Distinct right ventricle remodeling in response to pressure overload in the rat.

Pulmonary arterial hypertension (PAH), the most serious chronic disorder of the pulmonary circulation, is characterized by pulmonary vasoconstriction and remodeling, resulting in increased afterload on the right ventricle (RV). In fact, RV function is the main determinant of prognosis in PAH. The most frequently used experimental models of PAH include monocrotaline- and chronic hypoxia-induced PAH, which primarily affect the pulmonary circulation. Alternatively, pulmonary artery banding (PAB) can be performed to achieve RV overload without affecting the pulmonary vasculature, allowing researchers to determine the RV-specific effects of their drugs/interventions. In this work, using two different degrees of pulmonary artery constriction, we characterize, in full detail, PAB-induced adaptive and maladaptive remodeling of the RV at 3 wk after PAB surgery. Our results show that application of a mild constriction resulted in adaptive hypertrophy of the RV, with preserved systolic and diastolic function, while application of a severe constriction resulted in maladaptive hypertrophy, with chamber dilation and systolic and diastolic dysfunction up to the isolated cardiomyocyte level. By applying two different degrees of constriction, we describe, for the first time, a reliable and short-duration PAB model in which RV adaptation can be distinguished at 3 wk after surgery. We characterize, in full detail, structural and functional changes of the RV in its response to moderate and severe constriction, allowing researchers to better study RV physiology and transition to dysfunction and failure, as well as to determine the effects of new therapies.

Intraventricular pressure gradients in heart failure.

The aim of the present study was to characterize intraventricular pressure gradients (IVPGs) in an animal model of chronic heart failure. New Zealand rabbits were treated with doxorubicin (heart failure group, n=5) or saline (control group, n=5) and instrumented with pressure catheters placed in the apex and outflow-tract of left ventricle (LV) and with sonomicrometer crystals placed in the apex and base of the LV free wall. In heart failure animals, ventricular filling was delayed and slower when compared with control animals. Moreover, the physiological nonuniformity observed between apical and basal segments in normal hearts was abolished in failing hearts. Simultaneously, physiological IVPGs observed during normal ventricular filling were entirely lost in heart failure animals. During ventricular emptying physiological nonuniformity between apical and basal segments observed in control animals was also abolished in heart failure animals. In failing hearts minimal length occurred later and almost at same time both in apical and in basal myocardial segments. Simultaneously, the characteristic IVPG pattern observed in healthy hearts during systole, which promotes ventricular emptying, was not observed in failing hearts. The present study showed that diastolic IVPGs, a marker of normal ventricular filling, and systolic IVPGs, a marker of normal ventricular emptying, are abolished in heart failure.

Rodent models of heart failure: an updated review.

Heart failure (HF) is one of the major health and economic burdens worldwide, and its prevalence is continuously increasing. The study of HF requires reliable animal models to study the chronic changes and pharmacologic interventions in myocardial structure and function and to follow its progression toward HF. Indeed, during the past 40 years, basic and translational scientists have used small animal models to understand the pathophysiology of HF and find more efficient ways of preventing and managing patients suffering from congestive HF (CHF). Each species and each animal model has advantages and disadvantages, and the choice of one model over another should take them into account for a good experimental design. The aim of this review is to describe and highlight the advantages and drawbacks of some commonly used HF rodents models, including both non-genetically and genetically engineered models, with a specific subchapter concerning diastolic HF models.

Modulation of myocardial stiffness by ß-adrenergic stimulation--its role in normal and failing heart.

The acute effects of beta-adrenergic stimulation on myocardial stiffness were evaluated. New-Zealand white rabbits were treated with saline (control group) or doxorubicin to induce heart failure (HF) (DOXO-HF group). Effects of isoprenaline (10(-10)-10(-5) M), a non-selective beta-adrenergic agonist, were tested in papillary muscles from both groups. In the control group, the effects of isoprenaline were also evaluated in the presence of a damaged endocardial endothelium, atenolol (beta(1)-adrenoceptor antagonist), ICI-118551 (beta(2)-adrenoceptor antagonist), KT-5720 (PKA inhibitor), L-NNA (NO-synthase inhibitor), or indomethacin (cyclooxygenase inhibitor). Passive length-tension relations were constructed before and after adding isoprenaline (10(-5) M). In the control group, isoprenaline increased resting muscle length up to 1.017+/-0.006 L/L(max). Correction of resting muscle length to its initial value resulted in a 28.5+/-3.1 % decrease of resting tension, indicating decreased muscle stiffness, as confirmed by the isoprenaline-induced right-downward shift of the passive length-tension relation. These effects were modulated by beta(1)- and beta(2)-adrenoceptors and PKA. In DOXO-HF group, the effect on myocardial stiffness was significantly decreased. We conclude that beta-adrenergic stimulation is a relevant mechanism of acute neurohumoral modulation of the diastolic function. Furthermore, this study clarifies the mechanisms by which myocardial stiffness is decreased.

[Early experience in laparoscopic radical prostatectomy using the laparoscopic device for umbilical access SILS Port]. / Experiencia inicial en prostatectomía radical laparoscópica con el dispositivo de acceso laparoscópico umbilical Single-Incision Laparoscopic Surgery Port.

Since 2007, various urological procedures have been performed with laparoendoscopic single-site surgery (LESS surgery), including nephrectomy, pyeloplasty, simple prostatectomy and, with the refinement of laparoscopic instrumentation, radical prostatectomy. This paper reports our initial experience in radical prostatectomy using the SILS Port from Covidiem and two lateral 5-mm trocars for triangulation. The SILS Port allows for accurate, simple insertion through a Hadson incision. The flexible port accommodates three 5-mm cannulas or two 5-mm cannulas and a 12-mm port for easier instrument exchange through a single incision. This approach decreases morbidity from bleeding, hernia and/or internal organ damage and improves cosmetic. One-port single-incision laparoscopy is part of the natural development of minimally invasive surgery. Future research is required to assess the intraoperative and postoperative benefits of LESS surgery as compared to standard laparoscopy.

Experiencia inicial en prostatectomía radical laparoscópica con el dispositivo de acceso laparoscópico umbilical Single-Incision Laparoscopic Surgery Port® / Early experience in laparoscopic radical prostatectomy using the laparoscopic device for umbilical access SILS Port®

Desde el año 2007 se están realizando distintos procedimientos en cirugía laparoendoscópica por puerto único (laparoendoscopic single-site surgery), incluyendo nefrectomía, pieloplastia, adenomectomía prostática y, con el perfeccionamiento del instrumental laparoscópico, prostatectomía radical. Presentamos nuestra experiencia inicial en prostatectomía radical laparoscópica utilizando el dispositivo Single-Incision Laparoscopic Surgery Port® de Covidien y 2 trocares auxiliares de 5mm colocados lateralmente para triangulación. El Single-Incision Laparoscopic Surgery Port® permite una inserción precisa y sencilla a través de una incisión de Hadson. El puerto flexible contiene 3 cánulas de 5mm o 2 cánulas de 5mm y una de 12mm para facilitar el intercambio de instrumental a través de la incisión única. Este abordaje disminuye la morbilidad por sangrado, hernias y/o lesión de los órganos internos y mejora los resultados cosméticos. El puerto único forma parte del desarrollo natural de la cirugía mínimamente invasiva. Se necesita más experiencia para determinar los beneficios intra y postoperatorios de la cirugía laparoendoscópica por puerto único en comparación con la laparoscopia convencional (AU)

Since 2007, various urological procedures have been performed with laparoendoscopic single-site surgery (LESS surgery), including nephrectomy, pyeloplasty, simple prostatectomy and, with the refinement of laparoscopic instrumentation, radical prostatectomy. This paper reports our initial experience in radical prostatectomy using the SILS™ Port from Covidiem and two lateral 5-mm trocars for triangulation. The SILS™ Port allows for accurate, simple insertion through a Hadson incision. The flexible port accomodates three 5-mm cannulas or two 5-mm cannulas and a 12-mm port for easier instrument exchange through a single incision. This approach decreases morbidity from bleeding, hernia and/or internal organ damage and improves cosmetic results. One-port single-incision laparoscopy is part of the natural development of minimally invasive surgery. Future research is required to assess the intraoperative and postoperative benefits of LESS surgery as compared to standard laparoscopy (AU)

Nitric oxide and prostaglandins - important players in endothelin-1 induced myocardial distensibility.

This study investigated whether endothelin (ET)-1-induced increase in myocardial distensibility is preserved in heart failure (HF) and whether it is modulated by nitric oxide (NO) and prostaglandins. New Zealand white rabbits were treated with doxorubicin (1 mg/kg, intravenously twice a week for 8 weeks, DOX-HF group) or saline (control group). Effects of ET-1 (0.1, 1, 10 nM) were tested in papillary muscles from the DOX-HF group and a control group in the presence of: i) intact endocardial endothelium (EE); ii) damaged EE; iii) N(G)-nitro-L-arginine (L-NNA; NO synthase inhibitor), and iv) indomethacin (INDO; cyclooxygenase inhibitor). In the presence of an intact EE, ET-1 promoted concentration-dependent positive inotropic and lusitropic effects that were maintained after damaging the EE, in the presence of L-NNA or INDO and in the DOX-HF Group. ET-1 reduced resting tension at the end of the isometric twitch (increased diastolic distensibility) by 3.2+/-1.3 %, 6.0+/-1.6 % and 8.8+/-2.7 % (at 0.1, 1 and 10 nM, respectively), in muscles with intact EE, effect that was completely abolished after damaging EE, in the presence of L-NNA or INDO or in the DOX-HF Group. This study demonstrated that the increase in myocardial distensibility induced by ET-1 is absent in HF and is dependent of NO and prostaglandin release.

[Mechanisms underlying endothelin-1 effects on myocardial function]. / Mecanismos subjacentes aos efeitos da endotelina-1 sobre a função miocárdica.

INTRODUCTION: Endothelin-1 (ET-1) has potent vasoconstrictor, growth promoting and positive inotropic properties. Its effects on the intrinsic properties of the myocardium were recently described. The present study investigated the mechanisms underlying those effects. METHODS: The myocardial effects of 1 and 10 nM of ET-1 were evaluated in isolated rabbit papillary muscles (n = 9) and human atrial trabecula from CABG patients (Krebs-Ringer; 1.8 mM CaCl2; 35 degrees C). In papillary muscles the effects of 1 nM ET-1 were also studied in the presence of: (i) a selective ETA receptor antagonist, BQ-123 (0.1 microM; n = 9); (ii) a selective ETB receptor antagonist, BQ-788 (0.1 microM; n = 6); and (iii) an Na+/H+ exchanger inhibitor, methyl-isobutyl-amiloride (MIA; 1 microM; n = 6). Only significant results (mean +/- SE, p < 0.05) are given, expressed as delta % baseline. RESULTS: In AT by papillary muscles, 1 nM of ET-1 increased 64 +/- 16%, dT/dtmin 39 +/- 13% and decreased PT by 11 +/- 2%. The analysis of atrial strip contractions yielded similar results. In papillary muscles the effects of ET-1 were not affected by BQ-788, yet they were abolished by BQ-123, and reduced by 44% by MIA. CONCLUSIONS: The action of ET-1 on myocardial function is similar in human and non-human myocardium. The myocardial effects observed in the present study are mediated by the binding to ETA receptors, and partially dependent on Na+/H+ exchanger activation.