Hexarelin · research summary

Hexarelin treatment preserves myocardial function and reduces cardiac fibrosis in a mouse model of acute myocardial infarction.

Physiological reports · 2018. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Animal study investigating the effects of hexarelin on cardiac function and fibrosis in a mouse model of myocardial infarction
“This study determined whether hexarelin (HEX), a synthetic GHS, preserves cardiac function and morphology in a mouse model of myocardial infarction (MI).”

Subjects

Male C57BL/6JArc inbred mice
“MI was induced in 12–14 week old male C57BL/6JArc inbred mice (weight 25–30 g) (n = 21) (JAX stock number: 000664) by permanent ligation of the left anterior descending coronary artery (LAD).”

Sample size

21 mice underwent myocardial infarction induction and 11 mice underwent sham surgery
“MI was induced in 12–14 week old male C57BL/6JArc inbred mice (weight 25–30 g) (n = 21) (JAX stock number: 000664) by permanent ligation of the left anterior descending coronary artery (LAD).”

Duration

21 days of treatment with assessments at 24 hours, 14 days, and 21 days post-procedure
“All mice received their respective treatments once daily throughout the 21‐day study period.”

Reported findings

Hexarelin treatment significantly improved left ventricular ejection fraction compared to vehicle treatment after 14 days
“After 14 days treatment, HEX treatment significantly improved EF compared to MI‐VEH mice (HEX: 49.25% ± SEM 2.3; VEH: 36.96% ± SEM 3.82) (Fig. 1B).”
Chronic hexarelin treatment reduced left ventricular mass, interstitial collagen, and collagen concentration
“A significant decrease in LV mass, interstitial collagen and collagen concentration was demonstrated with chronic HEX treatment (for 21 days), accompanied by a decrease in TGF‐β1 expression, myofibroblast differentiation and an increase in collagen‐degrading MMP‐13 expression levels.”
Hexarelin treatment shifted autonomic nervous activity toward parasympathetic predominance and reduced levels of troponin-I, IL-1β, and TNF-α
“heart rate variability analysis demonstrated that HEX treatment shifted the balance of autonomic nervous activity toward a parasympathetic predominance and sympathetic downregulation. This was combined with a HEX‐dependent decrease in troponin‐I, IL‐1β and TNF‐α levels suggestive of amelioration of cardiomyocyte injury.”

Limitations stated by the authors

Hexarelin was administered immediately prior to ligation, reperfusion was not investigated, and mouse model infarct changes differ from human acute myocardial infarction
“HEX administration immediately prior to ligation represents a potential limitation. Timely reperfusion strategies act to limit infarct development, thus more logically; therapy would be initiated at this point, prior to reperfusion. The effect of reperfusion was not investigated in this study and represents a downfall. The temporal histopathological and functional infarct changes in mouse models of MI vary when compared to acute myocardial infarction patients, thus representing a limitation of this model.”

Source: PubMed 29756411 · DOI 10.14814/phy2.13699 · all study summaries

Reported findings

Hexarelin treatment significantly improved left ventricular ejection fraction compared to vehicle treatment after 14 days

“After 14 days treatment, HEX treatment significantly improved EF compared to MI‐VEH mice (HEX: 49.25% ± SEM 2.3; VEH: 36.96% ± SEM 3.82) (Fig. 1B).”

Chronic hexarelin treatment reduced left ventricular mass, interstitial collagen, and collagen concentration

“A significant decrease in LV mass, interstitial collagen and collagen concentration was demonstrated with chronic HEX treatment (for 21 days), accompanied by a decrease in TGF‐β1 expression, myofibroblast differentiation and an increase in collagen‐degrading MMP‐13 expression levels.”

Hexarelin treatment shifted autonomic nervous activity toward parasympathetic predominance and reduced levels of troponin-I, IL-1β, and TNF-α

“heart rate variability analysis demonstrated that HEX treatment shifted the balance of autonomic nervous activity toward a parasympathetic predominance and sympathetic downregulation. This was combined with a HEX‐dependent decrease in troponin‐I, IL‐1β and TNF‐α levels suggestive of amelioration of cardiomyocyte injury.”

Limitations stated by the authors

Hexarelin was administered immediately prior to ligation, reperfusion was not investigated, and mouse model infarct changes differ from human acute myocardial infarction

“HEX administration immediately prior to ligation represents a potential limitation. Timely reperfusion strategies act to limit infarct development, thus more logically; therapy would be initiated at this point, prior to reperfusion. The effect of reperfusion was not investigated in this study and represents a downfall. The temporal histopathological and functional infarct changes in mouse models of MI vary when compared to acute myocardial infarction patients, thus representing a limitation of this model.”