摘要:

Background—We studied the role of the central nervous system, neural feedback from contracting skeletal muscles, and sympathetic activity to the heart in the control of heart rate and blood pressure during 2 levels of dynamic exercise.Methods and Results—Spinal cord–injured individuals (SCI) with (paraplegia, n=4) or without (tetraplegia, n=6) sympathetic innervation to the heart performed electrically induced exercise. Responses were compared with those established by able-bodied individuals (control, n=6) performing voluntary exercise at a similar pulmonary oxygen uptake. In all subjects, cardiac output and leg blood flow increased, but in SCI they reached a maximal value. The increase in cardiac output was mainly elicited by an increase in stroke volume in individuals with tetraplegia, whereas in individuals with paraplegia it was by heart rate. The increase in SCI was slow compared with that in controls. During exercise, blood pressure was stable in controls, whereas it decreased over time in SCI and especially in individuals with tetraplegia.Conclusions—The autonomic nervous system provides for acceleration of the heart at the onset of exercise, but a slow increase in heart rate is established even without central command, neural feedback from working muscles, or autonomic influence on the heart. Yet an intact autonomic nervous system is a prerequisite for a large rise in cardiac output and in turn leg blood flow during exercise. Thus, when the sympathetic nervous system is injured at a level where it influences the heart, vasodilatation in working muscles challenges blood pressure.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Transplantation of endothelial progenitor cells (EPCs) improves vascularization and left ventricular function after experimental myocardial ischemia. However, tissue distribution of transplanted EPCs has not yet been monitored in living animals. Therefore, we tested whether radioactive labeling allows us to detect injected EPCs.Methods and Results—Human EPCs were isolated from peripheral blood, characterized by expression of endothelial marker proteins, and radioactively labeled with [111In]indium oxine. EPCs (106) were injected in athymic nude rats 24 hours after myocardial infarction (n=8) or sham operation (n=8). Scintigraphic images were acquired after 1, 24, 48, and 96 hours after EPC injection. Animals were then killed, and specific radioactivity was measured in different tissues. At 24 to 96 hours after intravenous injection of EPCs, ≈70% of the radioactivity was localized in the spleen and liver, with only ≈1% of the radioactivity identified in the heart of sham-operated animals. After myocardial infarction, the heart-to-muscle radioactivity ratio increased significantly, from 1.02±0.19 in sham-operated animals to 2.03±0.37 after intravenous administration of EPCs. Injection of EPCs into the left ventricular cavity increased this ratio profoundly, from 2.69±1.54 in sham-operated animals to 4.70±1.55 (P<0.05) in rats with myocardial infarction. Immunostaining of cryosections from infarcted hearts confirmed that EPCs homed predominantly to the infarct border zone.Conclusions—Although only a small proportion of radiolabeled EPCs are detected in nonischemic myocardium, myocardial infarction increases homing of transplanted EPCs in vivo profoundly. Radiolabeling might eventually provide an useful tool for monitoring the fate of transplanted progenitor cells and for clinical cell therapy.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—A T-cell–mediated inflammatory response occurs in the microcirculation during acute hypercholesterolemia. The objective of this study was to define the contribution of T-lymphocyte–derived interferon-&ggr; (IFN-&ggr;) to the leukocyte–endothelial cell adhesion induced by hypercholesterolemia.Methods and Results—Intravital videomicroscopy was used to quantify the adhesion and emigration of leukocytes and oxidant stress (dihydrorhodamine [DHR] oxidation) in cremasteric venules. Wild-type (WT), IFN-&ggr;−/−, and severe combined immunodeficiency (SCID) mice were placed on either a normal (ND) or high-cholesterol (HC) diet for 2 weeks. WT-HC mice exhibited exaggerated adhesion and emigration of leukocytes and enhanced DHR oxidation compared with WT-ND. The exaggerated adhesion responses and increased DHR oxidation were not seen in IFN-&ggr;−/−–HC mice. SCID-HC mice also exhibited attenuated inflammatory responses compared with WT-HC. Reconstitution of either SCID-HC or IFN-&ggr;−/−–HC mice with WT-HC splenocytes restored the inflammatory responses, whereas reconstitution of SCID-HC with IFN-&ggr;−/−–HC splenocytes did not. The HC-induced oxidant stress was restored in IFN-&ggr;−/−–HC mice reconstituted with WT-HC splenocytes.Conclusions—These findings implicate IFN-&ggr; as a cause of the inflammatory phenotype that is assumed by the microvasculature of hypercholesterolemic mice and suggest that T lymphocytes are a major source of this proinflammatory cytokine.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—In the heart, striking functional differences exist after stimulation of the &bgr;1- and &bgr;2-adrenergic receptor (AR) subtypes. These may be linked to differences in metabolic response during &bgr;1- and &bgr;2-AR stimulation.Methods and Results—The relation between work and metabolism was examined during selective &bgr;1- and &bgr;2-AR stimulation (&bgr;1and &bgr;2groups, respectively) in the isolated perfused rat heart. Measurements were made of rate-pressure product (RPP=LV developed pressure × heart rate), phosphorus-containing metabolites, and pH by31P nuclear magnetic resonance spectroscopy and of O2consumption by fiber-optic oximetry. Experiments were performed under high constant flow (HCF) and under flow-limiting conditions (constant pressure, CP). Despite substantially greater RPP increases relative to baseline during &bgr;1-AR (HCF, 475%; CP, 150%) than &bgr;2-AR (HCF, 90%; CP, 72%) stimulation, the relative decrease in the intracellular energy charge relative to baseline was similar for the &bgr;1(HCF, 49%; CP, 64%) and &bgr;2(HCF, 59%; CP, 55%) groups. For each group, an increase in oxygen consumption (M&OV0312;o2) occurred commensurate with workload during HCF (&bgr;1, 141%; &bgr;2, 30%). During CP, however, the M&OV0312;o2increase was similar (&bgr;1, 39%; &bgr;2, 34%), despite the large RPP difference between the groups. During both protocols, there was greater acidosis during &bgr;1-AR than during &bgr;2-AR stimulation. Thus, at a given workload, intracellular energy charge decreased, and M&OV0312;o2(CP) increased to a greater extent during &bgr;2than &bgr;1-AR stimulation.Conclusions—The bioenergetic differences are consistent with access to an additional substrate pool during &bgr;1-AR stimulation. This may occur via increased glycogenolysis during &bgr;1-AR stimulation, facilitating increased energy production by oxidative phosphorylation, and under flow-limiting conditions, anaerobic glycolysis.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—Late total occlusion after vascular brachytherapy (VBT) continues to be a serious complication. Delayed reendothelialization was suggested as a pivotal cause, but the time course for complete healing is unknown.Methods and Results—Seventy-two rabbit iliac arteries underwent stent implantation and were treated with &ggr;-radiation using192Ir. The prescribed doses were 0 Gy (controls, n=24 arteries), 15 Gy (n=24), or 30 Gy (n=24) at 2 mm. Animals were killed at 1 month (n=24), 3 months (n=24), or 6 months (n=24) and were analyzed for histomorphometry or scanning electron microscopy. Intimal area was reduced after VBT at 3 months with 15 and 30 Gy (0.66±0.07 and 0.66±0.04 mm2, respectively) compared with controls (1.01±0.11 mm2,P<0.05) and at 6 months with 30 Gy (0.75±0.09 versus 1.28±0.26 mm2in controls,P<0.01). Intimal area was similar at 6 months between 15 Gy and controls. At 1 month, 92±4% of the control stented segment was covered with endothelial cells, whereas only 37±4% and 37±8% was covered in the 15- and 30-Gy arteries, respectively. Similarly, at 3 and 6 months, there was a difference in the extent of reendothelialized areas (at 3 months, 95±2%, 32±12%, and 29±13%; and at 6 months, 98±2%, 40±8%, and 35±12% in control, 15-Gy, and 30-Gy arteries, respectively). Excess platelets and leukocytes were seen in irradiated arteries without complete coverage of endothelium.Conclusions—Reendothelialization after VBT is not completed at 6 months after VBT. Special care with prolonged antiplatelet therapy should be considered beyond that time point.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

摘要:

Background—The renal vasoconstrictor response to renal nerve stimulation is greater in congestive heart failure (CHF) rats than in control rats. This study tested the hypothesis that the enhanced renal vasoconstrictor response to renal nerve stimulation in CHF is a result of an impairment in the low-pass filter function of the renal vasculature.Methods and Results—In response to conventional graded-frequency renal nerve stimulation, the reductions in renal blood flow at each stimulation frequency were greater in CHF rats than control rats. A pseudorandom binary sequence pattern of renal nerve stimulation was used to examine the frequency response of the renal vasculature. Although this did not affect the renal blood flow power spectrum in control rats, there was a 10-fold increase in renal blood flow power over the frequency range of 0.01 to 1.0 Hz in CHF rats. On analysis of transfer function gain, attenuation of the renal nerve stimulation input signal was similar in control and CHF rats over the frequency range of 0.001 to 0.1 Hz. However, over the frequency range of 0.1 to 1.0 Hz, although there was progressive attenuation of the input signal (−30 to −70 dB) in control rats, CHF rats exhibited a flat gain response (−20 dB) without progressive attenuation.Conclusions—The enhanced renal vasoconstrictor response to renal nerve stimulation in CHF rats is caused by an alteration in the low-pass filter function of the renal vasculature, resulting in a greater transfer of input signals into renal blood flow in the 0.1 to 1.0 Hz range.

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID

ISSN:0009-7322    

出版商:OVID    

年代:2003

数据来源: OVID