of dopamine (D) and dobutamine (DB), alone and in combination with phentolamine (P), on the slope of the rectilinear segment of the P-Q curve (equivalent to vascular conductance), the extrapolated Ppa intercept (Ppai), and the Ppa at zero flow (Ppaz). Low-dose D (0.4-0.8 mg) and DB (1.0-5.0 mg) did not significantly alter any parameter from control. Higher-dose D (1.2-6.8 mg) and DB (13-38 mg) decreased vascular conductance 32.3 +/- 12.1 (SE) to 50.45 +/- 5.6% (P less than 0.05), and P alone increased conductance 12.0 +/- 2.6% (P less than 0.01) from control with no significant effect on Ppai or Ppaz. The change in conductance with D and DB alone was abolished when either drug was given in combination with P. Ppaz and Ppai decreased significantly from control with DB in combination with P when no significant effect on vascular conductance was noted. The results suggest that lung vessels determining changes in flow resistance are pharmacologically distinct from those subserving critical closure in the pulmonary vascular bed.

Animals↗

PubMed1983

Independent influence of blood flow rate and mixed venous PO2 on shunt fraction.

We have tested the independent and combined effects of changes in mixed venous PO2 (PvO2) and blood flow (QT) on shunt fraction (Qs/QT) in isolated blood-perfused canine left lower lobes with edema. The lobes were ventilated with pure O2. Inflow (Pi) and outflow (Po) pressures always exceeded lobar alveolar pressure. PvO2 was varied by means of a clinical bubble oxygenator with appropriate mixtures of O2 and N2. QT was varied by changes in Pi and Po with care not to produce changes in lobar weight. Changes in QT did not influence Qs/QT. Increasing PvO2 from 40 +/- 6 to 88.4 +/- 40 Torr at constant QT significantly increased Qs/QT from 5.5 +/- 2.0 to 15.6 +/- 7.0%. Combined increases in QT and PvO2 from 66.4 +/- 2.7 to 135.6 +/- 21.5 ml/min and from 38.8 +/- 1.3 to 61.8 +/- 2.2 Torr, respectively, also produced a significant increase in Qs/QT from 7.33 +/- 2.27 to 15.43 +/- 4.45%. However, this combined change was explained exclusively by changes in PvO2. We therefore concluded that, under the conditions of our experiment, changes in PvO2 influence Qs/QT, and this may account for apparent dependence of Qs/QT on cardiac output in pulmonary edema.

Animals↗