A Review of Potential Cardiovascular Uses of Intravenous Glucagon Administration

Abstract

Glucagon is a counter‐regulatory hormone that is classically used to treat hypoglycemia. However, it can elicit the generation of cAMP within the myocardium to cause positive inotropic and chronotropic effects without the need for beta‐1 adrenoceptor stimulation. Glucagon has been used extensively to treat beta‐blocker overdose and has evidence for use in verapamil and imipramine overdose as well. Glucagon has been used as adjunctive therapy in shock situations and heart failure but is inferior to catecholamines. An interesting potential indication for glucagon is in treating postcountershock asystole.

Glucagon and exenatide improve contractile recovery following ischaemia/reperfusion in the isolated perfused rat heart

“…Others, using the mouse heart, suggested instead that glucagon antagonism postreperfusion may improve remodeling and ejection fraction, and that glucagon agonism may impair contractile recovery postreperfusion (Ali et al, 2015;Karwi et al, 2019). Preischaemic inotropism, seen in rats, dogs, cats, guinea pigs, and humans (Farah & Tuttle, 1960;Rodgers et al, 1981;Rotella et al, 2020;White, 1999), was not observed in these mouse studies (Ali et al, 2015), suggesting that inter-species variation may explain the discrepancies between studies.…”

“…In addition to its metabolic effects, glucagon has been shown to be a cardio‐stimulant, which increases heart rate and myocardial contractility (chronotropic and inotropic effects) (Ceriello et al, 2016 ). Successful administration of glucagon has been reported in a range of cardiovascular disorders, including heart failure and cardiogenic shock (Lvoff & Wilcken, 1972 ; Parmley et al, 1968 ; White, 1999 ). Lvoff and Wilcken noted the beneficial effects of administering glucagon to patients with severe ischaemic heart disease (Lvoff & Wilcken, 1972 ).…”

“…Lvoff and Wilcken noted the beneficial effects of administering glucagon to patients with severe ischaemic heart disease (Lvoff & Wilcken, 1972 ). Glucagon has also been a first‐choice treatment for β‐blocker intoxication (Rotella et al, 2020 ; White, 1999 ), although this clinical efficacy has not been assessed in a controlled clinical trial.…”

“…This, coupled with the inotropic and metabolic effects described, suggests that glucagon could protect the heart against ischaemia/reperfusion injury, yet studies addressing this to date have painted a mixed picture. Some studies have shown improved vasodilation postischaemia in the rat heart, and cardiac benefits in humans (Lvoff & Wilcken, 1972 ; Rosic et al, 2010 ; White, 1999 ). Others, using the mouse heart, suggested instead that glucagon antagonism postreperfusion may improve remodeling and ejection fraction, and that glucagon agonism may impair contractile recovery postreperfusion (Ali et al, 2015 ; Karwi et al, 2019 ).…”

Antidotes in Clinical Toxicology—Critical Review

“…Furthermore, enzymes within myocardial cells metabolise glucagon into its COOH-terminal fragment, called miniglucagon. Miniglucagon activates phospholipase A2 and stimulates arachidonic acid production, the accumulation of which in myocardial cells leads to increased cardiac inotropy [ 113 ].…”