Left Ventricular Diastolic Pressure Research Articles

Ginsenoside Rb1 pretreatment attenuates myocardial ischemia by reducing calcium/calmodulin-dependent protein kinase II-medicated calcium release

Objective: The aim of this study was to investigate the protective effects of ginsenoside Rb1 and assess whether these protective effects are related to calcium/calmodulin-dependent protein kinase II (CaMKII).Methods: A myocardial ischemia (IS) rat. model and a myocardial H9C2 cell hypoxia model were established. MI was induced by occluding the left anterior descending artery for 120 min. Ginsenoside Rb1 (10 mg/kg) was administered 30 min before ischemia induction, and the treatment continued for 7 days. Results: In the rat IS injury model, ginsenoside Rb1 reduced myocardial infarct size, mean left ventricular diastolic pressure, incidence of arrhythmia, and levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde. However, the mean left ventricular systolic pressure, and maximal rising and falling rates of ventricular pressure (±dp/dtmax) increased. In the myocardial H9C2 cell hypoxia model, ginsenoside Rb1 reduced intracellular calcium concentrations ([Ca2+ ]i) during hypoxia, and markedly reversed the hypoxia-induced decrease in cell survival. Ginsenoside Rb1 was involved in the downregulation of CaMKII and the ryanodine receptor, as well as hypoxia-induced H9C2 cell survival. Conclusion: The findings of the present study suggest that ginsenoside Rb1 attenuates MI injury in rats, partially through the downregulation of CaMKII expression.

Hypothyroidism and the heart

The cardiovascular system is sensitive to the action of thyroid hormones, and thyroid dysfunction causes a wide spectrum of cardiovascular changes. The effect of overt hypothyroidism on the cardiovascular system has long been recognised. Nowadays, the clinical presentation of cardiovascular symptoms related to hypothyroidism is only rarely observed due to early diagnosis of hypothyroidism by easily available thyroid-stimulating hormone assays. Overt hypothyroidism causes changes in such parameters of cardiovascular function as heart rate, left ventricular systolic and diastolic function, blood, arterial pressure and systemic vascular resistance. During the last years, there has been increasing evidence that subclinical hypothyroidism may also impair the cardiovascular system. This review discusses the effect of hypothyroidism on the cardiovascular system.

Intermittent Occlusion of the Superior Vena Cava Reduces Cardiac Filling Pressures in Preclinical Models of Heart Failure.

Congestion is a major determinant of clinical outcomes in heart failure (HF). We compared the acute hemodynamic effects of occlusion of the superior (SVC) versus the inferior vena cava (IVC) and tested a novel SVC occlusion system in swine models of HF. IVC occlusion acutely reduced left ventricular (LV) systolic and diastolic pressures, LV volumes, cardiac output (CO), and mean arterial pressure (MAP). SVC occlusion reduced LV diastolic pressure and volumes without affecting CO or MAP. The preCARDIA system is a balloon occlusion catheter and pump console which enables controlled delivery and removal of fluid into the occlusion balloon. At 6, 12, and 18h, SVC therapy with the system provided a sustained reduction in cardiac filling pressures with stable CO and MAP. Intermittent SVC occlusion is a novel approach to reduce biventricular filling pressures in HF. The VENUS-HF trial will test the safety and feasibility of SVC therapy in HF.

Flaxseed and evening primrose oil slightly affect systolic and diastolic function of isolated heart in male but not in female rats.

Considering that sex related differences in cardiac response to flaxseed (FSO) and evening primrose oil (EPO) are insufficiently known present investigation assessed the effect of these two oils, on the cardiac function of isolated rat hearts and the possible role of sex in this. The present study was carried out on 60 adult male Wistar albino rats randomly divided into 6 groups: male rats treated with EPO, dose of 10mg/kg/day; female rats treated with EPO, dose of 10mg/kg/day; male rats treated with FSO, dose of 300mg/kg/day; female rats treated with FSO, dose of 300mg/kg/day; control group of female rats treated with regular laboratory diet for animals; control group of male rats treated with regular laboratory diet for animals. Using the Langendorff technique, markers of the heart function were evaluated: the maximum and minimum rates of pressure development in the left ventricle (LV; dP/dtmax, dP/dtmin), systolic and diastolic left ventricular pressure (SLVP, DLVP, respectively), heart rate (HR) and coronary flow (CF). Male rats treated with EPO had significantly higher (p=0.016) mean values of dP/dtmax, dP/dtmin, SLVP and DLVP (average increase for all CPPs 20%, 25%, 30% and 110%, respectively), compared to the group of male rats treated with FSO (p=0.914). Our study results indicate that both types of PUFA oils only slightly changed the function of the isolated rat heart in male but not in female rats. Nevertheless, the difference between oil treatments was found in male rats who had stronger cardiac response after supplementation with EPO.

Left Atrial Phasic Function in Patients with Hypertension and Recurrent Atrial Fibrillation: Gender Differences of the Relationship with Diastolic Dysfunction and Central Aortic Pressure

Aim. To evaluate gender-related differences of left atrial (LA) phasic function and structural remodeling in conjunction with the parameters of left ventricular (LV) diastolic dysfunction and central aortic pressure in patients with hypertension and recurrent atrial fibrillation (AF).Material and methods. The comparative study included 30 men and 37 women with non-valvular AF, hypertension and LV hypertrophy. Conventional echocardiographic measures were extended with LA measures, including its volume in three phases, LAemptying fraction (LAEF), passive and active ejection fraction. The parameters of central aortic pressure were estimated by applanation tonometry method.Results. No difference was observed between LA and LV structural parameters in men and women. However, in women LAEF (39 [28;50] vs 50 [42;55]%; p=0.02) and E/E’(9.7 [7.8;12] vs 7.1 [5.6;8.6]; p=0.001) were worse than in men. Active LA ejection fraction was higher in women (31 [21;42] vs 24 [19;31]%; p=0.04), whereas passive one – in men (12 [10;14] vs 33 [23;38]%; p<0.001), respectively. Men and women had comparable heart rate (HR), central and peripheral systolic and diastolic pressure, pulse wave velocity (PWV), but women had higher augmentation index (AI) values [33 [28;39] vs 23 [21;28]%; p<0.001], even adjusted by HR (AI 75) (34 [27;39] vs 26 [20;29]%; p<0.001). Only in men PWV weakly correlated with AI 75 (r=0.44; p=0.02 versus r=-0.11; p=0.51, respectively for men and women; intergroup differences: z=2.26; p=0.012). In a multivariate regression analysis in men LAEF was significantly associated with height, weight, E’, E/E’ and glomerular filtration rate (GFR), whereas in women – with E’ and AI 75.Conclusion. Patients of different genders with recurrent AF and hypertension have comparable LA structuralremodeling. However, women characterized by a more pronounced decrease in LAEF and impaired LV diastolic function than men. In women as distinct from men LV filling is predominantly due to LA systole. In a multivariate regression analysis in men LAEF was significantly associated with height, weight, E’, E/E’ and GFR, whereas in women – with E’ and AI 75.

TLR4/NF-kappaB p65 signaling pathway mediates protective effect of triptolide on endothelium in rats with endotoxemia

The aim of this paper was to observe the effect of triptolide( TP) on cardiovascular function and its possible mechanism by intraperitoneal injection of bacterial lipopolysaccharide in rats with endotoxemia. Sixty male Sprague-Dawley rats were randomly divided intonormal group( NC group),endotoxemia model group( LPS group),TP low concentration intervention group( LPS + TP-L group,25 μg·kg~(-1)),TP middle concentration intervention group( LPS+TP-M group,50 μg·kg~(-1)),TP high concentration intervention group( LPS+TP-H group,100 μg·kg~(-1)) and polymyxin B group( LPS+PMX-B group,0. 2 mg·kg~(-1)). 10 mg·kg~(-1) LPS was injected intraperitoneally for 6 h to replicate the endotoxemia rat model. The rats in TP intervention groups were pre-treated 15 min before intraperitoneal injection of LPS. Rats in each group underwent total arterial intubation to measure hemodynamic parameters: heart rate( HR),left ventricular diastolic pressure( LVDP),the maximum rate of the increase/decrease of left ventricular pressure( ±dp/dtmax). The levels of BNP,CK-MB and c Tn-Ⅰ in serum and levels of TNF-α and IL-6 in plasma were detected by ELISA. The contents of p65 protein in myocardium and contents of p65,TLR4,i NOS and e NOS protein in thoracic aorta were detected by Western blot. As compared with NC group,the hemodynamic indexes in LPS group were significantly decreased; the contents of BNP,CK-MB and c Tn-Ⅰ in serum,TNF-α and IL-6 in plasma,p65 in myocardium,i NOS,e NOS,TLR4 and p65 in vascular tissues were significantly increased. As compared with LPS group,the hemodynamic indexes were significantly improved in LPS+TP-M group,LPS+TP-H group and LPS+PMX-B group; the contents of BNP,CK-MB and c Tn-Ⅰ in serum,TNF-α and IL-6 in plasma,p65 in myocardium,i NOS,e NOS,TLR4 and p65 in vascular tissues were significantly decreased in each treatment group. Triptolide has a protective effect on cardiovascular damage in a dose-dependent manner in endotoxemia rats,probably through TLR4/NF-κB p65 signaling pathway to improve endothelial function.

P4351Validation by cardiac catheterization of noninvasive evaluation of left ventricular chamber and myocardial stiffness as a diastolic function using speckle tracking echocardiography

Abstract Background Left ventricular (LV) diastolic function is mainly composed of LV relaxation and LV stiffness. We reported that pulmonary capillary wedge pressure (ePCWP) and LV relaxation assessed by Tau (eTau) are noninvasively evaluated by speckle tracking echocardiography (STE). The minimum LV diastolic pressure (mLVP) was reported to have a strong correlation with Tau. Therefore, LV chamber stiffness (c-stiffness) may be assessed with the use of two LV diastolic pressure-volume coordinates: the mLVP and volume and the end-diastolic pressure (EDP) and volume. Purpose We sought to noninvasively assess LV stiffness using STE and validate the value by cardiac catheterization. Methods Echocardiography and catheterization were performed in 124 patients (age 72±8) (70 angina pectoris, 20 prior myocardial infarction, 19 hypertensive heart disease, 11 congestive heart failure and 4 paroxysmal atrial fibrillation). The ePCWP (mmHg) is noninvasively obtained as 10.8 − 12.4 × Log (left atrial active emptying function/minimum volume) and the eTau (ms) is obtained as isovolumic relaxation time/(ln 0.9 × systolic blood pressure − ln ePCWP) as previously reported. The mLVP (e-mLVP) was estimate using Tau. The estimated EDP (e-EDP) was calculated as 12.3 − 10.1 × Log (left atrial active emptying function / minimum volume). LV c-stiffness (mmHg/ml) was calculated as LV pressure change (from mLVP to EDP) obtained by catheterization divided by LV volume change during diastole which equals to stroke volume by echocardiography. Estimated c-stiffness (e-c-stiffness) was noninvasively obtained using e-mLVP and e-EDP. Furthermore, LV myocardial stiffness (m-stiffness) was calculated by LVED stress / LV longitudinal strain by STE, where LV stress (kdynes/cm2) was calculated as 0.334 × pressure × dimension / [thickness (1 + thickness/dimension)]. The estimated m-stiffness (e-m-stiffness) was calculated using e-EDP. Results The eTau and e-EDP estimated by STE had a good correlation with Tau and EDP invasively obtained by catheterization (r=0.75 and 0.63, respectively, both p<0.001). There was a good correlation between Tau and mLVP (Tau = 2.06 mLVP + 33.7, r=0.70). The estimated LVED stress had good correlation with ED stress obtained by catheterization (r=0.77, p<0.001). The e-c-stiffness and e-m-stiffness had a good correlation with those obtained by catheterization (e-c-stiffness; 0.116±0.07 and c-stiffness; 0.115±0.06, r=0.603, e-m-stiffness; 0.81±0.41 and m-stiffness; 0.85±0.45, r=0.89, respectively). Bland-Altman analysis revealed a good agreement between e-c-stiffness and c-stiffness, and between e-m-stiffness and m-stiffness without fixed and proportional bias. Conclusion This study demonstrated that LV stiffness may be noninvasively assessed by STE with reasonable accuracy and may have utility and value in the routine clinical practice for the diagnosis and treatment in patients with diastolic dysfunction.

P4384Noninvasive and novel method to evaluate left ventricular contractility using pressure-volume loop area obtained by 3-dimensional speckle tracking echocardiography

Abstract Introduction Left ventricular (LV) pressure-volume (P-V) loop area reflects stroke work (SW), but clinical use of this index is limited by the need of invasive pressure measurement. A noninvasive method to obtain LV pressure-strain loop was recently introduced to assess myocardial work (MW). The minimum LV diastolic pressure (mLVP) was reported to have a strong correlation with Tau and we reported that Tau was noninvasively evaluated by speckle tracking echocardiography (STE). Purpose We sought to evaluate the impact of preload change by leg lifts on LV SW noninvasively obtained by the novel method and to examine the utility to assess LV contractility by SW and end-diastolic (ED) volume relation (SW-VED). Methods Thirty six controls (age 71±10) and 30 patients with heart failure with reduced ejection fraction (EF) <50% (HF) (age 73±6) were enrolled. LV pressure in a cardiac cycle was estimated using systolic blood pressure (SBP), minimum diastolic pressure (mDP) and ED pressure (EDP) by utilizing the profile of an empiric, normalized reference curve. The mDP and EDP were estimated as (Tau − 33.7)/2.06 and as 12.3 − 10.1 x Log (left atrial active emptying function/minimum volume) as we reported. LVSW was obtained by P-V loop by the combination of these pressures and LV volume using 3-D STE. Results LVEF and longitudinal strain in HF before leg up by 3D-STE were lower compared to normal (LVEF; normal: 58±5 vs HF: 39±10*% and strain; −12±3 vs −8±3%*, *p<0.05 vs normal). LVEF was increased after leg up by 7±6% in normal and by 8±8% in HF associated with increased LVED volume (normal: 84±24 to 90±24 and HF: 124±36* to 136±42*ml). LV MW and SW in HF before leg up were lower compared to normal (MW: 1790±412 vs 1002±432*mmHg% and SW: 3946±1682 vs 3352±1026mmHgml). LV SW increased after leg up by 26±19% in normal and by 25±20% in HF. LV SW-VED in normal was greater than HF (241±151 vs 90±54*). Conclusion LV SW noninvasively obtained by P-V loop area was increased after leg up in both normal and HF but SW-VED in HF was smaller than normal, indicating reduced contractility in HF. This noninvasive method may be a new echocardiographic approach for quantification of LV SW and contractility.

Hemodynamic Congestion at Hospital Discharge Predicts Rehospitalization during Short Term Follow Up in Acute Heart Failure Patients

Background: Hemodynamic congestion is an increase in left ventricular diastolic pressure (LVEDP) without clinical symptoms and signs of congestion. Current acute heart failure (AHF) treatment goals only focused on improving clinical congestion. The purpose of this study was to investigate whether hemodynamic congestion measured by NT-proBNP level and ePCWP at hospital discharge could predict short term clinical outcomes in AHF patients.
 Method: This prospective cohort study was conducted at dr. Saiful Anwar General Hospital Malang from January to July 2018. All patients got AHF treatment according to the 2016 ESC guidelines for heart failure. All patients were discharged without symptoms and signs of clinical congestion. Hemodynamic congestion at hospital discharge was defined as failure of treatment during hospitalization to achieve a reduction in NT-proBNP level >30% and/or ePCWP at hospital discharge >16 mmHg. NT-proBNP level and ePCWP were measured at 0-12 hours after hospital admisssion and at hospital discharge. ePCWP was measured using echocardiography. The clinical outcomes assessed were AHF rehospitalization and cardiovascular mortality within 30 days after hospitral discharge. Subgroup analysis was performed to determine therapeutic regimens that are effective in improving hemodynamic congestion.
 Result: A total of 33 AHF patients were included in this study. 48% patients were discharged with hemodynamic congestion and 52% patients discharged without hemodynamic congestion. Patients with hemodynamic congestion at hospital discharge showed a higher rehospitalization within 30 days (8 [50%] vs 1 [5.9%]; P = 0.007). Mortality within 30 days in both groups did not show a significant difference (2 [12.5%] vs 0 [0%]; P = 0.277). Treatment regiment of optimal dose of ACEi/ARB, β-blockers, and diuretics was associated with improvement of hemodynamic congestion (P = 0.026; r = 0.454), a decrease in NT-proBNP> 66% (P = 0.02; r = 0,574), and achievement of ePCWP <16 (P = 0,013; r = 0,493) at hospital discharge in HFrEF patients.
 Conclusion: This study showed that hemodynamic congestion assessed with NT-proBNP level and ePCWP at hospital discharge increased 30 day rehospitalization in AHF patients. In HFrEF, improvements in hemodynamic congestion can be achieved by giving the treatment regiment of optimal dose of ACEi/ARB, β-blockers, and diuretics.
 Keyword: Acute heart failure, hemodynamic congestion, NT-proBNP, ePCWP

The influence of folic acid-induced acute kidney injury on cardiac function and redox status in rats.

The aim of this study was to evaluate the influence of acute kidney injury caused by high doses of folic acid on cardiac function and markers of oxidative stress in serum and isolated rat heart. Isolated hearts of Wistar albino rats (divided into two groups: control and folic acid group) were perfused according to Langendorff technique at basal coronary perfusion pressure CPP of 70cm H2O. After a stabilization period, CPP was lowered to 60cm H2O and then gradually increased to 80, 100, 120 and finally decreased to 40cm H2O in order to establish coronary autoregulation. For each perfusion pressure value, the left ventricular function parameters were determined. Samples of coronary venous effluent were collected for determination of coronary flow and biomarkers of oxidative stress. The blood samples were collected in order to examine the values of serum urea, creatinine, Na, K, and parameters of oxidative stress and antioxidant defense system. Heart and kidney tissue samples were collected for histopathological examination. Folic acid group showed reduction of systolic and diastolic left ventricular pressure and increase of coronary flow and minimum left ventricular pressure development rate. In coronary flow, folic acid group showed increased levels of TBARS and reduction of H2O2 and NO2-. Serum ROS concentrations were lower in rats treated with folic acid, particularly levels of TBARS and NO2- in which values were significantly lower. The parameters of systemic antioxidative stress were at significantly high levels especially SOD and GSH. This study is the experimental confirmation of cardio-renal syndrome type 3, which represents the acute kidney injury that causes a damage of a heart function. The data suggest that negative effects of acute kidney injury on myocardium do not necessarily involve oxidative stress, which may lead to future investigations which will be based on inflammation as a one of the important factors in the organ crosstalk.

Echocardiographic assessment of left ventricular function

Bedside echocardiography is a cornerstone tool in the management of critically ill patients with hemodynamic compromise. This technique should be considered not only as an imaging technique but as well as a hemodynamical method. Both transthoracic and transesophageal approach are used in intensive care unit (ICU) patients. Left ventricular (LV) systolic function can be assessed in daily clinical practice by measuring ejection fraction (EF) and cardiac output. But these indices are dependent on load conditions. Mitral anterior plane systolic excursion and tissue Doppler imaging (TDI) and speckle tracking by measuring the systolic motion velocity of the mitral annulus and the LV strain may together assess the true contractility of the left ventricle. dP/dt measured on mitral regurgitation flow could help to assess LV contractility. Maximal elastance was described to be the best parameter to evaluate myocardial systolic function but not available in daily practice at the bedside in ICU patients. LV diastolic function and pressure are useful to have a comprehensive evaluation of LV function and could be assessed by recording the mitral flow using pulsed Doppler and the early diastolic velocity of mitral annulus recorded using TDI. Echocardiography should be done in patients with shock to assess the pathophysiology of the shock and in pulmonary oedema to distinguish patients with cardiogenic oedema or acute respiratory distress syndrome (ARDS). Only echocardiography may assess the hemodynamic of patient with shock and/or respiratory failure and the only tool which permits to diagnose the cause of this hemodynamical failure.

Serum Aldosterone Is Related to Left Ventricular Geometry and Function in Young Adults with Never-Treated Primary Hypertension.

Background: Although aldosterone has been demonstrated to induce left ventricular (LV) hypertrophy not only in primary aldosteronism but also in primary hypertension (HT), it can be affected by multiple factors, including age, and the effect of aldosterone on LV function is controversial. This study was to investigate the relationship of aldosterone to changes in LV geometry and function in young adults with never-treated HT. Methods: Seventy-five consecutive patients (age, 29.8 ± 6.3 years) with never-treated HT and 45 normal controls were enrolled. Echocardiographic values and LV global longitudinal strain (LVGLS) were obtained. Serum aldosterone concentration (SAC) and serum procollagen type III amino-terminal peptide (PIIINP) level were obtained in HT patients. Results: HT patients had higher LV mass index, higher relative wall thickness (RWT), and worse LV function than normal controls. LVGLS and e’ velocity were worse in HT patients with normal geometry than in normal controls. SAC was well correlated with LV mass index, RWT, e’ velocity, LVGLS, and PIIINP (all p < 0.05). LV geometry pattern was most related to SAC among clinical parameters (p = 0.019). LVGLS was most related to LV geometry and diastolic blood pressure. In contrast, e’ velocity was most related to PIIINP. Conclusion: Our findings may indicate that in young patients with never-treated HT, aldosterone significantly contributes to changes in LV geometry and functional impairment through its pro-hypertrophic and myocardial fibrosis effects beyond blood pressure.

The prognostic value of pulmonary artery compliance in cardiogenic shock.

The aim of this study was to evaluate the pathophysiological role and the prognostic significance of pulmonary artery compliance (CPA), a measure of right ventricular pulsatile afterload, in cardiogenic shock. We retrospectively included 91 consecutive patients with cardiogenic shock due to primary left ventricular failure, monitored with a pulmonary artery catheter within the first 24 h. CPA was calculated as the ratio of stroke volume to pulmonary artery pulse pressure, and we determined whether CPA predicted mortality and whether it performed better than other pulmonary hemodynamic variables. The overall in-hospital mortality in our cohort was 27%. Survivors and nonsurvivors had comparable left ventricular ejection fraction, systolic, diastolic and mean pulmonary artery pressure, transpulmonary gradient, diastolic pressure gradient, and pulmonary vascular resistance at 24 h. In contrast, CPA was the only pulmonary artery variable significantly associated with mortality in univariate and multivariate analyses. Mortality increased from 4.5% at the highest quartile of CPA (3.6–6.5 mL/mmHg) to 43.5% at the lowest quartile (0.7–1.7 mL/mmHg). In 64 patients with a PAC inserted immediately upon admission, we calculated the trend of CPA between admission and 24 h. This trend was positive in survivors (+0.8 ± 1.3 ml/mmHg) but negative in nonsurvivors (−0.1 ± 1.0 mL/mmHg). The lower CPA in nonsurvivors was associated with more severe right ventricular systolic dysfunction. In conclusion, a reduced compliance of the pulmonary artery promotes right ventricular dysfunction and is independently associated with mortality in cardiogenic shock. Future studies should evaluate the impact on pulmonary arterial compliance and right ventricular afterload of therapies used in cardiogenic shock.

The impact of nine weeks swimming exercise on heart function in hypertensive and normotensive rats: role of cardiac oxidative stress.

The purpose of this study was to estimate the effects of 9-week swimming training on cardiodynamic parameters and coronary flow in a rat model of high salt-induced hypertension with a special focus on the role of oxidative stress. Rats involved in the research were divided randomly into four groups: healthy sedentary (SA), healthy trained (TA), sedentary hypertensive (SHA) and trained hypertensive animals (THA). Trained rats were exposed to 9-week swimming training (5 days/week, 60 min/day). Additionally, in order to induce hypertension animals from SHA and THA groups were on high sodium (8% NaCl solution) diet during 4 weeks. Afterwards all rats were sacrificed and hearts were isolated and retrogradely perfused according to Langendorff technique. The following parameters of cardiac function were continuously recorded: maximum and minimum rate of pressure development in left ventricle, systolic and diastolic left ventricular pressure and heart rate. Coronary flow was measured flowmetrically. Oxidative stress markers were determined in coronary venous effluent. Our findings demonstrated that 9 weeks of swimming training led to improvement of cardiac contractility, relaxation and systolic capacity of normotensive rats, while this training protocol induced enhanced diastolic function in hypertensive conditions. More pronounced effects of exercise in alleviating oxidative stress were observed in hypertensive rats. Obvious beneficial exercise-induced cardiac adaptations provide scientific basis for further researches which would thoroughly clarify the mechanisms through which swimming training alters myocardial function both in healthy conditions and in the presence of chronic diseases.

Echocardiographic assessment of left ventricular diastolic pressure.

Knowledge of the left ventricular pressures throughout the cardiac cycle is of considerable assistance in managing a haemodynamically unstable patient. Invasive pressure measurement is the only accurate way to analyze ventricular diastolic pressures but this is not feasible outside the catheterization laboratory, whereas the use of a pulmonary artery catheter or Doppler echocardiography, using surrogate measurements, is available at the bedside. The ever-increasing trend toward noninvasive monitoring puts echocardiography at the forefront and considerable effort has been made to define its role in this setting. Ongoing refinement of guidelines used to evaluate left ventricular diastolic function have provided a pathway for critical care physicians to better understand how to evaluate left ventricular end-diastolic pressure and/or left atrial pressures. A number of recent studies have investigated the accuracy of combined or single echocardiographic parameters in determining left ventricular diastolic pressures as compared to those obtained invasively. Specifically selected combined parameters have moderate accuracy. The recent literature on the clinical application of echocardiography on the accuracy in determining left ventricular noninvasively demonstrates that although far from perfect, it can be a very useful tool.

Preconditioning with hyperbaric oxygen and calcium and potassium channel modulators in the rat heart

The aim of this study was to establish the effect of combined therapy with hyperbaric oxygen (HBO2) therapy and verapamil, amlodipine or nicorandil on functional recovery and oxidative stress markers after ischemia in the isolated rat heart. The study included 48 rats (Wistar albino, male gender, eight weeks old, body weight 200±50g). All animals were exposed to HBO2 treatment over 14 days. Isolated heart rats were perfused by the Langendorff retrograde method at a constant coronary pressure of 70 cm H2O. After stabilization period the hearts were divided into the following groups: HBO2 group (animals exposed to only HBO2 preconditioning); HBO2 + verapamil; HBO2 + amlodipine; andHBO2 + nicorandil (animals pretreated with HBO2 and appropriate pharmacological agent). Afterward, the hearts in all groups were subjected to 20-minute global ischemia and 30-minute reperfusion. Parameters of heart function were registered, including maximum and minimum rate of pressure development, systolic and diastolic left ventricular pressure, heart rate and coronary flow. Levels of pro-oxidants such as index of lipid peroxidation, measured as thiobarbituric acid-reactive substances, nitrites, levels of superoxide anion radicals and hydrogen peroxide were determined in coronary venous effluent. Changes in cardiac tissue were evaluated by hematoxylin and eosin staining. Obtained results clearly indicate that blockage of calcium channel or the activation of adenosine triphosphate-sensitive potassium (KATP) in combination with HBO2 prevented ischemia/reperfusion-induced cardiac deleterious effects, thus contributing to improvement of functional recovery of the heart. However, future studies are certainly necessary for better understanding the mechanisms through which combination of these two maneuvers of preconditioning triggers cardioprotection.

5-OR: Cardioprotective Effect of Luseogliflozin in Patients with Type 2 Diabetes and Established Cardiovascular Disease

Recent published CV outcome trials have revealed that sodium-glucose cotransporter-2 inhibitors (SGLT2i) significantly reduced the combined CV endpoint and incidences of heart failure-associated hospitalizations in patients with type 2 diabetes mellitus (T2DM) and CV disease (CVD). However, detailed mechanisms of the benefits by SGLT2i still remain unknown. Especially, nobody can show the consensus opinion in the mechanistic effects of SGLT2i on the left ventricular (LV) diastolic dysfunction associated with T2DM. We focused the spectral tissue Doppler-derived E/e' ratio, which has been validated in simple and reproducible noninvasive assessment of LV diastolic pressures independent of rhythm, and evaluated whether or not the treatment of SGLT2i, luseogliflozin, used for 6 months could affect cardiac function in 25 patients with T2DM and CVD. Luseogliflozin used for 6 months significantly reduced HbA1c levels (8.2 ± 1.2% to 7.4 ± 0.6%, p &amp;lt; 0.01) and systolic blood pressure (SBP)(125.6 ± 18.1 mmHg to 119.3 ± 16.8 mmHg, p = 0.04) compared to baseline levels. Moreover, luseogliflozin also significant reduced left atrial (LA) (42.2 ± 5.7 mm to 39.9 ± 6.8 mm, p = 0.01) and LV diameters (diastolic, 49.5 ± 6.9 mm to 47.6 ± 7.6 mm, p = 0.01; systolic, 35.8 ± 9.1 mm to 33.9 ± 9.8 mm, p &amp;lt; 0.01). Remarkably, early annular tissue Doppler (e’) velocity and peak early diastolic velocity/basal septal diastolic velocity (E/e’) ratio were significantly improved, and these benefits were augmented in the group of e’&amp;lt; 6.0cm/sec of baseline (e’ velocity, 4.8 ± 0.6 cm/sec to 5.8 ± 0.9 cm/sec, p &amp;lt; 0.01; E/e’ ratio, 13.0 ± 4.9 to 10.9 ± 3.4, p = 0.03, respectively). There was a significant negative correlation between the changes in E/e’ ratio and baseline of E/e.’ These results indicated that lusegliflozin improved hemodynamics associated with LV diastolic function in the patients with T2DM and CVD, and support the cardio-protective effects of SGLT2i of T2DM with CVD. Disclosure Y. Ina: None. T. Kishi: None. N. Sekiguchi: None. N. Sakane: Board Member; Spouse/Partner; Kao Corporation.

Inhibition of gasotransmitters production and calcium influx affect cardiodynamic variables and cardiac oxidative stress in propofol-anesthetized male Wistar rats 1.

It has been assumed that the cardioprotective effects of propofol are due to its non-anesthetic pleiotropic cardiac and vasodilator effects, in which gasotransmitters (NO, H2S, and CO) as well as calcium influx could be involved. The study on isolated rat heart was performed using 4 experimental groups (n = 7 in each): (1) bolus injection of propofol (100 mg/kg body mass, i.p.); (2) L-NAME (NO synthase inhibitor, 60 mg/kg body mass, i.p.) + propofol; (3) DL-PAG (H2S synthase inhibitor, 50 mg/kg body mass, i.p.) + propofol; (4) ZnPPIX (CO synthase inhibitor, 50 μmol/kg body mass, i.p.) + propofol. Before and after the verapamil (3 μmol/L) administration, cardiodynamic parameters were recorded (dp/dtmax, dp/dtmin, systolic left ventricular pressure, diastolic left ventricular pressure, heart rate, coronary flow), as well as coronary and cardiac oxidative stress parameters. The results showed significant increases of diastolic left ventricular pressure following NO and CO inhibition, but also increases of coronary flow following H2S and CO inhibition. Following verapamil administration, significant decreases of dp/dtmax were noted after NO and CO inhibition, then increase of diastolic left ventricular pressure following CO inhibition, and increase of coronary flow following NO, H2S, or CO inhibition. Oxidative stress markers were increased but catalase activity was significantly decreased in cardiac tissue. Gasotransmitters and calcium influx are involved in pleiotropic cardiovascular effects of propofol in male Wistar rats.

The Immediate Results of Percutaneous Balloon Aortic Valvuloplasty in Patients with Congenital Aortic Valvular Stenosis

Objective: To assess the immediate-term effectiveness of percutaneous balloon aortic valvuloplasty (PBAV) for congenital aortic stenosis (AS). Design: Early clinical and instrumental evaluation of 34 consecutive PBAV performed from 2001&nbsp;to 2007. Setting:&nbsp; A tertiary referral center for heart diseases (Ibn Al-Bitar Cardiac Center). Patients: Thirty-four patients with congenital valvular AS, twenty-five males and nine females. Interventions: PBAV using Tayshak balloons of different sizes and lengths. Main outcome measures:&nbsp; Doppler and peak to peak pressure gradient (PG) across the aortic valve (AV) before and after valvuloplasty, the percent of PG reduction post dilatation, left ventricular (LV) systolic and diastolic pressures before and after valvuloplasty, number of the aortic cusps, degree of aortic regurgitation (AR) before and after valvuloplasty, left ventricular systolic function before and after valvuloplasty, associated anomalies,&nbsp; and the need for emergency surgery were the main outcome measures. Results: The peak to peak instantaneous PG across the AV was reduced acutely from 102 ± 42.7 (20 - 200) mm Hg to 40 ± 25.5 (10- 140) mm Hg (p&lt;0.001), left ventricular systolic pressure was reduced from 196 ± 48.57 (70 – 280) mm Hg to 133 ± 35.45 (65 – 240) mm Hg (p&lt;0.001) and both are statistically significant. Three patients had inadequate relief of obstruction but in one of them it was mainly due to subaortic obstruction and two patients had severe AR, one of them with acute pulmonary edema and required surgical AV repair. PBAV produced a gradient reduction ≥&nbsp;50% in 29&nbsp;patients, six patients&nbsp;having a residual peak to peak gradient of &gt;50 mm Hg and in one of whom the remaining PG was 70 mm Hg which was mainly subvalvular (50 mm Hg). Six patients had bicuspid AV while the other patients had tricuspid valve. Six had associated anomalies. There was no mortality during the procedure. Severe AR reported in two&nbsp;patients and moderate AR occurred in five patients. One significant complication (acute pulmonary edema) occurred immediately after the dilatation and surgery was done for that patient after few days. Two serious complications occurred during the procedure which responded to routine resuscitation. There was a residual maximum Doppler gradient of &lt;&nbsp;30 mm Hg in 12&nbsp;patients, ≥&nbsp;60 mm Hg in four (one of them had mainly subvalvular gradient) and between 30 to 48 mm Hg in the others. Twenty one patients developed new AR (62%), in fourteen of them (41%) it was mild. Conclusions: PBAV is an effective procedure and offers a good palliation for congenital AS.

Pressure and Volume Characteristics of the Left Ventriclе in Its Diastolic and Systolic Dysfunction

Cardiomyopathy in rats has been developed after 4 weeks doxorubicin administration(2 mg / kg weekly). Echocardiographic study of rats in 8 weeks from onset of doxorubicin administration showed preponderanceof systolic dysfunction (67 %) with decrease of left ventricular (LV) ejection fraction (EF) by 30 %. Simultaneous registration of LV pressureand volume showed that diastolic LV volume was preserved in doxorubicin-treated rats due to considerable lengthening of the diastole,the heart rate was reduced by 22 %. These hearts also showed slowing of relaxation, reduced maximal rate of pressure development andstroke work, as well as significant reduction in peripheral arterial resistance. Diastolic dysfunction differed from the systolic one by normalsystolic EF and preserved LV contractility index as well as lower diastolic LV pressure throughout the diastole. Based on thesedata, four compensatory mechanisms associated with cardiomyopathy were distinguished - 1) slowing of myocardial relaxation, prolongingmyofibrillar active state, 2) reduction of peripheral arterial resistance for easier LV ejection, 3) heart rate reduction, prolonging diastolicpause and thus facilitating better LV filling and 4) increased pressure in the small circle, also contributing to the LV rapid filling.