scholarly journals The role of parasympathetic mechanisms in the infarct-limiting effect of SGLT2 inhibitor ertugliflozin

2021 ◽  
Author(s):  
Maryna V Basalay ◽  
Sapna Arjun ◽  
Sean M Davidson ◽  
Derek M Yellon
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Myocardial Ischaemia ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Male Rats ◽  
Standard Diet ◽  
Atropine Sulphate ◽  
Selective Blocker

Introduction: Based on data that outcome in patients with acute myocardial infarction is predicted by final infarct size (IS), reducing IS is of paramount importance. Recent experimental studies have demonstrated a strong infarct-sparing effect of SGLT2 inhibitors – a class of drugs which have proved to be safe and beneficial in patients with heart failure. Repurposing SGLT2 inhibitors for the benefit of patients presenting with acute myocardial infarction should be preceded by investigation of the underlying mechanisms of this infarct limitation. Experimental and clinical data indicate a potential role for autonomic modulation in these mechanisms, specifically sympatho-inhibition. The aim of this study was to investigate the role of the parasympathetic mechanism in the infarct-limiting effect of SGLT2 inhibition. Methods: Fortyeight Sprague Dawley male rats were fed with a standard diet containing either the SGLT2 inhibitor ertugliflozin or vehicle, for 5-7 days. Myocardial ischaemia/reperfusion injury was initiated by a 40-min occlusion of the left anterior descending coronary artery followed by a 2hr period of reperfusion under isoflurane anaesthesia. Bilateral cervical vagotomy was performed 10min prior to myocardial ischaemia. Alternatively, muscarinic receptors were blocked systemically with the non-selective blocker atropine sulphate (2 mg/kg bolus, then 1 mg/kg/h) or the M3-selective blocker 4-DAMP (2 mg/kg bolus). Results: Pre-treatment with ertugliflozin reduced IS in comparison with the vehicle-treated controls (p<0.001). Bilateral vagotomy, atropine sulphate and 4-DAMP all abolished this infarct-limiting effect (IS 35±10%, 44±8%, and 35±4% respectively; P<0.01 vs. Ertu for vagotomy, P<0.001 vs. Ertu for both atropine sulphate and 4-DAMP). Conclusion: These results suggest that the Infarct-limiting effect of the SGLT2 inhibitor ertugliflozin, may be mediated via activation of the vagus nerve and M3-cholinoreceptors.

Cardioprotective effect of ranolazine in nondiabetic and diabetic male rats subjected to isoprenaline-induced acute myocardial infarction involves modulation of AMPK and inhibition of apoptosis

2019 ◽  
Vol 97 (7) ◽  
pp. 661-674 ◽  
Author(s):  
Mona K. Tawfik ◽  
Angie M. Ameen
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cellular Response ◽  
Diabetic Rats ◽  
Cardioprotective Effect ◽  
Male Rats ◽  
Saline Control ◽  
Stress Markers ◽  
Amp Activated Protein Kinase

Diabetes increases the sensitivity of myocardium to ischemic damage and impairs response of the myocardium to cardioprotective interventions. The present study aimed to elucidate the potential cardioprotective effect provided by ranolazine during myocardial infarction in nondiabetic and diabetic male rats. As AMP-activated protein kinase (AMPK) has been shown to be involved in the cellular response to ischemic injury, in this context, the present animal study evaluated the modulating role of ranolazine in the AMPK expression in isoprenaline-induced myocardial ischemic rat model. Male rats were divided into 2 experiments: experiment I and II (nondiabetic and diabetic rats) and assigned to normal control, saline control for isoprenaline, isoprenaline control, and ranolazine-treated groups. Ranolazine administration revealed effectiveness in attenuating the severity of isoprenaline-induced myocardial injury in both nondiabetic and diabetic rats as revealed by ECG signs, histopathological score, and apoptotic markers via abrogating the increments in the inflammatory and oxidative stress markers and modulating AMPK expression. Therefore, the current cardioprotective effect of ranolazine was, at least in part, mediated through inhibition of apoptosis and modulation of AMPK expression, encouraging considering the utility of ranolazine in protection from acute myocardial infarction.

scholarly journals The Role of B Cells in Acute Myocardial Infarction

2019 ◽  
Vol 28 ◽  
pp. S18
Author(s):  
Georgina Bird ◽  
Kathryn Hally ◽  
Anne La Flamme ◽  
Scott Harding ◽  
Peter Larsen
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
B Cells

The Role of Uric Acid in the Acute Myocardial Infarction: A Narrative Review

Angiology ◽  
2021 ◽  
pp. 000331972110125
Author(s):  
Atalay Demiray ◽  
Baris Afsar ◽  
Adrian Covic ◽  
Masanari Kuwabara ◽  
Charles J. Ferro ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Uric Acid ◽  
Adverse Outcomes ◽  
Narrative Review ◽  
Background Information ◽  
Pathophysiological Role ◽  
Artery Disease ◽  
Pathologic Processes

Increased serum uric acid (SUA) levels have been associated with various pathologic processes such as increased oxidative stress, inflammation, and endothelial dysfunction. Thus, it is not surprising that increased SUA is associated with various adverse outcomes including cardiovascular (CV) diseases. Recent epidemiological evidence suggests that increased SUA may be related to acute myocardial infarction (AMI). Accumulating data also showed that elevated UA has pathophysiological role in the development of AMI. However, there are also studies showing that SUA is not related to the risk of AMI. In this narrative review, we summarized the recent literature data regarding SUA and AMI after providing some background information for the association between UA and coronary artery disease. Future studies will show whether decreasing SUA levels is beneficial for outcomes related to AMI and the optimum SUA levels for best outcomes in CV diseases.

scholarly journals Role of diuretics on long-term mortality may differ in volume status in patients with acute myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Kawai ◽  
D Nakatani ◽  
T Yamada ◽  
T Watanabe ◽  
T Morita ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Propensity Score ◽  
Plasma Volume ◽  
Cox Regression ◽  
Volume Status ◽  
Increased Risk ◽  
Long Term Mortality

Abstract Background Diuretics has been reported to have a potential for an activation of the renin-angiotensin-aldosterone system and the sympathetic nervous system, leading to a possibility of poor clinical outcome in patients with cardiovascular disease. However, few data are available on clinical impact of diuretics on long-term outcome in patients with acute myocardial infarction (AMI) based on plasma volume status. Methods To address the issue, a total of 3,416 survived patients with AMI who were registered to a large database of the Osaka Acute Coronary Insufficiency Study (OACIS) were studied. Plasma volume status was assessed with the estimated plasma volume status (ePVS) that was calculated at discharge as follows: actual PV = (1 − hematocrit) × [a + (b × body weight)] (a=1530 in males and a=864 in females, b=41.0 in males and b=47.9 in females); ideal PV = c × body weight (c=39 in males and c=40 in females), and ePVS = [(actual PV − ideal PV)/ideal PV] × 100 (%). Multivariable Cox regression analysis and propensity score matching were performed to account for imbalances in covariates. The endpoint was all-cause of death (ACD) within 5 years. Results During a median follow-up period of 855±656 days, 193 patients had ACD. In whole population, there was no significant difference in long-term mortality risk between patients with and without diuretics in both multivariate cox regression model and propensity score matching population. When patients were divided into 2 groups according to ePVS with a median value of 4.2%, 46 and 147 patients had ACD in groups with low ePVS and high ePVS, respectively. Multivariate Cox analysis showed that use of diuretics was independently associated with an increased risk of ACD in low ePVS group, (HR: 2.63, 95% confidence interval [CI]: 1.22–5.63, p=0.01), but not in high ePVS group (HR: 0.70, 95% CI: 0.44–1.10, p=0.12). These observations were consistent in the propensity-score matched cohorts; the 5-year mortality rate was significantly higher in patients with diuretics than those without among low ePVS group (4.7% vs 1.7%, p=0.041), but not among high ePVS group (8.0% vs 10.3%, p=0.247). Conclusion Prescription of diuretics at discharge was associated with increased risk of 5-year mortality in patients with AMI without PV expansion, but not with PV expansion. The role of diuretics on long-term mortality may differ in plasma volume status. Therefore, prescription of diuretics after AMI may be considered based on plasma volume status. Funding Acknowledgement Type of funding source: None

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