{"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":"https://doi.org/10.1097/FJC.0000000000001675","url":null,"abstract":"<p><p>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: i.e. β receptor blockers with distinct selectivities (propranolol, metoprolol, and carvedilol), α1 receptor blocker (prazosin), inhibitor of the small conductance Ca2+ activated K+ (SK) channels (apamin), L-type Ca2+ 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 non-selective blocker of the β receptors, propranolol, and blockers of the L-type Ca2+ channels, only non-significant trends towards 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, that 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":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","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}
Aldo Bonaventura, Nicola Potere, Luca Liberale, Simon Kraler, Brittany W Weber, Antonio Abbate
{"title":"Colchicine in coronary artery disease: Where do we stand?","authors":"Aldo Bonaventura, Nicola Potere, Luca Liberale, Simon Kraler, Brittany W Weber, Antonio Abbate","doi":"10.1097/FJC.0000000000001672","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001672","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","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":"Effect of different doses of dexmedetomidine on atrial fibrillation in adults after cardiac surgery.","authors":"Xinling Zhang, Jian Liu, Yafei Shi, Huirong Wang, Fei Wang, Wenzhu Wang","doi":"10.1097/FJC.0000000000001674","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001674","url":null,"abstract":"<p><p>In this study, we compared the effects of various doses of dexmedetomidine on the incidence of atrial fibrillation following cardiac surgery in adults. 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 atrial fibrillation, 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 atrial fibrillation was significantly lower in the DEX1 group compared to the DEX0.5 group (10.6% vs. 21.8%, P = 0.029). Additionally, 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 atrial fibrillation. 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 to 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 atrial fibrillation following cardiac surgery.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028837","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}
Giuseppe Biondi-Zoccai, Giacomo Frati, Mariangela Peruzzi, Marco Bernardi, Luigi Spadafora, Elena Tremoli
{"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":"https://doi.org/10.1097/FJC.0000000000001669","url":null,"abstract":"<p><p>Patient-reported outcome measures (PROMs) are vital tools in cardiovascular disease (CVD) research and care, providing insights that complement traditional clinical outcomes like mortality and morbidity. PROMs capture patient experiences with CVD, such as quality of life, functional capacity, and emotional well-being, allowing clinicians to assess how interventions impact daily life. PROMs are integral to cardiovascular investigations as well as 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 like the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Seattle Angina Questionnaire (SAQ) 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 AI-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":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","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}
Antonio Abbate, Giuseppe Biondi-Zoccai, Raffaele Altara, George W Booz
{"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":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005958","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":"https://doi.org/10.1097/FJC.0000000000001671","url":null,"abstract":"<p><p>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 via G-protein-independent pathways, including G-protein-coupled-receptor kinase 2 (GRK2), which inhibits nitric oxide synthase (eNOS) activity and nitric oxide (NO) production in endothelial cells. Apelin causes endothelium-dependent, NO-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 (ACh) were impaired. Apelin had no effect on relaxation to DEA 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 WKY 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 via GRK2 impairs NO 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":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-21","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}
Marco Giuseppe Del Buono, Simone Filomia, Tommaso Sanna
{"title":"Optimizing Digoxin Use for Rate Control in Critically Ill Patients with Atrial Arrhythmias: Lessons from a Retrospective Study.","authors":"Marco Giuseppe Del Buono, Simone Filomia, Tommaso Sanna","doi":"10.1097/FJC.0000000000001668","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001668","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983587","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":"Efficacy and safety of Treating Pulmonary Arterial Hypertension With Imatinib:A meta-analysis of randomized controlled trials.","authors":"Xiaofa Chen, Lina Xu, Bijuan Xue","doi":"10.1097/FJC.0000000000001665","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001665","url":null,"abstract":"<p><p>Pulmonary vascular remodeling and arterial hypertension (PAH) correlate to increased platelet-derived growth factor (PDGF) activity and elevated KIT expression. Imatinib has emerged as a potential therapeutic agent for PAH. The purpose of this systematic review and meta-analysis was to assess the effectiveness of imatinib in treatment of PAH. A literature search was conducted with the PubMed, Embase, Web of Science, and Cochrane Library to obtain randomized controlled trials (RCTs) where the efficacy of imatinib and placebo in PAH patients was compared. Three RCTs that involved 262 patients were finally included in this study. Results showed that imatinib significantly improved six-minute walk distance (MD = 42.76, 95% CI [9.20 - 76.32], P = 0.01), reduced pulmonary vascular resistance (MD = -396.68, 95% CI [-474.50 - -318.85], P < 0.00001), and lowered mean pulmonary arterial pressure (MD = -7.29, 95% CI [-13.97 - -0.61], P = 0.03) in PAH patients. No significant difference was found between the imatinib and placebo groups in terms of mortality (OR = 1.25, 95% CI [0.49 - 3.18]) or adverse events (OR = 1.82, 95% CI [0.76 - 4.36], P = 0.18). Despite the significant improvement of key hemodynamic parameters, there was no advantage in reducing clinical adverse events or mortality. The prolonged efficacy and safety of imatinib in PAH patients warrants further studies.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914922","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":"IL-1 blockade in myocardial infarction and its efficacy in patients with complex coronary artery disease. Another brick in the wall.","authors":"M Sadler, C Madaudo, A Cannata, D Bromage","doi":"10.1097/FJC.0000000000001666","DOIUrl":"https://doi.org/10.1097/FJC.0000000000001666","url":null,"abstract":"","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914925","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":"Transient Receptor Potential Canonical Channels in Cardiovascular Pathology and Their Modulators.","authors":"Hussein N Rubaiy","doi":"10.1097/FJC.0000000000001643","DOIUrl":"10.1097/FJC.0000000000001643","url":null,"abstract":"<p><strong>Abstract: </strong>Ion channels play a crucial role in various aspects of cardiac function, such as regulating rhythm and contractility. As a result, they serve as key targets for therapeutic interventions in cardiovascular diseases. Cell function is substantially influenced by the concentration of free cytosolic calcium (Ca 2+ ) and the voltage across the plasma membrane. These characteristics are known to be regulated by Ca 2+ -permeable nonselective cationic channels, although our knowledge of these channels is still inadequate. The transient receptor potential (TRP) superfamily comprises of many nonselective cation channels with diverse Ca 2+ permeability. Canonical or classical TRP (TRPC) channels are a subgroup of the TRP superfamily that are expressed ubiquitously in mammalian cells. TRPC channels are multidimensional signaling protein complexes that play essential roles in a variety of physiological and pathological processes in humans, including cancer, neurological disorders, cardiovascular diseases, and others. The objective of this article was to focus on the role that TRPC channels play in the cardiovascular system. The role of TRPC channels will be deeply discussed in cardiovascular pathology. Together, a critical element in developing novel treatments that target TRPC channels is comprehending the molecular mechanisms and regulatory pathways of TRPC channels in related cardiovascular diseases and conditions.</p>","PeriodicalId":15212,"journal":{"name":"Journal of Cardiovascular Pharmacology","volume":" ","pages":"21-34"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142466351","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}