Biomedical subjects

A J Lechner

Publications and source records attributed to A J Lechner.

At least 37 records · Page 2Linked to original sources

PubMed1994

Liver-lung interactions during E. coli endotoxemia. TNF-alpha:leukotriene axis.

The liver modulates host responses to endotoxemia by production and clearance of tumor necrosis factor alpha (TNF-alpha) and eicosanoid lipoxygenation products. Reductions in liver blood flow (QL) are common during endotoxemia, but it is unknown whether the kinetics of TNF-alpha and leukotrienes (LTs) are thereby altered to amplify lung inflammation. To test this hypothesis, reductions in QL were modeled by an end-to-side portacaval shunt (PCS) in Sprague-Dawley rats. Conscious animals received 2.5 mg/kg of intravenous E. coli lipopolysaccharide (LPS) serotype 055:B5 (PCS + LPS; n = 17) or saline (n = 5). Responses were compared with those in sham-operated rats (sham + LPS; n = 13) and NSS-challenged control rats (n = 5). Cardiopulmonary changes, serum TNF-alpha, and formed elements were determined at t = 0, 1.5, 3.5, and 24 h, when organ wet/dry ratios (W/D) were measured with TNF-alpha, LTB4, and polymorphonuclear neutrophils (PMN) in bronchoalveolar lavage fluid (BALF). In PCS + LPS rats, mortality was 59% and serum TNF-alpha peaked at 1.5 h (2,784 +/- 658 U/ml, mean +/- SEM) coincident with the onset of hypotension. Despite equivalent endotoxemia and liver- and lung-associated TNF-alpha in sham + LPS rats at 1.5 h, peak serum TNF-alpha was 38% less and mortality was 15% (p < 0.05). Cardiac, hepatic, and cecal W/D were likewise increased in PCS + LPS versus sham + LPS rats, as were BALF PMNs (p < 0.05). In parallel studies, the disappearance kinetics of infused rTNF-alpha were not altered in nonendotoxemic PCS animals, implicating enhanced lung uptake of LPS and systemic export of TNF-alpha in PCS + LPS rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Acute lung injury during bacterial or fungal sepsis.

We compared physiological and ultrastructural indices of acute lung injury (ALI) during septic shock caused by taxonomically diverse pathogens to distinguish ALI due to endogenous inflammatory mediators vs. microbial exotoxins or other factors. Conscious rats were infected i.v. with gram-negative Escherichia coli (EC, serotype 055:B5), exotoxin-C producing gram-positive Staphylococcus aureus (SA), or yeast-phase Candida albicans (CA, a clinical isolate). Viable inocula of 10(10) EC, 10(10) SA, or 10(9) CA caused lethal shock in < 24 h, but distinct types of ALI were noted after bacteria vs. fungi. Within 0.5 h of EC infection, leukocytes marginated in the lung vasculature; by death at 6-14 h, animals were hyperoxemic but not acidemic, and showed slight interstitial edema with increased wet/dry weight ratios (W/D = 5.22 +/- 0.10, mean +/- SE, vs. 4.86 +/- 0.07 in controls, P < 0.05). Similarly mild ALI occurred after 10(10) SA. In contrast, within 0.5 h of CA infection, yeast were visible within lung intravascular leukocytes. By death at 6-12 h, CA animals showed hyperoxic acidemia and moderate ALI with capillary obstruction, interstitial hemorrhage, and elevated lung W/D (5.52 +/- 0.13, P < 0.01 vs. controls) associated with yeast-mycelial transformation. Prior neutropenia accelerated mortality and worsened ALI after CA, with hypoxemic acidemia, increased lung W/D (7.23 +/- 0.34, P < 0.05 vs. other groups), capillary occlusion, perivascular and alveolar hemorrhage, and septal disruption by mycelia. Bacteremia induced large increases in serum tumor necrosis factor-alpha (TNF) and interleukin-1 alpha within 1.5 h, but these cytokines remained low in CA animals, even at death. Neither survival nor ALI after EC or CA was altered by pentoxifylline, which attentuated TNF production, or by cyclooxygenase inhibition with ibuprofen. Thus, overall ALI severity correlated with physiological indices of pulmonary function, but ultrastructural changes correlated better with pathogen type than circulating cytokine or eicosanoid mediators. Whereas lethal bacteremia induced early cytokinemia and mild ALI with or without bacterial exotoxins, moderate ALI apparently was mediated by fungal exotoxins during lethal candidemia, which worsened during neutropenia due to enhanced mycelial proliferation.

Animals↗

PubMed1993

TNF-alpha and cyclooxygenase metabolites do not modulate C. albicans septic shock with disseminated candidiasis.

We analyzed differences in host regulation of tumor necrosis factor-alpha (TNF-alpha) production and pathophysiological responses in conscious rats after infection with two strains of pathogenic Candida albicans spp. (CA-1 and CA-2) compared with Escherichia coli serotype 055:B5 (EC). The hypothesis was tested that, in contrast to EC, hypotension, organ injury, and mortality after candidemia are not obligatorily dependent on TNF-alpha or TNF-alpha-induced cyclooxygenase pathway metabolites. Dose, viability, and strain-specific dependencies were established after intravenous 10(6) or 10(9) viable CA, as well as heat-killed (HK) or Formalin-inactivated (FI) CA blastospores, compared with live EC at the 24-h LD25 [10(9) colony-forming units (CFU)] and LD100 (10(10) CFU). Shock without endotoxemia developed 4-8 h after 10(9) live CA-1 or CA-2 (LD100 at 24 h) with disseminated yeast-mycelial transformation and increased microvascular permeability in multiple organs but not after HK or FI CA-1. Peak serum TNF-alpha after an LD100 of CA-1 or CA-2 was < 3% of LD25 EC values and was < 1% of peak values during lethal bacteremia. Similar pathogen-specific differences were found in liver- and lung-associated TNF. Production of functionally inactive TNF-alpha during candidemia was excluded by enzyme-linked immunosorbent assay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis with Western blotting. Passive immunization against TNF-alpha 2 h before microbial challenge was not protective against CA but prevented otherwise lethal EC sepsis. Cyclooxygenase inhibition also failed to attenuate candidemic shock. We conclude that the magnitude and kinetics of TNF-alpha production and TNF-alpha-dependent immunophysiological responses are differentially regulated after lethal fungal vs. gram-negative bacterial infection. Thus TNF-alpha is not a pivotal mediator of the acute Candida septic shock syndrome with disseminated candidiasis.

Animals↗

PubMed1993

Effects of pentoxifylline on tumor necrosis factor production and survival during lethal E. coli sepsis vs. disseminated candidiasis with fungal septic shock.

Lethal circulatory shock during microbial sepsis is thought to be initiated by early molecular events, including production of tumor necrosis factor (TNF) and cytokine-mediated upregulation of neutrophil (PMN) function, irrespective of the causative organism. The phosphodiesterase inhibitor pentoxifylline (PTX) inhibits TNF gene transcription and modulates PMN function, and has been shown to improve outcome in experimental sepsis. We hypothesized that PTX would attenuate gram-negative and fungal septic shock by different mechanisms: reduced TNF production in Escherichia coli (EC) sepsis vs. enhanced PMN-mediated defense during Candida albicans (CA) fungemia. Conscious chronically catheterized rats received PTX (25 mg/kg, i.v.) before i.v. challenge with 10(10) viable EC (serotype 055:B5), 10(9) viable serotype A yeast-phase CA (each the LD100 in < 24 hr in naive rats), or normal sterile saline (NSS), and then PTX posttreatment (6.5 mg/hr x 4.5 hr). Treatment controls received NSS before and after challenge. Serum TNF peaked 1.5 hr after EC infection in NSS-treated animals (1654 +/- 390 U/ml, mean +/- SE), and was significantly reduced by PTX (120 +/- 32 U/ml, P < 0.01), but PTX did not improve 24 hr survival. PTX also aggravated systemic hypotension after EC, and did not modify neutropenia, thrombocytopenia, or microvascular permeability assessed by organ wet/dry weight (W/D) ratios. Peak serum TNF in CA + NSS animals (130 +/- 45 U/ml) was delayed 8 hr compared to EC animals, and were not reduced by PTX (67 +/- 25 U/ml, P = NS). Moreover, PTX did not alter CA-induced mortality, hypothermia, hypotension, neutropenia, increased lung W/D, or interstitial and alveolar hemorrhage. We conclude that PTX-induced suppression of endogenous TNF production does not prevent gram-negative shock in this model, possibly due to impaired TNF-mediated antibacterial host defense. Since fungal septic shock with acute disseminated candidiasis evolves prior to significant increases in circulating TNF, PTX also appears ineffective in its treatment.

Animals↗

PubMed1992

Differential systemic and intrapulmonary TNF-alpha production in Candida sepsis during immunosuppression.

Candida albicans (CA) increasingly causes septic shock, acute lung injury, and multiple organ damage during immunosuppression-related neutropenia. However, the effects of neutrophil (PMN) depletion on induction of tumor necrosis factor-alpha (TNF) by CA and its potential mediation of Candida septic shock are unknown. We hypothesized that reduced CA uptake by circulating PMNs during cyclophosphamide (CY)-related neutropenia sensitizes to TNF-mediated shock from enhanced cytokine production after phagocytosis by tissue macrophages. Absolute or relative neutropenia (PMNs < or = 500/microliters or 2,500/microliters) was modeled in rats by intraperitoneal CY 4-8 days before 10(9) yeast-phase CA (acute studies < or = 24 h, n = 81 animals) or 10(6) CA (subacute studies < or = 72 h, n = 25). Compared with neutrophil-sufficient rats, absolute neutropenia accelerated hemodynamic collapse and respiratory distress after 10(9) CA, and pulmonary microvascular permeability was amplified. These changes evolved without increased candidemia or elevations in bioactive or antigenic serum TNF, which remained low even at death (42.3 +/- 14.8 U/ml vs. 12.6 +/- 2.9 U/ml for CY + saline, means +/- SE, P = NS). In contrast, significant TNF in lung tissue and bronchoalveolar lavage fluid (BALF) was evident within 6 h in CY + 10(9) CA rats. Electron microscopy confirmed hyphal proliferation into alveoli from yeast within mononuclear cells in lung capillaries. Subacute disseminated candidiasis after 10(6) CA was not associated with elevated serum, lung, or BALF TNF. We conclude that differential systemic and intrapulmonary TNF production occur in CA septic shock during preexisting neutropenia, with compartmentalized TNF production in the lower respiratory tract accompanying yeast-mycelial transformation. Thus TNF is not an obligate mediator of acute candidemic shock or subacute disseminated candidiasis during CY-induced immunosuppression but may initiate pulmonary injury accompanying high-grade candidemia.

Acute Disease↗

PubMed1991

Development of alveolar septa and cellular maturation within the perinatal lung.

To quantitate fetal lung cellularity and regional variation in alveolar maturation, guinea pig lungs were studied at 55, 60, and 65 d of gestation or within 2 h of birth (term = 68 d), and the data were analyzed for intralobar, interlobar, and age-group differences. Nine blocks from each left cranial and caudal lobe were all measured for volume, numerical, and surface densities in tissue (Vv(i,t), Nv(i,t), and Sv(i,t], and total volumes, numbers, and surface areas per lung (V, N, and S) of type I and type II epithelia, presumptive progenitor epithelium (cuboidal cells lacking lamellar bodies [LB]), interstitium, and endothelium. Total fixed lung volume, VL, increased 3-fold from day 55 through birth. At each age, there were no consistent intralobar or interlobar differences in Vv(i,t), Nv(i,t), or Sv(i,t) for any cell type. Within a septal tissue volume of 580 to 670 microliters at all ages, the N and V of type I cells did not vary with age, although their S increased from 1,240 cm2 at day 55 to 3,967 cm2 at birth. The N of morphologic type II cells per lung increased 7-fold from day 55 to day 60 and was constant thereafter, while the N of cuboidal cells decreased proportionally; type II cells contained only 4.8% (vol/vol) of LB at 55 d compared to 18.0% at birth. The N and V of interstitium did not vary by age. While endothelial V was constant over these ages, endothelial S increased from 897 cm2 to 3,398 cm2, and the V of capillary blood and the V of alveolar airspace each increased 4-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Surfactant content and type II cell development in fetal guinea pig lungs during prenatal starvation.

Prenatal caloric restriction in guinea pigs causes intrauterine growth retardation and reduced neonatal viability and surfactant phospholipid (PL). We report here fetal surfactant levels in this model, and correlate total lung PL with ultrastructural maturation of surfactant type II cells and lamellar bodies (LB). Pregnant guinea pigs were fed ad libitum throughout their 68-d gestation (control), or fed 50% rations from d 45 until term (starved). Fetal lungs were examined at d 55, 60, and 65 for PL content and composition, including disaturated phosphatidylcholine (DPC), and compared with neonates for both groups. Lung lobes were analyzed ultrastructurally in d 65 fetuses for the numerical, volume, and surface densities of type II cells and the volume densities of LB. Prenatal starvation caused significant intrauterine growth retardation at all ages; body and dry lung weights were reduced on d 65 by 26 and 23%, respectively. By d 55 and thereafter, starvation decreased total lung PL by 43-45% but did not alter PL composition. On d 65, the total lung volumes and relative numbers, surface densities, and volumes of type II cells in tissue and the relative volumes of LB within type II cells did not differ by caloric regimen. Thus, starved and control fetuses had similar total volumes of LB per lung (13-15 microL), although starved animals had significantly less lung DPC. Although the total volume of LB per lung correlated well with total lung DPC from d 55 through birth in controls, starvation led to a significant departure from this relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Ultrastructural analysis of regional type II cell development within fetal and neonatal lungs.

Type II cells within guinea pig lungs were studied beginning when lamellar bodies (LB) were first identifiable, to determine the pattern of their ultrastructural maturation through parturition and to search for regional differences suggested for other species in their numbers or maturity within the same lung. Fetuses were examined at gestational ages of 55, 60, and 65 days, as were newborn within 2 h of birth at 68 days. The stratified sampling system divided left lungs into nine blocks from each cranial and caudal lobe for electron-microscopic morphometry. Type II cells were compared among blocks within lobes, between lobes within age groups, and among ages for volume densities [VV(ep2, t)], numerical densities [NV(ep2, t)], and surface densities [SV(ep2, t)] per block; total tissue volumes [V(ep2)], numbers [N(ep2)], and cumulative surface areas [S(ep2)] per lung; and the VV(lb, ep2) and V(lb) of their LB. Within lobes, there were no significant differences among blocks for any parameter. Within age groups, significant interlobar differences were limited only to NV(ep2, t) (cranial greater than caudal at day 55, P less than 0.001). In age-by-age comparisons, the V(ep2), NV(ep2), and S(ep2) each increased dramatically from day 55 to 60 (P less than 0.001) but then remained unchanged through parturition. However, both VV(lb, ep2) and V(lb) increased linearly with fetal age (day 55 less than 60 less than 65 less than newborn), with VV(lb, ep2) achieving 18% type II cell volume in the postpartum group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Pulmonary development in growing guinea pigs exposed to chronic hypercapnia.

The role of lung stretch in causing pulmonary hyperplasia was studied in weanling male guinea pigs breathing air or 5% CO2 (in 22% O2, 73% N2) for 4 weeks. By the end of the exposure, oxygen consumptions were similar for both groups, but tidal volume and minute ventilation doubled in the hypercapnic group compared to controls. Arterial and venous blood gases reflected compensatory increases in plasma bicarbonate in animals breathing 5% CO2. The two groups did not differ in growth rate, lung volume or weight, alveolar surface area, anatomically estimated pulmonary diffusing capacity, or lung cellularity and protein content. Despite a chronic doubling of tidal volume during a peak growth period, hyperventilation did not stimulate pulmonary development, at least in normoxia and when oxygen consumption remained constant.

Animals↗

PubMed1987

Interaction of prenatal starvation and dexamethasone treatment on lung development in newborn guinea pigs.

Prenatal starvation causes pulmonary hypoplasia, retarded alveolarization, and reduced surfactant production in newborn guinea pigs. This study examined the potential benefit of simultaneous transplacental dexamethasone, which accelerates fetal lung maturation in other species. Pregnant guinea pigs were placed in 1 of 4 groups: Control (C), fed ad libitum until term (67 days) and given daily saline injections from Day 55 of gestation until term; Dexamethasone (D), fed as Group C but given daily injections of 2.0 mg dexamethasone/kg BW from Day 55 until term; Starved (S), given 50% rations from Day 45 until term and injected as Group C; Starved + Dexamethasone (SD), fed as Group S and injected as Group D. Controls and Group D did not differ in body or lung weight, DNA, protein, or lung volume (VL), but Group D lungs contained more lavageable and tissue surfactant, total alveolar surface area (Sa), and membrane diffusing capacity (DmO2) because of increased alveolar surface density. The S neonates weighed 38% less than controls, with proportional reductions in lung weight, DNA, protein, lavage and tissue phospholipids, VL, Sa septal tissue, capillary surface area (Sc), and DmO2. Compared with these S neonates, the SD neonates did not differ for BW, lung weight, DNA, protein, phospholipids, or VL, but their lungs contained significantly more Sa, Sc, epithelial and endothelial tissue volumes, and a higher alveolar surface density. These differences resulted in an average DmO2 for SD neonates that was indistinguishable from that of controls, and correlated with greater viability among the smallest SD animals compared with those in Group S.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Lung mechanics, cellularity, and surfactant after prenatal starvation in guinea pigs.

Prenatal starvation in the guinea pig causes reduced pulmonary diffusing capacity and retarded alveolarization among neonates. To study the impact of such starvation on biochemical and mechanical properties of the neonatal lung, pregnant guinea pigs were fed ad libitum throughout gestation or starved with 50% rations during their last trimester. Neonatal body weight was 35% less due to starvation, and dry lung weight, DNA, and protein contents were decreased 26, 36, and 31%, respectively (P less than 0.001 for all). Hematological data indicated no anemia, hypoproteinemia, or altered glucocorticoid levels due to starvation. Total surfactant phospholipids in these neonates were reduced 61% in lavage and 35% in the neonatal lung tissue, although surfactant compositions were similar to controls. Specific lung compliance in the air-filled lungs was not altered, but the saline-filled lungs were more distensible over deflation pressures of 9-18 cmH2O (transpulmonary). Although starvation retarded both lung cellularity and surfactant, only that portion of lung elastic recoil attributable to tissue forces was affected.

Animals↗

PubMed1986

Prenatal starvation retards development of the ventilatory response to hypoxia in newborn guinea pigs.

Prenatal starvation causes pulmonary hypoplasia in newborn guinea pigs, and is associated with postnatal cyanosis, hypothermia, and respiratory failure. To determine the effects of such starvation on ventilation, neonates from litters either fed ad libitum throughout gestation (control) or given 50% rations in the last trimester of pregnancy (starved) were studied at 29 degrees C by plethysmography in 21, 11, and 5% O2. After 15 min (steady-state) in 11% and then 5% O2, 13 of 14 controls (mean = 95 g) sustained increases in weight-specific minute ventilation of 46 and 75% compared to values in air (p less than 0.01), due to increases in respiratory frequency. Seven of 11 starved neonates (mean = 76 g) also sustained increases in respiratory frequency and weight-specific minute ventilation in 11 and 5% O2 similar in magnitude to those of the normal controls, although at higher weight-specific tidal volumes. One abnormal control (85 g) and four starved neonates (mean = 70 g) hyperventilated in air, did not respond to 11% O2, and then hypoventilated in 5% O2 due to a reduced weight-specific tidal volume. Neonates with normal ventilatory patterns did not alter weight-specific minute ventilation in 100% O2 and did not show a biphasic response in acute (1-5 min) exposures to moderate hypoxia, as noted for newborn of other species. Thus, hypoxia identified those starved neonates in which pulmonary immaturity or other starvation-induced pathologies necessitated a maximal ventilatory effect in air. The sustainable hyperventilation among normal guinea pigs during hypoxia emphasizes the precocial development in this species at birth, which may be compromised by intrauterine starvation.

Animals↗

PubMed1985

Increased capillarity in skeletal muscle of growing guinea pigs acclimated to cold and hypoxia.

Capillarity was evaluated on transverse sections of frozen gastrocnemius and soleus muscles of young, growing guinea pigs exposed to the combined stresses of cold (6 degrees C) (C) and hypoxia (ambient PO2 = 85 Torr) (H) for up to 16 weeks and these data were compared to those obtained in a control group of guinea pigs kept in Denver (22 degrees C, ambient PO2 = 133 Torr). Capillarity was assessed from measurements of capillary density and capillarity density to fiber density ratios. Mean (R) and maximal (R95) diffusion distances were measured by the closest individual method. The body growth rate of guinea pigs exposed to C + H was the same as that in the control condition. The gastrocnemius muscle grew at the same rate as in the control guinea pigs. Exposure to C + H produced a significant (P less than 0.001) increase in the capillary density and the C/F of the gastrocnemius, reducing the mean and the maximal diffusion distances. However, the soleus muscles of the guinea pigs in C + H did not grow at the same rate and relative to body size the soleus muscles of these guinea pigs in C + H were smaller due to their smaller fiber cross-section area; consequently, there was a relatively larger capillarity in these muscles. It is hypothesized that the increased muscle capillarity in animals exposed to C + H results from a marked lowering of the tissue PO2 which may result from a leftward shift of the Hb-O2 dissociation curve.

Acclimatization↗

PubMed1985

Pulmonary design in a microchiropteran bat (Pipistrellus subflavus) during hibernation.

The Eastern pipistrelle (Pipistrellus subflavus) is typical of exceptionally small bats capable of a 30-fold range in aerobic metabolism as they arouse from hypothermia and sustain foraging flight. This report describes their basic lung structure and the extent to which this organ is protected from protein depletion during hibernation. Bats were collected at the beginning (Fall), middle (Winter), and end (Spring) of hibernation from a permanent overwintering cave, and analyzed within several days of capture. Regardless of whether bats were examined in the Fall (average body weight = 6.22 g) or in the Spring (4.58 g) no significant differences existed for total lung volume (237 microliter), alveolar surface area (338 cm2), harmonic mean septal thickness, tau ht (0.221 micron), or membrane diffusing capacity (4.13 microliter O2/sec/mbar). These parameters exceed predictions based on body weights for either season, and resemble published data for another highly active mammalian group, the insectivorous shrews. Both tau ht and the minimal septal thickness of 0.083 micron approach the anatomical limits for thinning of alveolar septa without loss of epithelial continuity. Although both the heart and lungs lost 13% of their fresh weights during hibernation, compared to 25% for the liver, the lung contents of DNA (0.14 mg) and blood-free protein (7.38 mg) were not altered significantly. These small bats possess lungs which are well suited for the high aerobic cost of flight. Those lungs are resistant to hibernation-induced proteolysis, and also resistant to the deterioration of alveolar membranes which occurs in nonhibernators subjected to starvation-induced weight losses of similar magnitude.

Animals↗

PubMed1985

Morphometry and calcium contents in appendicular and axial bones of exercised ovariectomized rats.

To determine the effects of exercise and ovariectomy on calcium status in selected appendicular and axial bones, female Sprague-Dawley (8-9 mo) rats were assigned to groups based on the following combinations: control (C) or ovariectomized (O); sedentary (S) or exercised (E); and length of treatment (2 or 4 mo). Exercise consisted of treadmill running for 1 h/day, 5 days/wk at a speed of 14.1 m/min and 8 degrees elevation. After death, femurs, tibia-fibula complexes, ribs (T7), and vertebrae (T7) were excised, cleaned, and weighed, and selected morphometrics were measured. Tensile strength was measured for the femurs, and all bones were then acid-hydrolyzed and calcium concentration determined spectrophotometrically. Bone [Ca2+] was significantly greater for CE and OE animals when compared with their sedentary counterparts (CS, OS). Within 4 mo calcium losses were evident in the femur and tibia of the ovariectomized animals, and the moderate exercise program was of insufficient intensity to alter this loss. The average stress to failure for femur from all groups was 1.13 +/- 0.11 N/m2. However, the effects of exercise appeared beneficial in the axial bones where [Ca2+] increased in the ovariectomized animals.

Alkaline Phosphatase↗

PubMed1985

Starvation-induced organ hypoplasia in prenatal and postnatal guinea pigs.

The severity and permanence of growth retardation was measured in guinea pigs starved for 3 weeks with a 50% ration in late gestation (prenatal), at birth (neonatal), or at weaning. Acute and chronic effects were assessed as body mass, skeletal length, hematology, and the weight, DNA and protein contents of the hearts, the lungs, and the livers of the starved and refed animals. Organ hypoplasia was most pronounced in the prenatally starved group, and was associated with numerous stillbirths. Among survivors, catch-up growth was eventually complete. Prenatal starvation of this species provides a reproducible model of human intrauterine growth retardation, particularly of the pulmonary system.

Animals↗

PubMed1985

Perinatal age determines the severity of retarded lung development induced by starvation.

Susceptibility of the lung to caloric restriction is age-dependent, with more permanent damage occurring during the phases of growth and differentiation. Because the guinea pig is born with more well-developed alveoli than are other rodents, the postnatal lung of this species may better resist alveolar hypoplasia than the prenatal lung. Control animals were raised from sows provided food ad libitum during and after normal gestations (66 to 68 days). Starvation groups received 50% rations of control food intakes during 1 of three 21-day periods: prenatal starvation, with sows rationed during their last trimester (Day 45 to term); neonatal starvation, with nursing sows rationed during the 21 days postpartum before weaning; weanling starvation, with animals starved from 21 to 42 days postpartum. Lungs were fixed in situ with glutaraldehyde and analyzed for pulmonary morphometrics. At the end of starvation and before refeeding, lungs of prenatal and weanling starvation groups were significantly reduced for tissue volumes, alveolar and capillary surface areas, and pulmonary diffusing capacity. Recovery with feeding was complete for most parameters in the starved weanlings by maturity, but animals starved prenatally showed residual starvation effects as adults. The neonatally starved animals showed minimal effects of starvation on lung dimensions, both acutely and as adults. Morphologically, the lungs of some prenatally starved neonates were apparently retarded, at least to the saccular phase, and correlated with significant increases in the number of stillborn litters and in neonatal mortality within hours of parturition.

Age Factors↗

PubMed1985

Increased bone calcium following endurance exercise in the mature female rat.

In order to determine the effects of exercise on the calcium status of selected axial and appendicular bones of mature rats, female Sprague-Dawley rats (8-9 mo.) were divided into three groups including, two months (E2, n = 8) or four months (E4, n = 9) of exercise, and four month sedentary controls (S, n = 10). Exercise consisted of treadmill running for 1 hr/day, 5 days/wk at a speed of 14.1 m/min and 8 degrees elevation. After sacrifice all femurs, tibia/fibula complexes, ribs (T7), and vertebrae (T7) were excised, cleaned, weighed and measured for length and volume. After freeze-drying and bone hydrolysis in 5N HCl, total bone calcium contents and concentrations were determined spectrophotometrically. The acid soluble, appendicular bone calcium contents of the E4 group were significantly greater than S for the femur and tibia respectively: E4 = 159.78 +/- 3.44 mg (mean +/- SEM), 129.46 +/- 4.87 mg; S = 140.03 +/- 5.04 mg, 110.40 +/- 4.71 mg. Bone calcium concentration (mg/g dry bone) also was significantly greater in the tibia/fibulas, ribs and vertebrae of the E4 group than the S group. With respect to other training-induced effects, the oxygen carrying capacity of the blood, as well as the heart and lung DNA and protein concentrations did not change after four months of exercise training. Within four months, moderate exercise can increase the calcium deposition in the bones of mature, female rats.

Alkaline Phosphatase↗