التفاصيل البيبلوغرافية
| العنوان: |
Sodium-Hydrogen Exchanger Isoform-1 Inhibition: A Promising Pharmacological Intervention for Resuscitation from Cardiac Arrest |
| المؤلفون: |
Raúl J. Gazmuri, Jeejabai Radhakrishnan, Iyad M. Ayoub |
| المصدر: |
Molecules, Vol 24, Iss 9, p 1765 (2019) |
| بيانات النشر: |
MDPI AG, 2019. |
| سنة النشر: |
2019 |
| المجموعة: |
LCC:Organic chemistry |
| مصطلحات موضوعية: |
cardiopulmonary resuscitation, energy metabolism, ischemia, mitochondria, myocardium, reperfusion injury, sodium calcium exchanger, sudden cardiac arrest, ventricular function, Organic chemistry, QD241-441 |
| الوصف: |
Out-of-hospital sudden cardiac arrest is a major public health problem with an overall survival of less than 5%. Upon cardiac arrest, cessation of coronary blood flow rapidly leads to intense myocardial ischemia and activation of the sarcolemmal Na+-H+ exchanger isoform-1 (NHE-1). NHE-1 activation drives Na+ into cardiomyocytes in exchange for H+ with its exchange rate intensified upon reperfusion during the resuscitation effort. Na+ accumulates in the cytosol driving Ca2+ entry through the Na+-Ca2+ exchanger, eventually causing cytosolic and mitochondrial Ca2+ overload and worsening myocardial injury by compromising mitochondrial bioenergetic function. We have reported clinically relevant myocardial effects elicited by NHE-1 inhibitors given during resuscitation in animal models of ventricular fibrillation (VF). These effects include: (a) preservation of left ventricular distensibility enabling hemodynamically more effective chest compressions, (b) return of cardiac activity with greater electrical stability reducing post-resuscitation episodes of VF, (c) less post-resuscitation myocardial dysfunction, and (d) attenuation of adverse myocardial effects of epinephrine; all contributing to improved survival in animal models. Mechanistically, NHE-1 inhibition reduces adverse effects stemming from Na+−driven cytosolic and mitochondrial Ca2+ overload. We believe the preclinical work herein discussed provides a persuasive rationale for examining the potential role of NHE-1 inhibitors for cardiac resuscitation in humans. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1420-3049 |
| Relation: |
https://www.mdpi.com/1420-3049/24/9/1765; https://doaj.org/toc/1420-3049 |
| DOI: |
10.3390/molecules24091765 |
| URL الوصول: |
https://doaj.org/article/02d44954ee4f415fba8974741de8cd5f |
| رقم الانضمام: |
edsdoj.02d44954ee4f415fba8974741de8cd5f |
| قاعدة البيانات: |
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