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1.  Left Atrial Reverse Remodeling in Dogs with Moderate and Advanced Heart Failure Treated with A Passive Mechanical Containment Device: An Echocardiographic Study 
Journal of cardiac failure  2007;13(4):312-317.
Assessment of global LV remodeling is important in evaluating the efficacy of pharmacologic and device therapies for the treatment of chronic heart failure (HF). The effects of pharmacologic or device therapies on global left atrial (LA) remodeling in HF, while also important, are not often examined. We showed that long-term therapy with the Acorn Cardiac Support Device (CSD), a passive mechanical ventricular containment device, prevents and/or reverses LV remodeling in dogs with HF. This study examined the effects of the CSD on global LA remodeling in dogs with moderate and advanced HF.
Methods and Results
Studies were performed in 24 dogs with coronary microembolization-induced HF. Of these, 12 had moderate HF (ejection fraction, EF 30% to 40%) and 12 advanced HF (EF ≤25%). In each group, the CSD was implanted in 6 dogs and the other 6 served as controls. Dogs were followed for 3 months in the moderate group and 6 months in the advanced HF group. LA maximal volume (LAVmax), LA volume at the onset of the p-wave (LAVp), LA minimal volume (LAVmin), LA active emptying volume (LAAEV) and LA active emptying fraction (LAAEF) were measured from 2-dimensional echocardiograms obtained prior to CSD implantation and at the end of the treatment period. Treatment effect (Δ) comparisons between CSD-treated dogs and controls showed that CSD therapy significantly decreased LA volumes (ΔLAVmax: 3.33 ± 0.70 vs. −2.87±1.31 ml, p=0.002; 7.77 ± 1.76 vs. −0.37 ± 0.87 ml, p=0.002) and improved LA function (ΔLAAEF: −6.00 ± 1.53 vs. 1.85 ± 1.32 %, p=0.003; −2.39 ± 1.10 vs. 3.13 ± 1.66 %, p=0.02) in the moderate HF and advanced HF groups respectively.
Progressive LA enlargement and LA functional deterioration occurs in untreated dogs with HF. Monotherapy with the CSD prevents LA enlargement and improves LA mechanical function in dogs with moderate and advanced HF indicating prevention and/or reversal of adverse LA remodeling.
PMCID: PMC1939806  PMID: 17517352
Atrium; Echocardiography; Heart failure; Heart-assist device
2.  Differential Involvement of Toll-Like Receptors 2 and 4 in the Host Response to Acute Respiratory Infections with Wild-Type and Mutant Haemophilus influenzae Strains  
Infection and Immunity  2005;73(4):2075-2082.
We used a mouse model of acute respiratory infections to investigate the role of Toll-like receptor 2 (TLR2) and TLR4 in the host response to Haemophilus influenzae. Acute aerosol exposures to wild-type strains of H. influenzae showed that TLR4 function was essential for TNF-α induction, neutrophil influx, and bacterial clearance. To determine how lipooligosaccharide (LOS) modifications would affect the role of TLR4 in inducing the host response, we used acute infections with an H. influenzae strain expressing a mutation in the htrB gene. This mutant strain expresses an LOS subunit with decreased acylation. In response to H. influenzae htrB infection, tumor necrosis factor alpha (TNF-α) secretion remained TLR4 dependent. But the decrease in LOS acylation made the neutrophil influx and the bacterial clearance also dependent on TLR2, as shown by the decreased host response elicited in TLR2 knockout mice compared to C57BL/6 mice. A subsequent analysis of TLR2 and TLR4 gene expression by quantitative PCR indicated that TLR4 function induces TLR2 expression and vice versa. These results indicate that some changes in the LOS subunit of H. influenzae can favor signaling through non-TLR4 receptors, such as TLR2. The results also indicate a close interaction between TLR4 and TLR2 that tightly regulates the expression of both receptors.
PMCID: PMC1087404  PMID: 15784548

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