Lower Left Ventricular End-diastolic Pressure Research Articles

Renal sympathetic denervation inhibites the development of left ventricular mechanical dyssynchrony during the progression of heart failure in dogs

Objective To investigate whether transcatheter renal sympathetic denervation (RSD) by radiofrequency ablation interfere with the development of left ventricular (LV) mechanical dyssynchrony during the progression of heart failure (HF). Methods Nineteen beagles were randomly divided into sham-operated group (six dogs), control group (seven dogs), and RSD group (six dogs). Sham-operated group were implanted with pacemakers without pacing; Control group were implanted with pacemakers and underwent 3 weeks of rapid right ventricular pacing; and RSD group underwent catheter-based RSD bilaterally and were simultaneously implanted with pacemakers. LV dyssynchrony was analyzed via 2D speckle-tracking strain echocardiography to evaluate LV function.Longitudinal dyssynchrony was determined as the standard deviation for time-to-peak speckle-tracking strain on apical 4- and 2-chamber views. Radial and circumferential dyssynchrony was determined as the standard deviation for time-to-peak speckle-tracking strain in mid- and base-LV short-axis views. LV systolic pressure (LVSP) and LV end-diastolic pressure (LVEDP) were measured. The LV interstitial fibrosis was determined by histological analysis. Results After 3 weeks, all of the dogs in both the control and RSD groups showed greater LV end-diastolic volume compared with the sham-operated group; however, the dogs in the RSD group had a higher LV ejection fraction (LVEF) than the dogs in the control group (P<0.001). The LV systolic strains were higher in the RSD group than in the control group (P<0.001 for longitudinal, circumferential and radial strain, respectively). The levels of LV dyssynchrony were lower in the RSD group than in the control group (P<0.001 for longitudinal, circumferential and radial dyssynchrony, respectively). Compared with control group, RSD group had lower LV end-diastolic pressures and less fibrous tissue. Conclusions RSD inhibites the development of left ventricular mechanical dyssynchrony during the progression of heart failure in dogs. Key words: Echocardiography; Kidney; Sympathetic nervous system; Catheter ablation; Heart failure; Ventricular function, left; Ventricular dyssynchrony

Cardiosphere-Derived Cells Reverse Heart Failure With Preserved Ejection Fraction in Rats by Decreasing Fibrosis and Inflammation

SummaryThe pathogenesis of heart failure with a preserved ejection fraction (HFpEF) is unclear. Myocardial fibrosis, inflammation, and cardiac hypertrophy have been suggested to contribute to the pathogenesis of HFpEF. Cardiosphere-derived cells (CDCs) are heart-derived cell products with antifibrotic and anti-inflammatory properties. This study tested whether rat CDCs were sufficient to decrease manifestations of HFpEF in hypertensive rats. Starting at 7 weeks of age, Dahl salt-sensitive rats were fed a high-salt diet for 6 to 7 weeks and randomized to receive intracoronary CDCs or placebo. Dahl rats fed normal chow served as controls. High-salt rats developed hypertension, left ventricular (LV) hypertrophy, and diastolic dysfunction, without impairment of ejection fraction. Four weeks after treatment, diastolic dysfunction resolved in CDC-treated rats but not in placebo. The improved LV relaxation was associated with lower LV end-diastolic pressure, decreased lung congestion, and enhanced survival in CDC-treated rats. Histology and echocardiography revealed no decrease in cardiac hypertrophy after CDC treatment, consistent with the finding of sustained, equally-elevated blood pressure in CDC- and placebo-treated rats. Nevertheless, CDC treatment decreased LV fibrosis and inflammatory infiltrates. Serum inflammatory cytokines were likewise decreased after CDC treatment. Whole-transcriptome analysis revealed that CDCs reversed changes in numerous transcripts associated with HFpEF, including many involved in inflammation and/or fibrosis. These studies suggest that CDCs normalized LV relaxation and LV diastolic pressure while improving survival in a rat model of HFpEF. The benefits of CDCs occurred despite persistent hypertension and cardiac hypertrophy. By selectively reversing inflammation and fibrosis, CDCs may be beneficial in the treatment of HFpEF.

Renal sympathetic denervation inhibits the development of left ventricular mechanical dyssynchrony during the progression of heart failure in dogs.

BackgroundThe purpose of this study was to investigate whether transcatheter renal sympathetic denervation (RSD) interfere with the development of left ventricular (LV) mechanical dyssynchrony during the progression of heart failure (HF).MethodsNineteen beagles were randomly divided into sham-operated group (six dogs), control group (seven dogs), and RSD group (six dogs). Sham-operated group were implanted with pacemakers without pacing; Control group were implanted with pacemakers and underwent 3 weeks of rapid right ventricular pacing; and RSD group underwent catheter-based RSD bilaterally and were simultaneously implanted with pacemakers. Both LV strain and LV dyssynchrony were analyzed via 2D speckle-tracking strain echocardiography to evaluate LV function. Longitudinal dyssynchrony was determined as the standard deviation for time-to-peak speckle-tracking strain on apical 4- and 2-chamber views. Radial and circumferential dyssynchrony was determined as the standard deviation for time-to-peak speckle-tracking strain in mid- and base-LV short-axis views. Each myocardial function was also evaluated by averaging the peak systolic strains. LV systolic pressure (LVSP) and LV end-diastolic pressure (LVEDP) were measured. The LV interstitial fibrosis was determined by histological analysis. Plasma angiotensin II (Ang II), aldosterone and norepinephrine (NE) levels were also measured.ResultsAfter 3 weeks, all of the dogs in both the control and RSD groups showed greater LV end-diastolic volume compared with the sham-operated group; however, the dogs in the RSD group had a higher LV ejection fraction (LVEF) than the dogs in the control group (p < 0.001). The LV systolic strains were higher in the RSD group than in the control group (p < 0.001 for longitudinal, circumferential and radial strain, respectively). The levels of LV dyssynchrony were lower in the RSD group than in the control group (p < 0.001 for longitudinal, circumferential and radial dyssynchrony, respectively). Compared with dogs with control alone, RSD dogs had lower LV end-diastolic pressures and less fibrous tissue. The levels of plasma Ang II, aldosterone and NE were lower in the RSD group than in the control group.ConclusionsRSD inhibites the development of left ventricular mechanical dyssynchrony during the progression of heart failure in dogs.

Renal sympathetic denervation suppresses ventricular substrate remodelling in a canine high-rate pacing model.

This study sought to assess whether renal sympathetic denervation (RSD) could suppress ventricular substrate remodelling and attenuate heart failure (HF) progression. Nineteen dogs were randomised into three groups - seven sham-operated controls, six with right ventricular pacing to induce HF, and six with RSD followed eight weeks later by pacing induction of HF. Haemodynamic variables were monitored at baseline and after HF. Levels of ventricular interstitial fibrosis, BNP, Ang II, aldosterone and TGF-β were measured. All the dogs in the HF and HF﹢RSD groups showed increased left and right ventricular diastolic dimensions, but the dogs in the HF﹢RSD group had a higher left ventricular ejection fraction (LVEF) than the HF dogs (0.42±0.05 vs. 0.35±0.04, p<0.01). Compared with the dogs with HF alone, the HF+RSD dogs had lower left ventricular end-diastolic pressure (LVEDP) (3.3±1.6 vs. 25±3.7 mmHg, p<0.01) and less fibrous tissue. The levels of BNP, Ang II, aldosterone and TGF-β expression in ventricular tissue were higher in the HF dogs than in the sham-operated and HF﹢RSD dogs. RSD suppressed ventricular substrate remodelling induced by long-term rapid ventricular pacing.

β2-Adrenergic and M2-muscarinic receptors decrease basal t-tubular L-type Ca2+ channel activity and suppress ventricular contractility in heart failure

L-type Ca2+ channels (LTCC) play a crucial role in cardiac excitation–contraction coupling. We previously found that in failing ventricular myocytes of mice chronically treated with isoproterenol, basal t-tubular (TT) LTCC activity was halved by activation of protein phosphatase (PP)2A whereas basal surface sarcolemmal (SS) LTCC activity was doubled by inhibition of PP1. Interestingly, chronic treatment of these mice with pertussis toxin almost completely normalized TT and SS LTCC densities and cardiac contractility. In the present study, we therefore sought to identify the Gi/o protein-coupled receptors in cardiac myocytes (i.e. β2-adrenergic, M2-muscarinic and A1-adenosine receptors) that are responsible for these abnormalities in heart failure by chronically administrating mice a selective antagonist of each receptor (ICI118,551, atropine and 8-cyclopentyl-1,3-dipropilxanthine (DPCPX), respectively) with isoproterenol. Compared with mice treated with isoproterenol alone, mice treated with isoproterenol plus ICI118,551 or atropine, but not DPCPX showed significantly lower lung weight/tibial length, higher fractional shortening, lower left ventricular end-diastolic pressure and higher dP/dtmax and dP/dtmin. In addition, ventricular myocytes of mice treated with isoproterenol plus ICI118,551 or atropine, but not DPCPX exhibited significantly higher TT and lower SS LTCC current densities than those of mice treated with isoproterenol alone due to normalization of the PP activities. These results indicate that β2-adrenergic, M2-muscarinic, but not A1-adenosine receptors contribute to reduced ventricular contractility at least partially by decreasing basal TT LTCC activity in heart failure. Therefore, antagonists of β2-adrenergic and/or M2-muscarinic receptors can be good adjuncts to β1-adrenergic receptor antagonists in the treatment of heart failure.

Paravalvular aortic regurgitation as the reason for second CoreValve bioprosthesis implantation in a patient with native bicuspid valve

We present the case of a 70-year-old male patient who was admitted to our centre with severe symptomatic aortic stenosis. His medical history included: hypertension, stroke (1998 and 2013) with subsequent left-sided paraparesis and status after traumatic upper right limb amputation in his youth. Patient’s logistic EuroSCORE was 18.1%, EuroSCORE II 5.7% and the Society of Thoracic Surgeons Score 2.7%. Transthoracic echocardiography showed impaired left ventricular ejection fraction of 27%, mean aortic pressure gradient of 70.5 mm Hg, aortic valve area of 0.6 cm2, and peak velocity of 6.3 m/s. For precise aortic annulus measurement, transoesophageal echocardiography (TEE) and a computed tomography scan were performed and revealed a heavily calcified bicuspid valve with mean annulus diameter of 24 mm. Angiography demonstrated a significant lesion in the 3rd segment of right coronary artery (RCA). Due to the high operative risk, the patient was referred by the Heart Team for percutaneous coronary intervention of RCA and transcatheter aortic valve implantation (TAVI) via the femoral route (considering the absence of atherosclerotic lesions in ilio-femoral arteries). Native valve was predilated with a 22 mm Numed balloon catheteter (Fig. 1A). On the basis of pre-procedural imaging, a 29 mm Medtronic CoreValveTM bioprosthesis was implanted at the annulus level. However, control angio and TEE showed low implantation accompanied by significant paravalvular aortic regurgitation (Fig. 1B). Haemodynamic measurement also confirmed a suboptimal effect with low diastolic aortic pressure (DAP) and high left-ventricular end-diastolic pressure (LVEDP) (Fig. 2A). Therefore, the decision was made to implant a second bioprosthesis — another 29 mm CoreValve was placed and deployed 8–10 mm higher than the first one (Fig. 1C). Implantation of the second valve significantly decreased the magnitude of regurgitation from severe to no or mild, both in angiography and pressure recordings (Figs. 1D and 2A, respectively). It has been shown in several observational and randomised trials that even mild paravalvular regurgitation after TAVI is an independent predictor of long-term mortality. It is therefore of crucial importance to diagnose early and minimise the grade of regurgitation by post-dilatation or second valve deployment. This case demonstrates that apart from imaging modalities, direct pressure measurement is an easy, reliable and reproducible method of paravalvular leak detection. Recently, it has been shown in a non-selected population of TAVI procedures that pressure gradient DDAP-LVEDP is a powerful predictor of mortality.

Dynamin‐related protein 1 (Drp1)‐mediated diastolic dysfunction in myocardial ischemia‐reperfusion injury: therapeutic benefits of Drp1 inhibition to reduce mitochondrial fission

Mitochondrial fission, regulated by dynamin-related protein-1 (Drp1), is a newly recognized determinant of mitochondrial function, but its contribution to left ventricular (LV) impairment following ischemia-reperfusion (IR) injury is unknown. We report that Drp1 activation during IR results in LV dysfunction and that Drp1 inhibition is beneficial. In both isolated neonatal murine cardiomyocytes and adult rat hearts (Langendorff preparation) mitochondrial fragmentation and swelling occurred within 30 min of IR. Drp1-S637 (serine 637) dephosphorylation resulted in Drp1 mitochondrial translocation and increased mitochondrial fission. The Drp1 inhibitor Mdivi-1 preserved mitochondrial morphology, reduced cytosolic calcium, and prevented cell death. Drp1 siRNA similarly preserved mitochondrial morphology. In Langendorff hearts, Mdivi-1 reduced mitochondrial reactive oxygen species, improved LV developed pressure (92±5 vs. 28±10 mmHg, P<0.001), and lowered LV end diastolic pressure (10±1 vs. 86±13 mmHg, P<0.001) following IR. Mdivi-1 was protective if administered prior to or following ischemia. Because Drp1-S637 dephosphorylation is calcineurin sensitive, we assessed the effects of a calcineurin inhibitor, FK506. FK506 treatment prior to IR prevented Drp1-S637 dephosphorylation and preserved cardiac function. Likewise, therapeutic hypothermia (30°C) inhibited Drp1-S637 dephosphorylation and preserved mitochondrial morphology and myocardial function. Drp1 inhibition is a novel strategy to improve myocardial function following IR.

Intracoronary Delivery of Autologous Cardiac Stem Cells Improves Cardiac Function in a Porcine Model of Chronic Ischemic Cardiomyopathy

Relevant preclinical models are necessary for further mechanistic and translational studies of c-kit+ cardiac stem cells (CSCs). The present study was undertaken to determine whether intracoronary CSCs are beneficial in a porcine model of chronic ischemic cardiomyopathy. Pigs underwent a 90-minute coronary occlusion followed by reperfusion. Three months later, autologous CSCs (n=11) or vehicle (n=10) were infused into the infarct-related artery. At this time, all indices of left ventricular (LV) function were similar in control and CSC-treated pigs, indicating that the damage inflicted by the infarct in the 2 groups was similar; 1 month later, however, CSC-treated pigs exhibited significantly greater LV ejection fraction (echocardiography) (51.7±2.0% versus 42.9±2.3%, P<0.01), systolic thickening fraction in the infarcted LV wall, and maximum LV dP/dt, as well as lower LV end-diastolic pressure. Confocal microscopy showed clusters of small α-sarcomeric actin-positive cells expressing Ki67 in the scar of treated pigs, consistent with cardiac regeneration. The origin of these cycling myocytes from the injected cells was confirmed in 4 pigs that received enhanced green fluorescent protein -labeled CSCs, which were positive for the cardiac markers troponin I, troponin T, myosin heavy chain, and connexin-43. Some engrafted CSCs also formed vascular structures and expressed α-smooth muscle actin. Intracoronary infusion of autologous CSCs improves regional and global LV function and promotes cardiac and vascular regeneration in pigs with old myocardial infarction (scar). The results mimic those recently reported in humans (Stem Cell Infusion in Patients with Ischemic CardiOmyopathy [SCIPIO] trial) and establish this porcine model of ischemic cardiomyopathy as a useful and clinically relevant model for studying CSCs.

Transcatheter Closure of Secundum Atrial Septal Defect in Patients Over 60 Years Old

Transcatheter Closure of Secundum Atrial Septal Defect in Patients Over 60 Years Old

ASSOCIATION OF STAT3 WITH HSF1 PLAYS A CRITICAL ROLE IN G-CSF-INDUCED CARDIO-PROTECTION AGAINST ISCHAEMIA/REPERFUSION INJURY

ObjectivesGranulocyte Colony-stimulating Factor (G-CSF) has been shown to be cardio-protective against ischaemia through activating Jak2/Stat3 pathway, however, the mechanism is unclear. Heat shock transcription factor 1 (HSF1), a definite endogenous...

The vitamin D receptor activator paricalcitol prevents fibrosis and diastolic dysfunction in a murine model of pressure overload

BackgroundActivation of the vitamin D–vitamin D receptor (VDR) axis has been shown to reduce blood pressure and left ventricular (LV) hypertrophy. Besides cardiac hypertrophy, cardiac fibrosis is a key element of adverse cardiac remodeling. We hypothesized that activation of the VDR by paricalcitol would prevent fibrosis and LV diastolic dysfunction in an established murine model of cardiac remodeling. MethodsMice were subjected to transverse aortic constriction (TAC) to induce cardiac hypertrophy. Mice were treated with paricalcitol, losartan, or a combination of both for a period of four consecutive weeks. ResultsThe fixed aortic constriction caused similar increase in blood pressure, both in untreated and paricalcitol- or losartan-treated mice. TAC significantly increased LV weight compared to sham operated animals (10.2±0.7 vs. 6.9±0.3mg/mm, p<0.05). Administration of either paricalcitol (10.5±0.7), losartan (10.8±0.4), or a combination of both (9.2±0.6) did not reduce LV weight. Fibrosis was significantly increased in mice undergoing TAC (5.9±1.0 vs. sham 2.4±0.8%, p<0.05). Treatment with losartan and paricalcitol reduced fibrosis (paricalcitol 1.6±0.3% and losartan 2.9±0.6%, both p<0.05 vs. TAC). This reduction in fibrosis in paricalcitol treated mice was associated with improved indices of LV contraction and relaxation, e.g. dPdtmax and dPdtmin and lower LV end diastolic pressure, and relaxation constant Tau. Also, treatment with paricalcitol and losartan reduced mRNA expression of ANP, fibronectin, collagen III and TIMP-1. DiscussionTreatment with the selective VDR activator paricalcitol reduces myocardial fibrosis and preserves diastolic LV function due to pressure overload in a mouse model. This is associated with a reduced percentage of fibrosis and a decreased expression of ANP and several other tissue markers.

Association of Stat3 with HSF1 plays a critical role in G-CSF-induced cardio-protection against ischemia/reperfusion injury

Granulocyte colony-stimulating factor (G-CSF) has been shown to be cardio-protective against ischemia through activating Jak2/Stat3 pathway, however, the mechanism is unclear. Heat shock transcription factor 1 (HSF1), a definite endogenous protective protein in cardiomyocytes, may interact with Stat family under stress conditions. We hypothesized that G-CSF could induce cardio-protection against ischemia/reperfusion (I/R) through association of HSF1 with Stat3. To test the hypothesis, we built cardiac I/R injury model with HSF1 knockout (KO) mice and wild type (WT) mice by occlusion of the left anterior descending (LAD) coronary artery for 30min and subsequent release of the occlusion for 24h. These mice were administered with G-CSF (100μg/kg/day) or vehicle subcutaneously for 3days before surgery. As expected, G-CSF induced significant cardio-protections against I/R injury, characterized by higher ejection fraction (EF%), lower left ventricular end diastolic pressure (LVEDP), increased dp/dt value and decreased infarct area as compared with the vehicle treatment in WT mice. In HSF1-KO mice, however, these cardio-protections induced by G-CSF were greatly attenuated. Inhibition of oxidative stress-induced cardiomyocyte apoptosis by G-CSF also disappeared due to the deficiency of HSF1 in vitro and in vivo. Furthermore, G-CSF increased the phosphorylation and the association of Stat3 with HSF1, which enhanced transcriptional activity of HSF1. Inhibition of either Stat3 or HSF1 by pharmacological agents suppressed G-CSF-induced association of the two proteins and anti-apoptotic effect on cardiomyocytes. Our data suggest that G-CSF stimulates phosphorylation and association of Stat3 with HSF1 and therefore enhances transcriptional activity of HSF1, leading to the cardio-protection against I/R injury.

Angiotensin-(1-7)/Angiotensin-Converting Enzyme 2/Mas Receptor Axis and Related Mechanisms

Angiotensin-(1-7)/Angiotensin-Converting Enzyme 2/Mas Receptor Axis and Related Mechanisms

The Effect of the Thioether-Bridged, Stabilized Angiotensin-(1–7) Analogue Cyclic Ang-(1–7) on Cardiac Remodeling and Endothelial Function in Rats with Myocardial Infarction

Modulation of renin-angiotensin system (RAS) by angiotensin-(1–7) (Ang-(1–7)) is an attractive approach to combat the detrimental consequences of myocardial infarction (MI). However Ang-(1–7) has limited clinical potential due to its unfavorable pharmacokinetic profile. We investigated effects of a stabilized, thioether-bridged analogue of Ang-(1–7) called cyclic Ang-(1–7) in rat model of myocardial infarction. Rats underwent coronary ligation or sham surgery. Two weeks thereafter infusion with 0.24 or 2.4 μg/kg/h cAng-(1–7) or saline was started for 8 weeks. Thereafter, cardiac morphometric and hemodynamic variables as wells as aortic endothelial function were measured. The average infarct size was 13.8% and was not changed by cAng-(1–7) treatment. MI increased heart weight and myocyte size, which was restored by cAng-(1–7) to sham levels. In addition, cAng-(1–7) lowered left ventricular end-diastolic pressure and improved endothelial function. The results suggest that cAng-(1–7) is a promising new agent in treatment of myocardial infarction and warrant further research.

Assessment of left ventricular regional myocardial systolic function after bone marrow mesenchymal stem cells injection in rabbits with acute myocardial infarction by speckle tracking imaging

Objective To assess the left ventricular(LV) regional myocardial systolic function after bone marrow mesenchymal stem cells (BMSCs) injection in rabbits with acute myocardial infarction(AMI) by 2-dimensional ultrasound speckle-tracking imaging.Methods Twenty-four healthy rabbits were randomly divided into three groups:group of sham-operated,group of masculine control (AMI was induced by ligation of left anterior descending coronary artery),and group of cell infusion(after two weeks of AMI,bone marrow mesenchymal stem cells were injected to the region of AMI).Four weeks after cell deliver two-dimensional strain images were acquired from LV short-axis view(at the levels of mitral annulus,muscle papillary and apex),radial strain rate (SrR),circumference strain rate (SrC),rotation rate (RotR) and rotation (Rot) of three levels in short-axis views were measured by speckle-tracking imaging.The conventional echocardiography indices included LV diameter of end diastole(LVEDd),LV ejection fraction(LVEF),LV fractional shortening(LVFS).The catheter indices included LV systolic pressure(LVSP),LV end diastolic pressure (LVEDP)and maximum rate of rise and descend of LV pressure(LVdp/dtmax).ResultsCompared with sham-operated group,rabbits had significantly larger LVEDd,lower LVEF and LVFS,lower LVSP and LVdp/dtmax,higher LVEDP in control group,SrR,SrC,RotR and Rot of LV anterior regional myocardial function and global myocardial function of three levels in short-axis views were lower.Compared with control group,the rabbits had significantly smaller LVEDd,larger LVEF and LVFS,larger LVSP and LVdp/dtmax,lower LVEDP,SrR,SrC,RotR and Rot of LV anterior regional myocardial function and global myocardial function of three levels in short-axis views were larger in group of cell infusion.There was no significant between group of cell infusion and group of sham-operated.Conclusions Speckle tracking imaging can evaluate the regional myocardial systolic function of the area of BMSCs transplantation accurately. Key words: Echocardiography; Myocardial infarction; Mesenchymal stem cell transplantation; Ventricular function; Speckle tracking imaging

Volume loading reduces pulmonary vascular resistance in ventilated animals with acute lung injury: evaluation of RV afterload

During mechanical ventilation, increased pulmonary vascular resistance (PVR) may decrease right ventricular (RV) performance. We hypothesized that volume loading, by reducing PVR, and, therefore, RV afterload, can limit this effect. Deep anesthesia was induced in 16 mongrel dogs (8 oleic acid-induced acute lung injury and 8 controls). We measured ventricular pressures, dimensions, and stroke volumes during positive end-expiratory pressures of 0, 6, 12, and 18 cmH(2)O at three left ventricular (LV) end-diastolic pressures (5, 12, and 18 mmHg). Oleic acid infusion (0.07 ml/kg) increased PVR and reduced respiratory system compliance (P < 0.05). With positive end-expiratory pressure, PVR was greater at a lower LV end-diastolic pressure. Increased PVR was associated with a decreased transseptal pressure gradient, suggesting that leftward septal shift contributed to decreased LV preload, in addition to that caused by external constraint. Volume loading reduced PVR; this was associated with improved RV output and an increased transseptal pressure gradient, which suggests that rightward septal shift contributed to the increased LV preload. If PVR is used to reflect RV afterload, volume loading appeared to reduce PVR, thereby improving RV and LV performance. The improvement in cardiac output was also associated with reduced external constraint to LV filling; since calculated PVR is inversely related to cardiac output, increased LV output would reduce PVR. In conclusion, our results, which suggest that PVR is an independent determinant of cardiac performance, but is also dependent on cardiac output, improve our understanding of the hemodynamic effects of volume loading in acute lung injury.

E0033 Mechanisms of losartan attenuates ventricular remodelling and cardiac function in aortic banded rats with chronic heart failure

ObjectiveTo investigate the regulation of Losartan (Los) on ventricular remodelling and cardiac functioning chronic heart failure rats induced by aortic banded.MethodsSprague-Dawley (SD) rats underwent abdominal aorta coarctation to induce CHF,...

Does on-pump/beating-heart coronary artery bypass grafting offer better outcome in end-stage coronary artery disease patients?

The purpose of our study was to evaluate in a cohort of end-stage coronary artery disease (ESCAD) patients the effects of on-pump/beating-heart versus conventional coronary artery bypass grafting (CABG) requiring cardioplegic arrest. We report early and midterm survival, morbidity, and improvement of left ventricular (LV) function. Between January 1992 and October 1999, 107 (Group I) ESCAD patients underwent on-pump/beating-heart surgery and 191 (Group II) ESCAD patients underwent conventional CABG requiring cardioplegic arrest. Mean age in Group I was 65.8 +/- 6.5 years (58-79 years); New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) classifications were 3.2 +/- 0.4 and 3.3 +/- 0.5, respectively. LV ejection fraction (LVEF) was 24.8% +/- 4%, LV end diastolic pressure (LVEDP) was 28.2 +/- 3.8 mmHg, and LV end diastolic diameter (LVEDD) was 69.6 +/- 4.6 mm. Mean age in Group II was 64.1 +/- 5 years (57-76 years), NYHA class was 3 +/- 0.6, CCS class was 3.4 +/- 0.4, LVEF was 26.2% +/- 4.3%, LVEDP was 27.2 +/- 3.4 mmHg, and LVED was 68 +/- 4.2 mm. Preoperatively, Group I patients versus Group II patients had a markedly depressed LV function (LVEF, p = 0.006; LVEDP, p = 0.02; LVEDD, p = 0.003; and NYHA class, p = 0.002), older age (p = 0.012), and higher incidences of multiple acute myocardial infarction (AMI; p = 0.004), cardiovascular disease (CVD; p = 0.008), and chronic renal failure (CRH, p = 0.002). Cardiopulmonary bypass (CPB) time was longer in Group II patients (p = 0.028). The mean distal anastomosis per patient was similar between groups (p = NS). Operative mortality between Groups I and II was 7 (6.5%) and 19 (10%), respectively (p = NS). Perioperative AMI (p = 0.034), low cardiac output syndrome (LCOS; p = 0.011), necessity for ultrafiltration (p = 0.017), and bleeding (p = 0.012) were higher in Group II. Improvement of LV function within 3 months after the surgical procedure was markedly higher in Group I, demonstrated by increased LVEF (p = 0.035), lower LVEDP (p = 0.027), and LVEDD (p = 0.001) versus the preoperative data in Group II. The actuarial survivals at 1, 3, and 5 years were 95%, 86%, and 73% in Group I and 95%, 84%, and 72% in Group II (p = NS). ESCAD patients with bypassable vessels to two or more regions of reversible ischemia can undergo safe CABG with acceptable hospital survival and mortality and morbidity. In higher risk ESCAD patients, who may poorly tolerate cardioplegic arrest, on-pump/beating-heart CABG may be an acceptable alternative associated with lower postoperative mortality and morbidity. Such a technique offers better myocardial and renal protection associated with lower postoperative complications.

Apelin Antagonizes Myocardial Impairment in Sepsis

Background Apelin is a cardiovascular peptide with multiple functions regulating homeostasis of the circulatory system and is the endogenous ligand of angiotensin II receptor like-1 (AGTRL1). Apelin has anti-inflammatory and inhibitory effects on release of inflammatory mediators. We aimed to analyze whether apelin antagonizes myocardial impairment in sepsis by attenuating inflammatory responses. Methods and Results Male rats underwent sepsis by cecal ligation and puncture (CLP) after receiving low- or high-dose apelin for 3 days. Twenty hours later, rats with sepsis showed severe disturbance of hemodynamic features. Reverse transcription-polymerase chain reaction revealed decreased mRNA levels of apelin and AGTRL1 in myocardia of rats with sepsis. Enzyme immune assay detected a lower level of apelin in plasma and myocardia. Western blot analysis revealed decreased level of myocardial AGTRL1 protein. Low- and high-dose apelin administration ameliorated disorders of cardiac function: increased mean arterial blood pressure, attenuated heart rate, elevated +LVdp/dt max and LVdp/dt max, and lowered left ventricular end-diastolic pressure. Rats treated with low- or high-dose apelin showed lower content of plasma monocyte chemoattractant protein 1and interleukin 8. In cultured rat peritoneal macrophages, apelin directly inhibited the production of monocyte chemoattractant protein 1 and interleukin-8 induced by lipopolysaccharide. Conclusions These results suggest that apelin antagonizes cardiac impairment in sepsis by attenuating inflammatory responses and might be a promising therapeutic target for severe sepsis and septic shock.

Emotional Stress and Tako-Tsubo Cardiomyopathy

BackgroundTako-tsubo syndrome is a transient cardiomyopathy usually precipitated by an acute emotional or physiological stress. Our study objectives were to review and analyze the impact of emotional stress on clinical...