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Biomedical subjects

A J Lechner

Publications and source records attributed to A J Lechner.

53 records · Page 3Linked to original sources

Quantitative recovery of expired nitrogen and nitrous oxide from venous gas emboli.

It has not been previously established whether venous gas emboli dissolve from pulmonary blood vessels into adjacent airways, or pass as microbubbles directly into the systemic circulation. We reported here the quantitative recovery of embolized gases from the airways, in amounts which substantiate the complete elimination of such gases by dissolution. A computer controlled quadrupole mass spectrometer was used to measure the net expired volumes of N2 or N2O following the injection of 40 ml boluses of these gases into the airways (AW) or right ventricles (RV) of 5 mongrel dogs. Every 20 ms, linearized flow signals were multiplied by gas concentrations, and the products summed for inspired and expired volumes of each breath. Intubated dogs were ventilated with 100% oxygen under Na-pentobarbital and either succinylcholine chloride or pancuronium bromide anesthesia; Swan-Ganz catheters were used for RV injections and for monotoring cardiovascular parameters. The overall mean % volume recoveries were 70.4 for AW-N2O, 68.2 for RV-N2O, 83.7 for AW-N2, and 46.7 for RV-N2. As expected, the AW percent volume recoveries increased with decreasing aqueous solubilities, and represented maximal values obtainable for RV emboli, due to alveolar reabsorption of gases excreted from the pulmonary circulation. Although all RV-N2O could thus be accounted for, RV-N2 recoveries were significantly less than AW-N2. The remaining RV-N2 did not pass as bubbles into the pulmonary veins, but continued to obstruct the pulmonary arterioles, as demonstrated with the use of nitrous oxide challenges in the inspired gas mixture.

Animals↗

Advanced pulmonary development in newborn guinea pigs (Cavia porcellus).

Morphological and morphometric evidence is presented to support the hypothesis that lung growth is advanced in mammals born at a relatively mature stage. The lungs from fetal and postnatal guinea pigs ranging in age from gestational age 56 days (normal gestation is 68 days in this species) through 16 days postpartum were fixed in situ by intratracheal glutaraldehyde. Morphometry included measurements of lung volume (VL), tissue and air-space volumes, fraction of respiratory parenchyma, alveolar (SA) and capillary (SC) surface areas, and the arithmetic mean thickness of the tissue barrier (tau t). VL, SA, and SC all increased monoexponentially versus body weight (W) from birth to adulthood; the lungs appeared to be in the equilibrated growth phase, with no postnatal period of pronounced tissue proliferation as reported in the newborn rat and mouse. The prepartum value of tau t was 1.96 micrometers; this value decreased by parturition of 1.27 micrometers and did not change significantly with additional age. At the light-microscopical level, respiratory bronchioles could be visualized giving rise to alveolar ducts by a gestational age of 58 days (10 days preterm) with well-developed alveolar septal partitioning evident. Structures resembling the primitive pre-alveolar saccules of newborn rats were never seen in even the youngest fetal animals. Elastin fibers were also evident at this age, both in bronchiolar and duct walls, as well as in alveolar septa. Using electron microscopy, the air-blood barrier appeared mature by a gestational age of 61 days and thereafter, double capillary layers were only rarely seen in septal walls.

Animals↗

The distribution of diffusion distances in the gastrocnemius muscle of various mammals during maturation.

Large changes in fiber size, capillary density and capillary/fiber architecture occur during maturation of mammalian skeletal muscle. To examine the effect of these changes on oxygen diffusion distance, the mean (R) and maximal (R95) distances from the capillary to the tissue were measured in the gastrocnemius of maturing guinea pigs, rats and dogs. Hyperbolic relationships between capillary density and R and between capillary density and R95 were found for the combined data from these three species. The R and R95 increased with decreasing CD in growing guinea pigs and rats, but they remained constant in dogs. Statistical analyses showed that the capillaries in this muscle in all three species tended to be distributed in ordered arrays. These anatomical measurements are discussed in relation to their potential physiological impact on oxygen delivery to tissues.

Animals↗

Blood oxygen affinity in high- and low-altitude populations of the deer mouse.

There is little solid evidence for specific genetic adaptations in animal populations native to high altitude. There is also continuing debate over what oxygen transport characteristics are truly adaptive at high altitude. We have attempted to elucidate both problems through population genetic and physiological studies of the deer mouse, Peromyscus maniculatus. That species is noteworthy because it inhabits the widest range of altitudes of any North American mammal, and it shows a high degree of genetic variation in hemoglobins. Deer mice were collected from 35 populations representing ten nominal subspecies covering a broad geographical range of the United States. The mice were acclimated to low altitude (340 m); then a mixing method was used to determine P50 and other blood gas parameters on samples pooled from individuals of representative hemoglobin genotypes. When the data from all subspecies wee combined, there was a highly significant negative correlation between P50 and the native altitude of the population. Tests on progeny reared at low altitude indicated that the differences in P50 were primarily genetic. Part of the clinal variation in P50 could be attributed to 2,3-DPG effects; high-altitude populations showed lower baseline DPG/Hb ratios. Surprisingly, within those subspecies which inhabit a wide range of altitudes, there was no correlation between P50 and native altitude. Our tentative conclusion from these data and data presented elsewhere is that deer mouse populations do show genetic adaptations to high altitude. However, because of gene exchange between populations, the genetic characteristics of a population reflect the average altitude over a relatively broad geographic area.

2,3-Diphosphoglycerate↗

On comparing regression lines with unequal slopes.

For the situation in which the slopes of two regression lines may differ, procedures are discussed for the comparison of the lines at a single X, simultaneous comparison at several values of X, and determination of the range of X for which the difference between the lines is large enough to be statistically significant. These useful procedures have previously been discussed but do not seem to be well known. Their usefulness in the analysis of physiological data is demonstrated with data arising from a study of pulmonary response to hypoxia.

Adaptation, Physiological↗

Lung morphometry in guinea pigs acclimated to hypoxia during growth.

The effect of chronic hypoxic exposure on lung development has been assessed in growing guinea pigs (Cavia porcellus). Weanling males of initial W = 229 g were acclimated to a PO2 of 80 Torr for 2-14 weeks before sacrifice (range of W = 244-965 g). Growth was the same in hypoxic animals as in controls maintained at a PO2 of 133 Torr (range of W in controls = 89-1274 g). Lungs were fixed by tracheal instillation of glutaraldehyde and examined morphometrically with the electron microscope. Within 3 weeks of exposure, lung volume (VL) and alveolar surface area (Sa) were significantly increased by 32% and 27% respectively in the hypoxia acclimated animals compared to controls of similar W. However, these differences were progressively reduced with increasing time of exposure, and mean values of VL and Sa were not different between groups when W greater than 900 g. Chronic hypoxia accelerated lung development towards normal adult dimensions to a degree remarkably similar to that reported in cold acclimated guinea pigs. These findings are compatable with the theory of adaptive lung growth mediated by increased pulmonary blood flow, and suggest anatomical limitations to such growth related to an animal's age.

Adaptation, Physiological↗

Increased capillary supply in skeletal muscle of guinea pigs acclimated to cold.

The ATPase technique was used to visualize blood capillaries and to study fiber composition in 10-micrometer transverse sections of guinea pig gastrocnemius and soleus muscles. A control group of newborn, weanling, juvenile and adult male guinea pigs (GP) (BW = 89-1274 g) was studied in a 20-24 degrees C environment (22 degrees C GP) while 2-3 week old animals were exposed continuously to 5 degrees C for 2-18 weeks before sacrifice (5 degrees C GP) (BW = 239-1074 g). Body weight gain was not affected by cold exposure; however, the gastrocnemius and soleus muscles of the 5 degrees C GP grew at a slower rate than did the muscles of the 22 degrees C GP. The equations relating fiber cross sectional area (FCSA) and muscle weight (MW) were not different between the 22 degrees C GP and 5 degrees C GP for the soleus and gastrocnemius. Therefore, in both muscles at the same BW, FCSA was smaller in the 5 degrees C GP than in the 22 degrees C GP. In both of the two muscles of each group, capillary density (CD) decreased hyperbolically with increasing FCSA, while the capillary to fiber ratio (C/F) and the average number of capillaries around each fiber (CAF) increased linearly with increasing FCSA. The regression lines for CD, C/F and CAF versus FCSA for both muscles were parallel between groups, but at any FDSA, the CD, C/F and CAF were greater in the 5 degrees C GP than in the 22 degrees C GP. Percent fiber composition of the gastrocnemii of the 22 degrees C GP and 5 degrees C GP were not different; however, at the same FCSA each fiber type had a greater capillary supply in the 5 degrees C GP. The increased capillarity in the gastrocnemius and soleus muscles of the 5 degrees C GP suggests an improved capacity for oxygenation, a response which would correlate well with the increased oxygen utilization during prolonged cold exposure.

Adaptation, Physiological↗

Lung morphometry in guinea pigs acclimated to cold during growth.

Weanling male guinea pigs, Cavia porcellus [initial weight (W) = 200-250 g], were chronically acclimated to 5 degrees C for 2-18 wk before they were killed. Controls were raised at 22 degrees C. Food and water were given ad lib., and growth was the same in both groups. Under pentobarbital anesthesia (30 mg/kg), lungs were fixed by tracheal instillation of glutaraldehyde and processed for electron microscopy. Lung volume (VL, ml) was measured by displacement; alveolar and capillary surface areas (SA and Sc, m2) were determined morphometrically. Regressions of lung variables vs. W at 22 degrees C (range of W = 89-1,274 g) were as follows: VL = 0.175 W0.676, SA = 0.0097 W0.759, and Sc = 0.0055 W0.825; for 5 degrees C animals (range of W = 239-1,074 g): VL = 0.384 W0.584, SA = 0.0334 W0.594, and Sc = 0.032 W0.562. The total arithmetic mean thickness of lung tissue did not vary with W, and averaged 1.39 microns at 22 degrees C and 1.41 microns at 5 degrees C. VL, SA, and Sc are significantly greater in 5 degrees C guinea pigs than in 22 degrees C animals when W = 300-600 g, but are indistinguishable between groups when W > 700 g. Chronic increases in oxygen consumption, which occur with prolonged exposure to cold, result in accelerated lung development in immature guinea pigs toward normal adult dimensions.

Acclimatization↗

The scaling of maximal oxygen consumption and pulmonary dimensions in small mammals.

This report has reexamined the relationship between standard and maximal rates of oxygen consumption (VO2std and VO2max) and pulmonary surface area in mammals whose weights extend over the lower half of the total log weight range in mammals. For combined groups of wild and laboratory animals with body weights of 2--3700 g, the following equations pertain: VO2std (ml . min-1) = 0.0602 . W0.727; VO2std, or the factorial aerobic scope, is nearly constant over this weight range at approximately 6.6 (range 5.8--7.1). In view of this finding, earlier studies relating SA or pulmonary diffusion capacity to VO2std are still appropriate models for pulmonary constraints on metabolic rate. The data summarized here suggest that, at least for wild species of mammals, pulmonary diffusion capacity may limit VO2max.

Animals↗

Electrophoretic characterization of the hemoglobins in pocket gophers of the genus Thomomys.

1. Hemoglobin phenotypes have been determined for closely related pocket gopher subspecies in the genus Thomomys from sea level and high altitude. 2. A single hemoglobin band was demonstrated for each gopher population with cellulose acetate membrane electrophoresis, with a mobility of 73% relative to human Hb-A. 3. Using polyacrylamide gel electrophoresis, a major Hb component (94% of the total Hb) showed a relative mobility of 68-69%; the minor Hb component showed a relative mobility of 74-75%. 4. The electrophoretic and physiological similarities of the gopher hemoglobins have persisted despite extreme differences in ambient PO2 in the habitats of each subspecies.

Animals↗

Respiratory adaptations in burrowing pocket gophers from sea level and high altitude.

To examine the adaptations to low O2 and high CO2 among fossorial and nonfossorial rodents, hematological parameters were determined for laboratory rats, the valley pocket gopher (Thomomys bottae) from 250 m, and the mountain pocket gopher (T. umbrinus melanotis) from 3150 m. Hematocrit, hemoglobin concentration, and O2 capacity were higher in pocket gophers than in rats. Blood PO2 at 50% saturation and pH 7.4 was 33 mmHg for both gophers and 39 mmHg for rats. Bohr factors for all three rodents were similar (-0.55 to -0.61) but buffer value, delta log PCO2/delta pH, was -2.54 for T. umbrinus, -1.97 for T. bottae, and -0.98 for Rattus. Concentrations of total acid-soluble phosphates were 50-75% higher in gophers than in rats, while bicarbonate values were within the normal mammalian range. All three rodents had similar myoglobin concentrations in cardiac muscle. Myoglobin concentrations were significantly higher in skeletal muscles (diaphragm, gastrocnemius) of T. umbrinus when compared to T. bottae, and significantly higher in both gophers when compared to rats. These differences may constitute important adaptations to the hypoxia and hypercapnia in burrows; certain of these factors in pocket gophers respond to the additional stress of high altitude hypoxia.

Adaptation, Physiological↗