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PubMed1985

Effect of alteration of left ventricular activation sequence on the left ventricular end-systolic pressure-volume relation in closed-chest dogs.

We investigated the effect of pacing from the atrium and various ventricular sites on the left ventricular end-systolic pressure-volume relation following autonomic blockade in a total of 10 dogs chronically instrumented to measure left ventricular pressure and determine left ventricular volume from three ultrasonic endocardial dimensions. During ventricular pacing, left ventricular end-diastolic volume, stroke volume, and end-systolic pressure were decreased, while the end-systolic volume was relatively unchanged. Left ventricular end-systolic pressure-volume relations were generated by vena caval occlusions during pacing at a constant rate from the left atria, and the epicardium of the right ventricular free wall, right ventricular apex, and left ventricular free wall. The left ventricular end-systolic pressure-volume relations were described by straight lines for each site (r greater than 0.96 and SEE less than 2.9 mm Hg in all but one instance). Compared to atrial pacing, the left ventricular end-systolic pressure-volume relations were shifted (P less than 0.001) to the right during pacing from ventricular sites. During atrial pacing, the volume intercept of the left ventricular end-systolic pressure-volume relation was 16.0 +/- 7.2 ml (mean +/- SD), and increased to 18.7 +/- 7.8 ml (P less than 0.05) during pacing from the right ventricular free wall, to 19.6 +/- 7.7 ml (P less than 0.05) during pacing from the right ventricular apex, and to 20.0 +/- 7.5 ml (P less than 0.05) during pacing from the left ventricular free wall. These volume intercepts correlated roughly with the extent of dyssynchronous activation as estimated by the QRS duration (r = 0.59 to 0.93) and the time for left ventricular endocardial activation (r = 0.92 and 0.95). During ventricular pacing, the slope of the left ventricular end-systolic pressure-volume relation changed only slightly. Similar results were obtained during pacing from right ventricular endocardial sites. We conclude that alterations of the normal activation sequence produced by ventricular pacing depress left ventricular pumping function independent of loading conditions, as indicated by a rightward shift of the left ventricular end-systolic pressure-volume relation. The extent of this shift appears to be in proportion to the degree of dyssynchronous activation. The decreased stroke volume during ventricular pacing is due both to a decreased end-diastolic volume (decreased preload) and the rightward shift of the end-systolic pressure-volume relation (decreased pump function).

Animals↗
PubMed1986

Stimulation of angiogenesis by adenosine on the chick chorioallantoic membrane.

The effect of adenosine on the vascular density of the chick chorioallantoic membrane was studied. Elvax polymer pellets containing 0.2-3.0 mg of adenosine were placed on the chorioallantoic membrane of 10-day embryos. Control pellets containing mannitol were placed at least 1 cm away. After 4 days the membrane was formalin-fixed and removed. A thin plastic coverslip, inscribed with concentric circles (4-8 mm in diameter), was placed over the pellet. A vascular density index was estimated at 20 X by counting the number of intercepts between vessels and the inscribed circles. Adenosine stimulated a dose-dependent increase (p less than 0.01) in the vascular density index with the 3-mg pellets inducing a 15% increase. Inosine, a major metabolite of adenosine, did not cause a change in the number of intercepts counted. The adenosine-stimulated increase in vascularity was blocked with 110 micrograms of methyl-isobutyl-xanthine injected daily into the albumin. Partial inhibition was observed with 55 micrograms/day. Methyl-isobutyl-xanthine by itself did not affect the vascular density index. Dipyridamole enhanced adenosine's stimulation of vascular growth an additional 52%. Given alone, however, it had no effect on the membrane's vascularity. These data support an angiogenic role for adenosine. The modest, but consistent, increase in the vascular density index stimulated by adenosine, and the fact that it may be released during tissue hypoxia, is consistent with an hypothesis that this nucleoside plays a modulatory role in vessel proliferation accompanying conditions of long-term hypoxia.

Adenosine↗
PubMed1986

Micropuncture measurement of microvascular pressures in isolated lamb lungs during hypoxia.

To study the effect of alveolar hypoxia on the pulmonary circulation of the newborn, we determined the longitudinal distribution of vascular pressures and the distribution of blood flow in isolated blood perfused lungs of newborn lambs during normoxia and hypoxia. We also examined the effect of hypoxia on the slope and intercept of the vascular pressure-flow (P/Q) relation. In 14 lungs, we used the micropipette servonulling technique to measure pressures in 20-80 micron subpleural arterioles and venules during normoxia and hypoxia at constant blood flow. In 5 other lungs, we used radiolabelled microspheres to determine the effect of hypoxia on regional distribution of blood flow. Under baseline normoxic conditions, segmental pressure drops in arteries, microvessels, and veins were approximately equal. During hypoxia pulmonary artery pressure always increased, resulting in a 60% increase in total vascular resistance. All segmental pressure drops increased with hypoxia. Arterial and venous pressure drops increased by 80 and 70% respectively, contributing almost equally to the increase in total pulmonary vascular resistance. Regional distribution of blood flow was uniform during normoxia and was unchanged during hypoxia. Hypoxia increased both the slope and intercept of the P/Q relation significantly, with an increase in fluid filtration rate. We conclude that in the newborn lamb alveolar hypoxia leads to pulmonary arterial and venous constriction, resulting in increased microvascular pressure and fluid filtration.

Animals↗
PubMed1987

Instantaneous pressure-volume relation of the ejecting canine left atrium.

To characterize the pump function of the left atrium, we determined the instantaneous pressure-volume relation of the isolated supported left atrium. A physiologic after-loading system for the low-pressure atrium was created by coupling it to a real-time computer-simulated ventricle and a simulated venous impedance network via a volume servo-pump. In 10 atria loaded with such systems, multiple isochronal sets of pressure-volume data were collected from many ejecting or isovolumic contractions obtained under a constant inotropic state, and the time-varying elastance, E(t), as well as the volume-axis intercepts, VO(t), were calculated. E(t) is the ensemble of slopes, and VO(t), the volume-axis intercepts resulting from the linear regression of instantaneous pressure on instantaneous volume at multiple instants throughout the cardiac cycle. The systolic portion of the left atrial E(t) was insensitive to loading conditions, as was VO(t), which, in addition, proved to be similar to the right atrial and right ventricular VO(t) waveforms in its time dependence. These results indicate that E(t) and VO(t) adequately represent the instantaneous pressure-volume relation of the left atrium in systole irrespective of the mode of contraction. Whatever the underlying mechanism might be, the load insensitivity and similarity of the basic shape of the left atrial E(t) among different atria suggests that the characterization reflects fundamental features of left atrial contraction.

Animals↗
PubMed1988

Angiographic validation of eigenvolume to measure left ventricular size.

Radiopaque markers implanted in the left ventricle allow one to follow the motion of specific elements of myocardium and compute a measure of relative left ventricular volume, called "eigenvolume." Workers in our laboratory partially validated this measure in excised dog hearts by comparing eigenvolumes with volumes of balloons in the left ventricle. Perhaps because the balloon did not fully fill the left ventricle, there was a significant nonzero intercept in the relation between eigenvolume and balloon volume. Therefore, the results only partially confirmed the eigenvolume theory because eigenvolume should be proportional to cavity volume. This study compares eigenvolume with left ventricular volume measured by biplane angiography in intact beating hearts following hemodynamic interventions (atropine, phenylephrine, nitroprusside, volume loading, and propranolol). We performed 32 angiograms in five dogs. A high correlation (r = 0.958 +/- 0.029 [SD]) was found between eigenvolumes and left ventricular volumes. In contrast to earlier in vitro validations and consistent with theory, the intercept of the relation between eigenvolume and left ventricular cavity volume (angiovolume) was not significantly different from zero. These data strengthen the hypothesis that eigenvolume accurately reflects true left ventricular volume in vivo. These same data were used to assess the immediate (i.e., within a few beats) effect of angiography. Left ventricular volume loading associated with the angiogram modestly (6%) increases left ventricular end-diastolic and end-systolic eigenvolumes without changing stroke volume or pressures, consistent with a mild negative inotropic effect.

Angiography↗
PubMed1988

Progressive hypoxemia limits left ventricular oxygen consumption and contractility.

To study the cardiac effects of progressive hypoxemia, we measured the left ventricular end-systolic pressure-volume relation (ESPVR), myocardial oxygen consumption (MVO2), and myocardial oxygen delivery (MQO2) in eight thoracotomized dogs anesthetized with fentanyl and droperidol. We specifically looked for evidence of oxygen supply limitation of MVO2 and depressed contractility (altered ESPVR) during stepwise decreases in inspired oxygen fraction. We hypothesized that the reported relation between MVO2 and left ventricular pressure-volume area (PVA) may hold when inadequate MQO2 determines MVO2, which then may limit PVA, manifested partly as a change in the ESPVR. Initially, as arterial oxygen saturation was decreased from 95 +/- 3% to 64 +/- 14%, coronary blood flow increased so that MQO2 was maintained with no change in myocardial extraction ratio (ERm = MVO2/MQO2). During this first phase, lactate utilization, PVA, and ESPVR did not change. When oxygen saturation was further reduced, coronary blood flow rose no higher and ERm increased, but not enough to maintain MVO2. Lactate consumption decreased and ST segments rose, signaling a change from aerobic metabolism. MVO2 decrease was associated with a fall in PVA, which was due to a fall in blood pressure and a significant depression of the ESPVR. Specifically, the volume intercept of the ESPVR increased in all dogs (6.5-20.1 ml, p less than 0.0001), accounting for two thirds of the increase in end-systolic volume. The slope of the ESPVR decreased during hypoxia (13.3-6.1 mm Hg/ml, p less than 0.02), accounting for only one third of the observed increase in end-systolic volume. We believe that the evidence of anaerobic metabolism, the decrease in PVA, and the depression of the ESPVR demonstrates onset of oxygen supply limitation of MVO2. Our data are consistent with the hypothesis that limited MVO2 may limit PVA. The hypoxic volume intercept alteration of the ESPVR is different from changes in the slope of ESPVR seen with other interventions. This may be analogous to recent observations in isolated muscle that show hypoxic depression in contractility to be different from other interventions.

Animals↗
PubMed1990

Decreased contractile efficiency and increased nonmechanical energy cost in hyperthyroid rabbit heart. Relation between O2 consumption and systolic pressure-volume area or force-time integral.

Both systolic pressure-volume area (PVA) and force-time integral (FTI) have been used as measures of oxygen consumption per beat (VO2) in the isolated left ventricle. The reciprocal of the slope of the VO2-PVA relation has been considered to reflect the chemomechanical energy transduction efficiency of the contractile machinery (contractile efficiency), whereas its VO2 intercept consists of energy cost of excitation-contraction coupling and basal metabolism. To examine whether the increase in myosin isoform V1/V3 ratio in hyperthyroid rabbits decreases contractile efficiency and to determine overall mechanisms of higher oxygen consumption in hyperthyroid hearts, the VO2-PVA and VO2-FTI relations as well as the end-systolic pressure-volume relation were assessed in cross-circulated, isovolumically beating hearts isolated from normal, hyperthyroid, and hypothyroid rabbits. Normalized initial slopes of the rising limb of the curvilinearly fitted end-systolic pressure-volume relation (E'max, ventricular contractility index) were similar for normal and hyperthyroid groups. However, the slopes and VO2 intercepts of the VO2-PVA and VO2-FTI relations were greater in hyperthyroid hearts than in normal hearts. Accordingly, in the hyperthyroid hearts, the contractile efficiency (27 +/- 6%) was lower and left ventricular VO2 for excitation-contraction coupling (0.028 +/- 0.004 ml O2/beat/100 g) was higher than in normal hearts (40 +/- 4% and 0.021 +/- 0.005 ml O2/beat/100 g, respectively). This decreased contractile efficiency in the hyperthyroid hearts was attributable to myosin isoform alteration rather than to increased beta-adrenoceptors because isoproterenol did not affect the slope of the VO2-PVA relation in all groups. In contrast, the slope of the VO2-FTI relation was significantly increased by isoproterenol in all groups. Neither the VO2-PVA nor the VO2-FTI relations in hypothyroid hearts were different from those in normal hearts except for significantly lower VO2 for basal metabolism. We conclude that in hyperthyroid rabbits, the left ventricle has decreased contractile efficiency and increased energy cost of excitation-contraction coupling and that the decreased contractile efficiency in hyperthyroid hearts is probably due to the increased V1/V3 ratio of the myosin isoform component. In addition, this study demonstrates that the VO2-PVA and VO2-FTI relations dissociate depending on the intervention, even in the same isovolumic contraction mode.

Animals↗
PubMed1991

Intrarenal hemodynamics in patients with essential hypertension.

Intrarenal hemodynamics were estimated clinically in essential hypertension. Two-week studies were performed in 30 patients with essential hypertension who were given a regular sodium diet in the first week and a sodium-restricted diet in the second week. Intrarenal hemodynamic parameters such as afferent arteriolar (preglomerular) resistance, efferent arteriolar resistance, and glomerular hydrostatic pressure were calculated from renal clearances and plasma total protein concentration measured on the last day of the regular sodium diet. Calculations were based on Gomez's equations with the assumption that the gross filtration coefficient of glomerular capillaries was normal. The increase in afferent arteriolar resistance (8,100 +/- 500 dyne.sec.cm-5) was significantly correlated with an elevation in mean arterial pressure (120 +/- 2 mm Hg), whereas glomerular pressure (56 +/- 1 mm Hg) and efferent arteriolar resistance (2,500 +/- 100 dyne.sec.cm-5) remained normal. The renal function curve (pressure-natriuresis relation) was drawn by plotting urinary sodium excretion on the y axis as a function of mean arterial pressure on the x axis, both of which were measured on the last 3 days of each week. The extrapolated x intercept (107 +/- 2 mm Hg) of the renal function curve was strongly correlated in a 1:1 fashion with the sum of the arterial pressure drop from the aorta to the renal glomeruli plus the opposing pressures against glomerular filtration at glomeruli (r = 0.7, p less than 0.001) on the regular sodium diet, suggesting that the difference between mean arterial pressure on the regular sodium diet and the extrapolated x intercept represented the effective filtration pressure across the glomerular capillaries on the regular sodium diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

In-plane myocardial wall stress is not the primary determinant of coronary systolic flow impediment. A study in the isolated, perfused dog septum.

The hypothesis that ventricular in-plane tensile wall stresses are the major determinant of systolic coronary flow was investigated in this study. We measured coronary artery inflow in the maximally vasodilated bed of the isolated beating septum (n = 10) during two modes of contraction characterized by markedly different levels of developed in-plane stress. An increase in contractility was induced by changing from the control steady-state pacing state to a postextrasystolic potentiated state induced by a modified rapid pacing protocol. Over a range of increments of passive stretch, the systolic flow impediment versus the diastolic wall strain was described by an inverse linear relation. Despite the differences in developed in-plane wall stresses between the two modes of contraction (p less than 0.001), the slope and intercept of these relations in both the control and potentiated states were not different for the low versus high developed stress modes. The systolic flow impediment versus diastolic wall strain relation for the potentiated beats, compared with the control beats, was characterized by an increase in the intercept in both the low developed stress beats (p less than 0.05) and the high developed stress beats (p less than 0.05). These data indicate that the impediment to coronary flow during systole is not primarily determined by systolic myocardial in-plane tensile wall stresses but rather by the contractile state of the muscle.

Animals↗
PubMed1993

Effects of chronic mitral regurgitation on diastolic function in isolated cardiocytes.

We have previously shown that chronic mitral regurgitation (MR) increases the rate of left ventricular early diastolic filling. These changes in chamber diastolic function were felt to be secondary to alterations in left ventricular loading conditions. Therefore, cellular diastolic function measured in cardiac muscle cells (cardiocytes) isolated from animals with chronic MR (absent alterations in loading conditions) was expected to be normal. However, chronic MR caused a decrease in sarcomere lengthening rate. The purpose of the current study was to define the mechanisms causing this decreased sarcomere lengthening rate in chronic MR cardiocytes and to explain the apparent dichotomy between chamber and cellular diastolic properties. Accordingly, sarcomere motion was measured using laser diffraction techniques in enzymatically isolated cardiocytes from seven control dogs and 11 dogs with chronic MR (produced by closed-chest transection of the mitral chordae). In the MR cardiocytes, there were abnormalities in cellular systolic function (decreased extent and velocity of shortening) and in cellular diastolic function (decreased velocity of sarcomere lengthening). Because studies in papillary muscles have shown that there is a direct relation between abnormal diastolic function (decreased velocity of muscle lengthening) and abnormal systolic function (decreased extent of muscle shortening), it was unclear whether the changes in cellular relaxation rate observed in chronic MR merely reflected a concomitant decrease in the extent of shortening or instead reflected an impairment in intrinsic relaxation properties. To make this distinction, the relation between relaxation velocity (measured as peak sarcomere lengthening rate) and sarcomere shortening extent was examined in MR cardiocytes and compared with that in control cardiocytes. There was a direct relation between sarcomere relaxation velocity and sarcomere shortening extent in both control and MR cardiocytes. Over a wide range of shortening extent, the slopes and y intercepts of this relation were similar in control and MR cardiocytes (slope, 27.7 sec-1 in control cells versus 28.1 sec-1 in MR cells; y intercept, -1.1 microns/sec in control cells versus -1.7 microns/sec in MR cells; p = NS). At any common shortening extent, relaxation velocity was the same in control and MR cardiocytes. To prove that this relation could detect abnormalities in the intrinsic myocardial relaxation process, interventions known to produce primary alterations in the intrinsic myocardial relaxation process were examined: the effects of hypothermia (30 degrees C) and isoproterenol (10(-6) M) on the relaxation velocity-shortening extent relation were studied in normal and MR cardiocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Blood flow and metabolism during and after repeated partial brain ischemia in neonatal piglets.

BACKGROUND AND PURPOSE: Our investigation sought to determine whether neonatal brain ischemic vascular and metabolic effects were altered by repeated episodes of ischemia. METHODS: We studied twelve piglets using in vivo magnetic resonance spectroscopy to obtain multiple, simultaneous measurements of cerebral blood flow and phosphorylated metabolites from the same tissue volume. The relationship between cerebral blood flow and energy metabolism was examined over a range of reduced cerebral blood flow (90-10% of control). Three episodes of partial ischemia were studied, each lasting 10 minutes and separated by 45 minutes. RESULTS: During each interval of ischemia, plots of the percent reduction in cerebral blood flow versus the percent change in phosphorylated metabolites (phosphocreatine, inorganic phosphorus) or unit change in intracellular pH did not differ in slope and intercept. The relationship between beta-ATP and cerebral blood flow during repeated ischemia revealed similar slopes, but a lower intercept during the third interval of ischemia (p = 0.029). After ischemia, cerebral blood flow was reduced as a function of the severity of the preceding ischemia. After each interval of ischemia, phosphocreatine and intracellular pH were unchanged from preischemic values. Inorganic phosphorus remained elevated after ischemia (117 +/- 16 and 118 +/- 11% of control, p less than 0.005, following the first and second intervals of ischemia), and beta-ATP was restored to progressively lower values (92 +/- 10 and 83 +/- 11% of control, p less than 0.025). Calculated free ADP decreased after ischemia and correlated with the postischemic level of beta-ATP (r = 0.63, p = 0.001). CONCLUSIONS: These results demonstrate that the relationship between cerebral blood flow and metabolism was reasonably preserved during repeated partial ischemia. However, following ischemia, alterations occurred in both cerebral blood flow and metabolism. These alterations may reflect a relative inhibition of ATP production by metabolic regulators such as ADP on either glycolysis or oxidative phosphorylation or both.

Adenosine Diphosphate↗
PubMed1998

Spatio-temporal vernier acuity.

The study of space-time vernier (STV) provides information on the spatio-temporal structure of the visual system in the same way that the classical spatio-spatial vernier (SSV) provides information on its spatial structure. The transposition of a SSV task into a STV one yields the following experimental format: an object (in the present case a Gaussian Blob) drifts with a constant velocity, V, disappears at x0, t0 and reappears after a variable duration delta t at a position x1 +/- delta x with x1 the correct position (given a constant V) and delta x the minimum (positive and negative) spatial offset discriminable from x0, i.e. the STV threshold. Observer's task is to specify whether the reappearance position is ahead of, or behind x1. The STV functions of delta t measured for 1, 5 and 10 deg/s reference velocities are linear with non-zero spatial and temporal intercepts at the origin. We refer to these x and t intercepts as dynamic dmin and tmin. Dynamic dmin is the smallest instantaneous displacement (infinite velocity) discriminable from a continuous drift, V. Dynamic tmin is the shortest 'motion stop' discriminable from the same continuous drift, V. To our knowledge these quantities have not yet been assessed. Estimated dynamic dmin increases with V. whereas tmin is more or less V independent suggesting that the motion sensors presumably involved in the STV task have peak spatial frequencies inversely proportional with V and a temporal frequency characteristic independent of V (at least within the studied range). The observed STV linearity with the spatio-temporal separation implies that the STV task is equivalent to a velocity discrimination. Two additional observations yield support to this conclusion. (i) The slopes of these functions yield velocities very similar to those discriminable from the reference V in a standard V-discrimination experiment. (ii) The predicted STV performances based on a decomposition of the task into two velocity discrimination tasks run as independent experiments are reasonably accurate.

Depth Perception↗
PubMed1994

Nature of pulmonary hypertension in congestive heart failure. Effects of cardiac transplantation.

Pulmonary hypertension associated with congestive heart failure carries a risk of right ventricular failure after cardiac transplantation. Few data, however, are available on the hemodynamic behavior of the pulmonary circulation in these patients. We therefore studied mean pulmonary artery pressure minus left atrial pressure (estimated by pulmonary artery occluded pressure) versus cardiac output relationships in 20 patients with congestive heart failure evaluated for orthotopic cardiac transplantation, and we repeated this study either within the first 3 days postoperatively (n = 10) or 1 month postoperatively (n = 11). Cardiac output was increased by physical exercise or (in the early postoperative period) by an infusion of dobutamine. Reversibility of pulmonary hypertension was tested by an infusion of prostaglandin E1. At preoperative evaluation, the extrapolated pressure intercept of pulmonary vascular pressure:flow plots was negative in 10 of the patients, suggesting active exercise-induced pulmonary vasoconstriction. In the other 10 patients, the extrapolated pressure intercept was positive, suggesting that an increased closing pressure contributed to pulmonary hypertension. However, transplantation was constantly associated with proportional decreases of pulmonary artery pressure and left atrial pressure. On the other hand, pulmonary vascular pressure:flow plots were displaced to equal or lower pressures and to higher flows by prostaglandin E1 before as well as after transplantation. We conclude that in patients with congestive heart failure evaluated for cardiac transplantation, an increased pulmonary venous pressure more than a reversible increase in closing pressure determines the severity of pulmonary hypertension.

Adolescent↗
PubMed2001

Forced expiratory flow in uninfected infants and children born to HIV-infected mothers.

The Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV (P(2)C(2) HIV) Study is a multicenter study examining pulmonary and cardiac outcomes in offspring of HIV-infected mothers. This portion of the P(2)C(2) study tests the hypothesis that infants exposed to, but uninfected by, maternal HIV have normal maximal expiratory flow at functional residual capacity (V'max,(FRC)). We obtained 500 measurements of V'max,(FRC) by rapid thoracic compression in 285 children ages 6-30 mo in five U.S. centers. The data were compared with those from a healthy cohort of children described elsewhere. V'max,(FRC) rose with height in a linear relationship. The slope of the regression line in the exposed infants did not differ statistically from the slope in the comparison group, but the intercept was about 20% lower (p < 0.001). Height and weight were comparable in the two cohorts, and the differences between intercepts persisted after adjusting for birth weight and gestational age. However, maternal HIV infection cannot be assumed to be the cause as the cohorts may have differed in other variables, such as socioeconomic status and frequency of maternal smoking and drug use. Also, measurements varied substantially within and between our five centers, probably in part because of different racial and ethnic distributions. In summary, maternal HIV infection probably has only a modest effect, if any, on maximal expiratory flow at functional residual capacity in uninfected infants.

Age Factors↗
PubMed1987

Lysophosphatidylcholine augments elastase-induced alveolar epithelial permeability and emphysema in the hamster.

We administered low dose porcine pancreatic elastase (PPE) with and without lysophosphatidylcholine (lysoPC), a naturally occurring constituent of lung lipids with known membrane-perturbing properties, to test the hypothesis that alveolar epithelial solute permeability is a determinant of the severity of elastase-induced emphysema in experimental animals. Four age- and weight-matched groups of hamsters received intratracheal injections of one of the following in a total volume of 0.5 ml TRIS buffered saline: (1) no additions, (2) 4 units PPE, (3) 135 micrograms lysoPC, or (4) 4 units PPE plus 135 micrograms lysoPC. Thirty minutes later the permeability surface area products (PS) of the alveolar epithelium to 14C-sucrose and 125I-dextran 70 were measured in excised, perfused lungs from some animals from each group. The remaining animals were killed at 6 wk, at which time pressure-volume relationships were measured in excised lungs, and the mean linear intercept was determined from sections of fixed lung tissue. Neither PPE nor lysoPC alone caused statistically significant increases in PS for either tracer. The PPE plus lysoPC caused statistically insignificant increases in sucrose PS but approximate tenfold increases in dextran 70 PS, which were highly significant (p less than 0.001). Although focal air-space enlargement was observed in some lungs 6 wk after exposure to PPE, pressure-volume relationships and mean linear intercepts were not significantly different from control values. Lungs previously exposed to lysoPC were indistinguishable from control lungs for all measurements. Severe emphysema was uniformly observed in animals that received PPE in combination with lysoPC; lysoPC had no demonstrable effect upon PPE-induced hydrolysis of native elastin in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

A comparison of lung structure in male DBA and C57 black mice and their F1 offspring.

To test whether lung structure in mice is genetically determined, two inbred strains of mice and their F1 offspring of the same age and gender were studied. Body size and lung size were measured, and various morphometric parameters were calculated. Each parameter was analyzed to elucidate the effects of dam, sire, both, or none by a genetic analytical method. The two inbred lines differed in lung and body size as well as in morphometric parameters. These parameters were found to be under genetic control by sire, dam, both, or none. From the data of reciprocal crossing, it appears that there is a maternal effect on the following parameters: body weight, fresh lung weight, fixed lung volume/fresh lung weight, specific lung volume, alveolar wall proportion, mean alveolar wall thickness, and mean linear intercept. Through a more detailed genetic analysis, it was found that specific lung volume in one F1 offspring showed an additive effect. On the other hand, the following parameters indicated heterotic effects (an increase or decrease in dimension compared to the parents with many possibly favorable) in one or both F1 offspring: body weight, fresh lung weight, fixed lung volume/fresh lung weight, specific lung volume, alveolar wall proportion, mean alveolar wall thickness, mean linear intercept, mean chord length of alveoli, mean chord length of alveolar ducts, alveolar surface area, and alveolar surface area to lung volume ratio. These findings indicate that genetic effects are important factors in normal lung development.

Animals↗
PubMed1991

Measurement of breathlessness during exercise in asthmatics. Predictor variables, reliability, and responsiveness.

The purpose of this study was to determine the predictor variables for breathlessness and to investigate the criteria of reliability and responsiveness for measuring breathlessness during progressive, incremental exercise on the cycle ergometer. We studied a heterogeneous group of patients with stable asthma (mean +/- SEM age, 46 +/- 4 yr) for four visits at weekly intervals. Predictor variables were determined at the first visit. Nine independent physiologic variables were obtained at each minute during exercise; the Borg rating of breathlessness (range 0 to 10) was used as the dependent variable. The regression model relating the physiologic parameters to the Borg rating of breathlessness was highly significant (model F = 43.4; p = 0.0001). Backward elimination selected the strongest predictors of the Borg rating: peak inspiratory flow (VI); tidal volume (VT)/FVC; frequency of respiration (f); and peak inspiratory mouth pressures (Pm). These four variables explained 63% of the variance in the rating of dyspnea. Each of the four variables exhibited a linear relationship with the Borg rating. Test-retest reliability was assessed by comparing results at the first and second visits. Individual slopes (except for VT/FVC) and intercepts for the four predictor variables versus Borg ratings were highly reliable. The slope for work intensity (watts) and Borg ratings, but not the intercept, was highly reliable. Responsiveness was evaluated by randomly administering inhaled methacholine or inhaled metaproterenol, alternately, at the third and fourth visits to induce acute changes in lung function before exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1978

Volume-pressure and morphometric observations after acute alveolar injury in the dog from N-nitroso-N-methylurethane.

Volume-pressure diagrams during inflation with air and saline were made with the lungs of 6 control dogs and 24 dogs with acute alveolar injury induced by subcutaneous injection of 6 mg of N-nitroso-N-methylurethane per kg of body weight 3 to 14 days before study. The extent of alveolar closure was estimated by measuring the mean linear intercept of the remaining open air spaces after inflation of the lung with liquid formalin at a pressure of 40 cm H2O. This alveolar closure was defined as irreversible. The volume-pressure diagrams and compliance data derived from them during the 3 to 4, 5 to 7, and 9 to 14 day periods after injection were analyzed and compared with the morphometric data. The diagrams with air inflation showed a progressive downward shift beginning with the 3 to 4 day period. This shift was at least partly independent of volume loss. The diagrams with saline inflation were unchanged during the 3 to 4 day period, but showed a downward shift, largely due to volume loss thereafter. Irreversible alveolar closure, reflected by an increased mean linear intercept, was present in the 3 to 4 day period, and its extent increased with time, correlating inversely with total lung capacity and saline compliance. The data indicate that decreased lung compliance and volume during the first 7 days of injury induced by injection of N-nitroso-N-methylurethane were due largely to increased surface tension and that tissue forces became a significant factor later. They suggest that the altered tissue forces were due principally to irreversible alveolar closure.

Animals↗