https://www.mayoclinicproceedings.org/article/S0025-6196(12)60336-X/pdf

Incidence and Size of Patent Foramen Ovale During the First 10 Decades of Life: An Autopsy Study of 965 Normal Hearts

Malignant hyperthermia (MH) causes neurological, liver, and kidney damage and death in humans and major economic losses in the swine industry. A single point mutation in the porcine gene for the skeletal muscle ryanodine receptor (ryr1) was found to be correlated with MH in five major breeds of lean, heavily muscled swine. Haplotyping suggests that the mutation in all five breeds has a common origin. Assuming that this is the causal mutation for MH, the development of a noninvasive diagnostic test will provide the basis for elimination of the MH gene or its controlled inclusion in swine breeding programs.

https://science.sciencemag.org/content/sci/253/5018/448.full.pdf

Identification of a mutation in porcine ryanodine receptor associated with malignant hyperthermia

Sarcopenia is a loss of muscle mass and function in the elderly that reduces mobility, diminishes quality of life, and can lead to fall-related injuries, which require costly hospitalization and ex...

/pdf/sarcopenia-aging-related-loss-of-muscle-mass-and-function-2u9nyjfrxt.pdf

Sarcopenia: Aging-Related Loss of Muscle Mass and Function.

### A. The ryanodine receptor

The ryanodine receptor (RyR)c corresponds to the sarcoplasmic reticulum (SR) Ca2+ channel ([Inui et al., 1987][1]; [Imagawa et al., 1987][2]). Its structure and function have been reviewed recently ([Fleischer and Inui, 1989][3]; [Lai and Meissner, 1989][4];[McPherson

The Sarcoplasmic Reticulum Ca2+ Channel/Ryanodine Receptor: Modulation by Endogenous Effectors, Drugs and Disease States

Malignant hyperthermia (MH) is a potentially lethal condition in which sustained muscle contracture, with attendant hypercatabolic reactions and elevation in body temperature, are triggered by commonly used inhalational anaesthetics and skeletal muscle relaxants In humans, the trait is usually inherited in an autosomal dominant fashion, but in halothane-sensitive pigs with a similar phenotype, inheritance of the disease is autosomal recessive or co-dominant A simple and accurate non-invasive test for the gene is not available and predisposition to the disease is currently determined through a halothane- and/or caffeine-induced contracture test on a skeletal muscle biopsy Because Ca2+ is the chief regulator of muscle contraction and metabolism, the primary defect in MH is believed to lie in Ca2+ regulation Indeed, several studies indicate a defect in the Ca2+ release channel of the sarcoplasmic reticulum, making it a prime candidate for the altered gene product in predisposed individuals We have recently cloned complementary DNA and genomic DNA encoding the human ryanodine receptor (the Ca2(+)-release channel of the sarcoplasmic reticulum) and mapped the ryanodine receptor gene (RYR) to region q131 of human chromosome 19 (ref 14), in close proximity to genetic markers that have been shown to map near the MH susceptibility locus in humans and the halothane-sensitive gene in pigs As a more definitive test of whether the RYR gene is a candidate gene for the human MH phenotype, we have carried out a linkage study with MH families to determine whether the MH phenotype segregates with chromosome 19q markers, including markers in the RYR gene Co-segregation of MH with RYR markers, resulting in a lod score of 420 at a linkage distance of zero centimorgans, indicates that MH is likely to be caused by mutations in the RYR gene

Ryanodine receptor gene is a candidate for predisposition to malignant hyperthermia

SCh is unequivocally contraindicated in the management of patients who have sustainded thermal trauma or direct muscle trauma and those who have neurologic disorders involving motor deficits, including tetanus. The mechanism is clear in some, but not all, of these conditions, and is related to increased chemosensitivity of the muscle membrane due to the development of receptor sites in extrajunctional areas. Though SCh induces a small release of K+ in normal muscle, it produces a potentially lethal efflux in the presence of increased sensitivity. This K+-releasing action of SCh begins about 5 to 15 days after injury and persists for 2 to 3 months in patients who have sustained burns or trauma, and perhaps 3 to 6 months in patients with upper motor neuron lesions.

Pathophysiology of hyperkalemia induced by succinylcholine.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2883%2980739-X

Calcium-induced Ca2+ release from sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia. The effects of halothane and dantrolene.

Paradoxical Air Embolism from a Patent Foramen Ovale

The effectiveness of intravenous administration of dantrolene in prevention and treatment of fulminant malignant hyperthermia (MH) initiated by halothene and succinylcholine (SCh) in genetically susceptible swine was assessed. In six animals, prior administration of dantrolene in doses of 5 mg/kg or more prevented MH, while 1 or 3 mg/kg attenuated MH, and 0.1 mg/kg had no effect. In ten additional swine, therapy was not started until MH was fulminant. Five of these were then given supportive therapy only (discontinuation of anesthesia, hyperventilation with oxygen, surface cooling, and NaHCO3). The remaining five received the same supportive therapy, plus dantrolene (7.5 mg/kg). With supportive therapy only, arterial blood pH, Po2 and Pco2 returned toward normal, but oxygen consumption (Vo2), blood lactate, potassium (K+), catecholamines, and temperature continued to increase and the course of MH was unaltered. When dantrolene was added to supportive therapy, Vo2, lactate, K+, catecholamines, and temperature decreased, and the course of MH was dramatically slowed and, apparently, reversed.

Dantrolene in porcine malignant hyperthermia.

Recent studies by McDowall, Jennett, Barker, and Fitch [1–4] demonstrated that halothane may increase intracranial pressure, especially in patients with intracranial space-occupying lesions, and suggested that hypocapnia may not prevent such increases. A subsequent editorial [5] concluded that halothane is relatively contraindicated for intracranial surgery. The validity of this conclusion may be questioned because in the patients studied by the McDowall group, the levels of hypocapnia were inconstant, awake cerebrospinal fluid pressure (CSFP) was not measured, and the effect of halothane was observed for only 10 min. The present study was designed to examine the effect of continuous administration of halothane on CSFP at a constant level of hypocapnia induced either before or together with the introduction of halothane. In addition, the combined effect of droperidol, fentanyl, nitrous oxide, and hypocapnia on CSFP was examined.

Gerald A. Gronert

Papers

Pathophysiology of hyperkalemia induced by succinylcholine.

Calcium-induced Ca2+ release from sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia. The effects of halothane and dantrolene.

Paradoxical Air Embolism from a Patent Foramen Ovale

Dantrolene in porcine malignant hyperthermia.

Halothane, Hypocapnia, and Cerebrospinal Fluid Pressure in Neurosurgery