Angiotensin receptor-neprilysin inhibitior (thiorphan/irbesartan) decreased ischemia-reperfusion induced ventricular arrhythmias in rat; in vivo study

Abdulsalam, Takwa Mohammed; Hasanin, Amany Helmy; Mohamed, Reham Hussein; Badawy, Ahmed

doi:10.1016/j.ejphar.2020.173295

Cited by 9 publications

(8 citation statements)

References 30 publications

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“…A potential antiarrhythmic action is consistent with the favourable effects of sacubitril/valsartan on left ventricular remodelling, neurohumoral activity, potassium and circulating markers of collagen turnover, potentially reflecting myocardial fibrosis 6–9 . In pre‐clinical studies, neprilysin inhibition reduces cardiac fibrosis, sympathetic nervous system activity and inducibility of ventricular arrhythmias 10,11 . Several observational clinical case‐series have also reported a decrease in frequency of ventricular arrhythmias, after initiation of sacubitril/valsartan 12,13 …”

Section: Introductionmentioning

confidence: 80%

“…pre-clinical studies, neprilysin inhibition reduces cardiac fibrosis, sympathetic nervous system activity and inducibility of ventricular arrhythmias. 10,11 Several observational clinical case-series have also reported a decrease in frequency of ventricular arrhythmias, after initiation of sacubitril/valsartan. 12,13 To investigate the hypothesis that sacubitril/valsartan reduces the incidence of ventricular arrhythmias, we undertook a post hoc analysis of PARADIGM-HF, examining adverse event reports of ventricular arrhythmias, ICD discharges or resuscitated cardiac arrest, according to randomized treatment assignment.…”

Section: Introductionmentioning

confidence: 99%

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Effect of sacubitril/valsartan on investigator‐reported ventricular arrhythmias in PARADIGM‐HF

Curtain

Jackson

Shen

et al. 2022

European J of Heart Fail

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Section: Introductionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Effect of sacubitril/valsartan on investigator‐reported ventricular arrhythmias in PARADIGM‐HF

Curtain

Jackson

Shen

et al. 2022

European J of Heart Fail

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“…Evidence showed that inhibition of the renin-angiotensin system promoted anti-inflammatory, antioxidant, and antifibrotic effects [29]. ARNI improved lymphatic system remodeling in a hypertrophic cardiomyopathy model [30] while decreasing oxidative stress and increasing adenosine triphosphate and Na+/K+-ATPase pump activity in ischemic reperfusion-induced arrhythmia [31]. However, no study has yet investigated the angiogenic effects of ARNI for adaptation to increased oxygen demand during cardiac hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin Receptor Blocker and Neprilysin Inhibitor Suppresses Cardiac Dysfunction by Accelerating Myocardial Angiogenesis in Apolipoprotein E-Knockout Mice Fed a High-Fat Diet

Suematsu

Tashiro

Morita

et al. 2021

J Renin Angiotensin Aldosterone Syst

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Hypothesis. Myocardial angiogenesis is important for maintaining cardiac contractile function in patients with cardiac hypertrophy. Evidence shows that angiotensin receptor blocker and neprilysin inhibitors (ARNIs) improve heart failure. The present study investigated the myocardial angiogenic effect of valsartan plus sacubitril in early-stage cardiac dysfunction. Materials and Methods. Male apolipoprotein E-knockout mice fed a high-fat diet were divided into control (CTL), valsartan (30 mg/kg) (VAL), sacubitril (30 mg/kg) (SAC), and valsartan plus sacubitril (30 mg/kg each) (VAL/SAC) groups after 4 weeks of prefeeding and were subsequently treated for 12 weeks. Results. The VAL/SAC group exhibited significantly higher serum brain natriuretic peptide levels; more subtle changes in left ventricular systolic diameter, fractional shortening, and ejection fraction, and significantly higher expression levels of natriuretic peptide precursor B and markers of angiogenesis, including clusters of differentiation 34, vascular endothelial growth factor A, and monocyte chemotactic protein 1, than the CTL group. Conclusions. Valsartan plus sacubitril preserved left ventricular systolic function in apolipoprotein E-knockout mice fed a high-fat diet. This result suggests that myocardial angiogenic factors induced by ARNI might provide cardioprotective effects.

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“…A slipknot (5–0 silk) was done and allowed for a period of 35 min of ischemia that was confirmed by the presence of electrocardiographic changes (ST elevation) in lead II with subcutaneous stainless‐steel electrodes and appearance of cyanosis of the ischemic region of the left ventricle. Reperfusion for 60 min was initiated by release of the slipknot and confirmed by a color change in ventricular surface from cyanosis to hyperemia (Figure 1) [21].…”

Section: Methodsmentioning

confidence: 99%

“…Heart samples from five groups were cut for all the biochemical and immunohistochemistry studies. Heart homogenates were prepared according to the method described by [21][22][23]. The homogenates (1:4 w/v) were prepared by using phosphate buffer (pH = 7.5) containing 1 mM/L Na 2 EDTA; 10 ml of butylated hydroxytoluene (BHT) (0.5 M in acetonitrile) was added to prevent formation of new peroxides during the assay.…”

Section: Biochemical Studiesmentioning

confidence: 99%

Angiotensin receptor–neprilysin inhibitor (thiorphan/irbesartan) improved cardiac function in a rat model of myocardial ischemic reperfusion injury

Abdulsalam

Hasanin

Mohamed

et al. 2022

Fundamemntal Clinical Pharma

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Mitochondria‐mediated apoptosis plays a critical role in myocardial ischemia reperfusion (IR) injury and causes a negative impact on cardiac efficiency and function. The combined angiotensin receptor–neprilysin inhibitor (ARNI) is a promising cardioprotective pharmacological agent that could rescue the heart from IR injury. This study investigated the cardioprotective effect of thiorphan (TH) in combination with three different doses of irbesartan (IRB) on myocardial IR injury and detected the most effective dose combination. Male Wistar rats were used and divided into five groups (10 rats/group): (I) Sham, (II) ischemia–reperfusion I/R, (III) TH/IRB + IR (0.1/5 mg/kg), (IV) TH/IRB + IR (0.1/10 mg/kg), and (V) TH/IRB + IR (0.1/15 mg/kg) groups. Thiorphan and irbesartan were injected intraperitoneally 15 min before IR induction. Mean arterial blood pressure, left ventricular end diastolic pressure (LVEDP), left ventricular maximum rate of pressure (LVdp/dtmax), and cardiac levels of creatine kinase–MB, malondialdehyde, superoxide dismutase, and endothelin‐1 were measured. Cardiac mitochondria complexes activities, histopathological examination of myocardial tissues, immunohistochemistry studies for myocardial apoptosis (Bax and Bcl‐2), and electron microscopy examination of left ventricle were performed. TH/IRB combination preserved cardiac functions and mitochondria complex activities and mitigated cardiac damage, oxidative stress, and apoptosis following IR. Also, there was an evident improvement in histopathological changes and electron microscopy examination of left ventricle compared with I/R group. TH/IRB in a dose of 0.1/10 mg/kg showed significant improvement compared with the other treated groups. Thiorphan/irbesartan improved cardiac functions following IR injury. This could be explained by the reported improvement of mitochondria complex activities and reduction of oxidative stress, endothelin‐1, and apoptosis.

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Angiotensin receptor-neprilysin inhibitior (thiorphan/irbesartan) decreased ischemia-reperfusion induced ventricular arrhythmias in rat; in vivo study

Cited by 9 publications

References 30 publications

Effect of sacubitril/valsartan on investigator‐reported ventricular arrhythmias in PARADIGM‐HF

Effect of sacubitril/valsartan on investigator‐reported ventricular arrhythmias in PARADIGM‐HF

Angiotensin Receptor Blocker and Neprilysin Inhibitor Suppresses Cardiac Dysfunction by Accelerating Myocardial Angiogenesis in Apolipoprotein E-Knockout Mice Fed a High-Fat Diet

Angiotensin receptor–neprilysin inhibitor (thiorphan/irbesartan) improved cardiac function in a rat model of myocardial ischemic reperfusion injury

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