Biomedical subjects

T Wang

Publications and source records attributed to T Wang.

At least 523 records · Page 29Linked to original sources

PubMed1996

The immunophilin FKBP12 functions as a common inhibitor of the TGF beta family type I receptors.

The immunophilin FKBP12 is an evolutionarily conserved abundant protein; however, its physiological roles remain poorly defined. Here we report that FKBP12 is a common cytoplasmic interactor of TGF beta family type I receptors. FKBP12 binds to ligand-free TGF beta type I receptor, from which it is released upon a ligand-induced, type II receptor mediated phosphorylation of the type I receptor. Blocking FKBP12/type I receptor interaction with FK506 nonfunctional derivatives enhances the ligand activity, indicating that FKBP12 binding is inhibitory to the signaling pathways of the TGF beta family ligands. Overexpression of a myristylated FKBP12 in Mv1Lu cell specifically inhibits two separate pathways activated by TGF beta, and two point mutations on FKBP12 (G89P, I90K) abolish the inhibitory activity of FKBP12, suggesting that FKBP12 may dock a cytoplasmic protein to the type I receptors to inhibit TGF beta family mediated signaling.

Activin Receptors, Type I↗

PubMed1996

High-performance liquid chromatographic separation of an HIV-1 reverse transcriptase inhibitor and its enantiomer.

This article describes the direct separation of an HIV-1 reverse transcriptase inhibitor and its enantiomer by HPLC on a silica-bonded polyacrylamide (ChiraSpher) column. The column selection was based on specific interactions between the individual enantiomers and the chiral stationary phase. The influence of some chromatographic conditions, such as concentration of the polar modifier in the mobile phase, column flow-rate and column temperature, on column performance was investigated. The separation was applied to the determination of the minor enantiomer in the bulk drug and as low as 0.3% of minor enantiomer was detectable.

Binding, Competitive↗

PubMed1996

Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus.

Neurotrophins promote neuronal survival and differentiation, but the fact that their expression is modified by neuronal activity, suggests a role in regulating synapse development and plasticity. In developing hippocampus, the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB increases in parallel with the ability to undergo long-term potentiation (LTP). Here we report a mechanism by which BDNF modulates hippocampal LTP. Exogenous BDNF promoted the induction of LTP by tetanic stimulation in young (postnatal day 12-13) hippocampal slices, which in the absence of BDNF show only short-term potentiation (STP). This effect was due to an enhanced ability of hippocampal synapses to respond to tetanic stimulation, rather than to a direct modulation of the LTP-triggering mechanism. A TrkB-IgG fusion protein, which scavenges endogenous BDNF, reduced the synaptic responses to tetanus as well as the magnitude of LTP in adult hippocampus. Our results suggest that BDNF may regulate LTP in developing and adult hippocampus by enhancing synaptic responses to tetanic stimulation.

Animals↗

PubMed1996

A mouse model of gyrate atrophy of the choroid and retina. Early retinal pigment epithelium damage and progressive retinal degeneration.

Gyrate atrophy (GA) of the choroid and retina is a blinding chorioretinal degeneration caused by deficiency of ornithine delta-aminotransferase (OAT). The phenotype of GA is characterized by progressive concentric reduction of the visual fields and ornithine accumulation. To understand better the pathogenesis of GA and to develop a model to test therapeutic strategies, we produced an OAT-deficient mouse by gene targeting. Like human GA patients, adult OAT-deficient mice exhibit chronic hyperornithinemia to levels 10-15-fold above normal and massive ornithinuria. Slowly progressive retinal degeneration is reflected by a gradual decline in electroretinogram amplitudes over the first 12 mo of life. At 2 mo, the retinal pigment epithelium is histologically normal, but electron microscopy reveals sporadic degeneration of scattered pigment epithelial cells. By 6 mo there are more diffuse abnormalities of the pigment epithelium with accumulation of large phagosomes and crystalloid inclusions. Although morphologically normal at 2 mo, the photo-receptor outer segments become highly disorganized and shortened to 60% of control length by 10 mo. Additionally, there is cumulative loss of the photoreceptor cells, which reaches 33% by 10 mo and is most pronounced in the central region of the retina. Our results indicate that retinal pigment epithelial cells are the initial site of insult in GA and that the OAT-deficient mouse is an excellent animal model of GA in human patients.

Animals↗

PubMed1996

The p21(RAS) farnesyltransferase alpha subunit in TGF-beta and activin signaling.

The alpha subunit of p21(RAS) farnesyltransferase (FNTA), which is also shared by geranylgeranyltransferase, was isolated as a specific cytoplasmic interactor of the transforming growth factor-beta (TGF-beta) and activin type I receptors with the use of the yeast two-hybrid system. FNTA interacts specifically with ligand-free TGF-beta type l receptor but is phosphorylated and released upon ligand binding. Furthermore, the release is dependent on the kinase activity of the TGF-beta type II receptor. Thus, the growth inhibitory and differentiative pathways activated by TGF-beta and activin involve novel mechanisms of serine-threonine receptor phosphorylation-dependent release of cytoplasmic interactors and regulation of the activation of small G proteins, such as p21(RAS).

Activin Receptors↗

PubMed1996

Twenty-four-hour intermittent perfusion storage of the isolated rat heart. II. Perfusion pressure and functional preservation.

This study investigated the effect of intermittent perfusion (IP) pressures on functional preservation of the cold-stored isolated rat heart. The heart was flushed with cardioplegic solution #11 with ethylene diamine-tetraacetic acid and 2, 3-butanedione monoxime (CP-11EB), and stored at 0 degree C for 24 hr. During storage, the heart was intermittently perfused for 3 min at 10 and 17 hr of storage with 25 degrees C oxygenated CP-11EB. The IP pressures studied were: 20, 30, 40, 50, 60, 70, 80, and 100 mm Hg. Poststorage recovery of function was assessed with 30 min of working reperfusion. Control function of the unstored heart was: aortic flow (AF), 51.3 +/- 2.2 ml/min; coronary flow (CF), 25.8 +/- 1.2 ml/min; cardiac output (CO), 77.7 +/- 2.3 ml/min; work, 92.0 +/- 4.9 g-m/min; and coronary vascular resistance (CVR), 2.64 +/- .21 mm Hg-min/ml. Functional return in the 30,40,50,60,70, and 80 mm Hg groups was similar. Recovery in a representative group (60 mm Hg) was: AF, 52 +/- 3%; CF, 41 +/- 2%; CO, 48 +/- 3%; work, 42 +/- 3%; and CVR, 225 +/- 10% of the control. The total IP volume in this group was 71.0 +/- 1.7 ml; total lactate dehydrogenase (LDH) release during IP was 8.62 +/- .37 units/g dry; and end-storage tissue lactate was 52.6 +/- 6.4 mumole/g dry. As IP pressure decreased to 20 mm Hg, cardiac functional recovery declined significantly to AF, 35 +/- 6%; CF, 33 +/- 2%; CO, 34 +/- 5%; and work, 27 = 4% of control (P < .05 vs. 60 mm Hg group). The total IP volume decreased to 10.1 +/- .9 ml, tissue lactate content rose to 87.1 +/- 10.9 (P < .05 vs. 60 mm Hg group), but LDH release fell to 5.59 +/- .46 (P < .05 vs. 60 and 100 mm Hg groups). When IP pressure increased to 100 mm Hg, cardiac function was depressed with AF recovered to 25 +/- 3%; CF, 30 +/- 3%; CO, 26 +/- 3%; work, 21 +/- 3%; and CVR, 294 +/- 26% of control (P < .05 vs. 60 mm Hg group). IP volume increased to 100.7 +/- 2.4 ml; total LDH release increased to 19.1 +/- 1.2 (P < .05 vs. 60 mm Hg group), although tissue lactate (58.9 +/- 3.9) was not different from the 60 mm Hg group. End-storage tissue wet/dry weight ratio and myocardial adenosine triphosphate content were not different among the 20, 60, and 100 mm Hg groups. In conclusion, IP has a broad pressure optimum ranging from 30 to 80 mm Hg for 24-hr hypothermic preservation of the rat cardiac explant.

Adenosine Triphosphate↗

PubMed1996

Characterization of digoxigenin derivatives of human coagulation factors VIIa and X by electrospray mass spectrometry and enzyme kinetics.

Digoxigenin ester (Dig) derivatives of coagulation factors VIIa and X facilitate staining studies to localize tissue factor activity in human atherosclerotic plaques. The larger the number of attached Dig units the easier it is to form highly visual stains. Electrospray ionization was used to characterize the Dig derivatives, as a function of excess derivatization reagent, to determine the optimal derivatives, i.e. the highest number of Dig units attached with the product still retaining enzymatic activity. The enzymatic activity of factor VIIa derivatized at 50-fold Dig excess (with 28, 34, 48 or 52 Dig units attached, masses to 79 kDa) remained the same as that of native factor VIIa. In contrast, the enzymatic activity of factor X derivatives diminished above 15-fold Dig excess (15 Dig units attached, mass 65.6 kDa). The distribution of derivatized lysine, histidine, arginine, tryptophan and tyrosine residues was estimated for several possible configurations.

Amino Acids↗

PubMed1996

Enalaprilat, an angiotensin-converting enzyme inhibitor, enhances functional preservation during long-term cardiac preservation. Possible involvement of bradykinin and PKC.

We investigated the effect of enalaprilat (ET) on long-term preservation of cardiac explant. Isolated rat hearts (n = 7/group) were pretreated with 0 to 40 nM ET and stored at 0 degree C for 16 h. Functional viability was assessed after 30-min working reperfusion without ET. Prestorage control function (mean +/- S.E.M.) (n = 7) included heart rate (HR), 291 +/- 12 bpm; aortic flow (AF). 49.8 +/- 1.9 ml/min; coronary flow (CF), 25.2 +/- 1.3 ml/min; cardiac output (CO), 75.0 +/- 1.2 ml/min; and work, 89.4 +/- 4.7 g-m/min. Post-storage function of untreated hearts was: AF, 61%; CF, 43%; CO, 55%; work, 48% of control. ET (20 nM) enhanced AF recovery to 85%; CF, 58%; CO, 76%; work, 73% of control (P < 0.05 v untreated). Hoe 140 (D-Arg-[Hyp2, Thi5,8, D-Phe7]BK) (1 nM) a bradykinin receptor antagonist, inhibited ET effect; function returned to the untreated level. Protein kinase C (PKC) inhibitors staurosporine (15 nM) and bisindolylmaleimide I (0.5 microM) also blocked ET effect. After 4 h of cold storage, membrane PKC activity changed little from the prestorage level in the untreated hearts, but was elevated significantly from 52.8 +/- 5.2 pmol/min/mg to 74.7 +/- 8.2 by 20 nM ET (P < 0.05 v untreated). Cytosol PKC did not change during 4 h cold storage with or without ET. Neither end-storage nor end-reperfusion myocardial ATP content was affected by 20 nM ET treatment. In conclusion, ET improves cardiac preservation possibly via bradykinin receptor and PKC without affecting ATP metabolism.

Adenosine Triphosphate↗

PubMed1996

Expression of synapsin I correlates with maturation of the neuromuscular synapse.

Synapsins are a family of neuron-specific phosphoproteins that are localized within the presynaptic terminals in adult brain. Previous work has demonstrated that introduction of exogenous synapsins I(a + b) or IIa into Xenopus spinal neurons promoted maturation of the neuromuscular synapse in a nerve-muscle co-culture system. We have now studied the expression of endogenous Xenopus synapsin I during synaptic maturation in vivo and in culture, using a polyclonal antibody raised against Xenopus synapsin I. Immunoprecipitation experiments indicated that synapsin I was not detectable during the early phase of synaptogenesis in vivo, and exhibited a marked increase during the period of synaptic maturation. In contrast, the expression of synaptophysin, another synaptic vesicle protein, was detected at the start of nervous system formation, and remained at a high level thereafter. Similar expression profiles for the two proteins were also observed in immunocytochemical studies of Xenopus spinal neurons in culture: intense staining of synaptophysin was found on the first day, while synapsin I was not detected until after three days in culture. The expression of synapsin I correlated very well with the appearance of a bell-shaped amplitude distribution of spontaneous synaptic currents, a physiological parameter which reflects functional maturation of the neuromuscular synapse. In one-day-old cultures grown in the absence of laminin, an extracellular matrix protein known to be present at the neuromuscular junction, the amplitude distribution of virtually all synapses was skewed towards smaller values. In contrast, when laminin was used as a culture substrate, many synapses exhibited a bell-shaped amplitude distribution. Laminin treatment also induced synapsin I expression in one-day-old cultures. These results suggest that the expression of endogenous synapsin I may regulate maturation at neuromuscular synapses.

Animals↗

PubMed1996

Myocardial protection in normal and hypoxically stressed neonatal hearts: the superiority of hypocalcemic versus normocalcemic blood cardioplegia.

OBJECTIVES: The ideal cardioplegic calcium (Ca+2) concentration in newborns continues to be debated. Most studies examining cardioplegia calcium concentrations have been done with a nonclinical model (i.e., isolated heart preparation), the results of which may not be clinically applicable, and they have not examined the effect of calcium concentration in a clinically relevant stressed (hypoxic) heart. METHODS: Twenty neonatal piglets 5 to 18 days old were placed on cardiopulmonary bypass, and their aortas were crossclamped for 70 minutes with hypocalcemic or normocalcemic multidose blood cardioplegic infusions. Group 1 (n = 5; low Ca+2, 0.2 to 0.4 mmol/L) and group 2 (n = 5; normal Ca+2, 1.0 to 1.3 mmol/L) were nonhypoxic (uninjured) hearts. Ten other piglets were first ventilated at an FiO2 of 8% to 10% (O2 saturation 65% to 70%) for 60 minutes (i.e., causing hypoxia) and then reoxygenated at an FiO2 of 100% with cardiopulmonary bypass, which produces a clinically relevant stress injury. They then underwent cardioplegic arrest (as described above) with a hypocalcemic (n = 5, group 3) or normocalcemic (n = 5, group 4) blood cardioplegic solution. Myocardial function was assessed with pressure volume loops and expressed as a percentage of control values. Coronary vascular resistance was measured during each cardioplegic infusion. All values were reported as the mean +/- standard error. RESULTS: In nonhypoxic hearts (groups 1 and 2), good myocardial protection was achieved at either concentration of cardioplegia calcium, as demonstrated by preservation of postbypass systolic function (104% vs 99% end-systolic elastance), minimally increased diastolic stiffness (152% vs 162%), no difference in myocardial water (78.9% vs 78.9%), and no change in adenosine triphosphate levels or coronary vascular resistance. Low-calcium blood cardioplegia solution repaired the hypoxic reoxygenation injury in stressed hearts (group 3), resulting in no statistical difference in myocardial function, coronary vascular resistance, or adenosine triphosphate levels compared with nonhypoxic hearts (groups 1 and 2). Conversely, when a normocalcemic cardioplegia solution was used in hypoxic hearts (group 4), there was marked reduction in postbypass systolic function (49% +/- 4% end-systolic elastance; p < 0.05), increased diastolic stiffness (276% +/- 9%; p < 0.05), increased myocardial water (80.1% +/- 0.2%; p < 0.05), rise in coronary vascular resistance (p < 0.05), and lower adenosine triphosphate levels compared with groups 1, 2, and 3. CONCLUSIONS: This study demonstrates that, in the clinically relevant, intact animal model, good myocardial protection is independent of cardioplegia calcium concentration in nonhypoxic (noninjured) hearts; hypoxic (stressed) hearts are extremely sensitive to the cardioplegic calcium concentration; and normocalcemic cardioplegia is detrimental to neonatal myocardium subjected to a preoperative hypoxic stress.

Animals↗

PubMed1996

(--)-Timolol is a more potent antagonist of the positive inotropic effects of (--)-adrenaline than of those of (--)-noradrenaline in human atrium.

1. The affinity of (--)-timolol for beta 1- and beta 2-adrenoceptors was determined on isolated atrial preparations from patients undergoing open heart surgery. The times for onset and offset of antagonism of the positive inotropic effects of (--)-adrenaline and (--)-noradrenaline by (--)-timolol were measured. 2. The antagonism of the positive inotropic effects of (--)-adrenaline and (--)-noradrenaline by (--)-timolol (0.1-100 nM) was simple competitive in human atrium tissue. The slope of Schild-plots was not significantly different from 1.0 [0.93 +/- 0.09 for (--)-adrenaline, 0.97 +/- 0.09 for (--)-noradrenaline]. 3. The inotropic effects of (--)-adrenaline were antagonized significantly more by each concentration of (--)-timolol than those of (--)-noradrenaline. KB-values (-log M) were 10.10 +/- 0.09 against (--)-adrenaline and 9.43 +/- 0.07 against (--)-noradrenaline (P < 0.001). 4. Blocking kinetics of (--)-timolol for the beta-adrenoceptor were relatively slow. Half-times for the onset of blockade by 10 times KB of (--)-timolol were approximately 30 min for both (--)-adrenaline and (--)-noradrenaline; offset times were similar. 5. It is concluded that (--)-timolol has a higher affinity for the beta 2-adrenoceptor than for the beta 1-adrenoceptor in human atrium. This property may be beneficial clinically in protecting against the beta 2-adrenoceptor hypersensitivity induced by cardiac beta 1-adrenoceptor blockade, but also explain why severe asthma can occur after administration of very low intra-ocular doses of the drug.

Adrenergic beta-Agonists↗

PubMed1996

Modulation of cranial bone healing with a heparin-like dextran derivative.

Substituted dextran polymers have been shown to bind growth factors and protect them from enzymatic degradation. Using this information, other researchers have been able to use these substituted dextrans to enhance the healing of bone in an environment where bone would otherwise not regenerate. We used substituted dextran polymers to evaluate their ability to accelerate the healing of cranial bone in a rabbit model. We were able to document a more rapid rate of healing and demonstrate micrographic evidence to support that conclusion. Possible mechanisms are postulated.

Analysis of Variance↗

PubMed1996

Gastrointestinal absorption of insulinlike growth factor-I in neonatal pigs.

To determine if milk-borne insulinlike growth factor-I (IGF-I) is absorbed in neonatal piglets, recombinant human IGF-I was iodinated and then administered via an oral-gastric tube to newborn and 3-day-old piglets together with fluorescent isothiocyanate dextran (FITC-D70s, a macromolecular marker for assessment of gut closure). Results showed that total radioactivity and trichloroacetic acid (TCA)-precipitable radioactivity rose significantly in the plasma of both newborn and 3-day-old piglets 1 hour after oral-gastric administration of 125I-IGF-I, although the magnitude of increase was greater in newborns than in 3-day-old piglets. In contrast, significant absorption of FITC-D70s was observed only in newborn piglets but not in 3-day-old piglets. Chromatographic analysis revealed that 125I-IGF-I represented up to 20% of total plasma radioactivity in the newborns and up to 10% in the 3-day-old piglets. The 125I-IGF-I found in the plasma was mostly bound to IGF-binding proteins. These results indicate that milk-borne IGF-I can be absorbed in neonatal piglets and the absorption is independent of gut closure.

Animals↗

PubMed1996

Effects of angiotensin II on electrolyte transport in the early and late distal tubule in rat kidney.

We have demonstrated in previous studies that luminal administration of low doses of angiotensin II (ANG II) stimulate and high doses of ANG II inhibit fluid and HCO3- transport in proximal tubules of rat kidney. However, the role of ANG II on Na+ and HCO3- transport in the distal nephron has not yet been fully elucidated. The superficial early and late distal tubules (DT) of the nephron segments correspond to the distal convoluted tubule and initial collecting tubule. Accordingly, we investigated the effects of ANG II on Na+, HCO3-, and K+ transport in the early and late DT by separate perfusion of these tubule segments in vivo. [3H]inulin, Na+, K+, and total CO2 concentrations were measured in the perfusate and collected fluid, and transport of sodium (JNa), bicarbonate (JHCO3), potassium (JK), and fluid (JV) were analyzed as an index of the hormone effect. Intravenous infusion of the ANG II receptor antagonist [Sar1,Ile8]ANG II (1 microgram.kg-1.min-1) decreased JV, JNa, and JHCO3 in the early DT and decreased Jv and JNa in the late DT. Addition of ANG II (10(-11) M) to the tubular perfusate significantly increased the Jv, JNa, and JHCO3 in the early DT. Similar studies in late DT demonstrated an increase in Jv and JNa, decrease in JK, but no effect on JHCO3. The effects of ANG II on fluid and ion transport were abolished by the luminal application of amiloride (10(-3) M) and of the angiotensin-receptor blocker [Sar1,Ile8]ANG II (10(-6) M). These results suggest that ANG II stimulates Na+/H+ exchange in the early DT (distal convoluted tubule) and amiloride-sensitive Na+ transport (Na+ channels) in the late DT (initial collecting tubule) of cortical nephrons.

Angiotensin II↗

PubMed1996

Mechanisms of stimulation of proximal tubule chloride transport by formate and oxalate.

We have previously demonstrated that formate and oxalate stimulate volume absorption in the rat proximal tubule, consistent with Cl-/formate and Cl-/oxalate exchange process across the apical membrane. To sustain Cl- absorption by these processes requires mechanisms for recycling formate and oxalate from lumen to cell. The aims of the present study were to characterize these mechanisms of formate and oxalate recycling. Proximal tubules and peritubular capillaries were simultaneously microperfused in the rat kidney in situ. Serum formate concentration was determined to be 56.5 +/- 7.7 microM. Addition of 5, 50, and 500 microM formate to both luminal and capillary perfusates significantly increased net Cl- absorption (Jcl) by 26, 26, and 46%, respectively. Jcl was stimulated 38% by 1 microM oxalate added to the perfusates. Removal of sulfate completely prevented the stimulation of Jcl by 1 microM oxalate but had no effect on the stimulation of Jcl by formate. Luminal addition of the Na+/H+ exchange inhibitor ethylisopropylamiloride completely blocked the stimulation of Jcl by 50 microM formate but had no effect on stimulation by oxalate. We conclude that physiological concentrations of formate and oxalate markedly stimulate Cl- and fluid absorption in the rat proximal convoluted tubule. Whereas formate recycling most likely involves Na+/H+ exchange in parallel with H(+)-coupled formate entry, oxalate recycling involves sodium-sulfate cotransport in parallel with sulfate/oxalate exchange.

Amiloride↗

PubMed1996

Effects of colostrum feeding on intestinal development in newborn pigs.

To investigate what factors lead to rapid postnatal tissue growth and functional maturation in the newborn intestine, we compared intestinal tissue mass and digestive enzyme activities between newborn unsuckled piglets and piglets bottle fed for 3 days with either 5% lactose solution, intact porcine colostrum or trypsinized porcine colostrum. Bottle feeding of colostrum or trypsinized colostrum, but not lactose solution, led to a significant increase in the weight and length of the small intestine (p < 0.01) and a significant increase in the mucosal weight of the large intestine (p < 0.05). The mucosal protein content in the small and large intestine and the mucosal DNA content in the large intestine increased significantly following 3 days of bottle feeding of porcine colostrum or trypsinized colostrum. The total mucosal DNA contents in the small intestine of piglets fed colostrum or trypsinized colostrum were, respectively, 39 and 64% greater than that in the newborn unsuckled piglets. Intestinal digestive enzymes showed a differential response to the dietary treatment. Bottle feeding of intact porcine colostrum, but not trypsinized porcine colostrum led to a significant increase in lactase- and alkaline phosphatase-specific activities in the small intestine, while bottle feeding of lactose solution led to a significant decrease in the specific activity of lactase. In contrast, the specific activity of maltase in the small intestine increased significantly with age irrespective of dietary treatment. These results indicate that genetic and dietary factors are involved in regulating postnatal intestinal development, and porcine colostrum contains a trypsin-labile component which can increase lactase and alkaline phosphatase activities in the newborn intestine.

Alkaline Phosphatase↗

PubMed1996

The interaction of pulmonary ventilation and the right-left shunt on arterial oxygen levels.

In adult mammals, arterial blood gases closely reflect lung gas composition, and arterial blood gases can, therefore, be effectively regulated through changes in ventilation. This is not the case among most ectothermic vertebrates, where the systemic and pulmonary circulations are not completely separated, resulting in central vascular shunts. In the presence of a right-to-left shunt (R-L shunt), the O2 levels (PO2 and haemoglobin O2-saturation) of systemic arterial blood are depressed relative to those of the blood returning from the lungs. Arterial blood gas composition is, accordingly, not determined only by ventilation, but also by the magnitude of admixture as well as the blood gas composition of systemic venous blood. Changes in the central shunt patterns, therefore, represent an alternative mechanism by which to control arterial blood gas levels. The primary aim of this report is to evaluate the relative importance of the R-L shunt and ventilation in determining arterial blood gas levels. Using standard equations for gas exchange and the two-compartment model, we predicted arterial O2 levels at physiologically relevant levels of ventilation, R-L shunt and blood flows. The analyses show that the effects of changing ventilation and the size of the R-L shunt on arterial O2 levels vary with parameters such as the rate of O2 uptake, the blood O2-carrying capacity and the level of hypoxia. The relative importance of ventilation and the R-L shunt in determining arterial PO2 values is largely explained by the sigmoidal shape of the O2 dissociation curve. Thus, if lung PO2 is high relative to blood O2 affinity, a large change in ventilation may have little effect on pulmonary venous O2 content, although PO2 may have changed considerably. If an R-L shunt is taking place, this, in turn, implies that arterial O2 content is affected only marginally, with a correspondingly small effect on PO2. These predictions are discussed in the light of the limited existing experimental data on cardiac shunts in lower vertebrates; we propose that, in future experiments, the measurement of both ventilatory and cardiovascular parameters must be combined if we aim to understand the regulation of arterial blood gas levels in lower vertebrates.

Animals↗

PubMed1996

The effect of altering pulmonary blood flow on pulmonary gas exchange in the turtle Trachemys (Pseudemys) scripta.

In resting reptiles, the PO2 of pulmonary venous return (PLAO2; left atrial blood) may be 20 mmHg (1 mmHg = 0.1333 kPa) lower than the PO2 of gas in the lung. This level of PO2 is considerably higher than that observed in resting mammals and birds and results from ventilation-perfusion (V/Q) heterogeneity, pulmonary diffusion limitation and intrapulmonary shunting. However, the relative contribution of each of these factors is unknown. Many reptiles, particularly chelonians, exhibit an intermittent ventilation pattern where pulmonary blood flow (QL) increases during the ventilatory periods and, therefore, we hypothesized that V/Q matching would improve with increasing QL. We applied the multiple inert gas elimination technique in anaesthetized turtles at 22 degrees C. Turtles were continuously ventilated at a rate of 140 ml kg-1 min-1, equivalent to the rate of ventilation within a ventilatory period. Trace amounts of six inert gases were infused through the jugular vein. Blood samples from the pulmonary artery and the left atrium and mixed expired gases were collected for analysis. QL was reduced by a factor of six (low flow) using a vascular occluder placed around the common pulmonary artery or increased by a factor of two (high flow) through bolus injection of adrenaline. V/Q heterogeneity was significantly reduced with increasing pulmonary blood flow (P < 0.05). Consistent with these changes, the effective lung-pulmonary artery PO2 difference (PLO2-PLAO2) was reduced (P < 0.05) from 58 +/- 16 mmHg to 29 +/- 5 mmHg (means +/- S.E.M.) and PLAO2 increased significantly (P < 0.05) from 88 +/- 17 mmHg (low flow) to 120 +/- 14 mmHg (high flow). There was evidence of pulmonary diffusion limitation under all conditions, which was unchanged with increasing blood flow. These findings suggest that increased pulmonary blood flow during a ventilatory period results in both temporal and spatial matching of ventilation and perfusion, without altering pulmonary diffusion limitation.

Animals↗