Preclinical safety and anti-inflammatory activity of a standardized Justicia pectoralis Jacq. extract in experimental models of respiratory inflammation.

Objective: Myocardial infarction (MI) triggers inflammation and fibrosis that drive the progressive impairment of cardiac function. Yet most pharmacological studies still depend on single-time-point histological or imaging endpoints and lack longitudinal, non-invasive assessments of treatment response. Electrocardiography (ECG) detects conduction and repolarization abnormalities tightly associated with myocardial injury and structural remodeling. However, ECG monitoring in mice is limited by rigid or invasive hardware, which restricts its use for longitudinal assessment of cardiac structure and function. Approach: Here, we propose an ECG-based non-invasive post-MI cardiac remodeling assessment approach and develop a flexible electrocardiographic monitoring microsystem (FECMS). Using the anti-remodeling drug (colchicine) therapy in an MI mouse model (Sham n = 4, MI n = 7 survivors, Col n = 7 survivors) for validation, we longitudinally track drug-induced changes in ECG parameters and systematically evaluate their concordance with functional, structural, and molecular indicators of cardiac injury and remodeling. Results: Colchicine treatment induced progressive shortening of the QRS and QT intervals and gradual stabilization of the PR interval. These interval changes were accompanied by increased EF and FS, decreased LVESV, reduced myocardial fibrosis and inflammatory infiltration, and lower plasma troponin I levels at the endpoint. Correlation analyses revealed strong relationships between drug-induced changes in ECG parameters and functional recovery and inhibited structural remodeling. Significance: The FECMS provides a new, non-invasive tool for longitudinal cardiovascular drug evaluation. This approach has the potential to complement or reduce reliance on terminal histological endpoints and to facilitate the optimization of dosing strategies in preclinical cardiovascular pharmacology.

This pilot study evaluated the feasibility and learner acceptance of a blended learning model integrating Flipped Classroom (FC) and Think-Pair-Share (TPS) strategies in a cardiovascular pharmacology course for pharmacy students. A single-group, post-intervention evaluation was conducted with 62 undergraduate pharmacy students. The intervention featured: pre-class self-study with real prescriptions, interactive lectures, structured TPS activities, and gamified incentives. Evaluation focused on Kirkpatrick's Level 1 (Reaction), using a satisfaction survey to assess student perceptions. Student satisfaction was notably high. Most students perceived real prescriptions as highly effective for engagement (93.5%) and learning (90.3%). Peer discussions (74.2%), pre-class preparation (93.5%), and the instructor's explanations (93.6%) were also rated as highly effective. The majority (87.1%) preferred group exams and perceived the method as improving future consultation skills (90.3%). The FC/TPS model, augmented with authentic materials, demonstrated high feasibility and was exceptionally well received by students. These positive perceptions support its implementation in similar contexts and justify further research with controlled designs to measure its impact on objective learning outcomes.

Ursula Ravens — recipient of the Schmiedeberg Medal: a distinguished career dedicated to cardiovascular pharmacology and cardiac electrophysiology

Cardiovascular diseases remain the leading global cause of death and disability, prompting the need for precise mapping of molecular drivers that couple ionic flux to signaling. Because of its regulatory role in ionic balance and signaling, transient receptor potential melastatin 7 (TRPM7) channel-kinase has emerged as a key molecular determinant of cardiovascular physiology and pathophysiology. Following an overview of Ca2+ signaling in cardiovascular biology, we summarize current knowledge of TRPM7 from its structure to its function, including channel architecture, gating properties, and kinase regulation by metabolic and redox signals with a diverse substrate repertoire. Integration of evidence across cardiovascular systems biology shows that TRPM7 acts in a context-dependent manner. In the vasculature, TRPM7 shapes endothelial function, smooth muscle phenotype and remodeling, and participates in neurogenic control of blood pressure through carotid body glomus cells. In the heart, TRPM7 regulates pacemaking and conduction through transcription control of ion channel genes, contributes to atrial fibrogenesis via Ca2+-dependent fibroblast activation, and worsens ischemia-reperfusion injury through ionic overload and inflammasome signaling. In metabolic heart disease, TRPM7 kinase activity links mitochondrial oxidative stress to diastolic dysfunction, suggesting relevance to heart failure with preserved ejection fraction (HFpEF). Finally, we appraise pharmacological tools that target TRPM7, including natural and synthetic channel and kinase modulators, and outline translational considerations for organ- and disease-specific modulation. Overall, TRPM7 is a central integrator of ionic homeostasis and kinase signaling in cardiovascular biology and represents a promising, yet nuanced, therapeutic target that requires context-aware strategies.

Opioid-induced respiratory depression in cosmetic surgery: A medico-legal analysis of a fatal adverse event.

Traditional laboratory practicals exploring cardiovascular physiology and pharmacology rely on mammalian models, presenting ethical, financial, and logistical challenges. Danio rerio (zebrafish) larvae offer a compelling alternative that aligns with the partial replacement principle of replacement, reduction, and refinement (the 3Rs), while providing an opportunity for students to develop desirable in vivo skills to improve their employability. Here, we introduce an engaging set of in vivo laboratory practicals suitable for large undergraduate cohorts that utilizes larval zebrafish to investigate cardiac ion channels and receptors. The practical involves two 3-hour sessions where students measure heart rate in 72- and 96-hour postfertilization larvae in response to various treatments. The first session introduces students to handling larval zebrafish before exploring the effects of a reduced ambient temperature and application of the commonly used zebrafish anesthetic tricaine (MS-222) on both heart rate and the zebrafish startle reflex. Finally, students apply the well-known adrenergic agonist adrenaline. The second session empowers students to develop their own testable hypothesis regarding which ion channels or receptors are likely to influence zebrafish heart rate, providing them with the autonomy to select two pharmacologically active drugs from a carefully curated list [e.g. isoproterenol (β-adrenergic receptor agonist), propranolol (β-adrenergic receptor antagonist), and nifedipine (L-type calcium channel blocker)] that will enable them to address their hypothesis. Students' subsequent data for analysis allows them to develop an understanding of the conserved and divergent aspects of cardiac physiology between zebrafish and mammalian systems, and an appreciation of the importance of appropriate model selection in physiological and pharmacological research.NEW & NOTEWORTHY The document outlines how large-scale undergraduate practical classes involving Danio rerio (zebrafish) can be used to teach cardiovascular physiology. It emphasizes the educational value of using live zebrafish to explore heart rate, drug effects, and homeostasis. The process supports active, inquiry-based learning, fostering engagement, critical thinking, and collaborative skills. It also addresses ethical and logistical considerations. Overall, the approach effectively combines hands-on experimental experience with core physiological concepts in an impactful educational format.

Cardiovascular diseases remain the leading cause of global morbidity and mortality, highlighting the urgent need for more efficient, precise, and cost-effective drug development strategies. Traditional drug discovery pipelines face persistent challenges, including elevated expenses, prolonged timelines, and high attrition rates, particularly with the complex pathophysiology of cardiovascular conditions. Artificial intelligence (AI) has emerged as a transformative force capable of addressing these barriers across all stages of cardiovascular drug development. This review explores the integration of AI in target identification, compound screening, drug design, pharmacokinetic and toxicity prediction, and clinical trial optimization. We highlight state-of-the-art AI tools such as large language models (e.g., BioGPT, Geneformer), generative frameworks (e.g., Generative Tensorial Reinforcement Learning (GENTRL), Variational Autoencoders (VAEs), Generative Adversarial Networks (GANs)), and neural ordinary differential equations, illustrating their ability to accelerate drug discovery, personalize therapy, and improve clinical success rates. In the context of clinical trials, platforms such as Trial Pathfinder have been employed to optimize patient recruitment and improve generalizability. Despite these advancements, several challenges persist, particularly those related to data quality, population representativeness, interpretability, and regulatory oversight. Future directions involving the integration of AI with quantum computing, blockchain technology, and precision medicine offer additional opportunities to advance the field. Collectively, these innovations mark a paradigm shift toward faster, safer, and more personalized cardiovascular drug development.

Gamification in tertiary education aims to improve engagement and stimulate learning. Traditional pharmacology lessons, often delivered through lectures and tutorials, are sometimes perceived as suboptimal learning experiences. The objective was also to investigate the development of student self-efficacy and agency by comparing student behaviors in traditional versus game-based tutorials. A physical board game, modeled on the game "Guess Who?," featured drugs from cardiovascular pharmacology. Students in a second-year pharmacology course played in pairs, asking questions about the drugs to identify their opponent's selected card. To evaluate the game and compare the tutorial formats, students completed a 2-part anonymous survey with a Likert-scale and short-answer questions evaluating how each tutorial type contributed to learning outcomes. Sixty-two students participated in the traditional tutorial survey, and 60 in the gamified tutorial. Gamified tutorials increased motivation, engagement, and active participation. They were also more effective in assisting students to identify knowledge gaps, understand concepts, and retain information. Gamified lessons also facilitated peer collaboration and promoted self-regulated learning more effectively. Traditional tutorials, however, were seen as better for grasping complex concepts and preparing for real-world applications. The gamified pharmacology lesson positively influenced learning, engagement, and agency. Gamified tutorials can complement traditional lessons depending on the complexity of the content and learning objectives.

In this study, a detailed spectroscopic and computational analysis was carried out on 5-azanidyl-3-(morpholin-4-yl)-1,2,3λ⁵-oxadiazol-3-ylium (Linsidomine), a well-established nitric oxide donor with significant therapeutic relevance in cardiovascular pharmacology. The compound was characterized experimentally using FT-IR, FT-Raman, UV–Visible, and NMR spectroscopy, supported by quantum chemical simulations at the HF and B3LYP/6-311 + + G(d, p) levels. The observed vibrational frequencies were systematically assigned and validated through theoretical data, including the identification of key functional group vibrations such as N = O, C–N, and N = N. Frontier molecular orbital analysis revealed a moderate HOMO–LUMO gap of 3.836 eV, indicating a balance between stability and reactivity. Electrostatic potential mapping and Mulliken charge distributions highlighted electrophilic and nucleophilic zones responsible for biological interaction and NO release mechanisms. The drug-likeness, pharmacokinetic parameters, and medicinal chemistry filters confirm the compound’s oral bioavailability, metabolic safety, and synthetic accessibility. Moreover, the simulated Vibrational Circular Dichroism (VCD) spectrum and NMR chemical shifts reinforced its conformational and stereoelectronic consistency. Together, these results demonstrate Linsidomine’s strong potential as a bioactive molecule, offering insights into its structure-activity relationships and supporting its continued development in NO-based cardiovascular therapeutics.

Guinea pigs have been a standard model in cardiovascular pharmacology and physiology research, but the advent of transgenic models has largely replaced them with mouse and rat models. However, guinea pigs remain important models in cardiac electrophysiology, drug-induced arrhythmias, or atherosclerosis research, and they have recently gained importance for studying one specific research question, that is, transplantation of pluripotent stem cell derived cardiomyocytes to repair the cryo-injured heart. Their human-like cardiac electrophysiology, together with their small size that facilitates handling and housing, make guinea pigs a valuable experimental model for these studies. However, repeated open heart surgeries in guinea pigs are technically demanding and accompanied by high mortality. In this study, we retrospectively examined sequential protocol modifications and describe how protocol refinements led to improved survival rates. Cryo-injury was performed in female Dunkin-Hartley guinea pigs under general anesthesia with a liquid nitrogen-cooled probe via a lateral thoracotomy. Cells were transplanted during a second surgery 7 days later. We analyzed data from up to 558 animals to determine mortality rates and morphologic and functional parameters. Initial studies revealed a mortality rate of ∼50%. Sequential modifications led to a significant reduction, with the refined protocol achieving a perioperative mortality rate of ∼30%. The procedures were completed in <35 minutes, and survival rates for the observation period (up to 8 weeks) were 70%. Scar size was evaluated in 144 (4 weeks, n = 92; 8 weeks, n = 52) animals and showed a significant, but shallow correlation with echocardiographically determined heart function. Taken together, refined surgery protocols allow safe and reproducible cryo-injury with subsequent cell injections in guinea pigs with an improved mortality rate.

Retrospective translational analyses have shown a high rate of false negatives between clinical thorough QT studies (TQT) and preclinical cardiovascular safety pharmacology studies. The aim of this work was to model the results of clinical TQT studies from cardiovascular safety pharmacology studies conducted on a large set of reference drugs in beagle dogs by implanted telemetry. All preclinical studies were based on a standard four-animal crossover design comparing the vehicle to the reference drug. The model used was based on the one-step QTc correction model. This model was adapted in order to apply the same statistical method in preclinical studies as in clinical trials. The sensitivity of the model made it possible to detect QTc prolongation of at least 5 ms with all reference hERG blockers known to cause QT prolongation in humans. Modelling of moxifloxacin (10 mg/kg, po) effects was in agreement with data published from clinical TQT studies with moxifloxacin 400 mg showing a QTc prolongation greater than 5 ms between 1 and 4 hours post-dose. This study shows a noticeable reduction in the risk of false negatives with several references drugs associated with a phenomenon of concealed QTc prolongation. Moreover, several reference drugs did change the slope of the QT/HR slope justifying the principles of the one-step QTc model. Modelling results of TQT studies with the one-step QTc model for applying the same statistical approach as in the clinic can improve the translational value of preclinical cardiovascular safety pharmacology studies and reduce the risk of false negatives.

Background: Luteolin, a naturally occurring flavonoid abundantly found in various fruits, vegetables, and medicinal plants, has drawn increasing scientific attention due to its potent antioxidant, anti-inflammatory, and vasoprotective properties. Its pharmacological profile suggests therapeutic potential in cardiovascular diseases, particularly conditions characterized by endothelial dysfunction and vasospasm. Among these, Prinzmetal angina—a variant form of angina marked by transient coronary artery spasms—represents a clinical context in which luteolin’s endothelial and vascular effects may have significant therapeutic relevance. Objective: This narrative review aims to evaluate the pharmacological potential of luteolin in the management of Prinzmetal angina, emphasizing its mechanisms of action related to endothelial modulation, nitric oxide bioavailability, and vasodilatory response. Main Discussion Points: The review synthesizes evidence showing that luteolin enhances endothelial nitric oxide production, mitigates oxidative stress, and inhibits inflammatory mediators such as TNF-α and IL-6, which collectively contribute to improved vascular tone and reduced vasospastic activity. It also discusses how luteolin’s ability to regulate calcium channel activity and attenuate vascular smooth muscle contraction may counteract ischemic episodes characteristic of Prinzmetal angina. Conclusion: Emerging evidence indicates that luteolin may reduce the frequency and severity of coronary vasospasms by restoring endothelial balance and suppressing inflammatory and oxidative mechanisms. While preclinical findings are encouraging, large-scale clinical trials are essential to establish its safety, efficacy, and therapeutic integration into angina management protocols.

Dual-cardiotoxicity evaluation of torsadogenic risk drugs using human iPSC-derived cardiomyocytes.

Ruthenium complexes stand out as an excellent alternative in the field of organometallic chemistry with applications in various areas. Recently, in cardiovascular pharmacology, there has been a growing interest in investigating complexes that modulate the Nitric Oxide (NO) pathway without necessarily and directly donating NO. NO has a proven vasodilatory and cardioprotective effect, and it is known that reduced levels are associated with an increased risk of CardioVascular Diseases (CVD). Studies suggest that ruthenium complexes significantly contribute to the treatment of CVD pathophysiology through different pharmacological mechanisms, including the precise delivery of carbon monoxide (CO) to the molecular target, the release of nitric oxide species under visible and invisible (UV) light, the ability to stimulate the activation of soluble Guanylate Cyclase (sGC) enzyme, participation in the opening of potassium channels, and reduction of cytoplasmic calcium levels. This study aims to conduct a narrative review of the cardiovascular effects of ruthenium complexes, focusing on hypertension and myocardial injury, and demonstrate that metal complexes acting on the NO pathway may have promising targets for the development of therapeutic strategies in CVD treatment.

The constant progress in molecular biology and genetic engineering technologies within the field of cardiovascular pharmacology, along with the introduction of clinically applied drugs based on these advancements, compels us to reconsider our current understanding in this area. This article aims to provide an update on the underlying mechanisms, pharmacological design, and the clinical applications tested so far, and also to address the safety concerns associated with drugs that utilize RNA interference technology.

Implementation of automated blood sampling in a canine cardiovascular safety pharmacology study to support PK/PD assessment.

Statistical power analysis of standard cardiovascular safety pharmacology studies in telemetry implanted dogs and nonhuman primates

Human-based technologies are revolutionizing cardiovascular pharmacology by offering innovative platforms that more accurately reflect human biology and disease mechanisms than traditional animal models. These approaches include tissue chips, microphysiologic systems, engineered heart tissues, cardiac organoids, and human cardiac slices-each contributing to substantial improvements in drug testing, mechanistic understanding, and translational relevance. Complementary advances in biobanking, omics technologies, and advanced imaging offer the opportunity for multidimensional characterization of cardiovascular phenotypes, while digital health tools and wearables expand our translational armamentarium with real-time physiologic monitoring and decentralized clinical trials. Artificial intelligence and machine learning further contribute discovery pipelines by facilitating data integration and predictive modeling. The application of clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) genome editing and in vitro to in vivo extrapolation frameworks underscores the growing precision and clinical orientation of these methodologies. Together, these innovations are reshaping basic research, drug development, regulatory science, and personalized medicine in cardiology. However, to fully realize their promise, challenges related to standardization, scalability, and ethical governance must be addressed. With strategic investment and cross-sector collaboration, human-based approaches are poised to lead the next generation of cardiovascular research-delivering safer, more effective therapies tailored to human-specific biology.

Taurine, a naturally occurring sulfur-containing amino acid, has gained attention for its potential to lower blood pressure and improve vascular health. Through multiple biological actions, such as regulating ion channels, enhancing antioxidant defenses, and modulating autonomic nervous system activity, taurine supports blood vessel function and reduces vascular stiffness. Evidence from randomized controlled trials and meta-analyses consistently shows that taurine supplementation, particularly at doses of 1.5 to 6 grams per day, leads to significant reductions in systolic and diastolic blood pressure, with the strongest effects observed in hypertensive and metabolically at-risk populations. Importantly, taurine is well tolerated with minimal adverse effects reported. This literature review synthesizes the current mechanistic and clinical evidence to evaluate taurine’s role as a safe and effective adjunct therapy for managing elevated blood pressure and improving cardiovascular outcomes.