[Key-role of intracellular calcium overload in acute necrosis of the myocardium. Cardioprotection with verapamil].

Abstract

Ca ions are highly cardiotoxic if their influx into the myocardial fibres becomes abundant. The intracellular Ca overload initiates a deleterious high-energy phosphate deficiency by excessive activation of Ca-dependent intracellular ATPases and by impairing the phosphorylating capacity of mitochondria. This Ca-induced high-energy phosphate exhaustion is a crucial point in the etiology of the myocardial fibre necroses produced in rats by large doses of beta-adrenergic catecholamines, particularly isoproterenol, or by a number of other cardiotoxic agents. Accordinly, the myocardium is sensitized to necrotization by factors which favour Ca overload (dihydrotachysterol, 9alpha-flourocortisol acetate, NaH2PO4). Conversely, the structural integrity of the hearts can be protected by any substance or procedure which prevents an excessive intracellular Ca accumulation, particularly by inhibitors of the transmembrane Ca influx, such as verapamil, D 600 or prenylamine.

• Authors: J Janke, A Fleckenstein, H J Döring, O Leder
• Journal: Minerva medica (Minerva Med) Vol. 66 Issue 38 Pg. 1846-58 (May 23 1975) ISSN: 0026-4806 [Print] Italy
• Vernacular Title: Ruolo-chiave del sovraccarico di Ca intracellulare nella necrosi acuta del miocardio. Cardioprotezione con Verapamil
• PMID: 1128824 (Publication Type: English Abstract, Journal Article)

Chemical References

• Catecholamines
• Phosphates
• Adenosine Triphosphate
• Verapamil
• Prenylamine
• Isoproterenol
• Dihydrotachysterol
• Calcium
• Fludrocortisone

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Calcium (antagonists & inhibitors, metabolism)
• Catecholamines (metabolism)
• Dihydrotachysterol (pharmacology)
• Fludrocortisone (pharmacology)
• Heart (drug effects)
• Isoproterenol (pharmacology)
• Mitochondria (metabolism)
• Myocardial Infarction (metabolism, prevention & control)
• Myocardium (metabolism)
• Necrosis
• Phosphates (metabolism)
• Prenylamine (therapeutic use)
• Rats
• Verapamil (therapeutic use)