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In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine.
Anesthesiology. 2003 Apr; 98(4):944-9.A

Abstract

BACKGROUND

In human skeletal muscles, the phosphodiesterase-III inhibitor enoximone induces in vitro contracture development, and it has been suggested that enoximone could trigger malignant hyperthermia (MH). In this study, the in vitro and in vivo effects of enoximone in MH-normal (MHN) and MH-susceptible (MHS) swine were investigated.

METHODS

Malignant hyperthermia trigger-free general anesthesia was performed in MHS and MHN swine. Skeletal muscle specimens were excised for an in vitro contracture test with 0.6 mm enoximone. Thereafter, MHS and MHN swine were exposed to cumulative administration of 0.5, 1, 2, 4, 8, 16, and 32 mg/kg enoximone intravenously. Clinical occurrence of MH was defined by a Pco(2) greater than 70 mmHg, a pH less than 7.20, and an increase in body temperature of more than 2.0 degrees C.

RESULTS

Enoximone induced marked contractures in all MHS muscle specimens in vitro. In contrast, only small or no contracture development was observed in MHN muscle specimens, without an overlap in contractures between MHS and MHN muscles. However, in vivo, no clinical differences were found between MHS and MHN swine following cumulative enoximone doses. According to the defined criteria, none of the swine developed MH during the experiment. Furthermore, high enoximone doses induced progressive circulatory insufficiency, and after receiving 32 mg/kg enoximone, all animals died of cardiovascular failure.

CONCLUSIONS

The cumulative enoximone doses used in this study were 30- to 50-fold higher than therapeutic doses in humans. Enoximone does not trigger MH in genetically determined swine. However, enoximone might be useful for in vitro diagnosis of MH.

Authors+Show Affiliations

Department of Anesthesiology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. fiege@uke.uni-hamburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12657857

Citation

Fiege, Marko, et al. "In Vitro and in Vivo Effects of the phosphodiesterase-III Inhibitor Enoximone On Malignant Hyperthermia-susceptible Swine." Anesthesiology, vol. 98, no. 4, 2003, pp. 944-9.
Fiege M, Wappler F, Weisshorn R, et al. In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine. Anesthesiology. 2003;98(4):944-9.
Fiege, M., Wappler, F., Weisshorn, R., Gerbershagen, M. U., Kolodzie, K., & Schulte Am Esch, J. (2003). In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine. Anesthesiology, 98(4), 944-9.
Fiege M, et al. In Vitro and in Vivo Effects of the phosphodiesterase-III Inhibitor Enoximone On Malignant Hyperthermia-susceptible Swine. Anesthesiology. 2003;98(4):944-9. PubMed PMID: 12657857.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro and in vivo effects of the phosphodiesterase-III inhibitor enoximone on malignant hyperthermia-susceptible swine. AU - Fiege,Marko, AU - Wappler,Frank, AU - Weisshorn,Ralf, AU - Gerbershagen,Mark U, AU - Kolodzie,Kerstin, AU - Schulte Am Esch,Jochen, PY - 2003/3/27/pubmed PY - 2003/4/30/medline PY - 2003/3/27/entrez SP - 944 EP - 9 JF - Anesthesiology JO - Anesthesiology VL - 98 IS - 4 N2 - BACKGROUND: In human skeletal muscles, the phosphodiesterase-III inhibitor enoximone induces in vitro contracture development, and it has been suggested that enoximone could trigger malignant hyperthermia (MH). In this study, the in vitro and in vivo effects of enoximone in MH-normal (MHN) and MH-susceptible (MHS) swine were investigated. METHODS: Malignant hyperthermia trigger-free general anesthesia was performed in MHS and MHN swine. Skeletal muscle specimens were excised for an in vitro contracture test with 0.6 mm enoximone. Thereafter, MHS and MHN swine were exposed to cumulative administration of 0.5, 1, 2, 4, 8, 16, and 32 mg/kg enoximone intravenously. Clinical occurrence of MH was defined by a Pco(2) greater than 70 mmHg, a pH less than 7.20, and an increase in body temperature of more than 2.0 degrees C. RESULTS: Enoximone induced marked contractures in all MHS muscle specimens in vitro. In contrast, only small or no contracture development was observed in MHN muscle specimens, without an overlap in contractures between MHS and MHN muscles. However, in vivo, no clinical differences were found between MHS and MHN swine following cumulative enoximone doses. According to the defined criteria, none of the swine developed MH during the experiment. Furthermore, high enoximone doses induced progressive circulatory insufficiency, and after receiving 32 mg/kg enoximone, all animals died of cardiovascular failure. CONCLUSIONS: The cumulative enoximone doses used in this study were 30- to 50-fold higher than therapeutic doses in humans. Enoximone does not trigger MH in genetically determined swine. However, enoximone might be useful for in vitro diagnosis of MH. SN - 0003-3022 UR - https://www.unboundmedicine.com/medline/citation/12657857/In_vitro_and_in_vivo_effects_of_the_phosphodiesterase_III_inhibitor_enoximone_on_malignant_hyperthermia_susceptible_swine_ L2 - https://pubs.asahq.org/anesthesiology/article-lookup/doi/10.1097/00000542-200304000-00022 DB - PRIME DP - Unbound Medicine ER -