Osmolality Selectively Offsets the Impact of Hyperthermia on Mouse Skeletal Muscle in vitro

Abstract

Hyperthermia and dehydration can occur during exercise in hot environments. Nevertheless, whether elevations in extracellular osmolality contributes to the increased skeletal muscle tension, sarcolemmal injury, and oxidative stress reported in warm climates remains unknown. We simulated osmotic and heat stress, in vitro, in mouse limb muscles with different fiber compositions. Extensor digitorum longus (EDL) and soleus (SOL) were dissected from 36 male C57BL6J and mounted at optimal length in tissue baths containing oxygenated buffer. Muscles were stimulated with non-fatiguing twitches for 30 min. Four experimental conditions were tested: isotonic-normothermia (285 mOsm•kg-1 and 35°C), hypertonic-normothermia (300 mOsm•kg-1 and 35°C), isotonic-hyperthermia (285 mOsm•kg-1 and 41°C), and hypertonic-hyperthermia (300 mOsm•kg-1 and 41°C). Passive tension was recorded continuously. The integrity of the sarcolemma was determined using a cell-impermeable fluorescent dye and immunoblots were used for detection of protein carbonyls. In EDL muscles, isotonic and hypertonic-hyperthermia increased resting tension (P < 0.001). Whereas isotonic-hyperthermia increased sarcolemmal injury in EDL (P < 0.001), this effect was absent in hypertonic-hyperthermia. Similarly, isotonic-hyperthermia elevated protein carbonyls (P = 0.018), a response not observed with hypertonic-hyperthermia. In SOL muscles, isotonic-hyperthermia also increases resting tension (P < 0.001); however, these effects were eliminated in hypertonic-hyperthermia. Unlike EDL, there were no effects of hyperthermia and/or hyperosmolality on sarcolemmal injury or protein carbonyls. Osmolality selectively modifies skeletal muscle response to hyperthermia in this model. Fast-glycolytic muscle appears particularly vulnerable to isotonic-hyperthermia, resulting in elevated muscle tension, sarcolemmal injury and protein oxidation; whereas slow-oxidative muscle exhibits increased tension but no injury or protein oxidation under the conditions and duration tested.

ZBP1 and heatstroke

“…ALI was also found in mouse and rat models of heatstroke (21,99,158,(177)(178)(179)(180)(181)(182)(183). Rhabdomyolysis is more common in patients with EHS, and several possible mechanisms cause such phenomenon (3,166,(184)(185)(186)(187)(188)(189)(190)(191)(192)(193). One potential mechanism is the elevated muscle tension caused by strenuous activity, which increases the chance of tissue injury (184).…”

“…Rhabdomyolysis is more common in patients with EHS, and several possible mechanisms cause such phenomenon (3,166,(184)(185)(186)(187)(188)(189)(190)(191)(192)(193). One potential mechanism is the elevated muscle tension caused by strenuous activity, which increases the chance of tissue injury (184). Direct thermal cytotoxicity of hyperthermia may be another cause.…”

The Role of Skeletal Muscles in Exertional Heat Stroke Pathophysiology

“…Studies performed in rodents revealed that while the diaphragm tolerates temperature elevations up to 41 °C [41], the soleus muscle displays a 20 % decline in force after 60 min exposure at this temperature [42]. Even though muscles are resistant to heat, elevations in skeletal muscle temperature can disrupt its homeostasis [41,43]. Skeletal muscle temperature at rest is normally ~35 °C and remains ~0.65 °C to 0.95 °C higher than rectal temperature during exercise [44].…”

“…In isolated mouse skeletal muscle fibers, there are increases in skeletal muscle resting tension at 41 °C, a temperature achieved by the human skeletal muscle in exertion [46]. This increase in resting tension also occurs in greater magnitude in muscles composed predominantly of fasttwitch fibers [43] and is attributed to elevations in intracellular Ca 2 + [35,47] and ROS [48]. Increased resting tension augments the likelihood of skeletal muscle damage, which is possibly one of the mechanisms behind exertional rhabdomyolysis (ER).…”

Risk Factor Analysis and Nomogram for Predicting In-Hospital Mortality in ICU Patients with Heat Stroke: A National Multicenter Study

“…18,20,[25][26][27] While skeletal muscles exhibit relatively higher tolerance to heat injury, increased muscle tension and competition for blood flow between the skin and muscles can potentially lead to reduced muscle blood flow, tissue damage, including rhabdomyolysis, and subsequently renal overload and failure. 10,[28][29][30][31] Currently, there is a lack of specific and sensitive assessment scales to evaluate the condition and potential in-hospital outcomes of patients with severe heat stroke, leading to ineffective treatment guidance in clinical practice.…”