Channel Blocker Research Articles

Impact of prior aspirin use on left ventricular function in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: An echocardiographic evaluation.

Previous studies have investigated the potential influence of prior aspirin use on cardiac function in patients with ST-elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PPCI). However, the results from these studies have been conflicting. This study aimed to investigate whether prior aspirin use affects left ventricular (LV) function in these patients using echocardiography. The study included 260 consecutive STEMI patients, who were divided into two groups based on the presence or absence of prior aspirin use. Echocardiographic parameters, such as maximal left atrial (LA) size, LV ejection fraction (LVEF), early diastolic velocity (e'), E/A ratio, and E/e' ratio, were assessed within 72 hours of admission. Aspirin users had an older age compared to non-users, as well as lower body mass index and renal function. They also had a greater history of hypertension and were more likely to be taking statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and calcium channel blockers. There were no significant differences in LVEF, maximal LA size, E/A ratio, E/e' ratio, and deceleration time between aspirin users and non-users. e' wave was marginally lower in aspirin users (P=0.054). After controlling for confounding variables, the previous use of aspirin did not show a significant impact. Prior aspirin use in STEMI patients does not have a significant impact on LV echocardiographic parameters. Our conclusions remained consistent even after adjusting for potential confounders.

Importance of Zinc Homeostasis for Normal Cardiac Rhythm

<p>Current arrhythmia therapies such as ion channel blockers, catheter ablation, or implantable cardioverter defibrillators have limitations and side effects, and given the proarrhythmic risk associated with conventional, ion channel-targeted anti-arrhythmic drug therapies, a new approach to arrhythmias may be warranted. Measuring and adjusting the level of particular ions that impact heart rhythm can be a simple and low-complication strategy for preventing or treating specific arrhythmias. In addition, new medicines targeting these ions may effectively treat arrhythmias. Numerous studies have shown that intracellular and extracellular zinc concentrations impact the heart's electrical activity. Zinc has been observed to affect cardiac rhythm through a range of mechanisms. These mechanisms encompass the modulation of sodium, calcium, and potassium ion channels, as well as the influence on beta-adrenergic receptors and the enzyme adenylate cyclase. </p><p> Moreover, zinc can either counteract or induce oxidative stress, hinder calmodulin or the enzyme Ca (2+)/calmodulin-dependent protein kinase II (CaMKII), regulate cellular ATP levels, affect the processes of aging and autophagy, influence calcium ryanodine receptors, and control cellular inflammation. Additionally, zinc has been implicated in the modulation of circadian rhythm. Additionally, zinc has been implicated in the modulation of circadian rhythm. In all the above cases, the effect of zinc largely depends on the normal or increased cellular level of zinc, which shows the importance of maintaining the serum and intracellular levels of zinc within the normal range.</p>

Mechanisms of NMDA Receptor Inhibition by Biguanide Compounds.

N-methyl-D-aspartate (NMDA) receptors are inhibited by many medicinal drugs. The recent successful repurposing of NMDA receptor antagonists ketamine and dextromethorphan for the treatment of major depressive disorder further enhanced the interest in this field. In this work, we performed a screening for the activity against native NMDA receptors of rat CA1 hippocampal pyramidal neurons among biguanide compounds using the whole-cell patch-clamp method. Antimalarial biguanides proguanil and cycloguanil, as well as hypoglycemic biguanide phenformin, inhibited them in micromolar concentrations, while another hypoglycemic biguanide metformin and antiviral biguanide moroxydine were practically ineffective. IC50 values at -80 mV holding voltage were 3.4 ± 0.6 µM for cycloguanil, 9.0 ± 2.2 µM for proguanil and 13 ± 1 µM for phenformin. The inhibition by all three compounds was not competitive. Cycloguanil acted as an NMDA receptor voltage-dependent trapping channel blocker, while proguanil and phenformin acted as allosteric inhibitors. Our results support the potential clinical repurposing of biguanide compounds for the treatment of neurodegenerative disorders linked to glutamatergic excitotoxicity while also providing a better understanding of structural determinants of NMDA receptor antagonism by biguanides.

How effective is disopyramide in treating pediatric hypertrophic cardiomyopathy? State of the art and future directions.

Pediatric hypertrophic cardiomyopathy (HCM) has a wide range of clinical manifestations. Left ventricular outflow tract obstruction (LVOTO) at rest is present in up to one-third of children with HCM, with a further 50-60% of symptomatic children developing a gradient under exertion. Treatment options are limited, and there is a relative lack of data on the pediatric population. Disopyramide is a sodium channel blocker with negative inotropic properties. This therapy effectively reduces LVOTO in adults with HCM and delays surgical interventions, but it is not licensed for use in children. We aimed to review and analyze the influence of disopyramide over the pathophysiological, clinical, electrocardiographic, and echocardiographic characteristics of patients with HCM in infancy, childhood, adolescence, and adult age. While disopyramide remains a cornerstone in the management of pediatric HCM, the advent of mavacamten and aficamten heralds a new era of potential advancements. These emerging therapies could significantly improve the quality of life and prognosis for young patients with HCM.

Understanding the Role of the SMN Complex Component GEMIN5 and Its Functional Relationship with Demethylase KDM6B in the Flunarizine-Mediated Neuroprotection of Motor Neuron Disease Spinal Muscular Atrophy.

Dysregulated RNA metabolism caused by SMN deficiency leads to motor neuron disease spinal muscular atrophy (SMA). Current therapies improve patient outcomes but achieve no definite cure, prompting renewed efforts to better understand disease mechanisms. The calcium channel blocker flunarizine improves motor function in Smn-deficient mice and can help uncover neuroprotective pathways. Murine motor neuron-like NSC34 cells were used to study the molecular cell-autonomous mechanism. Following RNA and protein extraction, RT-qPCR and immunodetection experiments were performed. The relationship between flunarizine mRNA targets and RNA-binding protein GEMIN5 was explored by RNA-immunoprecipitation. Flunarizine increases demethylase Kdm6b transcripts across cell cultures and mouse models. It causes, in NSC34 cells, a temporal expression of GEMIN5 and KDM6B. GEMIN5 binds to flunarizine-modulated mRNAs, including Kdm6b transcripts. Gemin5 depletion reduces Kdm6b mRNA and protein levels and hampers responses to flunarizine, including neurite extension in NSC34 cells. Moreover, flunarizine increases the axonal extension of motor neurons derived from SMA patient-induced pluripotent stem cells. Finally, immunofluorescence studies of spinal cord motor neurons in Smn-deficient mice reveal that flunarizine modulates the expression of KDM6B and its target, the motor neuron-specific transcription factor HB9, driving motor neuron maturation. Our study reveals GEMIN5 regulates Kdm6b expression with implications for motor neuron diseases and therapy.

Emergency Department and Critical Care Use of Clevidipine for Treatment of Hypertension in Patients with Acute Stroke.

Clevidipine is a parenteral dihydropyridine calcium channel blocker that received Food and Drug Administration (FDA) approval in 2008 for the reduction of blood pressure (BP) when oral therapy is not feasible or not desirable. Soon after approval, our institution incorporated clevidipine into protocols for management of hypertension among acute stroke patients, based on the drug's rapid onset of action and straightforward titration to goal. A subsequent retrospective review of its use in otherwise alteplase-eligible ischemic stroke patients with BP greater than 185/110 mmHg (n=32, in 2014) revealed that clevidipine in that setting demonstrated the shortest median time to BP control, the shortest median door to alteplase administration time, and the lowest administered volume of any parenteral antihypertensive used. As a result, clinical protocols in our institution were modified to make clevidipine first-line antihypertensive in both ischemic and hemorrhagic acute stroke. In this study we report our institution's experience with clevidipine in acute stroke, comprising the largest such report to date. . We conducted a retrospective chart review of all acute stroke patients who received clevidipine in the Emergency Department (ED) or intensive care unit (ICU) (n=295) for the management of clinically significant hypertension between January 1, 2015 and December 31, 2017. Metrics analyzed included target (goal) BP for thrombolysis eligibility among patients intended for lytic therapy according to stroke management guidelines in effect at the time of care. The median time for initial parenteral antihypertensive Dose-to-Goal (DTG) BP for all ischemic stroke patients (both those intended for and those not intended for lytic therapy) with complete data (n= 71 of 204) was 15 minutes; median time for Door-to-IV-alteplase administration for ischemic stroke patients with complete data (n=14 of 34 treated patients) was 59 minutes. The median time for initial parenteral antihypertensive DTG BP for all hemorrhagic stroke patients with complete data (n=33 of 91 treated patients) was 39 minutes. We conclude that the salutary findings of the initial small study are valid across a larger patient sample of all acute stroke types. Based on these data, clevidipine is shown to be safe, consistent, and effective in the treatment of acute hypertension in ischemic and hemorrhagic stroke events, and is a reasonable first-line treatment option for acute hypertension in this setting.

Amlodipine-Induced gingival hyperplasia in a nepalese patient experiencing high dosages: a case report

Introduction and Importance: Amlodipine is a third-generation calcium channel blocker used in the treatment of Hypertension. One of the side effects associated with amlodipine is gingival hyperplasia mostly occurring at a higher dose (10 mg). There are very few cases of gingival hyperplasia associated with amlodipine at a lower dose (5 mg) or short-term administration. Case presentation: A 51-year-old male patient with diagnosed hypertension sought medical attention for gingival swelling and bleeding from the gums while brushing. He had been under amlodipine 5 mg for 12 months, which was increased to 10 mg for the last 2 months. The history and physical examination were consistent with amlodipine-induced gingival hyperplasia. The first line of treatment consisted of discontinuation of amlodipine and substitution with another class of anti-hypertensive. Clinical discussion and conclusion: The presented case highlights the challenge of balancing economic considerations with potential side effects in the use of amlodipine for hypertension in low-income countries like Nepal. Given its availability at no cost or minimal expense, amlodipine is often initiated as a first-line therapy. However, the decision to increase the dosage to 10 mg/day, influenced by economic constraints and the drug’s affordability, raises the risk of gingival hyperplasia. This case emphasizes the importance of physicians being mindful of potential adverse effects when prescribing higher doses of amlodipine and underscores the need for continued vigilance in managing hypertension in resource-limited settings.

Association Between Long- Versus Short-Acting Angiotensin II Receptor Antagonists and Hypotension During Anesthesia Induction: A Retrospective Study.

The withdrawal or continuation of angiotensin II receptor blockers (ARBs) before surgery continues to be debated. We hypothesized that this is because ARBs with different half-lives have not been studied individually. This retrospective study aimed to clarify whether the degree of hypotension during anesthesia induction differs among ARBs with different half-lives. We included patients who received general anesthesia with regular oral administration of telmisartan (group T) or valsartan (group V), which have half-lives of approximately 24 and 6 hours, respectively. The frequency of hypotension and vasopressor frequency and dose during anesthesia induction were compared between the two groups. At our hospital, ARBs were withdrawn on the day of surgery in all patients. Groups T and V included 190 and 132 patients, respectively. Patient backgrounds in group V were significantly more strongly associated with the use of calcium channel blockers. No significant differences were observed in the use of other concomitant antihypertensive medications, cardiovascular complications, or renal function. The time during which the mean arterial blood pressure was < 60 mmHg during anesthesia induction was significantly greater in group T than in group V (11 min vs. 7 min, P=0.030). The proportion of patients who used vasopressors was significantly higher in group T than that in group V (74.2% vs. 56.0%, P < 0.001). Patients taking telmisartan showed more hypotensive during the induction of general anesthesia than those taking valsartan, even after withdrawal on the day of surgery.

Nuciferine analogs block voltage-gated sodium, calcium and potassium channels to regulate the action potential and treat arrhythmia

Dysfunction of the Nav1.5, Cav1.2, and Kv channels could interfere with the AP and result in arrhythmias and even heart failure. We herein present a novel library of nuciferine analogs that target ion channels for the treatment of arrhythmias. Patch clamp measurements of ventricular myocytes revealed that 6a dramatically blocked both the INa and ICa without altering the currentvoltage relationship (including the activation potential and peak potential), accelerated the inactivation of Nav and Cav channels and delayed the resurrection of these channels after inactivation. Additionally, 6a significantly decreased the APA and RMP without affecting the APD30 or APD50. The IC50 values of 6a against Nav1.5 and Cav1.2 were 4.98 μM and 4.62 μM, respectively. Furthermore, 6a (10 μM) blocked IKs, IK1, and Ito with values of 17.01 %±2.54 %, 9.09 %±2.78 %, and 11.15 %±3.52 %, respectively. Surprisingly, 6a weakly inhibited hERG channels, suggesting a low risk of proarrhythmia. The cytotoxicity evaluation of 6a with the H9c2 cell line indicated that this compound was noncytotoxic. In vivo studies suggested that these novel nuciferine analogs could shorten the time of arrhythmia continuum induced by BaCl2 and normalize the HR, QRS, QT and QTc interval and the R wave amplitude. Moreover, 6a dose-dependently affected aconitine-induced arrhythmias and notably improved the cumulative dosage of aconitine required to evoke VP, VT, VF and CA in rats with aconitine-induced arrhythmia. In conclusion, nuciferine analogs could be promising ion channel blockers that could be further developed into antiarrhythmic agents.

Inhibitory effects of calcium channel blockers nisoldipine and nimodipine on ivacaftor metabolism and their underlying mechanism.

Ivacaftor is the first potentiator of the cystic fibrosis transmembrane conductance regulator (CFTR) protein approved for use alone in the treatment of cystic fibrosis (CF). Ivacaftor is primarily metabolized by CYP3A4 and therefore may interact with drugs that are CYP3A4 substrates, resulting in changes in plasma exposure to ivacaftor. The study determined the levels of ivacaftor and its active metabolite M1 by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). We screened 79 drugs and 19 severely inhibited ivacaftor metabolism, particularly two cardiovascular drugs (nisoldipine and nimodipine). In rat liver microsomes (RLM) and human liver microsomes (HLM), the half-maximal inhibitory concentrations (IC50) of nisoldipine on ivacaftor metabolism were 6.55μM and 9.10μM, respectively, and the inhibitory mechanism of nisoldipine on ivacaftor metabolism was mixed inhibition; the IC50 of nimodipine on ivacaftor metabolism in RLM and HLM were 4.57μM and 7.15μM, respectively, and the inhibitory mechanism of nimodipine on ivacaftor was competitive inhibition. In pharmacokinetic experiments in rats, it was observed that both nisoldipine and nimodipine significantly altered the pharmacokinetic parameters of ivacaftor, such as AUC(0-t) and CLz/F. However, this difference may not be clinically relevant. In conclusion, this paper presented the results of studies investigating the interaction between these drugs and ivacaftor in vitro and in vivo. The objective is to provide a rationale for the safety of ivacaftor in combination with other drugs.

Blood pressure management strategies and podocyte health.

Hypertension (HTN) is one of the key global cardiovascular risk factors, which is tightly linked to kidney health and disease development. Podocytes, glomerular epithelial cells that play a pivotal role in maintenance of the renal filtration barrier, are significantly affected by increased glomerular capillary pressure in HTN. Damage or loss of these cells causes proteinuria, which marks the initiation of the HTN-driven renal damage. It goes without saying that effective BP management should not only mitigate cardiovascular risks but also preserve renal function by protecting podocyte integrity. This review offers a comprehensive examination of current blood pressure (BP) management strategies and their implications for podocyte structure and function and emphasizes strategies for the reduction of proteinuria in HTN. We explore primary and secondary antihypertensive agents, including ACE inhibitors, ARBs, calcium channel blockers, diuretics, as well as newer therapies (SGLT2 blocking and endothelin receptor antagonism), emphasizing their mechanistic roles in safeguarding podocytes and curtailing proteinuria.

Effect of Dihydropyridine Calcium Channel Blockers (CCB) on the Progression of Diabetic Nephropathy in Aranyaprathet Hospital, Sakeaw Province, Thailand

&amp;lt;i&amp;gt;Importance&amp;lt;/i&amp;gt; From Thailand, has standardized therapeutic drugs of Calcium channel blockers (CCB) in reduce the progression of chronic renal failure in diabetic and hypertension that is advantages for use in patients. However, use of Amlodipine that is more accessible and also a drug used by all community hospitals to treat patients, inexpensive and highly effective.&amp;lt;i&amp;gt; Objective&amp;lt;/i&amp;gt; To study effective of Dihydropyridine Calcium channel blockers (CCB) on kidney function (eGFR), urinary protein creatinine and sugar blood level. &amp;lt;i&amp;gt;Design, Setting, and Participants&amp;lt;/i&amp;gt; This study is retrospective cohort study by study in patients with diabetic nephropathy. By study in patients with diabetes nephropathy with stage 3 or higher and receiving Dihydropyridine Calcium channel blockers (CCB). &amp;lt;i&amp;gt;Exposures&amp;lt;/i&amp;gt; Dihydropyridine Calcium channel blockers (CCB) in reducing the complications of diabetic nephropathy which is consistent with Strategy No.2 Providing quality and excellent health services. And literature reviews in Thailand have not found empirical evidence that mean Calcium Channel can reduce the complications of diabetic nephropathy. &amp;lt;i&amp;gt;Main Outcomes and Measures&amp;lt;/i&amp;gt; The effectiveness of Dihydropyridine Calcium channel blockers (CCB) increases the complications of diabetic nephropathy. &amp;lt;i&amp;gt;Results&amp;lt;/i&amp;gt; In volunteer, female patient proportion was 69.0%. Average age was 69.3 (± 9.69), minimum age is 40 years, maximum age is 97 years. Most patients were between 60-79 years, follow by 40-59 years follow by16.8% and more than 80 years 16.1%. In congenital disease, kidney disease, kidney failure, diabetes and hypertension are 100%, follow by 24% obesity and 0.2% cancer. The effect of Dihydropyridine Calcium channel blockers (CCB) on kidney function (eGFR), urine microalbumin and creatinine when compare with use drug CCB 2 groups including Amlodipine and Amlodipine+enalapril/losartan/valsartan. Found that volunteer that received CCB drug compare with month 3 and 12, the level of eGFR decreases (t=1.085) and Urine Microalbumin increases (t=1.496) by statistically significance (P = 0.002) and Dihydropyridine Calcium channel blockers (CCB) on Fasting blood sugar compares with month 3 and 12, Fasting blood sugar (t = 0.566) and HbA1C (t=0.677) was typically decreased significantly (P &amp;lt; 0.005). &amp;lt;i&amp;gt;Conclusions and Relevance&amp;lt;/i&amp;gt; Calcium channel blockers (CCBs) was decline kidney function (decrease eGFR) and CCB leads to the decrease of eGFR and provides monitoring of CCB use, as this may lead to the decrease of kidney function.

Erectile dysfunction in the hypertensive patient

Hypertensive patients are frequently affected by erectile dysfunction (20-25%). This is often a manifestation of atherosclerosis, a systemic disease that itself requires management. Dietary measures and physical activity are beneficial for these patients. Regarding pharmacological options, these include modifying the antihypertensive treatment or using a phosphodiesterase type 5 inhibitor (PDE5 inhibitor) in males. The preferred antihypertensive treatments are angiotensin 2 receptor antagonists, ACE inhibitors, calcium channel blockers, and if necessary, a vasodilating beta-blocker (nébivolol). Thiazide and thiazide-like diuretics (with the exception of indapamide), traditional beta-blockers, and central antihypertensive agents should be avoided.

Cardiac automaticity is modulated by IKACh in sinoatrial node during pregnancy.

Pregnant women have a significantly elevated resting heart rate (HR), which makes cardiac arrhythmias more likely to occur. Although electrical remodeling of the sinoatrial node (SAN) has been documented, the underlying mechanism is not fully understood. The acetylcholine-activated potassium current (IKACh), one of the major repolarizing currents in the SAN, plays a critical role in HR control by hyperpolarizing the maximal diastolic potential (MDP) of the SAN action potential (AP), thereby reducing SAN automaticity and HR. Thus, considering its essential role in cardiac automaticity, this study aims to determine whether changes in IKACh are potentially involved in the increased HR associated with pregnancy. Experiments were conducted on non-pregnant (NP, 2-3 months old) and pregnant (P, 17-18 gestation days) female CD-1 mice. IKACh was recorded on spontaneously beating SAN cells using the muscarinic agonist carbachol (CCh). Voltage-clamp data showed a reduction in IKACh density during pregnancy, which returned to control values shortly after delivery. The reduction in IKACh was explained by a decrease in protein expression of Kir3.1 channel subunit and the muscarinic type 2 receptor. In agreement with these findings, current-clamp data shows that the MDP of SAN cells from P mice were less hyperpolarized following CCh administration. Surface electrocardiograms (ECGs) recorded on anesthetized mice revealed that the cholinergic antagonist atropine and the selective KACh channel blocker tertiapin-Q increased HR in NP mice and had only a minimal effect on P mice. AP and ECG data also showed that pregnancy is associated with a decrease in beating and heart rate variability, respectively. IKACh function and expression are decreased in the mouse SAN during pregnancy, strongly suggesting that, in addition to other electrical remodeling of the SAN, reduced IKACh also plays an important role in the pregnancy-induced increased HR.

Creating cell-specific computational models of stem cell-derived cardiomyocytes using optical experiments.

Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have gained traction as a powerful model in cardiac disease and therapeutics research, since iPSCs are self-renewing and can be derived from healthy and diseased patients without invasive surgery. However, current iPSC-CM differentiation methods produce cardiomyocytes with immature, fetal-like electrophysiological phenotypes, and the variety of maturation protocols in the literature results in phenotypic differences between labs. Heterogeneity of iPSC donor genetic backgrounds contributes to additional phenotypic variability. Several mathematical models of iPSC-CM electrophysiology have been developed to help to predict cell responses, but these models individually do not capture the phenotypic variability observed in iPSC-CMs. Here, we tackle these limitations by developing a computational pipeline to calibrate cell preparation-specific iPSC-CM electrophysiological parameters. We used the genetic algorithm (GA), a heuristic parameter calibration method, to tune ion channel parameters in a mathematical model of iPSC-CM physiology. To systematically optimize an experimental protocol that generates sufficient data for parameter calibration, we created in silico datasets by simulating various protocols applied to a population of models with known conductance variations, and then fitted parameters to those datasets. We found that calibrating to voltage and calcium transient data under 3 varied experimental conditions, including electrical pacing combined with ion channel blockade and changing buffer ion concentrations, improved model parameter estimates and model predictions of unseen channel block responses. This observation also held when the fitted data were normalized, suggesting that normalized fluorescence recordings, which are more accessible and higher throughput than patch clamp recordings, could sufficiently inform conductance parameters. Therefore, this computational pipeline can be applied to different iPSC-CM preparations to determine cell line-specific ion channel properties and understand the mechanisms behind variability in perturbation responses.

"Emerging clinical approaches in diabetic cardiomyopathy: insights from clinical trials and future directions".

We aim to explore the potential of diverse treatments, including perhexiline, calcium channel blockers, anti-hypertensives, PDE5 inhibitors, anti-anginal drugs, aldose reductase inhibitors, and SGLT-2 inhibitors, supported by clinical evidence. Additionally, this review seeks to identify novel therapeutic targets and future avenues for improving cardiovascular outcomes in diabetic populations. We performed a comprehensive literature review of English-language studies across multiple electronic databases, such as PubMed, ScienceDirect, Scopus, and Google Scholar, focusing on clinical trials. The search utilized keywords including 'Anti-hyperglycaemic drug,' 'Diabetic cardiomyopathy,' 'DPP-4 inhibitors,' 'GLP-1 receptor agonists,' 'Heart failure,' and 'SGLT-2 inhibitors.' We assessed clinical investigations in the treatment of cardiomyopathy and diabetes mellitus (DM) that are enhancing our understanding through trials evaluating the Polypill, Perhexiline, Eplerenone, IMB-1018972, AT-001, tadalafil, and dapagliflozin inhibitors. The development of new targeted interventions is of paramount importance due to the overlooked early symptoms, the complexity of the cellular and molecular pathways involved, and the absence of effective drug therapies. Pharmacological treatments like GLP-1 agonists, SGLT-2 inhibitors, NHE-1, NHE-3, and PPAR-γ agonists show promise for treating DCM. These treatments improve myocardial glucose absorption, address dysregulated glucose and lipid metabolism, and lower heart failure and cardiovascular events. Further research is needed to confirm effectiveness and safety.

Is Arterial Stiffness Interconnected with Cardiovascular Drug Prescription Patterns, Body Composition Parameters, and the Quality of Blood Pressure Regulation in Hypertensive Patients?

Arterial hypertension (AH) is a significant risk factor for cardiovascular disease and is associated with increased arterial stiffness, particularly as measured by pulse wave velocity (PWV). This study aims to explore the relationships between age groups, antihypertensive and new oral antidiabetic drugs, body composition, and arterial stiffness parameters in hypertensive patients. A single-center cross-sectional study was conducted including 584 participants who underwent 24 h ambulatory blood pressure monitoring (including central blood pressure (BP) and PWV measurement), body composition analysis, and provided medical history and current pharmacotherapy data. The study found that PWV was significantly higher in patients with poorly regulated BP in those aged 65 years and older. Significant PWV predictors included systolic BP, heart rate, peripheral mean arterial pressure, peripheral pulse pressure, augmentation index, calcium channel blockers, moxonidine, sodium-glucose co-transporter 2 inhibitors, urapidil, and statin prescription. Also, statistically significant negative correlations were found between PWV and visceral fat level, fat-free mass, and the percentage of muscle mass. The findings suggest that arterial stiffness is interconnected with peripheral and central blood pressure parameters, body composition parameters, and prescribed hypertensive and new antidiabetic drugs.

Involvement of different K+ channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery.

Changes in K+ channel expression/function are associated with disruption of vascular reactivity in several pathological conditions, including hypertension, diabetes, and atherosclerosis. Gasotransmitters achieve part of their effects in the organism by regulating ion channels, especially K+ channels. Their involvement in hydrogen sulfide (H2S)-mediated vasorelaxation is still unclear, and data about human vessels are limited. To determine the role of K+ channel subtypes in the vasorelaxant mechanism of H2S donor, sodium-hydrosulfide (NaHS), on isolated human internal mammary artery (HIMA). NaHS (1 × 10-6-3 × 10-3mol/L) induced a concentration-dependent relaxation of HIMA pre-contracted by phenylephrine and high K+. Among K+ channel blockers, iberiotoxin, glibenclamide, 4-aminopyridine (4-AP), and margatoxin significantly inhibited NaHS-induced relaxation of phenylephrine-contracted HIMA (P < 0.01), whereas in the presence of apamin/1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) combination, the HIMA relaxation was partially reduced (P < 0.05). The effect of NaHS was antagonized by NO pathway inhibitors, L-NAME and KT5823, and by cyclo-oxygenase inhibitor, indomethacin (P < 0.01). Under conditions of blocked NO/prostacyclin synthesis and release, apamin/TRAM-34 and glibenclamide caused further decrease in NaHS-induced vasorelaxation (P < 0.01), while iberiotoxin, 4-AP, and margatoxin were without additional effect (P > 0.05). In the presence of nifedipine, NaHS induced partial relaxation of HIMA (P < 0.01). Our results demonstrated that H2S donor, NaHS, induced concentration-dependent relaxation of isolated HIMA. Vasorelaxant mechanisms of H2S included direct or indirect opening of different K+ channel subtypes, KATP, BKCa, SKCa/IKCa, and KV (subtype KV1.3), in addition to NO pathway activation and interference with extracellular Ca2+ influx.

SP4.11 - Retrospective review of achalasia management in a tertiary UGI centre

Abstract Introduction Achalasia is a rare disorder significantly impacting quality of life (QoL). Medical management includes calcium channel blockers (CCB), Pneumatic dilatation (PD) and Peroral endoscopic myotomy (POEM). Surgical management includes laparoscopic Heller’s myotomy (HM) or more recently robotic assisted Heller’s Myotomy. Aim This is a retrospective study of management of patients with achalasia in a tertiary Upper GI centre. Material and method Data was collected retrospectively between 2013-2023 (10 years) and analysed using Prism 10. In this period, 193patients with suspected achalasia were analysed and only 89patients with confirmed diagnosis were included. Results Of these 89 patients, 46 were female (48%) and 43 were male (52%). The median age was 61years (range 21-94years). 64 patients (72%) were local referrals and 25 patients (28%) were referred via the network. 3 patients (3%) were acute admissions. 45 patients (50%) received medical therapy initiated by gastroenterologists. 6 patients (6.7%) received CCB, 17 patients (19%) received endoscopic Botox and 22 patients (25%) underwent PD. 6 patients (27%) developed perforation post PD; of these, 3 patients underwent surgical repair and had a prolonged hospital stay. Of the 66 patients (74%) who underwent surgery, 55 patients (61%) had laparoscopic HM, 8 patients (9%) underwent robotic assisted HM and 1 patient (1%) had open HM. Average Length of stay was 5.8 days for laparoscopic HM and 3.9 days for robotic HM. In the laparoscopic HM group 3 patients (5%) had iatrogenic oesophageal injury repaired perioperatively and a further 5 patients (8%) needed oesophageal dilation for residual dysphagia. No complication was noted in the robotic HM group. Conclusion Surgery remains the treatment of choice for achalasia. Early outcomes of robotic surgery look promising, with lesser complication rates thus improving quality of life.

Outcome of COVID-19 infection in patients on antihypertensives: A cross-sectional study.

Patients with coronavirus disease 2019 (COVID-19) infection frequently have hypertension as a co-morbidity, which is linked to adverse outcomes. Antihypertensives may affect the outcome of COVID-19 infection. To assess the effects of antihypertensive agents on the outcomes of COVID-19 infection. A total of 260 patients were included, and their demographic data and clinical profile were documented. The patients were categorized into nonhypertensive, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), calcium channel blocker (CCB), a combination of ACEI/ARB and CCB, and beta-blocker groups. Biochemical, hematological, and inflammatory markers were measured. The severity of infection, intensive care unit (ICU) intervention, and outcome were recorded. The mean age of patients was approximately 60-years-old in all groups, except the nonhypertensive group. Men were predominant in all groups. Fever was the most common presenting symptom. Acute respiratory distress syndrome was the most common complication, and was mostly found in the CCB group. Critical cases, ICU intervention, and mortality were also higher in the CCB group. Multivariable logistic regression analysis revealed that age, duration of antihypertensive therapy, erythrocyte sedimentation rate, high-sensitivity C-reactive protein, and interleukin 6 were significantly associated with mortality. The duration of antihypertensive therapy exhibited a sensitivity of 70.8% and specificity of 55.7%, with a cut-off value of 4.5 years and an area under the curve of 0.670 (0.574-0.767; 95% confidence interval) for COVID-19 outcome. The type of antihypertensive medication has no impact on the clinical sequence or mortality of patients with COVID-19 infection. However, the duration of antihypertensive therapy is associated with poor outcomes.