Overlapping Mechanisms of Exertional Heat Stroke and Malignant Hyperthermia: Evidence vs. Conjecture

Laitano, Orlando; Murray, Kevin; Leon, Lisa R.

doi:10.1007/s40279-020-01318-4

Cited by 25 publications

(16 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In summary, by taking advantage of local heating technology, we demonstrated that abnormal RyR1 heat sensing caused HICR in RyR1 mutant–expressing HEK293 cells and in skeletal muscles from MH mice. These findings suggest that an additional positive feedback loop between thermogenesis and heat-sensing via heat-hypersensitive RyR1 mutants irrepressibly elevates body temperature during MH and, presumably, during exertional heat stroke under extreme environmental conditions ( 63 – 65 ).…”

Section: Discussionmentioning

confidence: 90%

Heat-hypersensitive mutants of ryanodine receptor type 1 revealed by microscopic heating

Oyama

Zeeb

Yamazawa

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Thermoregulation is an important aspect of human homeostasis, and high temperatures pose serious stresses for the body. Malignant hyperthermia (MH) is a life-threatening disorder in which body temperature can rise to a lethal level. Here we employ an optically controlled local heat-pulse method to manipulate the temperature in cells with a precision of less than 1 °C and find that the mutants of ryanodine receptor type 1 (RyR1), a key Ca 2+ release channel underlying MH, are heat hypersensitive compared with the wild type (WT). We show that the local heat pulses induce an intracellular Ca 2+ burst in human embryonic kidney 293 cells overexpressing WT RyR1 and some RyR1 mutants related to MH. Fluorescence Ca 2+ imaging using the endoplasmic reticulum–targeted fluorescent probes demonstrates that the Ca 2+ burst originates from heat-induced Ca 2+ release (HICR) through RyR1-mutant channels because of the channels’ heat hypersensitivity. Furthermore, the variation in the heat hypersensitivity of four RyR1 mutants highlights the complexity of MH. HICR likewise occurs in skeletal muscles of MH model mice. We propose that HICR contributes an additional positive feedback to accelerate thermogenesis in patients with MH.

show abstract

Section: Discussionmentioning

confidence: 90%

Heat-hypersensitive mutants of ryanodine receptor type 1 revealed by microscopic heating

Oyama

Zeeb

Yamazawa

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…52 In other reports, patients with HS have been found to have histories or family histories of MH or an association among MHrelated genetic flaws such as RYR1 variants. [53][54][55] The correlation between MH and non-anesthetic stress is also supported by studies performed on animals. Pigs carrying a mutant RYR1 gene can be induced to experience an MH episode by both halothane and stressful conditions, such as elevated environmental temperatures and/or emotional or physical stress.…”

Section: Non-anesthetic Induced Mhmentioning

confidence: 96%

Malignant Hyperthermia: A Killer If Ignored

Bin

Wang

Tang

2022

Journal of PeriAnesthesia Nursing

View full text Add to dashboard Cite

“…Ca 2 + dysregulation has been proposed as a link between EHS and malignant hyperthermia, a condition where exposure to the haloalkane class of anesthetics gases triggers a massive Ca 2 + release from the SR, results in dysregulated muscle contraction, and leads to lethal hyperthermia [39]. The evidence for Ca 2 + dysregulation in EHS is only indirect and more studies are warranted to determine whether Ca 2 + dysregulation occurs in EHS victims [39]. ▶ Figure 1 highlights the ATP dependent processes where heat generation takes place within the myofiber, including the pathways associated with Ca 2 + homeostasis.…”

Section: Eccentricmentioning

confidence: 99%

The Role of Skeletal Muscles in Exertional Heat Stroke Pathophysiology

2021

Self Cite

View full text Add to dashboard Cite

The active participation of skeletal muscles is a unique characteristic of exertional heat stroke. Nevertheless, the only well-documented link between skeletal muscle activities and exertional heat stroke pathophysiology is the extensive muscle damage (e. g., rhabdomyolysis) and subsequent leakage of intramuscular content into the circulation of exertional heat stroke victims. Here, we will present and discuss rarely explored roles of skeletal muscles in the context of exertional heat stroke pathophysiology and recovery. This includes an overview of heat production that contributes to severe hyperthermia and the synthesis and secretion of bioactive molecules, such as cytokines, chemokines and acute phase proteins. These molecules can alter the overall inflammatory status from pro- to anti-inflammatory, affecting other organ systems and influencing recovery. The activation of innate immunity can determine whether a victim is ready to return to physical activity or experiences a prolonged convalescence. We also provide a brief discussion on whether heat acclimation can shift skeletal muscle secretory phenotype to prevent or aid recovery from exertional heat stroke. We conclude that skeletal muscles should be considered as a key organ system in exertional heat stroke pathophysiology.

show abstract

Overlapping Mechanisms of Exertional Heat Stroke and Malignant Hyperthermia: Evidence vs. Conjecture

Cited by 25 publications

References 72 publications

Heat-hypersensitive mutants of ryanodine receptor type 1 revealed by microscopic heating

Heat-hypersensitive mutants of ryanodine receptor type 1 revealed by microscopic heating

Malignant Hyperthermia: A Killer If Ignored

The Role of Skeletal Muscles in Exertional Heat Stroke Pathophysiology

Contact Info

Product

Resources

About