摘要:

Studies were conducted in extracorporeally perfused, intact, working pig hearts to determine whether, in heart muscle, trace-labeled deoxyglucose serves as an accurate marker of glycolytic flux in reperfusion after exposures to mild to moderate regional ischemia. In the main study, two groups of hearts were compared, as distinguished by levels of glucose in the whole-blood perfusate (euglycemic hearts [group I], blood glucose of 7.4±0.2 amol/ml, n=7; hyperglycemic hearts [group II], blood glucose of 12.9±0.5 μmol/ml, n=8). Both groups were subjected to a 60% reduction in anterior descending coronary flow for 30 minutes followed by reperfusion for 40 minutes. Modest and comparable regional mechanical stunning during reflow was noted in both groups. Glucose utilization, as estimated from the release of3H2O from the steady-state infusion of [5-3H] glucose during aerobic perfusion, was modest but during reperfusion was noted to increase significantly above aerobic values in each of the two groups, with a doubling of rates in group II hearts compared with group I hearts (p<0.041 orp<0.090). Net lactate extraction was comparable in reflow in both groups, suggesting in this specific instance a preferential enhancement of glucose oxidation in hyperglycemic group II hearts. Shifts in accumulation of tissue radioactivity of [U-14C]2-deoxyglucose in reperfused myocardium were not able to track these trends. The variability of14C-labeled radioactivity among animals was marked and essentially masked any ability to discern trends in glycolysis as described by tritiated glucose between the aerobic and reperfusion intervals. When the data were arrayed by linear regression analysis, the slopes derived from14C-labeled deoxyglucose were either discordant or insensitive to those described by3H-labeled glucose. Tissue glycogen levels were slow to recover in early reflow and at end reperfusion were still significantly depressed from aerobic levels. The present data indicate that coronary reperfusion and hyperglycemia have influence in determining glycolytic flux in myocardium. Labeled deoxyglucose, considered solely as a marker of exogenous glucose utilization, appears to be an insensitive agent in describing these events at conditions of relatively low glucose flux.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Mechanical interdependence between intrapulmonary structures and parenchyma has not been studied previously in immature postnatal lungs. To study these interactions, lung elastic moduli were measured by pressure-volume and punch indentation studies in lobes excised from 3-day-old (n=6), 1-month-old (n=6), and 3-month-old (n=7) piglets. After extra-alveolar arteries were filled with a radiopaque fluid silicone compound, transpulmonary pressure and arterial pressure were varied independently as the lobar vein was occluded. Arterial diameters and lengths were measured from radiographs. Behavior of 3-month-old lungs was consistent with previous studies of adult lungs, but results were unique in 3-day-old lungs. That is, during stepwise deflation of the immature lungs 1) intravascular pressures fell when arteries were occluded experimentally, 2) arteries increased their diameters when kept at a constant intravascular pressure, and 3) arterial lengths decreased by <3%. Behavior of 1-month-old lungs was intermediate. A previous continuum mechanics analysis of pressure-diameter behavior was modified to account for compression by alveolar pressure as vascular diameters increase. It was concluded that 1) radial and axial dimensions of extra-alveolar arteries are virtually independent of parenchymal expansion in newborn piglet lungs and 2) periarterial interstitial pressures increase as these lungs are inflated. Our interpretation of these findings is that a mechanical association of the arteries to the parenchyma occurs gradually with postnatal maturation.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We wish to understand the process of smooth muscle cell (SMC) proliferation and maturation during late fetal development and have examined some of the molecular changes associated with blood vessel maturation in late gestational and early neonatal life. By differential screening of a fetal aortic smooth muscle cDNA library, we identified a gene (F-31) that was developmentally regulated in aortic smooth muscle. The F-31 gene encodes a 2.3-kb RNA that was highly expressed in fetal aortic smooth muscle (25-day gestation), was lower in newborns, and was undetectable in the aortic smooth muscle of 4-week-old animals. F-31 was also highly expressed in fetal muscle, esophagus, heart, liver, lung, and placenta; its expression was lower in skin, kidney, and brain. By contrast, the expression of F-31 was low or undetectable in the corresponding tissue of adult animals. DNA sequence analysis of cDNAs encoding F-31 and data base comparison revealed a 73% homology with a previously identified, developmentally regulated gene called H19. We also found that insulin-like growth factor II (IGF-II) expression was developmentally regulated in smooth muscle. However, unlike F-31, expression of IGF-II was undetectable in the aortic smooth muscle of newborn animals. Analysis of the mRNA level of several genes that encode cytoskeletal proteins in neonatal, newborn, and adult smooth muscle indicates that total actin mRNA level, α-smooth muscle actin, and α-tropomyosin mRNA levels were similar between the late gestational period and 4 weeks after birth. By contrast, the mRNA levels of smooth myosin heavy chain increased sixfold. Expression of both F-31 and IGF-II was maintained in cultured cells obtained from fetal smooth muscle but was not detectable in adult SMCs. Interestingly, their expression was shut off in high-density growth-arrested cells. However, growth-arrested cells treated with 0.5% serum, 10−6M insulin, and 5 μg/ml transferrin reexpressed F-31 but not IGF-II. Morphological comparison of fetal and adult SMCs in culture revealed that although proliferating fetal and adult SMCs were indistinguishable, in high density cultures, fetal cells fail to form the “hill and valley” morphology characteristic of adult SMCs.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

By using pharmacological tools, the biological actions of adenosine (ADO) were manipulated in rat intestine that had been rendered ischemic for 5 or 15 minutes and reperfused for 1 or 24 hours. With 100 μM ADO topically administered for 30 minutes after ischemia and then washed out, intestinal arteriolar blood flow (BF) and tissue ATP were restored to preocclusion levels, and histological damage was minimal after 1 hour of reperfusion. For comparison, with vehicle treatment after ischemia, BF was reduced by 50%, tissue ATP was reduced by 50%, myeloperoxidase levels in the intestine and lung were increased at least twofold, and mucosal villi were shortened and thickened after 1 hour of reperfusion. Furthermore, with vehicle treatment, both baseline BF and reactivity to endothelium-dependent (acetylcholine) and endothelium-independent (2-chloroadenosine) vasodilators were significantly depressed after 24 hours of reperfusion. In contrast, with ADO, baseline BF remained near normal, and vascular reactivity to 2-chloroadenosine and acetylcholine was preserved after 24 hours. The salutary effect of ADO on BF was reduced by simultaneous application of the antagonist 8-phenyltheophylline or the cellular uptake inhibitor dipyridamole. The nonmetabolized agonist 2-chloroadenosine, the purine precursor aminoimidazole carboxamide riboside, or dipyridamole alone all had favorable effects relative to the vehicle, but all were less potent than ADO. The conclusions are as follows: 1) Endogenous ADO modulates the inflammatory response evoked by intestinal reperfusion because aminoimidazole carboxamide riboside or dipyridamole, which increases its availability, generally had favorable effects, whereas 8-phenyltheophylline tended to have opposite effects. 2) Exogenous ADO arrests most of the inflammatory changes associated with reperfusion by mechanisms that include both extracellular (e.g., receptor-mediated vasodilation and granulocyte inhibition) and intracellular (e.g., restoration of ATP) actions. 3) The effectiveness of ADO-related compounds even when administered after ischemia attests to the practicality of salvaging ischemic bowel, at least in some conditions.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Recently a putative K+channel with homology to theShakerfamily of potassium channels has been cloned from human ventricular myocardium. However, proof that the cDNA encodes a K+channel requires appropriate translation and expression of a functional ion-selective channel. Therefore, expression of this putative human K+channel DNA was attempted by cytoplasmic injections of in vitro transcribed cRNA intoXenopus laevisoocytes and screening by two-electrode voltage-clamp methods. This resulted in expression of voltage-gated channels that rapidly inactivated (time constant of inactivation, 47.6±3.6 msec; 0 mV; n=10) and were at least 50 times more selective for K+than Na+(Na+/K+permeability ratio of 0.02). The channels showed voltage-dependent activation (half-maximal voltage, −34±0.7 mV; n=5), and 50% of the channels were inactivated within 2 seconds when the membrane potential was clamped near −60 mV (half-maximal voltage, −62±7 mV; n=10). The expressed protein resulted in a K+current that had many properties similar to the 4-aminopyridine-sensitive calcium-insensitive component of the cardiac transient outward current that is observed in native cardiac myocytes and thus may serve as one molecular substrate for this current.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

In the heart, the rapid propagation and synchronization of action potentials necessary for a normal heart rhythm and an effective cardiac output are mediated by specialized ionic channels that link adjacent cells and are known collectively as gap junctions. Cardiac gap junctions are gated by various physiological and pharmacological agents, but the role of voltage in their gating is unclear. Whereas embryonic or neonatal ventricular cells have voltage-gated gap junctions, adult cells are reported to have only voltage-independent gap junctions. We studied the voltage dependence of adult rat atrial gap junctions by individually voltage clamping each cell of a connected cell pair and controlling the transjunctional voltage (Vj), measuring transjunctional current (Ij), and calculating junctional conductance (gj). Two distinct populations of cell pairs were observed: highly coupled pairs with the peak gjs ranging from 3.4 to 40 nS and weakly coupled pairs with the peak gjs ranging from 0.3 to 2.0 nS. gjwas dependent on Vj, and Ijdecayed exponentially, with the time constants being voltage dependent. Voltage dependence was most apparent when cells were poorly coupled. The gjdid not decrease to zero. The normalized conductance-Vjplot was fit with a two-state Boltzmann model as a first approximation, resulting in a half-inactivation potential and gating charge of 42.5 mV and 1.14 eV, respectively, for the weakly coupled cell pairs. For highly coupled cell pairs, the half-inactivation potential shifted to 53.3 mV. Single gap junctional channels had a gj of 36.2±7.6 pS (range, 27–49 pS), which was Vjindependent. The junctional current as obtained by ensemble average of single-channel recordings has a time constant of current decay comparable to that observed for Ijat similar Vj. These findings suggest that the voltage-dependent kinetics of Ijresult from the all-or-none gating of a population of 36-pS conductance channels. It is interesting to speculate that voltage gating of gap junction channels provides rapid fine control of cell-to-cell interaction, particularly in poorly coupled cells, and importantly determines both cardiac excitability and impulse propagation.

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1992

数据来源: OVID