Hyperkalemia and Cardiovascular Collapse after Verapamil and Dantrolene Administration in Swine

Saltzman, L.; Kates, Robert E.; Corke, B. C.; Norfleet, Edward A.; Heath, Kevin

doi:10.1213/00000539-198405000-00001

Cited by 76 publications

(21 citation statements)

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“…Animals pretreated with verapamil had lower cardiac index and arterial pressure. In another inves tigation, low dose verapamil plus dantrolene in pigs produced hemodynamic collapse and death associated with the development of hy perkalemia [12], These studies show an interaction in vivo but do not differentiate between a direct effect on the heart or a complex interaction which may have been due to a number of factors. For example, the primary effect could be on vascular smooth muscle causing hypotension and ventricular dysfunction secondary to im paired coronary perfusion, although this was not suggested by the canine studies.…”

Section: Discussionmentioning

confidence: 91%

Effect of Hyperkalemia on Myocardial Depression by Verapamil in Isolated Hearts

Jolly¹,

Wilson²,

Movahed³

et al. 1993

Pharmacology

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Verapamil can produce depression of left ventricular function, delayed atrioventricular conduction, and hypotension, which can be potentiated by hyperkalemia. We sought to investigate a direct cardiac interaction between verapamil and hyperkalemia. Studies utilized isolated guinea pig hearts (Langendorff) paced at 250 beats/min. Hearts were randomly assigned to perfusion (Krebs-Henseleit buffer) with potassium concentrations ([K]⁺) of 1.5, 3, 6 and 9 mmol/l. Infusion of verapamil at rates of 0.2 to 60 µg/min (approximately 3 × 10^–8 to 10^–5 mol/l) produced concentration-dependent reduction of isovolumic left ventricular developed pressure. As [K]⁺ increased, concentration response curves showed parallel shifts to the left. The ED₅₀ for reduction of left ventricular developed pressure significantly decreased: 8.2 ± 3.7, 2.9 ± 1.4, 1.2 ± 0.7, 0.6 ± 0.2 µg/min (mean ± SD), respectively. Nifedipine and diltiazem were also studied in hearts perfused with 3 and 9 mmol/l [K]⁺. Infusion of nifedipine 0.003-1 µg/min (approximately 10^–9 to 3 × 10^–7 mol/l) produced concentration-dependent reduction of left ventricular developed pressure but the ED₅₀ was not affected by [K]⁺: 0.06 ± 0.03 and 0.05 ± 0.04 µg/min, respectively. Nifedipine vehicle was without effect at the infusion rates tested. Infusion of diltiazem 2–200 µg/min (approximately 3 × 10^–7 to 3 × 10^–5 mol/l) also produced concentration-dependent reduction of left ventricular developed pressure. The ED₅₀ for diltiazem-induced reduction of left ventricular developed pressure was significantly reduced by elevated [K]⁺: 20.1 ± 6.7 and 3.5 ± 0.9 µg/min with 3 and 9 mmol/l [K]\ respectively. Conclusion, verapamil-induced reduction of left ventricular developed pressure was significantly influenced by buffer potassium concentration, showing a direct interaction between hyperkalemia and verapamil on the heart. A similar interaction was observed with diltiazem but not nifedipine, suggesting that the interaction was not general for all calcium entry blockers.

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Section: Discussionmentioning

confidence: 91%

Effect of Hyperkalemia on Myocardial Depression by Verapamil in Isolated Hearts

Jolly¹,

Wilson²,

Movahed³

et al. 1993

Pharmacology

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“…Observation and monitoring: as much as 25% of patients with MH will present a recrudescence of the syndrome several hours after its initial control 133 . As a result, authors recommend observation in Intensive Care Units for 24-72 hours postoperatively 32 .…”

Section: Postoperativelymentioning

confidence: 99%

Malignant Hyperthermia in Liver Transplantation

Fernandes¹,

Marinho²,

Cavalcante³

2012

Liver Transplantation - Basic Issues

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“…Während Dantrolen an sich keine Effekte auf das Myokard zeigt, führt die Kombination mit Verapamil zu einer deutlichen Reduktion der myokardialen Funktion bei Schweinen und Hunden [29]. Obwohl diese Interaktion beim Menschen nie beschrieben wurde, gilt die gleichzeitige Gabe beider Medikamente bei Tachyarrhythmien im Rahmen einer MH-Krise als kontraindiziert.…”

Section: Wechselwirkungenunclassified

Dantrolen

Gerbershagen¹,

Fiege²,

Krause³

et al. 2003

Der Anaesthesist

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Malignant hyperthermia (MH) is a genetic, potentially life-threatening disorder of the skeletal muscle presenting during or following general anaesthesia. Trigger agents are volatile anaesthetics and depolarising muscle relaxants. Dantrolene is the only available drug for effective and specific MH therapy, which reduces significantly the mortality rate. Dantrolene is a skeletal muscle relaxant that depresses the excitation-contraction coupling,however, the specificity of action remains unknown. Recent studies identified the ryanodine receptor, the calcium release channel of the sarcoplasmic reticulum, as the direct molecular target of dantrolene. In addition to its use for MH, dantrolene is used in other disorders such as neuroleptic malignant syndrome and spasticity. Since dantrolene is weakly water soluble, the clinical preparation is time and manpower consuming. New agents have been synthesized, but because of economic considerations no registration for clinical usage has been realised.

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Hyperkalemia and Cardiovascular Collapse after Verapamil and Dantrolene Administration in Swine

Cited by 76 publications

References 0 publications

Effect of Hyperkalemia on Myocardial Depression by Verapamil in Isolated Hearts

Effect of Hyperkalemia on Myocardial Depression by Verapamil in Isolated Hearts

Malignant Hyperthermia in Liver Transplantation

Dantrolen

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