Hibernation induction trigger reduces hypoxic damage of swine skeletal muscle

Abstract

A link between the cardioprotective benefits of pharmacological preconditioning and natural mammalian hibernation is considered to involve the cellular activation of opioid receptors and subsequent opening of K(ATP) channels. In previous studies, we have demonstrated the protective effects of specific delta-opioid agonists against porcine cardiac ischemia/reperfusion injury. We hypothesize here that preincubation with hibernation induction trigger (HIT) should confer a similar protection in skeletal muscles. Therefore, muscle bundles from swine were pretreated with plasma from hibernating woodchucks (HWP) for 30 min, then exposed to hypoxia for 90 min and reoxygenation for 120 min. Stimulated twitch forces were assessed. The functional effects of pretreatment with nonhibernation (summer) woodchuck plasma, a K(ATP) blocker, or opioid antagonist were also studied. During the reoxygenation period, significantly greater force recoveries were observed only for bundles pretreated with HWP; this response was blocked by naloxone (P < 0.05). We conclude that HIT pretreatment could be used to confer protection against hypoxia/reperfusion injury of skeletal muscles of nonhibernators; it could potentially be utilized to prevent injury during surgical procedures requiring ischemia.

Extreme Respiratory Sinus Arrhythmia Enables Overwintering Black Bear Survival—Physiological Insights and Applications to Human Medicine

“…Our laboratory has previously shown that delta opioid agonists, which are considered to be a component of the hibernation induction trigger in black bears, reduce ischemia-reperfusion injury of both cardiac and skeletal muscle of non-hibernators [16,34]. Relative to the findings of the present study, the ability to induce extremely low heart rates without risking global ischemic damage or cardiac remodeling would be of value in numerous clinical scenarios and/or for long distance space travel.…”

“…Decreases in cardiac mass as well as electrophysiological changes have also been observed in healthy humans during periods of prolonged inactivity and/or during space travel [29,30,36]. Although it has been reported that circulating proteins such as "hibernation induction trigger" and "hibernation-specific protein" complex (HPc) may play an important role in conserving cardiac form and function in hibernating mammals, the physiological mechanisms of the heart that aid in the prevention of ischemic tissue damage during overwintering have not been fully characterized [3,16,18].…”

Hibernation induces pentobarbital insensitivity in medulla but not cortex

“…Liganddriven mechanisms controlling hibernation have been investigated for more than 30 years (22,38,48). Some of the proposed molecules include circulating hormones such as vasopressin (21), and neurotransmitters, such as serotonin (45), histamine (61), and GABA (49).…”

δ-Opioid Receptor Expression in the Ventral Tegmental Area Protects Against Elevated Alcohol Consumption

“…The ␦-opioid receptor (DOR) plays a protective role in cerebral ischemia, hypoxia, cardiac dysfunction, skeletal muscle damage, peripheral organ survival, and vulnerability to stress (Borlongan et al, 2004;Hebb et al, 2005;Hong et al, 2005;Saitoh et al, 2005;Chao et al, 2007;Förster et al, 2007). Interestingly, CNS expression of DORs is often dynamically induced following physiological challenge (Commons, 2003;Hack et al, 2005;Cahill et al, 2007) and trafficking to the plasma membrane is regulated through a variety of mechanisms, which are dependent on stimulus type and duration (Cahill et al, 2007).…”