Ventilation inhomogeneity in oleic acid-induced pulmonary edema

Tsang, John Y. C., Michael J. Emery, and Michael P. Hlastala. Ventilation inhomogeneity in oleic acid-inducedpulmonary edema. J. Appl. Physiol.82(4): 1040-1045, 1997.Oleic acid causes permeability pulmonaryedema in the lung, resulting in impairment of gas-exchange andventilation-perfusion heterogeneity and mismatch. Previous studies haveshown that by using the multiple-breath helium washout (MBHW)technique, ventilation inhomogeneity (VI) can be quantitativelypartitioned into two components, i.e., convective-dependent inhomogeneity (cdi) and diffusive-convective-dependent inhomogeneity (dcdi). Changes in VI, as represented by the normalized slope of thephase III alveolar plateau, were studied for 120 min in fiveanesthetized mongrel dogs that were ventilated under paralysis by aconstant-flow linear motor ventilator. These animals received oleicacid (0.1 mg/kg) infusion into the right atrium att = 0. MBHWs were done induplicate for 18 breaths every 40 min afterward. Three other dogs thatreceived only normal saline served as controls. The data show that,after oleic acid infusion, dcdi, which represents VI in peripheralairways, is responsible for the increasing total VI as lung wateraccumulates progressively over time. The cdi, which represents VIbetween larger conductive airways, remains relatively constantthroughout. This observation can be explained by increases in theheterogeneity of tissue compliance in the periphery, distal airwayclosure, or by decreases in ventilation through collateral channels.

     

Skeletal muscle mass and the reduction of VO2 max in trained older subjects

Proctor, David N., and Michael J. Joyner. Skeletalmuscle mass and the reduction ofO_{2 max} in trainedolder subjects. J. Appl. Physiol.82(5): 1411-1415, 1997.The role of skeletal muscle mass in theage-associated decline in maximalO₂ uptake (O_{2 max}) is poorlydefined because of confounding changes in muscle oxidative capacity andin body fat and the difficulty of quantifying active muscle mass duringexercise. We attempted to clarify these issues byexamining the relationship between several indexes of muscle mass, asestimated by using dual-energy X-ray absorptiometry and treadmillO_{2 max} in 32 chronically endurance-trained subjects from four groups(n = 8/group): young men(20-30 yr), older men (56-72 yr), young women(19-31 yr), and older women (51-72 yr).O_{2 max} per kilogrambody mass was 26 and 22% lower in the older men (45.9 vs. 62.0 ml · kg¹ · min¹)and older women (40.0 vs. 51.5 ml · kg¹ · min¹).These age differences were reduced to 14 and 13%, respectively, whenO_{2 max} was expressedper kilogram of appendicular muscle. When appropriately adjusted forage and gender differences in appendicular muscle mass by analysis ofcovariance, whole body O_{2 max} was 0.50 ± 0.09 l/min less (P < 0.001) in theolder subjects. This effect was similar in both genders.These findings suggest that the reducedO_{2 max} seen in highlytrained older men and women relative to their younger counterparts isdue, in part, to a reduced aerobic capacity per kilogram of activemuscle independent of age-associated changes in body composition, i.e.,replacement of muscle tissue by fat. Because skeletal muscleadaptations to endurance training can be well maintained in oldersubjects, the reduced aerobic capacity per kilogram of muscle likelyresults from age-associated reductions in maximalO₂ delivery (cardiac outputand/or muscle blood flow).

     

Augmented sympathetic tone alters muscle metabolism with exercise: lack of evidence for functional sympatholysis

Shoemaker, J. Kevin, Prasant Pandey, Michael D. Herr, DavidH. Silber, Qing X. Yang, Michael B. Smith, Kristen Gray, and LawrenceI. Sinoway. Augmented sympathetic tone alters muscle metabolismwith exercise: lack of evidence for functional sympatholysis. J. Appl. Physiol. 82(6):1932-1938, 1997.It is unclear whether sympathetic tone opposesdilator influences in exercising skeletal muscle. We examined highlevels of sympathetic tone, evoked by lower body negative pressure(LBNP, 60 mmHg) on intramuscular pH and phosphocreatine (PCr)levels (³¹P-nuclear magnetic resonance spectroscopy) duringgraded rhythmic handgrip (30 contractions/min; ~17, 34, 52 and 69%maximal voluntary contraction). Exercise was performedwith LBNP and without LBNP (Control). At the end of exercise, LBNPcaused lower levels of muscle pH (6.59 ± 0.09) comparedwith Control (6.78 ± 0.05; P < 0.05). PCr recovery, an index of mitochondrial respiration, was lessduring the recovery phase of the LBNP trial. Exercise mean arterialpressure was not altered by LBNP. The protocols were repeated withmeasurements of forearm blood flow velocity and deep venous samples(active forearm) of hemoglobin (Hb) saturation, pH, and lactate. WithLBNP, mean blood velocity was reduced at rest, during exercise, andduring recovery compared with Control (P < 0.05). Also, venous Hbsaturation and pH levels during exercise and recovery were lower withLBNP and lactate was higher compared with Control(P < 0.05). We concludethat LBNP enhanced sympathetic tone and reduced oxygen transport. Athigh workloads, there was a greater reliance on nonoxidativemetabolism. In other words, sympatholysis did not occur.

     

Cardiovascular adaptations to 10days of cycle exercise

Mier, Constance M., Michael J. Turner, Ali A. Ehsani, andRobert J. Spina. Cardiovascular adaptations to 10 days of cycleexercise. J. Appl. Physiol. 83(6):1900-1906, 1997.We hypothesized that 10 days of training wouldenhance cardiac output (CO) and stroke volume (SV) during peak exerciseand increase the inotropic response to -adrenergic stimulation. Tensubjects [age 26 ± 2 (SE) yr] trained on a cycleergometer for 10 days. At peak exercise, training increasedO₂ uptake, CO, and SV(P < 0.001). Left ventricular (LV)size and function at rest were assessed with two-dimensional echocardiography before (baseline) and after atropine injection (1.0 mg) and during four graded doses of dobutamine. LV end-diastolic diameter increased with training (P < 0.02), whereas LV wall thickness was unchanged. LV contractileperformance was assessed by relating fractional shortening (FS) to theestimated end-systolic wall stress(_ES). Training increased theslope of the FS-_ES relationship (P < 0.05), indicating enhancedsystolic function. The increase in slope correlated with increases inCO (r = 0.71,P < 0.05) and SV(r = 0.70,P < 0.05). The increase in bloodvolume also correlated with increases in CO(r = 0.80, P < 0.01) and SV (r = 0.85, P < 0.004). These datashow that 10 days of training enhance the inotropic response to-adrenergic stimulation, associated with increases in CO and SVduring peak exercise.

     

Nitric oxide and vasodilation in human limbs

Joyner, Michael J., and Niki M. Dietz.Nitric oxide and vasodilation in human limbs. J. Appl. Physiol. 83(6): 1785-1796, 1997.Both theskeletal muscle and skin of humans possess remarkable abilities tovasodilate. Marked vasodilation can be seen in these vascular beds inresponse to a variety of common physiological stimuli. These stimuliinclude reactive hyperemia (skin and muscle), exercise hyperemia(muscle), mental stress (muscle), and whole body heating (skin). Thephysiological mechanisms that cause vasodilation in response to thesestimuli are poorly understood, and the substance(s) responsible for itremain unclear. In this context, recent attention has been focused onthe possible contribution of nitric oxide (NO) to the regulation ofhyperemic responses in human skin and skeletal muscle. The emergingpicture is that NO is not an essential component of the dilatorresponse seen during reactive hyperemia. However, it does appear thatNO may play a modest role in exercise hyperemia. NO appears to play amajor role in the skeletal muscle vasodilation seen in response tomental stress in humans. Preliminary evidence also indicates that NO isnot essential for the normal dilator responses observed in thecutaneous circulation during body heating in humans, but this issueneeds further study. There are a number of possible mechanisms thatmight mediate NO release in humans, and the role of these mechanisms inthe various hyperemic responses is also poorly understood. The role ofaltered NO-mediated vasodilation in some disease states is alsodiscussed. Whereas NO is a potent vasodilating substance, the actionsof NO alone do not explain a variety of poorly understood vasodilatormechanisms in conscious humans. Much work remains for those interestedin the role of NO in the regulation of blood flow to the skin and skeletal muscle of humans.

     

Population genetics of Cordia alliodora (Boraginaceae), a neotropical tree. 2. Mating system

A multilocus mixed mating model was used to evaluate the mating system of a natural population of Cordia alliodora (Boraginaceae), a neotropical tree. The population was highly outcrossed (t_m = 0.966 ± 0.027), in agreement with results from controlled crosses. Departures from the mixed mating model were evident, suggesting some nonrandom, correlated mating. Pollen pool heterogeneity and variation in estimates of individual outcrossing rates indicated that the population may be genetically substructured. Individual outcrossing rates obtained for the samples taken from within different parts of the same tree indicated reduced levels of outcrossing due to limited sampling of the pollen pool. The incompatibility mechanism in C. alliodora, combined with variation in flowering and stand density, appears to lead to both temporal and spatial substructuring of the population.     

Metabolism of 3H-1α,25-dihydroxyvitamin D3 in cultured human keratinocytes

In the present investigation we studied the metabolism of 1α,25-dihydroxy-[1β-³H] vitamin D₃ (³H-1,25(OH)₂D₃) in culture-grown human keratinocytes (CHK). Our results showed that the cellular uptake of ³H-1,25(OH)₂D₃, upon incubation with CHK, occurred very rapidly; and it paralleled a decrease in the concentration of ³H-1,25(OH)₂D₃ in the medium. The amount of ³H-calcitroic acid, on the other hand, increased slowly in the medium, while the concentration of ³H-calcitroic acid in the cell remained undetectable during the whole period of incubation. When the cells were preincubated with 1,25(OH)₂D₃ (10^?8M), conversion of ³H-1,25(OH)₂D₃ to ³H-calcitroic acid increased almost twofold, indicating that 1,25(OH)₂D₃ catalyzed its own catabolism. © 1995 Wiley-Liss, Inc.     

Prothrombin cleavage by human vascular smooth muscle cells: A potential alternative pathway to the coagulation cascade

Thrombin is a potent mitogen for human vascular smooth muscle cells (HVSMC) and its enzymatic activity is required for this function. The present study demonstrates that prothrombin is also mitogenic for HVSMC due to the generation of enzymatically active thrombin which occurs upon incubation of prothrombin with the cells. Analysis by SDS-PAGE, immunoblotting, and amino acid sequencing revealed that prothrombin incubated with HVSMC undergoes limited proteolysis. Prethrombin 1 was formed through cleavage at R¹⁵⁵-S¹⁵⁶. Cleavage at R²⁷¹-T²⁷² generated fragment 1.2 and prethrombin 2 whilst cleavage at R²⁸⁴-T²⁸⁵ yielded truncated prothrombin 2 (prethrombin 2′). However, cleavage at R³²⁰-I³²¹ which, during prothrombin activation produces two-chain α-thrombin, was not detectable. Studies on HVSMC-conditioned medium revealed that a similar pattern of prothrombin cleavage occurred by a cell-secreted factor(s). Amidolytic activity analysis indicated that 1–3% catalytically active thrombin-like activity was generated upon incubation of prothrombin with HVSMC-conditioned medium. By treating conditioned medium with various classes of proteinase inhibitors or hirudin, it was determined that prothrombin is cleaved by a cell-derived serine proteinase-like factor(s) at R²⁷¹-S²⁷² and by α-thrombin at R¹⁵⁵-S¹⁵⁶ and R²⁸⁴-T²⁸⁵. Antibodies neutralising the activity of either urokinase, tissue plasminogen activator, or factor Xa failed to alter the prothrombin cleaving activity of conditioned medium. This activity which may catalyse an alternative pathway for the generation of thrombin, was eluted from a gel filtration column as a single peak with apparent molecular mass of 30–40 kDa. © 1995 Wiley-Liss, Inc.     

Complete nucleotide sequence of thePorphyra purpurea chloroplast genome

The complete nucleotide sequence of the chloroplast genome of the red algaPorphyra purpurea has been determined (accession number=U38804). The circular genome is 191,028 bp in length and encodes approximately 250 genes.