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Calcium entry blockers: potential applications in shock
Insights
Intracellular calcium overload contributes to cell death in shock. Calcium channel blockers may offer a therapeutic strategy for managing shock by preventing this calcium imbalance.
Area of Science:
- Cardiovascular Physiology
- Cellular Biology
- Pathophysiology
Background:
- Myocardial and vascular smooth muscle cells rely on calcium homeostasis to prevent cell death and necrosis.
- Conditions like hypoxia, low-flow states, and reperfusion injury can lead to intracellular calcium overload.
- The shock syndrome, encompassing cardiogenic, septic, and hemorrhagic shock, presents scenarios conducive to calcium overload.
Purpose of the Study:
- To discuss the pathophysiologic sequence of the shock syndrome.
- To illustrate the potential role of intracellular calcium overload in shock progression.
- To review existing data on slow calcium channel blockers in shock and propose future research.
Main Methods:
- Review of pathophysiologic mechanisms in various shock states.
- Analysis of the role of intracellular calcium in cellular damage.
- Examination of data concerning slow calcium channel blockers in shock models.
Main Results:
- Intracellular calcium overload is a common pathway in diverse shock etiologies, leading to cell death.
- Shock syndromes share a potential for intracellular calcium overload.
- Slow calcium channel blockers have been studied in shock, suggesting a basis for further investigation.
Conclusions:
- Intracellular calcium overload is a critical factor in the pathophysiology of shock.
- Calcium channel blockers represent a promising therapeutic avenue for shock management.
- Further studies are warranted to explore the efficacy of calcium entry blockers in treating shock.
Abstract:
Failure of the myocardium and vascular smooth muscle to maintain intracellular calcium homeostasis results in intracellular calcium overload leading in turn to cell death and tissue necrosis. This phenomenon can occur in myocardium in response to such diverse etiologies as catecholamine-induced necrosis, prolonged periods of hypoxia, low-flow states, and reperfusion of a previously ischemic vascular bed. Such conditions exist in the shock syndrome with its various etiologies. Cardiogenic shock is associated with primary myocardial failure and a low-flow state. The later stages of septic and endotoxin shock are associated with increasing peripheral vascular resistance and decreasing cardiac output. Experimental and clinical hemorrhagic shock are both associated with prolonged periods of low flow, and then with subsequent transfusion, reperfusion of previously ischemic vascular beds occurs. Therefore, in the shock syndrome, at least the potential for intracellular calcium overload exists. It is the purpose of this communication to discuss the pathophysiologic sequence of the shock syndrome, to illustrate the potential role of intracellular calcium overload in the progression of shock, to present a data base of the use of slow calcium channel blockers in the study of shock, and to suggest a future study of calcium entry blockers as potential therapeutic agents in the shock syndrome.