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Papademetriou V.,Cardiovascular Research | Tsioufis C.,National and Kapodistrian University of Athens | Gradman A.,Temple University | Punzi H.,Trinity Hypertension Research Institute | Punzi H.,Southwestern Medical Center
International Journal of Hypertension | Year: 2011

Despite the many therapeutic options available today for the treatment of hypertension, a sizable number of patients still remain resistant to treatment. The prevalence of resistant hypertension in the general population under optimal conditions is about 3-5. Although several factors and conditions can be identified and corrected a percentage of hypertensive patients remain with unacceptably high blood pressure levels. The high prevalence of hypertension in the general population renders this small percentage significant, in terms of actual patient numbers. This special issue of the journal expoars a whole spectrum of topics related to resistant hypertension: several articles address pathophysiolog and secondary causes of resistant hypertension and modern approaches to therapy. Of interest is the referance to the newer interventional approaches, that is, Baroreceptor stimulation therapy and catheter based sympathetic renal denervation. © 2011 Vasilios Papademetriou et al.

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex but increased left ventricular (LV) diastolic stiffness plays a key role. A load-independent, non-invasive, direct measure of diastolic stiffness is lacking. The diastolic wall strain (DWS) index is based on the linear elastic theory, which predicts that impaired diastolic wall thinning reflects resistance to deformation in diastole and thus, increased diastolic myocardial stiffness. The objectives of this community-based study were to determine the distribution of this novel index in consecutive HFpEF patients and healthy controls, define the relationship between DWS and cardiac structure and function and determine whether increased diastolic stiffness as assessed by DWS is predictive of the outcome in HFpEF. Consecutive HFpEF patients (n = 327, EF ≥ 50%) and controls (n = 528) from the same community were studied. Diastolic wall strain was lower in HFpEF (0.33 ± 0.08) than in controls (0.40 ± 0.07, P < 0.001). Within HFpEF, those with DWS ≤ median (0.33) had higher LV mass index, relative wall thickness, E/e', Doppler-estimated LV end-diastolic pressure to LV end-diastolic volume ratio, left atrial volume index, and brain natriuretic peptide (BNP) levels than those with DWS > median. Heart failure with preserved ejection fraction patients with DWS ≤ median had higher rate of death or HF hospitalization than those with DWS > median (P = 0.003) even after the adjustment for age, gender, log BNP, LV geometry, or log E/e' (P < 0.01). These data suggest that DWS, a simple index, is useful in assessing diastolic stiffness and that more advanced diastolic stiffness is associated with worse outcomes in HFpEF.

Shin J.T.,Harvard University | Pomerantsev E.V.,Harvard University | Mably J.D.,Cardiovascular Research | MacRae C.A.,Harvard University
Physiological Genomics | Year: 2010

Phenotype-driven screens in larval zebrafish have transformed our understanding of the molecular basis of cardiovascular development. Screens to define the genetic determinants of physiological phenotypes have been slow to materialize as a result of the limited number of validated in vivo assays with relevant dynamic range. To enable rigorous assessment of cardiovascular physiology in living zebrafish embryos, we developed a suite of software tools for the analysis of high-speed video microscopic images and validated these, using established cardiomyopathy models in zebrafish as well as modulation of the nitric oxide (NO) pathway. Quantitative analysis in wild-type fish exposed to NO or in a zebrafish model of dilated cardiomyopathy demonstrated that these tools detect significant differences in ventricular chamber size, ventricular performance, and aortic flow velocity in zebrafish embryos across a large dynamic range. These methods also were able to establish the effects of the classic pharmacological agents isoproterenol, ouabain, and verapamil on cardiovascular physiology in zebrafish embryos. Sequence conservation between zebrafish and mammals of key amino acids in the pharmacological targets of these agents correlated with the functional orthology of the physiological response. These data provide evidence that the quantitative evaluation of subtle physiological differences in zebrafish can be accomplished at a resolution and with a dynamic range comparable to those achieved in mammals and provides a mechanism for genetic and smallmolecule dissection of functional pathways in this model organism. Copyright © 2010 the American Physiological Society.

The clinical impact of embolic debris released during lower-limb interventions is a source of discussion and controversy. Yet, the sheer magnitude of their number, overall area, and morphology suggest significance, especially in complex and high-risk patients. Technologies designed for lowering embolic burden are required to improve peripheral vascular intervention (PVI) outcomes and to reduce complication rates in a timely and cost-effective manner. This work details capture and removal of atheromatous plaque during post-atherectomy dilatation of long, in-stent, restenotic superficial femoral artery (SFA) lesions in two complex comorbid patients. In both cases, embolic removal was obtained by deployment of an embolic protection device (EPD) prior to the main intervention and by postdilating the lesion using the Proteus aspiration balloon. Captured and removed particles were analyzed and compared for content, count, and dimensions from both the EPD and the Proteus device. Both cases were successfully resolved, as determined by angiography with no sequelae. In both procedures, Proteus surpassed the EPD in the magnitude of removed embolic shower. In case 1, the Proteus balloon captured 228 particles, with a mean major axial dimension of 0.4 ± 0.43 mm (range, 0.12-3.29 mm), while the distally positioned EPD captured 16 particles with a mean major axial dimension of 0.88 ± 1.25 mm. Similarly, 719 particles of a mean 0.24 ± 0.43 mm major axial dimension (range, 0.03-4.83 mm) were recovered in case 2. The capture efficiency presented by the Proteus device over the EPD suggests its potential to serve as a viable tool in complex PVIs, particularly in the dilatation of irregular atherectomized lesions.

Deschodt-Arsac V.,University of Bordeaux Segalen | Calmettes G.,University of Bordeaux Segalen | Raffard G.,University of Bordeaux Segalen | Massot P.,University of Bordeaux Segalen | And 3 more authors.
American Journal of Physiology - Regulatory Integrative and Comparative Physiology | Year: 2010

Levosimendan is a calcium sensitizer developed for the treatment of heart failure. It increases contractile force by enhancing the sensitivity of myofilaments to calcium. Besides this sensitizing effect, the drug has also been reported to show some inhibitory action on phosphodiesterase 3 (PDE3). The inotropic effects of levosimendan have been studied on guinea pig paced perfused hearts by using modular control analysis (MoCA) (Diolez P, Deschodt-Arsac V, Raffard G, Simon C, Santos PD, Thiaudiere E, Arsac L, Franconi JM. Am J Physiol Regul Integr Comp Physiol 293: R13-R19, 2007.), an integrative approach of heart energetics using noninvasive 31P NMR. The aim was to evaluate quantitatively the respective effects of this drug on energy supply and demand modules. Under our experimental conditions, 0.7 μM levosimendan induced a 45% increase in paced heart output associated with a 7% decrease in phosphocreatine and a negligible increase in oxygen consumption. Because MoCA allows in situ study of the internal regulations in intact beating heart energetics, it was applied to describe quantitatively by which routes levosimendan exerts its inotropic action. MoCA demonstrated the absence of any significant effect of the drug on the supply module, which is responsible for the lower increase in oxygen consumption, compared with epinephrine, which increases the ratio between myocardial oxygen consumption and cardiac contraction. This result evidences that, under our conditions, a possible effect of levosimendan on PDE3 activity and/or intracellular calcium remains very low on mitochondrial activity and insignificant on integrated cardiac energetics. Thus, levosimendan inotropic effect on guinea pig heart depends almost entirely on the calcium-sensitizing properties leading to myofilament activation and the concomitant activation of energy supply by the decrease in PCr, therefore improving energetic efficiency of contraction. Copyright © 2010 the American Physiological Society.

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