The impact of 4-chloro-m-cresol in heparin formulas on malignant hyperthermia: in vitro and in vivo.

BACKGROUND: The preservative 4-chloro-m-cresol (4CmC) is a specific activator of sarcoplasmic Ca2- release and induces contractures in skeletal muscles of malignant hyperthermia susceptible (MHS) patients in vitro. Clinical formulas of heparin contain 4CmC. We studied whether (a) these heparin formulas induce contractures in isolated MHS and normal (MHN) human skeletal muscles and whether (b) significant serum levels of 4CmC are reached after heparinization in cardiopulmonary bypass patients. METHODS: (a) In vitro, muscle bundles of 16 MHS and 22 MHN patients were exposed to the heparin formula Liquemin (containing 4CmC 0.08 mg/500 IU), to chlorocresol and to preservative-free heparin in the in vitro contracture test. (b) In vivo, serum 4CmC levels of 12 patients receiving Liquemin 500 IU/ kg before cardiopulmonary bypass were determined at 1, 5 and 60 min by high-pressure liquid chromatography. RESULTS: (a) For Liquemin and 4CmC, significant contractures were measured with MHS muscles compared to MHN muscles at 61.4 microM 4CmC. (b) In control sera, the detection threshold for 4CmC was 4 microM. Concentrations of 4CmC in all patients' serum samples were below this threshold. CONCLUSION: Heparin formulas, containing 4CmC, induce dose-dependent contractures in vitro in MHS human skeletal muscle at about 60 microM 4CmC. However, in vivo, 4CmC serum concentrations with therapeutic heparinization are less than 1/15 of the in vitro concentration. The lipophilicity of 4CmC with a high volume of distribution may account for these findings. MHS patients seem not to be at risk from clinical heparin formulas containing chlorocresol.

[Are morphologic changes in skeletal muscles of patients with malignant hyperthermia diagnostically useful?]. / Sind morphologische Veränderungen im Skelettmuskel von Patienten mit Maligner Hyperthermie diagnostisch verwertbar?

Malignant Hyperthermia (MH) represents a functional myopathy triggered by volatile anesthetics and depolarizing muscle relaxants, and leading to metabolic disturbances of intracellular Calcium homeostasis. Central-Core-like-structures (CCLS) were recently described as central defects in enzyme-histochemical stains and well correlated to the autosomal-dominant MH-predisposition. We studied the correlation of a MH-predisposition with specific myopathological signs. Skeletal muscles of suspected MH-individuals were histochemically stained by SDH-, NADH-, COX-, Gomori-Trichrome-, ATPase-, Acid Phosphatase-, Oil-red O- und PAS-stain und evaluated without knowing MH-diagnosis by the in-vitro-contracture test. Out of 118 patients (30% MHS ["susceptible"], 63% MHN [normal], 7% MHE ["equivocal"]) 19% revealed pathological findings corresponding to CCLS. 45% of these findings were associated with MHS/MHE. With HE-staining internal nuclei were not specific, but increased with the probability of MHS/MHE from 24% to 80%. Central Cores were correlated in 100% with MHS/MHE (4 out of 118 patients). CCLS were found with about similar frequency in skeletal muscle of MHS/MHE and MHN individuals. Internal nuclei were, however, not specifically, associated with MHS. In contrast, Central Cores correlated significantly with MHS/MHE diagnosis. In conclusion, histopathological findings in skeletal muscle seem to be a reliable marker for MH-predisposition only with Central Cores.

[Stereoroentgenology in endourology]. / Stereo-Röntgen in der Endourologie.

Three-dimensional stereofluoroscopic pictures of the kidney and renal calyces were first used for percutaneous renal surgery with a laboratory prototype equipment. The grid-controlled X-ray tube provides sequential images, which are separated into pairs by digital image processing and storage and can be seen on a 3-D display unit. This method allows exact and rapid puncture of a suitable calyx for percutaneous nephrolithotomy, shortens the learning process for the endourologist, reduces the radiation exposure, and thus makes the method safer.