Down-regulation of Plasminogen Activator Inhibitor 1 Expression Promotes Myocardial Neovascularization by Bone Marrow Progenitors

Human adult bone marrow–derived endothelial progenitors, or angioblasts, induce neovascularization of infarcted myocardium via mechanisms involving both cell surface urokinase-type plasminogen activator, and interactions between β integrins and tissue vitronectin. Because each of these processes is regulated by plasminogen activator inhibitor (PAI)-1, we selectively down-regulated PAI-1 mRNA in the adult heart to examine the effects on postinfarct neovascularization and myocardial function. Sequence-specific catalytic DNA enzymes inhibited rat PAI-1 mRNA and protein expression in peri-infarct endothelium within 48 h of administration, and maintained down-regulation for at least 2 wk. PAI-1 inhibition enhanced vitronectin-dependent transendothelial migration of human bone marrow–derived CD34+ cells, and resulted in a striking augmentation of angioblast-dependent neovascularization. Development of large, thin-walled vessels at the peri-infarct region was accompanied by induction of proliferation and regeneration of endogenous cardiomyocytes and functional cardiac recovery. These results identify a causal relationship between elevated PAI-1 levels and poor outcome in patients with myocardial infarction through mechanisms that directly inhibit bone marrow–dependent neovascularization. Strategies that reduce myocardial PAI-1 expression appear capable of enhancing cardiac neovascularization, regeneration, and functional recovery after ischemic insult

Prognostic Impact of Tricuspid Regurgitation in Patients Undergoing Aortic Valve Surgery for Aortic Stenosis.

BackgroundThe prognostic significance of tricuspid regurgitation (TR) and right ventricular (RV) function in patients undergoing aortic valve replacement (AVR) for severe aortic stenosis (AS) is unknown. The aim of the present study was to evaluate the impact of TR and RV systolic dysfunction on early and late mortality in this setting.MethodsThis was a prospective single-center observational study. 465 consecutive patients who were referred to AVR for severe AS were investigated. Significant TR was defined as TR≥moderate by transthoracic echocardiography.ResultsAt baseline, significant TR was present in 26 (5.6%) patients. Patients with TR presented with a higher EuroSCORE I (p = 0.001), a higher incidence of previous cardiac surgery (pConclusionsTR, RV dysfunction, age, and concomitant CABG are associated with outcome in patients undergoing AVR for severe AS. This finding underlines the importance of a thorough echocardiographic evaluation with particular consideration of the right heart in these patients

Factors determining patient-prosthesis mismatch after aortic valve replacement--a prospective cohort study.

OBJECTIVE: "Patient-prosthesis mismatch" (PPM) after aortic valve replacement (AVR) has been reported to increase morbidity and mortality. Although algorithms have been developed to avoid PPM, factors favouring its occurrence have not been well defined. DESIGN AND SETTING: This was a prospective cohort study performed at the Medical University of Vienna. PATIENTS: 361 consecutive patients who underwent aortic valve replacement for isolated severe aortic stenosis were enrolled. MAIN OUTCOME MEASURES: Patient- as well as prosthesis-related factors determining the occurrence of moderate and severe PPM (defined as effective orifice area indexed to body surface area ≤ 0.8 cm(2)/m(2)) were studied. RESULTS: Postoperatively, 172 patients (48%) were diagnosed with PPM. The fact that predominantly female patients were affected (58% with PPM diagnosis in women versus 36% in men, p<0.001) was explained by the finding that they had smaller aortic root diameters (30.5±4.7 mm versus 35.3±4.2 mm, p<0.0001) and a higher proportion of bioprosthetic valves (82% versus 62%, p<0.0001), both independent predictors of PPM (aortic root diameter: OR 0.009 [95% CI, 0.004;0.013]; p = 0.0003, presence of bioprosthetic valve: OR 0.126 [95% CI, 0.078;0.175]; p<0.0001). CONCLUSIONS: The occurrence of PPM is determined by aortic root diameter and prosthesis type. Novel sutureless bioprostheses with optimized hemodynamic performance or transcatheter aortic valves may become a promising alternative to conventional bioprosthetic valves in the future

Operative data.

<p>Values are expressed as numbers or frequency (%). CABG indicates coronary artery bypass graft; TV, tricuspid valve.</p><p>Operative data.</p

The Temperature Side Channel and Heating Fault Attacks

In this paper, we present practical results of data leakages of CMOS devices via the temperature side channel---a side channel that has been widely cited in literature but not well characterized yet. We investigate the leakage of processed data by passively measuring the dissipated heat of the devices. The temperature leakage is thereby linearly correlated with the power leakage model but is limited by the physical properties of thermal conductivity and capacitance. We further present heating faults by operating the devices beyond their specified temperature ratings. The efficiency of this kind of attack is shown by a practical attack on an RSA implementation. Finally, we introduce data remanence attacks on AVR microcontrollers that exploit the Negative Bias Temperature Instability (NBTI) property of internal SRAM cells. We show how to recover parts of the internal memory and present first results on an ATmega162. The work encourages the awareness of temperature-based attacks that are known for years now but not well described in literature. It also serves as a starting point for further research investigations

Overall survival in patients with versus without significant TR.

<p>TR indicates tricuspid regurgitation.</p

Baseline patient characteristics

<p>Values are expressed as mean±SD or frequency (%). BSA indicates body surface area; BMI, body mass index; CAD, coronary artery disease, defined as any degree of coronary lumen diameter narrowing; ≥2 vessels, affecting two or three coronary arteries; COPD, chronic obstructive pulmonary disease; NYHA, New York Heart Association; AV, aortic valve; LVEF, left ventricular ejection fraction; LV, left ventricle; RV, right ventricle; EDD, end-diastolic diameter from the apical 4-chamber view; LA, left atrial longitudinal diameter from the apical 4-chamber view; RA, right atrial longitudinal diameter from the apical 4-chamber view; IVS, interventricular septal thickness by M-Mode from the parasternal short-axis view; sPAP, systolic pulmonary artery pressure.</p><p>Baseline patient characteristics</p

Echocardiographic and Doppler parameters used for grading of TR severity.

<p>Presence of three or more of the five parameters shown defines severity grade (mild, moderate or severe).</p><p>RV indicates right ventricular; RA, right atrium; IVC, inferior vena cava; VC, vena contracta; PISA, proximal isovelocity surface area.</p><p>* Unless there are other reasons for RV or RA enlargement (e.g. pulmonary hypertension, pulmonary valve disease).</p><p>Echocardiographic and Doppler parameters used for grading of TR severity.</p

Causes of death.

<p>Values are expressed as numbers or frequency (%).</p><p>Causes of death.</p

Operative data.

<p>Values are expressed as numbers or frequency (%). CABG indicates coronary artery bypass graft; TV, tricuspid valve.</p><p>Operative data.</p