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Hemodynamic Studies (hemodynamic + studies)
Selected AbstractsReversal of portal hypertension and hyperdynamic splanchnic circulation by combined vascular endothelial growth factor and platelet-derived growth factor blockade in rats,HEPATOLOGY, Issue 4 2007Mercedes Fernandez Vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) pathways are crucial to angiogenesis, a process that contributes significantly to the pathogenesis of portal hypertension. This study determined the effects of inhibition of VEGF and/or PDGF signaling on hyperdynamic splanchnic circulation and portosystemic collateralization in rats with completely established portal hypertension, thus mimicking the situation in patients. Portal vein,ligated rats were treated with rapamycin (VEGF signaling inhibitor), Gleevec (PDGF signaling inhibitor), or both simultaneously when portal hypertension was already fully developed. Hemodynamic studies were performed by transit-time flowmetry. The extent of portosystemic collaterals was measured by radioactive microspheres. The expression of angiogenesis mediators was determined by Western blotting and immunohistochemistry. Combined inhibition of VEGF and PDGF signaling significantly reduced splanchnic neovascularization (i.e., CD31 and VEGFR-2 expression) and pericyte coverage of neovessels (that is, ,-smooth muscle actin and PDGFR-, expression) and translated into hemodynamic effects as marked as a 40% decrease in portal pressure, a 30% decrease in superior mesenteric artery blood flow, and a 63% increase in superior mesenteric artery resistance, yielding a significant reversal of the hemodynamic changes provoked by portal hypertension in rats. Portosystemic collateralization was reduced as well. Conclusions: Our results provide new insights into how angiogenesis regulates portal hypertension by demonstrating that the maintenance of increased portal pressure, hyperkinetic circulation, splanchnic neovascularization, and portosystemic collateralization is regulated by VEGF and PDGF in portal hypertensive rats. Importantly, these findings also suggest that an extended antiangiogenic strategy (that is, targeting VEGF/endothelium and PDGF/pericytes) may be a novel approach to the treatment of portal hypertension. (HEPATOLOGY 2007.) [source] Endothelial nitric oxide synthase is not essential for the development of fibrosis and portal hypertension in bile duct ligated miceLIVER INTERNATIONAL, Issue 5 2005Abraham Koshy Abstract: Background/Aims: It is postulated that nitric oxide (NO) is responsible for the hyperdynamic circulation of portal hypertension. Therefore, we investigated induction of fibrosis and hyperdynamic circulation in endothelial NO synthase knock-out (KO) mice. Methods: Fibrosis was induced by bile duct ligation. Hemodynamic studies were performed after portal vein ligation. All studies were performed in wild-type (WT) and KO mice. Results: Three to 4 weeks after bile duct ligation (BDL), both WT and KO groups had similar degrees of portal hypertension, 12 (9,14) and 11(8,15) mmHg, median (range), and liver function. Fibrosis increased from 0.0% in sham operated to 1.0 and 1.1% in WT and KO mice, respectively. Cardiac output was similar after portal vein ligation (20 and 17 ml/min in WT and KO mice, respectively). There was no difference in liver of mRNA for endothelin 1, inducible NO synthase (iNOS) and hem-oxygenase 1 (HO1); proteins of iNOS, HO1 and HO2; nor in endothelin A and B (EtA and EtB) receptor density between WT and KO mice after BDL. Conclusions: These results suggest that endothelial NO synthase is neither essential for the development of fibrosis and portal hypertension in bile duct ligated mice, nor for the hyperdynamic circulation associated with portal hypertension in the portal vein ligated mice. [source] Influence of beta-2 adrenergic receptor gene polymorphism on the hemodynamic response to propranolol in patients with cirrhosis,HEPATOLOGY, Issue 1 2006Juan Turnes The beta-2-adrenergic receptor (,2- -AR) has several single-nucleotide polymorphisms. These influence the functional response to adrenergic stimulation; genotypes homozygous for Gly16-Glu27 or Gly16-Gln27 alleles (Gly16-Glu/Gln27 haplotypes) are associated with enhanced response, whereas genotypes homozygous for Arg16-Gln27 alleles (Arg16-Gln27) show a decreased response. We hypothesized that gene polymorphisms at the ,2 -AR may influence the hemodynamic response to propranolol in patients with cirrhosis. The ,2 -AR gene polymorphisms were determined by direct sequencing of the polymerase chain reaction (PCR) products in 48 patients with cirrhosis. All patients also had hepatic and systemic hemodynamic studies before and after propranolol administration. Prevalence of Gly16-Glu/Gln27 haplotypes was 29.1%, Arg16-Gln27 haplotype was 16.7%, and 54.2% were compound heterozygotes. Patients with cirrhosis with Gly16-Glu/Gln27 haplotypes had a greater decrease in heart rate, cardiac index, and hepatic blood flow after propranolol administration than those with Arg16-Gln27 haplotype. However, the HVPG response to propranolol was similar in both groups, whereas estimated hepatic sinusoidal resistance increased significantly in Gly16-Glu/Gln27 haplotypes but not in Arg16-Gln27 (+27.1 ± 17.8% vs -17.9 ± 13.9%, P = .042), suggesting that unopposed vasoconstrictive activity at the intrahepatic circulation hinders the fall in HVPG despite enhanced hemodynamic response to propranolol in Gly16-Glu/Gln27 haplotypes. In conclusion, ,2 -AR gene polymorphisms influence the response to beta-blockade. However, HVPG reduction cannot be predicted from polymorphism analysis. Patients with the Gly16-Glu/Gln27 haplotypes may benefit from the association of hepatic vasodilators to propranolol therapy. (HEPATOLOGY 2005;43:34,41.) [source] Impairment of Coronary Microvascular Function in Patients with Neurally Mediated SyncopePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 2p1 2003JAW-WEN CHEN CHEN, J.-W., et al.: Impairment of Coronary Microvascular Function in Patients with Neurally Mediated Syncope.Recent evidence suggests that myocardial ischemia may occur in patients with neurally mediated syncope and normal coronary angiograms. This study was conducted to evaluate if coronary microvascular function is impaired in such patients. Coronary hemodynamic studies and head-up tilt table tests (HUTs) were performed on 30 consecutive patients with normal coronary angiograms and recurrent syncope. Another ten subjects with atypical chest pain and no evidence of myocardial ischemia or syncope served as a control. Great cardiac vein flow (GCVF) and coronary sinus flow (CSF) were measured by the thermodilution method at baseline and after dipyridamole infusion (0.56 mg/kg IV for 4 minutes). Coronary flow reserve (CFR), derived from CSF and GCVF, was significantly lower in the 15 patients with positive HUT than in the other 15 patients with negative HUT (1.75 ± 0.48vs2.64 ± 0.8, P < 0.01and2.29 ± 0.45vs3.07 ± 0.63, P < 0.01, respectively). Ischemic-like ECG was noted during treadmill exercise test in 40% of the former and in 7% of the latter group(P = 0.01). There was no significant difference in CFR between patients with negative HUT and control subjects. Coronary microvascular function was impaired in syncopal patients with positive HUT and relatively preserved in those with negative HUT, suggesting the possible linkage between coronary microvascular dysfunction and the development of neurally mediated syncope. (PACE 2003; 26[Pt. I]:605,612) [source] Promigratory Activity of Oxytocin on Umbilical Cord Blood-Derived Mesenchymal Stem CellsARTIFICIAL ORGANS, Issue 6 2010Yong Sook Kim Abstract Recent studies show that oxytocin has various effects on cellular behaviors. Oxytocin is reported to stimulate cardiomyogenesis of embryonic stem cells and endothelial cell proliferation. Mesenchymal stem cells (MSCs) are widely used for cardiac repair, and we elucidated the effect of oxytocin on umbilical cord derived-MSCs (UCB-MSCs). UCB-MSCs were pretreated with oxytocin (100 nM) and washed with saline prior to experiments. To evaluate their angiogenic potential and migration activity, tube formation assay and Boyden chamber assay were performed. For in vivo study, ischemia-reperfusion was induced in rats, and UCB-MSCs with or without oxytocin pretreatment were injected into the infarcted myocardium to evaluate the engraftment of injected cells. Histological and hemodynamic studies were performed. Oxytocin-treated UCB-MSCs showed a decrease in tube formation but a drastic increase in transwell migration activity. The transcription level of matrix metalloproteinase (MMP)-2 was increased in oxytocin-treated UCB-MSCs. Knock-down of MMP-2 by use of siRNA restored the tube formation, while reducing transmigration activity. In rats injected with oxytocin-treated UCB-MSCs, cardiac fibrosis and CD68 infiltration in the peri-infarct zone were reduced, whereas cell engraftment and connexin43 expression were greater than in rats injected with untreated UCB-MSCs. By contrast, angiogenesis did not differ significantly between the two groups. Cardiac contractility was higher in the group injected with oxytocin-treated UCB-MSCs than in the group injected with phosphate-buffered saline alone. Collectively, oxytocin is an effective priming reagent for stem cells for application to damaged heart tissue. [source] | ||||||||||