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Effect of hyperkalemia on experimental myocardial depression by verapamil
S R Jolly1, N Keaton, A Movahed
1Department of Internal Medicine, East Carolina University School of Medicine, Greenville, N.C. 27858-4354.
Insights
Intravenous calcium effectively reversed dangerous hypotension and bradycardia caused by verapamil and hyperkalemia. This study highlights calcium
Area of Science:
- Cardiology
- Pharmacology
- Internal Medicine
Background:
- Systemic hypotension and sinus bradycardia can be refractory to conventional therapies.
- Verapamil, a calcium channel blocker, can cause significant cardiovascular adverse effects.
- Hyperkalemia is a known risk factor that can potentiate drug toxicity.
Purpose of the Study:
- To investigate the interaction between verapamil and hyperkalemia on hemodynamic function.
- To evaluate the efficacy of intravenous calcium administration in reversing verapamil-induced cardiovascular depression, particularly in the context of hyperkalemia.
Main Methods:
- Case reports of three patients treated with intravenous calcium for verapamil-induced hypotension and bradycardia.
- Anesthetized dog model to assess the effects of verapamil and potassium chloride infusion on arterial pressure, heart rate, and myocardial contractility.
- Comparison of hemodynamic responses to verapamil in normokalemic versus hyperkalemic states.
- Assessment of the reversal effects of calcium administration on verapamil-induced adverse events.
Main Results:
- Three patients refractory to standard treatment showed positive responses to intravenous calcium.
- In dogs, hyperkalemia significantly potentiated the hypotensive and bradycardic effects of verapamil.
- Verapamil reduced arterial pressure and heart rate in both normokalemic and hyperkalemic dogs, with more pronounced effects in the latter.
- Intravenous calcium administration effectively reversed the negative hemodynamic and contractile effects of verapamil in hyperkalemic dogs.
Conclusions:
- Concomitant hyperkalemia can dangerously exacerbate the negative hemodynamic effects of verapamil.
- Intravenous calcium administration is a potentially life-saving antidote for verapamil-induced cardiovascular toxicity, especially when associated with hyperkalemia.
- This interaction underscores the importance of monitoring potassium levels in patients receiving verapamil.
Abstract:
Three patients with systemic hypotension and sinus bradycardia that were initially refractory to conventional therapy responded well to intravenous calcium administration. Two-dimensional echocardiography revealed immediate reversal of severe left ventricular dysfunction after intravenous administration of calcium in two instances. Common factors were hyperkalemia and verapamil therapy. This interaction was examined further by evaluation of contractility, heart rate, and arterial blood pressure in anesthetized dogs. Controls (n = 9) received saline infusion, and a second group (n = 10) received saturated potassium chloride (approximately 0.2 ml/min intravenously). In control dogs, administration of verapamil (1195 +/- 181 micrograms/kg intravenously) reduced systemic arterial pressure from 113 +/- 7 mm Hg to 74 +/- 5 mm Hg, and heart rate from 147 +/- 9 beats/min to 86 +/- 11 beats/min. Potassium chloride infusion alone increased blood [K+] from 3.4 +/- 0.1 to 6.2 +/- 0.2 mEq/L, but was without hemodynamic effects. In hyperkalemic dogs, a significantly lower dose of verapamil (428 +/- 42 micrograms/kg intravenously) reduced systemic arterial pressure from 102 +/- 8 mm Hg to 36 +/- 4 mm Hg, and heart rate from 150 +/- 5 beats/min to 104 +/- 15 beats/min. Myocardial contractile function was examined with right ventricular isometric contractile force and left ventricular segment length changes. In normokalemic and hyperkalemic groups, contractility was decreased by verapamil. Effects of verapamil on arterial pressure and contractility could be reversed significantly by administration of calcium, 0.4 mEq/kg intravenously. The present results support the theory that the negative hemodynamic effects of verapamil may be exaggerated to a harmful degree by concomitant hyperkalemia. These adverse events may be reversed by calcium administration.