Changes In Ventricular Pressure Research Articles

Activation of ALDH2 alleviates hypoxic pulmonary hypertension in mice by upregulating the SIRT1/PGC-1α signaling pathway

To investigate whether activation of mitochondrial acetal dehydrogenase 2 (ALDH2) alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway. Thirty 8-week-old C57 BL/6 mice were randomized into control, hypoxia, and hypoxia +Alda-1 (an ALDH2 activator) group (n=10), and the mice in the latter two groups, along with 10 ALDH2 knockout (ALDH2-/-) mice, were exposed to hypoxia (10% O2, 90% N2) with or without daily intraperitoneal injection of Alda-1 for 4 weeks. The changes in right ventricular function and pressure (RVSP) of the mice were evaluated by echocardiography and right ventricular catheter test, and pulmonary artery pressure was estimated based on RVSP. Pulmonary vascular remodeling, right ventricular injury, myocardial α -SMA expression, distal pulmonary arteriole muscle normalization, right ventricular cross-sectional area, myocardial cell hypertrophy, and right cardiac hypertrophy index were assessed with HE staining, immunofluorescence staining and WGA staining, and the expressions of ALDH2, SIRT1, PGC-1α, P16INK4A and P21CIP1 were detected. In pulmonary artery smooth muscle cells with hypoxic exposure, the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting. The wild-type mice with hypoxic exposure showed significantly increased RVSP, right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1, which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/- mice. In cultured pulmonary artery smooth muscle cells, hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1, which were all lowered by treatment with Alda-1, but its effect was obviously attenuated by EX527 treatment. ALDH2 alleviates hypoxiainduced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Atrial refractoriness early after transcatheter aortic valve implantation TAVI in patients with severe aortic stenosis and sinus rhythm.

Aortic valve stenosis (AS) is a common valvular heart disease, especially in the elderly, and is associated with a high prevalence of atrial fibrillation. Although the risk of atrial fibrillation is expected to decrease after the intervention, atrial fibrillation develops in many patients undergoing surgical or percutaneous transaortic valve implantation. We aimed to evaluate atrial refractoriness since it may play a key role in the occurrence of atrial fibrillation after transaortic valve implantation. Seventy-nine consecutive patients who underwent TAVI between October 2021 and May 2023 were enrolled in this trial. Sixty-seven patients underwent electrophysiology study before and after TAVI. We evaluated the changes in PA and AH intervals, as well as atrial effective refractory periods. Besides the hemodynamic changes, atrial effective refractory periods increased, and atrial effective refractory period dispersion (39.8±21.6 vs. 31.1±18.0) decreased significantly after TAVI. The change in atrial effective refractory period dispersion after TAVI was correlated only with the changes in left ventricular end-diastolic pressure (r=0.77, P=0.001) and the changes in aortic gradient (r=0.4, P=0.001). The independent variables affecting the changes in atrial effective refractory period dispersion were basal pro-BNP levels, besides the changes in left ventricular end-diastolic pressure and aortic gradient after transaortic valve implantation. Our results show an acute improvement in atrial refractoriness after TAVI, though high atrial fibrillation rates are reported in the literature. The timing of aortic valve replacement is important, as irreversible maladaptive changes might have already developed by the time of intervention.

Reducing Left Ventricular Wall Stress through Aortic Valve Enlargement via Transcatheter Aortic Valve Implantation in Severe Aortic Stenosis.

Background: In aortic stenosis, the left ventricle exerts additional force to pump blood through the narrowed aortic valve into the downstream arterial vasculature. Adaptive hypertrophy helps to maintain wall stress homeostasis but at the expense of impaired compliance. Advanced ventricular deformation impacts the extent of functional recovery benefits achieved through transcatheter aortic valve implantation. Methods and Results: Subgroups were stratified based on output, with low-flow severe aortic stenosis defined as stroke volume index <35 mL· m-2. Before intervention, the low-flow subgroup exhibited worse effective orifice area index and arterial and global impedance, along with thinner wall thickness and larger chamber volume marginally. LV performance, including stroke volume index, ventricular elastance, and ventricular-arterial coupling, were notably inferior, consistent with worse adverse remodeling. Although the effective orifice area index was similarly augmented after TAVI, inferior recovery benefits were noted. Persistently higher wall stress and energy consumption were observed, along with poorer ventricular-arterial coupling. These changes in wall stress showed an inverse relationship with alterations in wall thickness and were proportional to changes in dimension and volume. Additionally, they were proportional to changes in left ventricular end-systolic pressure, pressure-volume area, and ventricular-arterial coupling but inversely related to ventricular end-systolic elastance. Conclusions: The study revealed that aortic valve enlargement through transcatheter aortic valve implantation reduces left ventricular wall stress in severe aortic stenosis. The reduced recovery benefits in the low-flow subgroup were evident. Wall stress could serve as a marker of mechanical benefit after the intervention.

Macrophage to Myofibroblast Transition Promotes Hypertension-Induced Cardiac Diastolic Dysfunction

Cardiac diastolic dysfunction is a pathological continuum of hypertension eventually leading to heart failure—which is responsible for ~13% of all deaths in the United States. A hallmark of this disease is cardiac fibrotic remodeling, in which excessive extracellular matrix components are deposited into the myocardium. Recent studies have shown the novel ability of macrophages to differentiate into a fibrotic myofibroblast-like phenotype—termed macrophage to myofibroblast transition (MMT). This phenomenon has been implicated in renal fibrosis but, has not been investigated in the heart during hypertension or diastolic dysfunction. Therefore, we hypothesize that MMT plays a causal role in cardiac fibrotic remodeling in hypertension, promoting diastolic dysfunction. As such, we seek to investigate the prevalence of myofibroblast-transitioned macrophages in the heart, as well as determine the gravity of MMT-mediated fibrotic cardiac remodeling. To understand the pathological progression of hypertension to diastolic dysfunction, we utilized the classic DOCA + NaCl model of hypertension in C57BL/6 mice. This investigation is multi-pronged, in that, we seek to gauge diastolic function in vivo, as well as investigate the microenvironment of the heart in primary in vitro experiments. To achieve this, we employ echocardiography and direct left ventricular pressure and volume measurements to determine the progression of hypertension to diastolic dysfunction in the adult mouse heart. For primary in vitro analyses, mouse hearts were isolated and digested, and leukocytes were isolated by Percoll gradient. Cells were stained with α-SMA (myofibroblast) and CD68 (monocyte/macrophage). Finally, the deposition of fibrotic collagen was assessed by both Masson’s trichrome and picrosirius red tissue stains. Mice were subjected to DOCA + salt to induce hypertension. Ten days after this treatment, the left ventricular pressure change as a function of time was measured in the left ventricle. This analysis revealed degraded heart function, realized by a significant decrease in -dp/dt as soon as ten days following the onset of hypertension. Following, another cohort of hypertensive WT mouse hearts was isolated for staining. The results of these assays revealed increased cardiac fibrosis in the hearts of hypertensive mice—likely contributing to the deficit in cardiac function. Finally, in addition to this, flow cytometric analyses of isolated cardiac leukocytes revealed that hypertensive mice had a significant increase in the α-SMA+/CD68+ population of cells in the hypertensive mouse heart, implicating MMT in the rapid pathological progression of hypertension to diastolic dysfunction. These results characterize the presence of MMT cells in the hypertensive mouse heart. Furthermore, the increase of myofibroblast transition is accompanied by decreased cardiac diastolic function and enhanced fibrotic remodeling in the heart—alluding to the role of MMT in the pathological progression of hypertension to diastolic dysfunction. Future efforts into this phenomenon involve the real-time progression of hypertension to diastolic dysfunction via echocardiography, as well as a final, definitive measurement of diastolic function by PV loop. Finally, we will employ an angiotensin II model of hypertension to ensure that this phenomenon is encapsulated in other forms of hypertension, rather than just the DOCA + Salt model. We thank our sources of funding:NIG R01-HL146713, AHA 23TPA1076467. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

ATP releasing channels and the ameliorative effects of high intensity interval training on diabetic heart: a multifaceted analysis

Type 2 diabetes (T2D) can cause severe cardiac complications at functional, histologic and molecular levels. These pathological complications could be mediated by ATP-releasing channels such as Panx1 and ATP receptors, in particular P2X7. The aim of our study was to investigate the effect of high-intensity interval training (HIIT) on T2D-induced cardiac complications at the functional, histopathological and molecular levels, with a particular focus on ATP-releasing channels. 48 male Wistar rats at the age of 8 weeks were randomly allocated into four groups: control (Con), Diabetes (T2D), Training (TR), and Diabetes + Training (T2D + TR). T2D was induced by a high-fat diet plus a low dose (35 mg/kg) of STZ administration. Rats in the TR and T2D + TR groups underwent an 8-weeks training program involving intervals ranging from 80 to 100% of their maximum running speed (Vmax), with 4–10 intervals per session. Protein expression of Interleukin 1β (IL1β), Interleukin 10 (IL-10), Pannexin 1 (Panx1), P2X7R (purinergic P2X receptor 7), NLRP1 (NLR Family Pyrin Domain Containing 1), BAX, and Bcl2 were measured in the heart tissue. Additionally, we assessed heart function, histopathological changes, as well as insulin resistance using the homeostasis model assessment of insulin resistance (HOMA-IR). In contrast to the T2D group, HIIT led to increased protein expression of Bcl2 and IL-10 in the heart. It also resulted in improvements in systolic and diastolic blood pressures, heart rate, ± dp/dt (maximum and minimum changes in left ventricular pressure), while reducing protein expression of IL-1β, Panx1, P2X7R, NLRP1, and BAX levels in the heart. Furthermore, left ventricular diastolic pressure (LVDP) was reduced (P ≤ 0.05). Moreover, heart lesion scores increased with T2D but decreased with HIIT, along with a reduction in fibrosis percentage (P ≤ 0.05). The results of this study suggest that the cardioprotective effects of HIIT on the diabetic heart may be mediated by the modulation of ATP-releasing channels. This modulation may lead to a reduction in inflammation and apoptosis, improve cardiac function, and attenuate cardiac injury and fibrosis.

Effect of Metformin on Oxidative Stress and Left Ventricular Geometry in Nondiabetic Heart Failure Patients: A Randomized Controlled Trial.

Introduction: There is an increasing interest in using metformin in cardiovascular diseases and its potential new roles. Only two randomized controlled trials investigated the effect of metformin in nondiabetic heart failure (HF) patients. However, none of these studies assess the role of metformin in reducing oxidative stress. We hypothesized that metformin might improve oxidative stress and left ventricular remodeling in nondiabetic HF patients with reduced ejection fraction (HFrEF). Methods and Methods: Seventy HFrEF patients (EF 37% ± 8%; median age 66 years) were randomized to metformin (n = 35) or standard of care (SOC) for HF (n = 35) for 6 months in addition to standard therapy. Outcomes included the difference in the change (Δ) in total antioxidant capacity (TAC) and malondialdehyde (MDA), both assessed colorimetrically and left ventricular mass index (LVMI) assessed through transthoracic echocardiography. Results: Compared with the SOC, metformin treatment increased TAC [Δ = 0.12 mmol/L, confidence intervals (95% CIs): 0.03-0.21; P = 0.007]. TAC increased significantly only in the metformin group (0.90 ± 0.08 mmol/L at baseline vs. 1.04 ± 0.99 mmol/L at 6 months, P < 0.05). Metformin therapy preserved LVMI (Δ = -23 g/m2, 95% CI: -42.91 to -4.92; P = 0.014) and reduced fasting plasma glucose (Δ = -6.16, 95% CI: -12.31 to -0.02, P = 0.047) compared with the SOC. Results did not change after adjusting for baseline values. Changes in MDA left ventricular ejection fraction (LVEF) and blood pressure were not significantly different between groups. Conclusion: Metformin treatment in HF patients with reduced LVEF improved TAC and prevented the increase in LVMI compared with the SOC. These effects of metformin warrant further research in HF patients without diabetes to explore the potential benefits of metformin. Trial Registration Number: This protocol was registered in ClinicalTrials.gov under the number NCT05177588.

Long-term inorganic nitrate administration protects against myocardial ischemia-reperfusion injury in female rats

BackgroundThe favorable effects of nitrate against myocardial ischemia-reperfusion injury (MIRI) have primarily focused on male rats and in short term. Here we determine the impact of long-term nitrate intervention on baseline cardiac function and the resistance to MIRI in female rats.MethodsFemale Wistar rats were randomly divided into untreated and nitrate-treated (100 mg/L sodium nitrate in drinking water for 9 months) groups (n = 14/group). At intervention end, levels of serum progesterone, nitric oxide metabolites (NOx), heart NOx concentration, and mRNA expressions of NO synthase isoforms (NOS), i.e., endothelial (eNOS), neuronal (nNOS), and inducible (iNOS), were measured. Isolated hearts were exposed to ischemia, and cardiac function indices (CFI) recorded. When the ischemia-reperfusion (IR) period ended, infarct size, NO metabolites, eNOS, nNOS, and iNOS expression were measured.ResultsNitrate-treated rats had higher serum progesterone (29.8%, P = 0.013), NOx (31.6%, P = 0.035), and higher heart NOx (60.2%, P = 0.067), nitrite (131%, P = 0.018), and eNOS expression (200%, P = 0.005). Nitrate had no significant effects on baseline CFI but it increased recovery of left ventricular developed pressure (LVDP, 19%, P = 0.020), peak rate of positive (+ dp/dt, 16%, P = 0.006) and negative (–dp/dt, 14%, P = 0.014) changes in left ventricular pressure and decreased left ventricular end-diastolic pressure (LVEDP, 17%, P < 0.001) and infarct size (34%, P < 0.001). After the IR, the two groups had significantly different heart nitrite, nitrate, NOx, and eNOS and iNOS mRNA expressions.ConclusionsLong-term nitrate intervention increased the resistance to MIRI in female rats; this was associated with increased heart eNOS expression and circulating progesterone before ischemia and blunting ischemia-induced increased iNOS and decreased eNOS after MIRI.

Acute aerobic exercise regulation of myocardial calcium homeostasis involves CASQ1, CASQ2, and TRDN.

Exercise maintains cardiac calcium homeostasis and promotes cardiovascular health. This study explored temporal changes of calcium-related myocardial transcriptome changes during the recovery phase following a single bout of moderate-intensity aerobic exercise. Healthy male Sprague-Dawley rats were anesthetized with sodium pentobarbital after moderate-intensity aerobic exercise at four time points (0, 12, 24, and 72 h postexercise). The hearts were removed and RNA-seq and bioinformatics analyses were used to examine temporal transcriptional changes in the myocardium. Casq1, Casq2, and Trdn were identified as key genes in the regulation of calcium homeostasis during myocardial recovery. The highest expression of Casq1, Casq2, and Trdn genes and the proteins they encode occurred 24 h after exercise. An in vitro calcium overload heart model using the Langendorff heart perfusion method was used to examine myocardial calcium buffering capacity. Calcium overload caused the least changes in left ventricular developed pressure, infarct area, Lactate dehydrogenase release, and extent of morphological damage to myocardial cells, with the highest protein expressions of CASQ1, CASQ2, and TRDN at 24 h after acute exercise. This study indicates that maximal myocardial Ca2+ buffering capacity occurs 24 h postexercise in rats. Our study provides insights into exercise-mediated improvements in cardiovascular function and exercise preconditioning.NEW & NOTEWORTHY Acute aerobic exercise upregulates myocardial Casq1, Casq2, and Trdn genes and the proteins they encode in rats. Higher protein levels of CASQ1, CASQ2, and TRDN conferred an improved ability of the myocardium to resist calcium overload. Furthermore, 24 h postexercise is the time point with optimal myocardial calcium buffer capacity.

Downregulation of microRNA-23a confers protection against myocardial ischemia/reperfusion injury by upregulating tissue factor pathway inhibitor 2 following luteolin pretreatment in rats.

Downregulation of microRNA-23a confers protection against myocardial ischemia/reperfusion injury by upregulating tissue factor pathway inhibitor 2 following luteolin pretreatment in rats.

Effects of balloon pulmonary angioplasty procedure on electrocardiographic parameters in patients with chronic thromboembolic pulmonary hypertension

AimThe aim of the present study was to evaluate the value of electrocardiography (ECG) in predicting postoperative hemodynamic improvement in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing balloon pulmonary angioplasty (BPA). Material and methodsA total of 32 patients were included in the study. During ECG analysis, parameters that have been suggested to be related to right ventricular hypertrophy and/or dilatation were evaluated. The significance of the change in each parameter obtained at the pre-BPA visit and at the scheduled control visit 6 months after BPA was tested. In addition to ECG analysis, data related to right heart catheterization (RHC) and echocardiography, B-type natriuretic peptide (BNP) levels and World Health Organization (WHO) functional classifications of all patients were also recorded. The relationship between the amount of possible change in ECG parameters and the amount of possible change in hemodynamic parameters was investigated. ResultsThe Daniel score, which has been suggested to have prognostic value in acute pulmonary embolism, decreased from 8.22 ± 5.68 to 6.56 ± 5.55 after the BPA procedure (p: 0.035). Among all parameters studied, only T wave height (V2 t) in V2 derivation changed significantly from −0.77 ± 2.39 to 1.27 ± 2.58 mm (p: 0.036). The amount of change in V2 T was found to significantly correlate with the amount of change in systolic right ventricular pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and systemic vascular resistance. ConclusionPostprocedural T wave changes in lead V2 might serve as a marker of hemodynamic improvement in patients with CTEPH who undergo BPA.

Improvement in LV end-diastolic pressure after primary PCI and its impact on patients' recovery.

In this study, we evaluated the change in left ventricular end-diastolic pressure (LVEDP) after primary percutaneous coronary intervention (PCI) and its impact on in-hospital outcomes and 30-day and three-month quality of life (SAQ-7), ejection fraction (EF), and major adverse cardiovascular events (MACE). LVEDP ≥19 mmHg was taken as elevated LVEDP. In a sample of 318 patients, 18.9% (n=60) were females and mean age was 55.7 ± 10.52 years. Post-procedure elevated LVEDP was observed in 20.8% (n=66) with a mean reduction of 1.65 ± 4.35 mmHg. LVEDP declined in 39% (n=124) and increased in 10.7% (n=34). In-hospital mortality rate (9.1% vs. 2.4%, p=0.011), 30-day MACE (9.1% vs. 4.0%), and three-month MACE (21.2% vs. 5.6%) were found to be significantly higher among patients with elevated LVEDP, respectively. Elevated LVEDP was found to be associated with a reduced SAQ-7 score (89.84 ± 8.09 vs. 92.29 ± 3.03, p<0.001) and reduced (25-40%) EF (55.6% vs. 22.6%) at three-month follow-up. LVEDP declined acutely in a significant number of patients after primary PCI. Post- procedure elevated LVEDP was found to be associated with poor quality of life and an increased risk of immediate and short-term MACE.

ATP-Sensitive Potassium Channel Opener Diazoxide Reduces Myocardial Stunning in a Porcine Regional With Subsequent Global Ischemia Model.

Background ATP-sensitive potassium channels are inhibited by ATP and open during metabolic stress, providing endogenous myocardial protection. Pharmacologic opening of ATP potassium channels with diazoxide preserves myocardial function following prolonged global ischemia, making it an ideal candidate for use during cardiac surgery. We hypothesized that diazoxide would reduce myocardial stunning after regional ischemia with subsequent prolonged global ischemia, similar to the clinical situation of myocardial ischemia at the time of revascularization. Methods and Results Swine underwent left anterior descending occlusion (30 minutes), followed by 120 minutes global ischemia protected with hyperkalemic cardioplegia±diazoxide (N=6 each), every 20 minutes cardioplegia, then 60 minutes reperfusion. Cardiac output, time to wean from cardiopulmonary bypass, left ventricular (LV) function, caspase-3, and infarct size were compared. Six animals in the diazoxide group separated from bypass by 30 minutes, whereas only 4 animals in the cardioplegia group separated. Diazoxide was associated with shorter but not significant time to wean from bypass (17.5 versus 27.0 minutes; P=0.13), higher, but not significant, cardiac output during reperfusion (2.9 versus 1.5 L/min at 30 minutes; P=0.05), and significantly higher left ventricular ejection fraction at 30 minutes (42.5 versus 15.8%; P<0.01). Linear mixed regression modeling demonstrated greater left ventricular developed pressure (P<0.01) and maximum change in ventricular pressure during isovolumetric contraction (P<0.01) in the diazoxide group at 30 minutes of reperfusion. Conclusions Diazoxide reduces myocardial stunning and facilitates separation from cardiopulmonary bypass in a model that mimics the clinical setting of ongoing myocardial ischemia before revascularization. Diazoxide has the potential to reduce myocardial stunning in the clinical setting.

Abstract 10050: Omecamtiv Mecarbil and Its Effects on Cardiac Parameters in Heart Failure With Reduced Ejection Fraction (HFrEF). A Meta-Analysis of Randomized Controlled Trials

Introduction: Omecamtiv mecarbil (OM) is a novel selective cardiac myosin activator that has been shown to improve cardiac function in patients with HFrEF. Proposed mechanism of action suggests that it increases myocardial systolic function and systolic ejection time without associated increases in intracellular concentrations of calcium or the rate of change in left ventricular pressure or any direct effects on vascular tissue, cardiovascular receptors, or ion channels. Methods: Systematic review identified phase II/III randomized controlled trials (RCTs) evaluating OM versus placebo. Mean Difference (MD) of different echocardiographic parameters from baseline and Odds Ratios (OR) of cardiovascular (CV) death (along with 95% confidence intervals; CI) were extracted to compute pooled MD and OR using RevMan v.5.3. Random effects model was employed when there was significant heterogeneity (&gt;40%, as assessed by I-squared). Results: Four RCTs were finalized (n=9331; OM: 4722, placebo: 4609). Majority of the patients were males (n=7359; 79%), of white ethnicity (n=7345; 78.7%), and had ischemic heart failure (n=5109; 54.7%). All patients had EF &lt;40% and were on guideline-directed therapy. When patients were pooled for stroke volume; OM increased mean SV to 4.34 ml from baseline as compared to placebo (MD 4.34, 95% CI 2.03-6.65; p=0.0002; I 2 =0%). Mean LV ejection time increased to 32 milliseconds (ms) (MD 32.60, 27.34-37.87; p&lt;0.00001; I 2 =84%). OM resulted in 1.68 mm reduction in mean LV end-systolic diameter (MD -1.68; -2.73 to -0.62; p=0.002; I 2 =0%)). However, reduction in mean end-diastolic diameter (MD -1.05; -1.98 to -0.12; p=0.34; I 2 =42%) was statistically non-significant. Mean LV Fractional Shortening improved to 2% with OM but was statistically insignificant (MD 2.18; 0.54-3.82; p=0.09; I 2 =42%). OM resulted in slightly decreased heart rate (MD -1.77 beats/min; -2.29 to -1.24; p&lt;0.00001; I 2 =0%) with no effect on mean systolic BP (MD -0.05; -0.73 to 0.64; p=0.89; I 2 =0%). In terms of CV mortality, OM decreased the odds for mortality but results were statistically non-significant (OR 0.93, 95% CI 0.80 to 1.08; p=0.34; I 2 = 0%). Conclusion: Omecamtiv mecarbil improved the echocardiographic parameters in patients with HFrEF.

Echocardiographic changes after arteriovenous fistula creation in hemodialysis patients.

Pulmonary hypertension (PH) is common in end-stage renal disease (ESRD) patients and is associated with increased all-cause and cardiovascular mortality in this group. There is scarce data on the long-term effect of arteriovenous fistula (AVF) creation on pulmonary hypertension (PH) and the reflected changes in echocardiographic measurements. This is a retrospective study of 54 patients who underwent AVF creation between 2009 and 2014 and with echocardiographic evaluations before and after surgery. We analyzed pairwise changes in right ventricular systolic pressure (RVSP), right atrial pressure (RAP) during systole, left ventricular mass (LVM), tricuspid regurgitation (TR), mitral E/E' ratio, and ejection fraction (EF), as well as the factors that predicted change in RVSP after surgery. The median time for the preoperative echocardiogram was 0.3 years (interquartile range (IQR) 0.2-0.7 years) prior to AVF creation, while the follow-up echo was done 1.3 (0.6-2.1) years after surgery. 67% of the patients had RVSP&gt;37 mmHg at baseline. There was a significant reduction in RVSP after AVF creation compared to baseline (median 33 (IQR 26-43) vs. 46mmHg, p=0.0015), with 59% of the patients experiencing a decrease and 19% remaining stable. There were also significant decreases in LVM (201 (143-256) vs. 215 (163-276), p=0.045) and RAP systole (10 (10-15) vs. 3 (3-8); p&lt;0.001) after surgery. Higher preoperative weight (p=0.038) and RVSP (p=0.006), and use of loop diuretics (p=0.015) were significantly associated with improvement in RVSP after AVF creation. Our results suggest that AVF creation is associated with a significant reduction or stable measurements of RVSP in the ESRD population, likely due to an improvement in volume status.

Polyphyllin I improves myocardial damage in coronary artery disease via modulating lipid metabolism and myocardial apoptosis.

Polyphyllin I (PPI) is a famous traditional medicine ingredient, which has been explored in wide range of areas. Nevertheless, whether PPI exerts any functions in coronary artery disease (CAD) is still uncertified. Herein, we probed the effect and mechanism of PPI on lipid metabolism and myocardial dysfunction in myocardial cells and CAD rat model. Hypoxia/reoxygenation (H/R)-treated H9c2 cells model was constructed for the in vitro experiments, and CAD model in vivo was established by high-fat feeding. After management with PPI, the correlated factors of lipid metabolism and myocardial function were investigated. The apoptosis of myocardial cells was assessed by Annexin V-FITC/PI kit and TUNEL staining. The apoptosis-associated factors (caspase 3, cleaved caspase 3, Bax, and Bcl-2) were tested by Western blot analysis. The MEK/ERK inhibitorwas applied and the functions of MEK/ERK pathway in myocardial damage were investigated. H/R-treated H9c2 cells model was constructed for the in vitro experiments, and CAD model in vivo was established by high-fat feeding. After management with PPI, the correlated factors of lipid metabolism and myocardial function were investigated. The apoptosis of myocardial cells was assessed by Annexin V-FITC/PI kit and TUNEL staining. The apoptosis-associated factors (caspase 3, cleaved caspase 3, Bax, and Bcl-2) were tested by Western blot analysis. The MEK/ERK inhibitorwas applied and the functions of MEK/ERK pathway in myocardial damage were investigated.PPI improved lipid metabolism disorder in H/R-induced H9c2 cells or in CAD rat model. Additionally, PPI attenuated myocardial dysfunction in CAD rats via enhancing left ventricular systolic pressure, maximum rate of change of left ventricular pressure (±dp/dtmax ), and arterial blood flow (CF). The apoptosis of myocardial cells was lessened by PPI management, which was further verified by reducing Bax and cleaved caspase 3 expression. Furthermore, PD0325901 (MEK/ERK inhibitor) weakened the effect of PPI on myocardial dysfunction, lipid metabolism, and myocardial cell apoptosis in CAD rats. The research confirmed the protective effect of PPI on myocardial damage in CAD, which was regulated by MEK/ERK pathway.

S-adenosyl-L-methionine improves ventricular remodeling after myocardial infarction by regulating angiogenesis and fibrosis

Purpose: To investigate the effect of S-adenosyl-L-methionine (SAM) on angiogenesis and fibrosis in the heart of rats with myocardial infarction (MI), and to determine the mechanism of action.Methods: Sprague Dawley rats with MI received SAM treatment (15 mg/kg) intraperitoneally. The cumulative survival (%) of rats was recorded to determine their rate of survival. Hematoxylin-eosin staining, echocardiography, and hemodynamics were also performed. In addition, the effects of SAM vascular regeneration in the rats were analyzed by determining the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hypoxia-inducible factor 1-α (HIF1-α) in rats.Results: The 8-week survival rate of the MI group was significantly lower than that of the sham group, while SAM significantly improved the survival rate of the rats. In addition, SAM improved the contractile and diastolic heart function in the rats and also increased the ventricular pressure change. Furthermore, SAM elevated the expressions of VEGF, bFGF and HIF1-α in rat myocardium and serum. In myocardial tissues of SAM-treated rats, the expressions of collagen I, collagen III and α-sma were reduced, indicating that SAM inhibited myocardial fibrosis. In addition, SAM promoted cardiac angiogenesis by activating Jagged1/Notch1 signaling pathway.Conclusion: SAM promotes angiogenesis of the myocardium by activating Jagged1/Notch1 signaling pathway and inhibiting fibrosis in rat myocardium. Therefore, SAM effectively inhibits ventricular remodeling in rats after MI, thereby improving the rats’ heart structure and function. The results may provide new targets for the treatment of myocardial infarction.

The effect of ovariectomy on hemodynamic functions and the level of nitric oxide metabolites in the heart of rats

Background. A higher prevalence of cardiovascular disorders has been observed in women after menopause. This study aimed to determine the long-term effects of ovariectomy on hemodynamic functions and the level of nitric oxide metabolites (NOx) in the heart tissue of ovariectomized rats. Methods. Fourteen female Wistar rats were divided into two groups (n=7 in each group) of control and ovariectomized (OVX). OVX rat model was induced using the two dorsolateral skin incision method. Cardiac hemodynamic function indices, including the left ventricular developed pressure (LVDP), peak rate of positive changes in the left ventricular pressure (+dp/dt), and peak rate of negative changes in the left ventricular pressure (-dp/dt) were measured at the time of systole in hearts after 11 months of the ovariectomy. Serum and left ventricular levels of NOx were measured at the end of the study. Results. At the end of the study, OVX rats had lower LVDP (19%, P=0.001), +dp/dt (30%, P&lt;0.001) and -dp/dt (23%, P=0.004) than control group. In addition, the OVX group had lower serum NOx levels (30%, P=0.021) compared to the control group; heart tissue NOx was also lower by 31% in the OVX rats, but it was not statistically significant (P=0.056). Conclusion. Long-term ovariectomy disrupts cardiac hemodynamic function in ovariectomized rats, which is associated with decreased NOx levels in serum. Practical Implications. Our findings indicated impaired cardiac function following long-term estrogen deficiency in OVX rats. These results can be used to prevent and treat the cardiovascular disease in post-menopausal women. However, these results need to be confirmed in humans.

Ventricular-arterial decoupling is associated with in-hospital adverse events in normotensive pulmonary embolism.

During acute pulmonary embolism (PE) a compensatory increase in right ventricular (RV) contractility is required to match increased afterload to maintain right ventricular-pulmonary arterial (RV-PA) coupling. The aim of this study was to assess the prognostic utility of RV-PA decoupling in acute PE. We assessed the association between measures of transthoracic echocardiography (TTE)-derived RV-PA coupling including tricuspid annular plane systolic excursion (TAPSE)/right ventricular systolic pressure (RVSP) and right ventricular fractional area change (FAC)/RVSP as well as stroke volume index (SVI)/RVSP (a measure of pulmonary artery capacitance) with adverse PE-related events (in-hospital PE-related mortality or cardiopulmonary decompensation) using logistic regression analysis. In 820 normotensive patients TTE-derived markers of RV-PA coupling were associated with PE-related adverse events. For each 0.1mm/mmHg decrease in TAPSE/RVSP the odds of an adverse event increased by 2.5-fold [adjusted OR (aOR) 2.49, 95% confidence interval (CI) 1.46-4.24, p = 0.001], for every 0.1%/mmHg decrease in FAC/RVSP the odds of an adverse event increased by 1.4-fold (aOR 1.42, CI 1.09-1.86, p = 0.010), and for every 0.1mL/mmHgm2 decrease in SVI/RVSP the odds of an event increased by 2.75-fold (aOR 2.78, CI 1.72-4.50, p < 0.001). In multivariable analysis, TAPSE/RVSP and SVI/RVSP were independent of other risk stratification methods including computed tomography-derived right ventricular dysfunction (RVD), the Bova score, and subjective assessment of TTE-derived RVD. In patients with normotensive acute PE, TTE-derived measures of RV-PA coupling are associated with adverse in-hospital PE-related events and provide incremental value in the risk assessment beyond computed tomography-derived RVD, the Bova score, or subjective TTE-derived RVD.

Reversal of Right Ventricular Hypertrophy and Dysfunction by Prostacyclin in a Rat Model of Severe Pulmonary Arterial Hypertension.

Prostacyclin analogs are among the most effective and widely used therapies for pulmonary arterial hypertension (PAH). However, it is unknown whether they also confer protection through right ventricle (RV) myocardio-specific mechanisms. Moreover, the use of prostacyclin analogs in severe models of PAH has not been adequately tested. To further identify underlying responses to prostacyclin, a prostacyclin analogue, treprostinil, was used in a preclinical rat Sugen-chronic hypoxia (SuCH) model of severe PAH that closely resembles the human disease. Male Sprague–Dawley rats were implanted with osmotic pumps containing vehicle or treprostinil, injected concurrently with a bolus of Sugen (SU5416) and exposed to 3-week hypoxia followed by 3-week normoxia. RV function was assessed using pressure–volume loops and hypertrophy by weight assessed. To identify altered mechanisms within the RV, tissue samples were used to perform a custom RNA array analysis, histological staining, and protein and transcript level confirmatory analyses. Treprostinil significantly reduced SuCH-associated RV hypertrophy and decreased the rise in RV systolic pressure, mean pulmonary arterial (mPAP), and right atrial (RAP) pressure. Prostacyclin treatment was associated with improvements in RV stroke work, maximum rate of ventricular pressure change (max dP/dt) and the contractile index, and almost a complete reversal of SuCH-associated increase in RV end-systolic elastance, suggesting the involvement of load-independent improvements in intrinsic RV systolic contractility by prostacyclin treatment. An analysis of the RV tissues showed no changes in cardiac mitochondrial respiration and ATP generation. However, custom RNA array analysis revealed amelioration of SuCH-associated increases in newly identified TBX20 as well as the fibrotic markers collagen1α1 and collagen 3α1 upon treprostinil treatment. Taken together, our data support decreased afterload and load-independent improvements in RV function following prostacyclin administration in severe PAH, and these changes appear to associate with improvements in RV fibrotic responses.

Protective Effect of Hydrogen Sulphide in Cardioplegia on Global Myocardium Ischemia‐reperfusion Injury

ObjectiveThe endogenous gaseous transmitter hydrogen sulfide (H2S) is an important regulator of the cardiovascular system and is reported to have cardioprotective activity against ischemia/reperfusion (I/R) injury. We investigated the cardioprotective effect of H2S added in cardioplegia against I/R injury in global cardioplegic arrest.MethodsIsolated Wistar rat hearts were perfused in Langendorff apparatus and underwent 30 min perfusion, 120 min cold ischemia, and 90 min reperfusion. The rats were randomly divided into 5 groups: Control group, ischemic and reperfusion (I/R), St. Thomas cardioplegia (St. Thomas +I/R), St. Thomas plus H2S donor NaHS (NaHS+St.Thomas+I/R), St.Thomas plus NaHS and glibenclamide (an antagonist of KATP channel; NaHS+Glib+St.Thomas+I/R). The following indices were compared among the groups: the change of left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), heart rate, heart rhythm, and coronary blood flow. The difference in left ventricular developed pressure (LVDP), the maximum left ventricular pressure rise rate (+dp/dtmax), and the maximum left ventricular pressure drop rate (‐dp/dtmax) were also compared. Western blot was used to detect the changes of related myocardial enzymes among different groups.ResultsNaHS+St.Thomas+I/R treatment significantly improved cardiac function (LVSP, LVDP, +dp/dtmax and ‐dp/dtmax) compared to other groups (p&lt;0.05), although no significant differences on coronary flow and heart rate were observed. After reperfusion, the frequency of ventricular arrhythmia in I/R group and St.Thomas+I/R group was significantly higher than that in NaHS+St.Thomas+I/R group. Further, the expression of cardiac Troponin T, troponin I, and creatine kinase in the NaHS+St.Thomas+I/R group was significantly lower than that in other groups (p&lt;0.05).ConclusionCardioplegia containing H2S confers significant protection against global I/R injury during cold cardioplegic arrest. This effect is associated with opening of the myocardial KATP channels. Therefore, H2S may be a useful adjunct to cardioplegic solutions in heart surgery.