Electrophysiologic Effects of Growth Hormone Post-Myocardial Infarction

Abstract

Myocardial infarction remains a major health-related problem with significant acute and long-term consequences. Acute coronary occlusion results in marked electrophysiologic alterations that can induce ventricular tachyarrhythmias such as ventricular tachycardia or ventricular fibrillation, often heralding sudden cardiac death. During the infarct-healing stage, hemodynamic and structural changes can lead to left ventricular dilatation and dysfunction, whereas the accompanying fibrosis forms the substrate for re-entrant circuits that can sustain ventricular tachyarrhythmias. A substantial proportion of such patients present clinically with overt heart failure, a common disease-entity associated with high morbidity and mortality. Several lines of evidence point toward a key role of the growth hormone/insulin-like growth factor-1 axis in the pathophysiology of post-infarction structural and electrophysiologic remodeling. Based on this rationale, experimental studies in animal models have demonstrated attenuated dilatation and improved systolic function after growth hormone administration. In addition to ameliorating wall-stress and preserving the peri-infarct myocardium, antiarrhythmic actions were also evident after such treatment, but the precise underlying mechanisms remain poorly understood. The present article summarizes the acute and chronic actions of systemic and local growth hormone administration in the post-infarction setting, placing emphasis on the electrophysiologic effects. Experimental and clinical data are reviewed, and hypotheses on potential mechanisms of action are discussed. Such information may prove useful in formulating new research questions and designing new studies that are expected to increase the translational value of growth hormone therapy after acute myocardial infarction.

Growth hormone-releasing hormone agonists ameliorate chronic kidney disease-induced heart failure with preserved ejection fraction

“…Two-way ANOVA; P values are shown in the last column. Growth hormone-releasing hormone agonists ameliorate chronic kidney disease-induced heart failure with preserved ejection fraction reduction seen with GH therapy (31), was also seen with this GHRH analog; this is at present a poorly understood effect, and further studies will be conducted to elucidate underlying mechanisms.…”

Effectiveness of Growth Hormone–Releasing Hormone Agonists (GHRH-A) in Chronic Kidney Disease-Induced Heart Failure with Preserved Ejection Fraction

“…In a mouse model of HFpEF, GHRH-A inhibited cardiomyocyte sarcomere and contractile dysfunction, preventing Ca 2+ leak from the sarcoplasmic reticulum and improving sarcomere relaxation and calcium handling 9 . The anti-arrhythmogenic effect, independent of the scar reduction seen in GH therapy 18 , was also seen with this GHRH-analogue, a poorly understood effect. To our knowledge, this is the first study evaluating GHRH-A in a large animal model of HFpEF.…”

Left Ventricular Mass after Growth Hormone Replacement Therapy

“…It is debatable if GH can boost contractility. Studies have suggested that fractional shortening has increased, whereas others showed no change (25) .…”