Sermorelin analog MR-409 reduced heart attack scar mass by 21.9% in a swine model of ischemic cardiomyopathy

Following a myocardial infarction (MI), or heart attack, the heart muscle undergoes a process called ventricular remodeling, which often leads to the formation of non-functional scar tissue and can progress to heart failure. Previous research in rat models suggested that activating the heart's intrinsic Growth Hormone-Releasing Hormone (GHRH) signaling pathway could stimulate cardiac repair. These smaller animal models showed promise, but it was crucial to validate these findings in a large animal model, like swine, whose cardiovascular system more closely resembles that of humans. This study was designed to bridge that gap by testing if a GHRH agonist could prevent adverse remodeling and reduce scar tissue after an MI in a subacute swine model, leveraging the presence of GHRH receptors in cardiac tissue.

Twelve female Yorkshire swine underwent a procedure to induce a myocardial infarction (transient occlusion of the left anterior descending coronary artery). Two weeks after the MI, the swine were randomized into two groups of n=6 each. The treatment group received daily subcutaneous injections of the GHRH agonist MR-409 at 30 μg/kg, while the control group received a vehicle (placebo). The treatment period lasted for four weeks. Researchers used cardiac magnetic resonance imaging (MRI) and pressure-volume loop analysis at multiple time points to assess cardiac structure and function. They also used immunohistochemistry to examine GHRH receptor density in different zones of the heart tissue.

After four weeks of treatment, the GHRH-A group showed a significant reduction in scar tissue compared to the placebo group. The GHRH-A group's scar mass decreased by -21.9 ± 6.42% (P=0.02), whereas the placebo group's scar mass trended upwards by 10.9 ± 5.88% (P=0.25), with a highly significant difference between groups (2-way ANOVA; P=0.003). This was accompanied by improved diastolic strain.

The most striking result was the reduction in scar size as a percentage of left ventricular mass, which decreased by -38.38 ± 4.63% in the GHRH-A group (P=0.0002) compared to a non-significant reduction of -14.56 ± 6.92% in the placebo group (P=0.16). Interestingly, unlike previous rat studies, this significant reduction in infarct size did not translate to improved overall cardiac function as measured by serial hemodynamic pressure-volume analysis. Immunohistochemistry confirmed GHRH receptors were abundant in heart tissue, with a greater density observed in the border zone of the GHRH-A treated group.