Journal of Cardiovascular Pharmacology最新文献

To identify the functional roles of human H1-histamine and H2-histamine receptors when they coexist in the heart, we crossbred mice that overexpressed human H1-histamine receptors only in the heart (H1-TG) with mice that overexpressed human H2-histamine receptors only in the heart (H2-TG) to obtain double transgenic mice (H1xH2-TG) and compared them with wild type (WT) mice. We measured the force of contraction (FOC) in isolated, electrically stimulated left atrial (LA) preparations and spontaneously beating right atrial (RA) preparations. We noted that when cumulatively applied (1 nM - 30 µM), histamine did not affect the force of contraction in the LA of WT mice. In H1xH2-TG mice, low concentrations (30 nM - 1 µM) of histamine increased the FOC in the LA, whereas higher concentrations (3 µM, 10 µM, 30 µM) of histamine reduced the FOC in the LA. Likewise, histamine in low concentrations (10 nM and higher) increased the beating rate in the RA, while higher concentrations of histamine (3 µM, 10 µM) reduced the beating rate in the RA. Dimaprit, an H2-histamine receptor agonist increased the force of contraction in the LA of H1xH2-TG mice but not in the LA of WT mice. 2-2-thiazol-ethan-amine (ThEA) an H1-histamine receptor agonist, increased the FOC in the LA of H1xH2-TG mice but not in the LA of WT mice. These data indicate that histamine, at least under our experimental conditions, at lower concentrations activates cardiac H2-histamine receptors, and at higher concentrations activated H1-histamine receptors.

Cardiac hypertrophy, initially referred to as an adaptive response, would gradually transit to decompensated states over time, contributing to hypertension, and ultimately heart failure under salt overload. The cellular and molecular mechanisms driving salt-induced cardiac hypertrophy, as well as the signaling pathways responsible for this shift from compensation to decompensation, still remain insufficiently understood. Transient receptor potential vanilloid 4 (TRPV4) is ubiquitously expressed in cardiomyocytes, participating in cardiac remodeling and dysfunction. This study investigated TRPV4-relevant mechanisms in salt-induced cardiac hypertrophy. Knockdown of TRPV4 with cardiac gene transfer of Lv-shTRPV4 attenuated salt-induced cardiac hypertrophy, ROS generation, perivascular fibrosis and Akt & mTOR phosphorylation in adult rats. The in vitro results suggest that exposing cardiomyocytes to high-salt induced a concentration-dependent increase in autophagy, which was initially a rising phase and later followed by a declining phase. Salt-induced autophagic activity was enhanced by inhibiting Class I PI3-Kinase (PI3KC1) with LY294002 or Akt with AZD5363, but got undermined by AMPK inhibition with Compound C (CC) or SIRT1 inhibition with EX-527. Additionally, blockade of PI3KC1/Akt pathway significantly attenuated high salt-induced ROS generation and cardiac hypertrophy, whilst blockade of AMPK/SIRT1 pathway exacerbated high salt-induced cardiac hypertrophy via ROS accumulation. Thus, both PI3KC1 and AMPK signaling pathways participate in salt-induced cardiac hypertrophy via shared upstream component of TRPV4: lower salt triggers AMPK, scavenges ROS, preventing cardiac hypertrophy, whilst higher salt activates PI3KC1 with opposite effects. Our findings illuminate potential therapeutic effects of interfering TRP-related channels on high salt-induced hypertrophy and other mechanical stretch force-associated diseases.

The effect of atorvastatin compared with rosuvastatin on the prevention of contrast-associated acute kidney injury (CA-AKI) after percutaneous coronary intervention (PCI) has been heterogeneous in different studies, which may be due to the small size of the initial studies. This systematic review and meta-analysis aimed to compare the effect of atorvastatin versus rosuvastatin on preventing CA-AKI in patients undergoing PCI. The databases PubMed, Embase, Google Scholar, Cochrane Library, and Web of Science were searched by two independent investigators from 2000 to 2024 to find articles that evaluated the effect of atorvastatin versus rosuvastatin on the prevention of CA-AKI in cardiac patients undergoing PCI. An absolute increase of serum creatinine (SCr) ≥0.3 mg/dl or an increase of ≥50% from baseline within 48 to 72 hours after contrast exposure was defined as CA-AKI. This systematic review and meta-analysis were conducted according to the PRISMA guidelines. Eight studies involving 3,998 Patients who underwent PCI were included. A pooled estimate of 8 studies showed that the overall incidence of CA-AKI after PCI in patients receiving statins, regardless of type, was 8.5 % (95% CI: 7.6, 9.3%). Subgroup analysis showed that the incidence of CA-AKI in patients receiving atorvastatin and rosuvastatin was 8.5% and 8.7%, respectively. The protective effect of atorvastatin on preventing CA-AKI in cardiac patients undergoing PCI was similar to that of rosuvastatin. Both atorvastatin and rosuvastatin similarly reduced the overall incidence of CA-AKI in patients undergoing PCI. The effects of atorvastatin and rosuvastatin on preventing CA-AKI after PCI were also similar.

Tramadol, a widely prescribed analgesic for moderate to severe pain, is associated with significant cardiovascular risks. This study investigated the effects of high-intensity interval training (HIIT), methylphenidate (MPH), and their combination on oxidative stress and mitochondrial quality in the hearts of male Wistar rats subjected to long-term tramadol treatment. Experimental groups included control (CTL), MPH, tramadol (TR), HIIT, MPH+HIIT, TR+HIIT, and MPH+TR+HIIT. Rats underwent HIIT; 5 days per week for 8 weeks. Real-time PCR was used to quantify MFN-2, DRP-1, PINK-1, and Parkin mRNA levels. Superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities, and malondialdehyde (MDA) levels were measured using colorimetry. Histopathological evaluations were assessed for cardiac damage and fibrosis by H&E and Masson's trichrome staining. Tramadol significantly decreased SOD and GPX activities and increased MDA levels compared with the CTL group. Both HIIT and MPH, either alone or in combination, were associated with a significant increase in SOD and GPX and a reduction of MDA levels. Both HIIT and MPH partially repaired the tramadol-induced changes in mRNA expression of DRP-1, and PINK-1. In addition, HIIT, MPH, and their combination significantly reversed histopathological changes associated with long-term tramadol use. These findings suggested that tramadol administration associated with a significant increase in oxidative stress parameters and cardiac damage in heart tissues of rats, which could be ameliorated by HIIT, MPH alone, or their combination.

Abstract: Erectile dysfunction is one of the most underestimated complications of diabetes. Menthol, known for its cooling sensation, is commonly featured in products that claim to enhance sexual performance, yet its effects on penile vasculature lack scientific validation. This study aimed to evaluate whether menthol induces relaxation in the corpus cavernosum and pudendal arteries isolated from diabetic mice. Male lean and db/db mice (20-24 weeks old) were used. Assessments included murinometric data, histology, confocal microscopy to evaluate arterial structure, DHE staining for reactive oxygen species (ROS), immunofluorescence, and Western blotting for TRPM8 expression. The isometric force was measured on a wire myograph (pudendal artery) or organ bath (corpus cavernosum). Our results demonstrated that menthol induced a similar relaxation in pudendal arteries from db/db and lean, although it had a reduced effect in the corpus cavernosum from db/db. The db/db exhibited distinct structural and functional phenotypes characterized by increased fibrosis, ROS levels in the corpus cavernosum, and reduced relaxation to acetylcholine and sildenafil in pudendal arteries. TRPM8 was expressed but it seems not to be the exclusive target for menthol-induced relaxation in the corpus cavernosum of lean mice and in the pudendal arteries of both groups. Furthermore, menthol pre-exposure decreased the efficacy of phenylephrine in pudendal arteries from both groups and in the corpus cavernosum of lean mice, without affecting the potency or efficacy of acetylcholine. These findings suggest that menthol-induced relaxation and reduction of phenylephrine efficacy may hold promise for decreasing penile vascular resistance and enhancing blood flow to the penis.

Artificial intelligence (AI) has emerged as a transformative tool in healthcare through data analysis, pattern recognition and predictive modeling capabilities. AI-driven approaches have the potential to positively transform patient care through personalized treatment regimens comprising antiplatelet and anticoagulant therapy. This review explores the integration of AI in guiding antithrombotic therapies, highlighting the potential to improve patient outcomes through personalized medicine. Following a rigorous screening process, a total of 15 studies from the PubMed database were included in the review. We further explore studies investigating the role of Al in anticoagulation choices for acute coronary syndrome, during PCI and for long-term treatment. We also explore studies of antiplatelet agent selection and duration, as well as AI-guided platelet function testing and genotyping. The few studies that exist have demonstrated the integration of AI into antiplatelet and anticoagulation therapy holds substantial promise for enhancing patient-specific treatment strategies in cardiovascular care. AI can provide predictive insights that could surpass less objective traditional approaches in accuracy and personalization. Furthermore, the development of AI-driven tools for therapy duration assessment, genetic testing, and mobile applications for patient monitoring underscores AI's role in supporting real-time clinical decision-making and improving patient adherence. Future studies will be crucial in order to address the current limitations in applicability and validate these AI systems with respect to patient centered outcomes.

Abstract: In this study, we compared the effects of various doses of dexmedetomidine on the incidence of atrial fibrillation (AF) after cardiac surgery in adults. A total of 224 adult patients who underwent elective cardiac surgery were randomly assigned to two groups. The DEX0.5 group received a continuous infusion of dexmedetomidine at a rate of 0.5 μg·kg⁻ 1 ·h⁻ 1 , while the DEX1 group received it at a rate of 1 μg·kg⁻ 1 ·h⁻ 1 during the induction of anesthesia, which was maintained for 24 hours. The primary outcome was the incidence of AF, while the secondary outcomes included other tachyarrhythmias, bradycardia, hypotension, duration of mechanical ventilation, time spent in the cardiac care unit, and length of hospitalization. A total of 101 patients were included in the DEX0.5 group, while 104 patients were included in the DEX1 group. The incidence of AF was significantly lower in the DEX1 group compared with the DEX0.5 group (10.6% vs. 21.8%, P = 0.029). In addition, the duration of mechanical ventilation was shorter in the DEX1 group than in the DEX0.5 group (8.9 vs. 15.2 hours, P = 0.018). Logistic regression analyses were conducted to investigate the factors influencing AF. The results indicated that the dose of dexmedetomidine was the only independent predictor (odds ratio = 0.394, 95% confidence interval 0.172 to 0.903, P = 0.028). Compared with a continuous infusion of 0.5 μg·kg⁻ 1 ·h⁻ 1 , this study suggested that administering dexmedetomidine at a dose of 1 μg·kg⁻ 1 ·h⁻ 1 for 24 hours is effective in reducing the incidence of AF after cardiac surgery.

Abstract: Acute coronary syndromes (ACS) continue to pose significant challenges for clinical practitioners, particularly regarding the prediction of mid- to long-term outcomes. This study aims to investigate the impact of in-hospital bleeding (IHB) at 1-year follow-up in patients admitted for ACS. Data from 23,270 patients enrolled in the international PRAISE registry and discharged after ACS were analyzed. A total of 1060 patients experienced IHB, whereas 18,765 did not; 3445 were excluded because of missing data. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints included major bleeding, reinfarction, and composite endpoints at 1 year. Patients with IHB were older, more frequently female, and had a higher prevalence of cardiovascular risk factors (all P < 0.05). At discharge, IHB patients were less likely to receive optimal medical therapy. At the 1-year follow-up, all-cause mortality, major bleeding, and reinfarction were significantly higher in the IHB group (all P s < 0.001). Bivariate analysis showed a strong association between IHB and all the outcomes of interest (all odds ratios >1; all P s < 0.001). These associations remained significant even after adjusting for several covariates, except for reinfarction (odds ratio 1.3; 95% confidence interval 0.9-2.11; P = 0.149). Age, female sex, hypertension, and peripheral artery disease were found to be independent predictors of IHB, whereas drug-eluting stent implantation, radial access, and left ventricular ejection fraction were identified as protective factors. IHB is a hallmark of frailty in patients with ACS; therefore, greater attention should be given during follow-up to patients experiencing this condition.