Journal of Cardiovascular Pharmacology最新文献

{"title":"Chronotropic Effects of Milrinone in a Guinea Pig Ex Vivo Model: A Pilot Study to Screen for New Mechanisms of Action.","authors":"Piero Pollesello, Jouko Levijoki, Zoltán Papp","doi":"10.1097/FJC.0000000000001675","DOIUrl":"10.1097/FJC.0000000000001675","url":null,"abstract":"<p><strong>Abstract: </strong>Positive inotropic responses upon administration of milrinone, an inhibitor of the phosphodiesterase enzyme (PDE), involve a well-pronounced positive chronotropic effect. Here, we tested whether milrinone evokes this chronotropic response solely by PDE inhibition or by a concerted action that involve additional pharmacological targets. Milrinone-stimulated increases in heart rate were studied in right atrial preparations of guinea pig in the presence or absence of inhibitors of putative ancillary molecular pathways or ion channels: ie, β receptor blockers with distinct selectivities (propranolol, metoprolol, and carvedilol), α1 receptor blocker (prazosin), inhibitor of the small conductance Ca 2+ activated K + (SK) channels (apamin), L-type Ca 2+ channel blockers (verapamil and diltiazem), and different Na + channel blockers (lidocaine, tetrodotoxin, and quinidine). Carvedilol, which inhibits β1, β2, α1, and 5-HT receptors, limited the positive chronotropic effects of milrinone to about 40%, ( P < 0.01). In the presence of another nonselective blocker of the β receptors, propranolol, and blockers of the l -type Ca 2+ channels, only nonsignificant trends toward reductions of the milrinone effects were seen. The α1 receptor blocker prazosin did not limit the milrinone-evoked positive chronotropy. Blockers of Na + channels, SK channels, or the β1 receptor blocker, metoprolol also did not affect the positive chronotropy evoked by milrinone. We conclude that milrinone increases heart rate in response to adrenergic signaling, which besides PDE inhibition, may involve a 5-HT receptor-dependent component. Our exploratory approach paves the way to more focused experiments with the use of selective 5-HT receptor antagonists to confirm or reject the involvement of a specific 5-HT receptor-dependent pathway.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"278-286"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mineralocorticoid Receptor Antagonist versus Placebo in a Patient With End-Stage Kidney Disease Under Renal Replacement Therapy: A Systematic Review and Meta-Analysis.","authors":"Sagun Dawadi, Dhan Bahadur Shrestha, Prakash Raj Oli, Jurgen Shtembari, Sajog Kansakar, Suman Paudel, Kailash Pant","doi":"10.1097/FJC.0000000000001661","DOIUrl":"10.1097/FJC.0000000000001661","url":null,"abstract":"<p><strong>Abstract: </strong>The number of patients living with chronic kidney diseases is increasing, and so are the patients with end-stage renal disease (ESRD) undergoing renal replacement therapy. Although there is a common understanding that these patients face higher risks of fatal or nonfatal cardiovascular and cerebrovascular events, and mineralocorticoid receptor antagonists (MRAs) have been an essential pillar in managing heart failure, their use in this subset of patients has been overshadowed because of concerns of hyperkalemia. Patients with ESRD under renal replacement therapy have often been excluded from landmark trials. This meta-analysis was conducted based on the PRISMA guideline after registering the protocol with PROSPERO (CRD42024499835). A database search included articles until April 2024, and relevant data were extracted from the included studies. Analysis was done using RevMan web (version 5.4). A total of 15 studies among 1086 studies were included in the final analysis. Our meta-analysis revealed MRA significantly reduced all-cause mortality (odds ratio (OR) 0.35, confidence interval (CI), 0.23-0.54) and cardiovascular mortality (OR 0.37, 0.21-0.65). With some possible increase in the risk of hyperkalemia (OR 1.56, CI, 1.01-2.42), with no discernible difference in the occurrence of stroke (OR 0.57, CI, 0.25-1.28) or myocardial infarction (OR 0.63, CI, 0.08-4.72). The utilization of MRA in patients with ESRD under dialysis is linked to improved mortality outcomes, albeit with slight concerns for hyperkalemia. Although current evidence leans toward MRA usage, prospective randomized controlled trials involving a broader patient cohort are essential to establish robust guidance for MRA application in this subset of patients.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"270-277"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-Induced Spontaneous Intramural Hematoma of the Gastrointestinal Tract: A Real-World Pharmacovigilance Analysis.","authors":"Xuehong Wang, Min Luo, Wenyu Li, Yuqian Zhou","doi":"10.1097/FJC.0000000000001662","DOIUrl":"10.1097/FJC.0000000000001662","url":null,"abstract":"<p><strong>Abstract: </strong>It is unclear whether drugs other than warfarin can cause spontaneous gastrointestinal intraluminal hematomas (SGIH). This study aimed to investigate the drugs that induced SGIH based on the US Food and Drug Administration's Adverse Event Reporting System data. A retrospective pharmacovigilance study was conducted. The disproportionality analysis was performed to assess the reports of drug-induced SGIH from the first quarter of 2004 to the fourth quarter of 2023. Logistics regression analysis was used to explore drug-related SGIH risk factors. Weibull distribution was applied for the onset time of SGIH. A total of 116 drugs associated with SGIH have been reported in the US Food and Drug Administration's Adverse Event Reporting System database. After removing duplicates, 88 unique drugs involving 210 patients were identified. These drugs can be broadly classified into 4 categories: (1) anticoagulants, (2) new direct oral anticoagulants, (3) antiplatelet agents, and (4) others. The first group is dominated by warfarin (59/210), while the second group, rivaroxaban, accounts for the most significant proportion (9/210). As for the third group, aspirin is the dominant drug (16/210), and for the fourth group, drugs that cause thrombocytopenia are dominant. The median number of reported cases was 11.5 per year, accounting for a median percentage of 0.0094% of all adverse events related to target drugs. The median time to drug-related SGIH onset was 12.5 days (interquartile range 1-220.25 days). When patients on the related drugs present with corresponding abdominal symptoms, it is crucial to consider the differential diagnosis of SGIH despite its low incidence.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"297-304"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Colchicine in Coronary Artery Disease: Where Do We Stand?","authors":"Aldo Bonaventura, Nicola Potere, Luca Liberale, Simon Kraler, Brittany N Weber, Antonio Abbate","doi":"10.1097/FJC.0000000000001672","DOIUrl":"10.1097/FJC.0000000000001672","url":null,"abstract":"<p><strong>Abstract: </strong>Colchicine is an anti-inflammatory drug for different inflammatory conditions and is approved for secondary prevention of cardiovascular events in patients with coronary artery disease, mainly based on the results of the LODOCO2 and COLCOT trials. The recently published CLEAR SYNERGY trial reported neutral results for colchicine in patients with acute myocardial infarction undergoing percutaneous coronary intervention, challenging the previous reported benefits of colchicine. While colchicine appeared rather safe across the different studies, the variation in efficacy may suggest that the one-size-fits-all for the treatment of acute and chronic forms of coronary artery disease may not be appropriate, and that low-dose colchicine may be beneficial as an add-on therapy in patients who are stable or recovering from acute event, and not so helpful in patients with acute myocardial infarction already receiving intensive pharmaco-invasive therapies.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"243-247"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes for 2025 at Journal of Cardiovascular Pharmacology: Introducing Our Junior Associate Editors, Podcasts, Feature, and New Board Members.","authors":"Antonio Abbate, Giuseppe Biondi-Zoccai, Raffaele Altara, George W Booz","doi":"10.1097/FJC.0000000000001673","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001673","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":"85 4","pages":"239-242"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143784359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-Reported Outcome Measures in Cardiovascular Research and Care: PRO(M)s and CONS.","authors":"Giuseppe Biondi-Zoccai, Giacomo Frati, Mariangela Peruzzi, Marco Bernardi, Luigi Spadafora, Elena Tremoli","doi":"10.1097/FJC.0000000000001669","DOIUrl":"10.1097/FJC.0000000000001669","url":null,"abstract":"<p><strong>Abstract: </strong>Patient-reported outcome measures (PROMs) are vital tools in cardiovascular disease research and care, providing insights that complement traditional clinical outcomes such as mortality and morbidity. PROMs capture patient experiences with cardiovascular disease, such as quality of life, functional capacity, and emotional well-being, allowing clinicians to assess how interventions affect daily life. PROMs are integral to cardiovascular investigations and management, especially in chronic conditions and rehabilitation, where they inform on the impact of personalized care plans by tracking symptom progression and patient adherence. Selecting and applying to cardiovascular research and practice effective PROMs involves evaluating their validity, reliability, and sensitivity to change, with instruments such as the Kansas City Cardiomyopathy Questionnaire and the Seattle Angina Questionnaire widely used for heart failure and coronary artery disease, respectively. Implementing PROMs in real-world practice requires addressing challenges related to workflow integration and patient adherence, emphasizing their value in patient-centered care. As digital health advances, remote PROM data collection through mobile applications and wearable devices will enhance access to and extent of PROMs, and artificial intelligence-driven analytical tools will provide real-time, automated and plausible more poignant insights for personalized treatment. Future efforts should focus on culturally adapting PROMs for diverse populations to ensure global applicability. PROMs should also be established as essential components of innovative research and responsive, patient-centered cardiovascular care.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"261-266"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Latest Evidence and Perspectives of Panax Notoginseng Extracts and Preparations for the Treatment of Cardiovascular Diseases.","authors":"Chenyu Zhao, Jiamei Fu, Yingyu Wang, Yabin Zhou","doi":"10.1097/FJC.0000000000001670","DOIUrl":"10.1097/FJC.0000000000001670","url":null,"abstract":"<p><strong>Abstract: </strong>Cardiovascular diseases are a major cause of death worldwide, and their high incidence poses a significant threat to human health and public health systems. Panax notoginseng , a traditional Chinese medicinal herb with a long history, has shown promise in treating cardiovascular diseases. This review examines the diverse mechanisms through which Panax notoginseng addresses cardiovascular diseases, including anti-inflammatory, antiplatelet aggregation, anticoagulation, anti-oxidative stress, regulation of angiogenesis, antiatherosclerosis, improvement of microcirculatory disorders, and protection against myocardial ischemia-reperfusion injury, highlighting saponins as the principal active components. It also summarizes studies involving Panax notoginseng preparations like Xueshuantong and Xuesaitong in treating coronary heart disease and myocardial infarction, and discusses the safety, limitations, and future research directions of these extracts. In conclusion, the cardiovascular protective mechanism of Panax notoginseng is multitargeted and multipathways, and its clinical application is relatively safe, with rare and mild adverse drug reactions, suggesting a promising therapeutic potential.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"248-260"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of APJ Receptors by CMF-019, But Not Apelin, Causes Endothelium-Dependent Relaxation of Spontaneously Hypertensive Rat Coronary Arteries.","authors":"Santo Anto, Chengwen Sun, Stephen T O'Rourke","doi":"10.1097/FJC.0000000000001671","DOIUrl":"10.1097/FJC.0000000000001671","url":null,"abstract":"<p><strong>Abstract: </strong>Receptors for the vasoactive adipokine apelin, termed APJ receptors, are G-protein-coupled receptors and are widely expressed throughout the cardiovascular system. APJ receptors can also signal through G-protein-independent pathways, including G-protein-coupled receptor kinase 2 (GRK2), which inhibits endothelial nitric oxide synthase (eNOS) activity and nitric oxide production in endothelial cells. Apelin causes endothelium-dependent, nitric oxide-mediated relaxation of coronary arteries from normotensive animals, but the effects of activating APJ receptor signaling pathways in hypertensive coronary arteries are largely unknown. We hypothesized that apelin-induced relaxation is impaired in coronary arteries from spontaneously hypertensive rats (SHR). Western blot and mRNA analysis revealed increased GRK2 expression in cultured SHR coronary endothelial cells. Apelin failed to cause relaxation in isolated SHR coronary arteries but, in the presence of apelin, relaxations to acetylcholine were impaired. Apelin had no effect on relaxation to diethylamine NONOate. The GRK2 inhibitor, CMPD101, increased apelin-induced phosphorylation of Akt and eNOS in SHR endothelial cells and restored relaxation to apelin in SHR arteries. CMPD101 also blocked the inhibitory effect of apelin on ACh-induced relaxation. Relaxations to the APJ receptor-biased agonist, CMF-019, which preferentially activates the G-protein-dependent pathway with minimal effect on GRK2, were similar in SHR and Wistar Kyoto coronary arteries. Immunoblot analysis in SHR coronary endothelial cells demonstrated that CMF-019 increased Akt and eNOS phosphorylation whereas apelin had no effect. Thus, APJ receptor signaling through GRK2 impairs nitric oxide production or release from SHR endothelial cells. APJ receptor-biased agonists, such as CMF-019, may be more effective than apelin in causing vasodilation of SHR coronary arteries.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"287-296"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease Under Renal Replacement Therapies: Bridging the Gap Between Cardiovascular and Systemic Benefit, From Heart Failure to Myocardial Infarction.","authors":"Giuseppe Galati, Olga Germanova","doi":"10.1097/FJC.0000000000001677","DOIUrl":"10.1097/FJC.0000000000001677","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"267-269"},"PeriodicalIF":2.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cinnamaldehyde attenuates diabetic cardiomyopathy by ameliorating energy metabolism disturbance and activating autophagy.","authors":"Ming-Qiao Hu, Ke-Zhao Wei, Shi-Yu Wu, Xu Zhang, Xiao-Ting Zhang, Xu Xu, Xu-Hua Shen, Jian-Ping Gao","doi":"10.1097/FJC.0000000000001694","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001694","url":null,"abstract":"<p><p>Diabetic Cardiomyopathy (DCM) is a diabetes mellitus-induced pathophysiological condition that can lead to heart failure. Cinnamaldehyde (CA), a bioactive phytochemical derived from the bark of Cinnamon, exhibits cardioprotective properties against heart injury in metabolic syndrome. This study aims to explore the role of CA on DCM and its cardioprotective mechanisms. Diabetic rats were established by injection of streptozotocin (STZ, 60∼85 mg/kg). Subsequently, CA (50 mg/kg) was administered via gavage daily for 28-day duration. Following this treatment, abnormalities levels of fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and LDL-C to HDL-C ratio were ameliorated. Additionally, CA inhibited cardiac histopathological alterations and hypertrophy, reduced brain natriuretic peptide (BNP) level, shortened S-T and P-R intervals on electrocardiogram, decreased tissue malondialdehyde content, and enhanced myocardial energy metabolism, including Creatine (Cr), adenosine triphosphate (ATP), adenosine monophosphate (AMP) and total adenine nucleotides (TAN). Furthermore, CA improved oxidative stress, improved myocardial Ca2+-Mg2+-ATPase activity and downregulated the mRNA expression of AMP protein activation kinase α2 (AMPK-α2), receptor γ coactivator-1 alpha (PGC-1α) and peroxisome proliferator-activated receptor α (PPARα), while also ameliorating protein expressions, including ratio of phosphorylated mammalian target of rapamycin to mechanistic target of rapamycin (p-mTOR/mTOR), level of SQSTM1/p62, and ratio of microtubule-associated protein 1 light chain 3 beta to microtubule-associated protein 1 light chain 3 alpha (LC3Ⅱ/ LC3Ⅰ). In conclusion, these findings indicate that CA can alleviate DCM by modulating AMPK-α2/PPAR-α/PGC-1α signaling pathway to restore energy metabolism and activating autophagy through mTOR signaling pathway.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}