摘要:

AbstractRecently, Spach et al (Circ Res. 1998;83:1144–1164) measured the transmembrane action potential 150 to 200 &mgr;m below the tissue surface during longitudinal and transverse propagation. They found that “during longitudinal propagation there was initial slowing of Vm[action potential] foot that resulted in deviations from a simple exponential… ” (p 1144). They attributed this behavior to the effects of capillaries on propagation. The purpose of this commentary is to show that the perfusing bath plays an important role in determining the time course of the action potential foot, even when the transmembrane potential is measured 150 &mgr;m below the tissue surface. Using numerical simulations based on the bidomain model, we find that the action potential foot for transverse propagation is nearly exponential (&tgr;foot=314 &mgr;s). For longitudinal propagation, the action potential foot is not exponential because of an initial slowing (best-fit &tgr;foot=483 &mgr;s). We conclude that the perfusing bath must be taken into account when interpreting data showing differences in the shape of the action potential foot with propagation direction, even if the transmembrane potential is measured 150 &mgr;m below the tissue surface. The full text of this article is available at http://www.circresaha.org.

ISSN:0009-7330    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

AbstractElectrical waveforms measured during propagation at microscopic level are considerably affected by normal variations in cardiac microstructure as well as by the superfusing fluid. On the basis of evidence we present in this article, we argue that the anisotropic waveform variations discussed here are explained primarily by the associated variations in different microstructural components of myocardial architecture rather than by the effects of the perfusing bath. The results suggest that different components of myocardial architecture have preferential effects on &OV0312;maxand on the shape of the foot of the transmembrane action potential (Vmfoot). Resistive discontinuities primarily affect &OV0312;max, and an additional capacitive component in the local circuit due to the capillaries in interstitial space primarily affects Vmfoot. Resistive discontinuities also have an important influence on cardiac conduction. These discontinuities include spatial variations in the size of interstitial space (interstitial resistive discontinuities) and the role of cellular scaling (effects of cell size) when changes occur in the cellular and multicellular distribution of gap junctions during remodeling of normal mature myocardium to proarrhythmic structural substrates. The full text of this article is available at http://www.circresaha.org.

ISSN:0009-7330    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

AbstractVascular endothelial growth factor-B (VEGF-B) is closely related to VEGF-A, an effector of blood vessel growth during development and disease and a strong candidate for angiogenic therapies. To further study the in vivo function of VEGF-B, we have generatedVegfbknockout mice (Vegfb−/−). UnlikeVegfaknockout mice, which die during embryogenesis,Vegfb−/−mice are healthy and fertile. Despite appearing overtly normal,Vegfb−/−hearts are reduced in size and display vascular dysfunction after coronary occlusion and impaired recovery from experimentally induced myocardial ischemia. These findings reveal a role for VEGF-B in the development or function of coronary vasculature and suggest potential clinical use in therapeutic angiogenesis. The full text of this article is available at http://www.circresaha.org.

ISSN:0009-7330    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

AbstractConditions associated with impaired nitric oxide (NO) activity and accelerated atherosclerosis have been shown to be associated with a reduced bioavailability of tetrahydrobiopterin (BH4). We therefore hypothesized that BH4 supplementation may improve endothelial dysfunction of chronic smokers. Forearm blood flow (FBF) responses to the endothelium-dependent vasodilators acetylcholine (ACh; 0.75, 1.5, and 3.0 &mgr;g/100 mL tissue/min) or serotonin (5-HT; 0.7, 2.1, and 6.3 ng/100 mL tissue/min), to the inhibitor of endothelial nitric oxide synthase (NOS)NG-monomethyl-L-arginine (L-NMMA; 2, 4, and 8 &mgr;mol/min), and to the endothelium-independent vasodilator sodium nitroprusside (SNP; 0.1, 0.3, and 1.0 &mgr;g/100 mL tissue/min) were measured by venous occlusion plethysmography in controls and chronic smokers. Drugs were infused into the brachial artery, and FBF was measured before and during concomitant intra-arterial infusion of BH4, tetrahydroneopterin (NH4; another reduced pteridine), or the antioxidant vitamin C (6 and 18 mg/min). In control subjects, BH4 had no effect on FBF in response to ACh, 5-HT, and SNP. In contrast, in chronic smokers, the attenuated FBF responses to ACh and 5-HT were markedly improved by concomitant administration of BH4, whereas the vasodilator responses to SNP were not affected. L-NMMA-induced vasoconstriction was significantly reduced in smokers compared with controls, suggesting impaired basal NO bioactivity. BH4 improved L-NMMA responses in smokers while having no effect on L-NMMA responses in controls. Pretreatment with vitamin C abolished BH4 effects on ACh-dependent vasodilation. In vitro, NH4 scavenged superoxide created by the xanthine/xanthine oxidase reaction equipotent like BH4 but failed to modify ACh-induced changes in FBF in chronic smokers in vivo. These data support the concept that in addition to the free radical burden of cigarette smoke, a dysfunctional NOS III due to BH4 depletion may contribute at least in part to endothelial dysfunction in chronic smokers. The full text of this article is available at http://www.circresaha.org.

ISSN:0009-7330    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

AbstractGap junctions formed between transfected cells expressing connexin (Cx) 40 and Cx43 (Cx43-RIN, Cx40-HeLa, and Cx43-HeLa) revealed a relationship,gj=f(Vj), at steady state, that is typified by a nonsymmetrical behavior similar to that previously reported for other heterotypic channels (gap junction conductance [gj]; transjunctional voltage [Vj]). The unitary conductance of the channels was sensitive to the polarity ofVj. A main state conductance of 61 pS was found when the Cx43 cell was stepped positively or the Cx40 cell negatively (Vj=70 mV); the reverse polarities yielded a conductance of 100 pS. These heterotypic channels were permeable to carboxyfluorescein. In addition, two other heterotypic forms are illustrated to demonstrate that endogenous Cx45 expression cannot explain the results. The demonstration of heterotypic Cx40–Cx43 channels may have implications for the propagation of the electrical impulse in heart. For example, they may contribute to the slowing of the impulse propagation through the junctions between Purkinje fibers and ventricular muscle. The full text of this article is available at http://www.circresaha.org.

ISSN:0009-7330    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:2000

数据来源: OVID