Optimal antiplatelet treatment for percutaneous coronary intervention: clopidogrel vs. ticlopidine

Antiplatelet treatment for patients undergoing percutaneous coronary interventions is a rapidly changing area. Thienopyridines derivatives (ticlopidine and clopidogrel) have shown to decrease major cardiovascular events. Ticlopidine can cause rare but serious side effects, especially during the first 3 months of treatment. Clopidogrel appears to be a safer alternative to ticlopidine. However, resistance to clopidogrel therapy may increases the risk of recurrent cardiovascular events. Whether increased doses of clopidogrel might overcome this resistance in nonresponsive patients warrants further investigation.     

Minimal vs median sternotomy for aortic valve replacement

The aim of this study was to compare postoperative outcomes in patients undergoing aortic valve replacement through a ministernotomy or conventional sternotomy. Sixty patients were randomized into 2 groups of 30 each: group 1 had a full sternotomy and group 2 had a ministernotomy. Pain was evaluated on a daily basis, pulmonary function tests were performed perioperatively. The skin incision was shorter in group 2 (7.17 vs 24.50 cm in group 1). There was significantly less mediastinal drainage in group 2 (233 vs 590 mL in 24 hours in group 1). Group 1 patients had more blood transfusions and longer ventilation time. In group 1, 96.7% experienced severe pain, whereas 93.3% in group 2 reported minimal pain. Hospital stay was 17.7 days in group 1 and 8.0 days in group 2. The ministernotomy had a cosmetic advantage, less blood loss and transfusion requirement, greater sternal stability, better respiratory function, and earlier extubation and hospital discharge.     

The influence of hemodynamic forces on biomarkers in the walls of elastase-induced aneurysms in rabbits

Introduction Biological and biophysical factors have been shown to play an important role in the initiation, progression, and rupture of intracranial aneurysms. The purpose of this study was to evaluate the association between hemodynamic forces and markers of vascular remodeling in elastase-induced saccular aneurysms in rabbits. Methods Elastase-induced aneurysms were created at the origin of the right common carotid artery in rabbits. Hemodynamic parameters were estimated using computational fluid dynamic simulations based on 3-D-reconstructed models of the vasculature. Expression of matrix metalloproteinases (MMPs), their inhibitors (TIMPs) and markers of vascular remodeling were measured in different spatial regions within the aneurysms. Results Altered expression of biological markers relative to controls was correlated with the locations of subnormal time-averaged wall shear stress (WSS) but not with the magnitude of pressure. In the aneurysms, WSS was low and expression of biological markers was significantly altered in a time-dependent fashion. At 2 weeks, an upregulation of active-MMP-2, downregulation of TIMP-1 and TIMP-2, and intact endothelium were found in aneurysm cavities. However, by 12 weeks, endothelial cells were absent or scattered, and levels of pro- and active-MMP-2 were not different from those in control arteries, but pro-MMP-9 and both TIMPs were upregulated. Conclusion These results reveal a strong, spatially localized correlation between diminished WSS and differential expression of biological markers of vascular remodeling in elastase-induced saccular aneurysms. The ability of the wall to function and maintain a healthy endothelium in a low shear environment appears to be significantly impaired by chronic exposure to low WSS.     

Effects of Fructus Piperis Longi extract on fibrotic liver of gamma-irradiated rats

Background  

A major biomarker for liver fibrosis is transglutaminase which catalyzes cross-linking of epsilon-amines and alpha-glutamyl residues among amino acids leading to fibrosis. Fructus Piperis Longi is a common herb used in Chinese medicine. The present study evaluates the role of the ethanol extract of Fructus Piperis Longi in the modulation of liver function in liver fibrosis.     

Genomic modeling of atherosclerosis in peripheral arterial disease and its variant phenotype in patients with diabetes

Microarrays can be used to discover candidate genes associated with peripheral arterial disease (PAD) and develop models that predict patient clinical status. We hypothesize that multiple phenotypes of PAD with distinct patterns of gene expression exist. We histologically characterized and extracted ribonucleic acid from 31 arterial samples collected from the lower extremities of patients undergoing amputation or free fibular grafting. Analysis using the Affymetrix U133A microarray identified 335 genes with twofold or greater differences in expression between normal and diseased arteries (p< .01) and 104 genes with twofold or greater differences between diabetic and nondiabetic atherosclerotic arteries (p< .1). Many genes identified have known roles in inflammatory and lipid uptake pathways. Predictive models were developed that could predict PAD and the associated diabetic phenotype with an accuracy of 71 to 90%. Developing distinct genomic models of PAD will serve as the first step toward understanding the molecular and genetic basis of PAD and subsequent application of novel therapeutics to this condition.     

Hemorrhagic shock and resuscitation-mediated tissue water distribution is normalized by adjunctive peritoneal resuscitation

BACKGROUND: Adjunctive direct peritoneal resuscitation (DPR) from hemorrhagic shock (HS) improves intestinal blood flow and abrogates postresuscitation edema. HS causes water shifts as a result of sodium redistribution and changes in transcapillary Starling forces. Conventional resuscitation (CR) with crystalloid aggravates water sequestration. We examined the compartment pattern of organ tissue water after HS and CR, and modulation of tissue edema by adjunctive DPR. STUDY DESIGN: Rats were hemorrhaged (40% mean arterial pressure for 60 minutes) and assigned to four groups (n = 7): sham, no HS; HS no resuscitation; HS+CR (shed blood plus 2 volumes Ringer's lactate); and HS+CR+DPR (20 mL clinical intraperitoneal (IP) dialysis fluid). Isotopic markers determined equilibrium distribution volumes [V(D)] in gut, liver, lung, and muscle by quantitative autoradiography (2-hour postresuscitation). Total tissue water (TTW) was determined by wet-dry weights. Extracellular water was measured from (14)C-mannitol V(D), and intravascular volume (IVV) from (131)I-labeled IgG V(D). Cellular and interstitial water volumes were calculated. RESULTS: HS alone decreased IVV in all tissues and TTW in gut, lung, and muscle, but not liver, compared with shams. IVV remained decreased with all resuscitations despite restoration of central hemodynamics. CR caused interstitial edema in gut, liver, and muscle, and cellular edema in lung. DPR reduced (liver, muscle) or prevented (gut, lung) these volume shifts. CONCLUSIONS: HS decreases IVV. HS-induced water shifts are organ-specific and prominent in gut, lung, and muscle. CR restores central hemodynamics, does not restore IVV, and alters organ-specific TTW distribution. Adjunctive DPR with IP dialysis fluid normalizes TTW and water compartment distribution and prevents edema. Combined effect of DPR and intravascular fluid replacement appears to prevent global tissue edema and improve outcomes from HS.     

Cellular edema regulates tissue capillary perfusion after hemorrhage resuscitation

BACKGROUND: Hemorrhage-induced activation of endothelial cell Na+/H+ -exchanger results in cellular swelling, which physically impedes capillary filling and compromises gut perfusion. We hypothesized that correction of the vascular volume deficit by conventional resuscitation does not improve capillary filling unless cellular swelling is prevented. Also, we hypothesized that adjunctive direct peritoneal resuscitation (DPR) with topical peritoneal dialysis solution (Delflex; Fresenius USA, Inc., Ogden, Ut) enhances capillary filling and gut perfusion by mechanisms that are independent of the Na+/H+ function. METHODS: In vivo intravital videomicroscopy and Doppler velocimeter were used by us to measure microvascular diameter and flow, capillary filling (index of functional capillary density, FCD), and endothelial cell function in the terminal ileum of anesthetized rats. Rats were bled to 50% mean arterial pressure for 60 min and resuscitated with the shed blood plus 2 volumes of saline (conventional resuscitation). Prevention of endothelial cell swelling was achieved with topical amiloride (specific Na+/H+ inhibitor) in the tissue bath before hemorrhage or simultaneously with conventional resuscitation. DPR was simulated by instillation of Delflex in the tissue bath as adjunctive to conventional resuscitation. Sham no hemorrhage group and a simulated DPR group that received topical amiloride treatment served as controls. RESULTS: Conventional resuscitation from hemorrhagic shock restored and maintained central hemodynamics but caused progressive and persistent intestinal vasoconstriction and hypoperfusion associated with low FCD and endothelial cell dysfunction. Prevention of endothelial cell swelling when combined with conventional resuscitation, preserved endothelial cell function, and restored local intestinal microvascular variables to near-prehemorrhage levels. Simulated adjunctive DPR produced rapid, sustained, and generalized vasodilation associated with restoration of endothelial cell function, and maximum recruitment of FCD independent of the Na+/H+ -exchanger function. CONCLUSIONS: Paradoxical endothelial cell swelling occurs early during hemorrhagic shock because of activation of the Na+/H+ exchanger. This cellular edema, which is not resolved by correction of the vascular volume deficit, explains the persistent postresuscitation endothelial cell dysfunction and gut hypoperfusion. Simulated adjunctive DPR in this study reversed endothelial cell swelling and enhanced gut perfusion by mechanisms that are independent of the Na+/H+ exchanger activity.