Porcine malignant hyperthermia: false negatives in the halothane test.

Purebred Pietrain pigs presumed (on the basis of pedigree) to be homozygous for malignant hyperthermia (MH) susceptibility were subjected to a 3% halothane challenge test. A few (6%) pigs that should have been MH susceptible on the basis of parental genotype did not develop muscle rigidity in response to repeated halothane tests. Three of these animals were brought into the laboratory, and muscle biopsy specimens were obtained for in vitro analysis. Bundles of intact muscle cells dissected from biopsy specimens were electrically stimulated, and mechanical responses were monitored during exposure to halothane. In all instances, the muscle bundles from the halothane-negative (ie, not sensitive to halothane), but genetically susceptible, pigs gave in vitro responses that were similar of those of halothane-positive MH-susceptible pigs in that tetanic tension was depressed, tetanus relaxation was slowed, and small contractures were produced upon halothane exposure. Thus, the presence of a halothane-sensitive abnormality in the skeletal muscles, in and of itself, is not always sufficient for development of in vivo muscle rigidity during a brief halothane test. Furthermore, when the halothane testing of pigs is conducted by recommended techniques, false negatives still occur in a small percentage of the genetically MH-susceptible animals.