Antiarrhythmic effects of growth hormone—in vivo evidence from small-animal models of acute myocardial infarction and invasive electrophysiology

Råmunddal, Truls; Gizurarson, Sigfús; Lorentzon, Mattias; Ömerovic, Elmir

doi:10.1016/j.jelectrocard.2007.09.002

Cited by 7 publications

(9 citation statements)

References 33 publications

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“…The surgical procedure for LCA ligation as demonstrated in this report is a reliable and reproducible method for induction of experimental MI in mice 3,6 . The ligation of LCA according to this protocol induces myocardial ischemia engaging typically ~40% of left ventricle 3 .…”

Section: Discussionmentioning

confidence: 87%

“…The ligation of LCA according to this protocol induces myocardial ischemia engaging typically ~40% of left ventricle 3 . This induces significant ECG changes in ST segment 7 and visible pallor on the anterior surface of the heart.…”

Section: Discussionmentioning

confidence: 99%

“…

Myocardial infarction (MI) is one of the most important causes of mortality in humans [1][2][3] . In order to improve morbidity and mortality in patients with MI we need better knowledge about pathophysiology of myocardial ischemia.

…”

mentioning

confidence: 99%

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Modified Technique for Coronary Artery Ligation in Mice

Shao

Redfors

Ömerovic

2013

JoVE

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Myocardial infarction (MI) is one of the most important causes of mortality in humans(1-3). In order to improve morbidity and mortality in patients with MI we need better knowledge about pathophysiology of myocardial ischemia. This knowledge may be valuable to define new therapeutic targets for innovative cardiovascular therapies(4). Experimental MI model in mice is an increasingly popular small-animal model in preclinical research in which MI is induced by means of permanent or temporary ligation of left coronary artery (LCA)(5). In this video, we describe the step-by-step method of how to induce experimental MI in mice. The animal is first anesthetized with 2% isoflurane. The unconscious mouse is then intubated and connected to a ventilator for artificial ventilation. The left chest is shaved and 1.5 cm incision along mid-axillary line is made in the skin. The left pectoralis major muscle is bluntly dissociated until the ribs are exposed. The muscle layers are pulled aside and fixed with an eyelid-retractor. After these preparations, left thoracotomy is performed between the third and fourth ribs in order to visualize the anterior surface of the heart and left lung. The proximal segment of LCA artery is then ligated with a 7-0 ethilon suture which typically induces an infarct size ~40% of left ventricle. At the end, the chest is closed and the animals receive postoperative analgesia (Temgesic, 0.3 mg/50 ml, ip). The animals are kept in a warm cage until spontaneous recovery.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Modified Technique for Coronary Artery Ligation in Mice

Shao

Redfors

Ömerovic

2013

JoVE

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“…Based on the previously demonstrated correlation between arrhythmogenesis and the extent of the ischemic myocardium in animal models [13], the hypothesis has been put forward that GH may confer antiarrhythmic actions during acute MI. This hypothesis was explored in two experimental studies in rats [14,15] investigating the effects of pre-treatment with GH on the incidence of post-MI VTs.…”

Section: Growth Hormone Confers Antiarrhythmic Actionsmentioning

confidence: 99%

Electrophysiologic Effects of Growth Hormone Post-Myocardial Infarction

Stamatis

Kontonika²,

Daskalopoulos

et al. 2020

IJMS

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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.

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“…The theory that GH is exerting an arrhythmogenic effect in the absence of myocyte hypertrophy seems uncertain, and, indeed, administration of GH has been associated with a reduced susceptibility to arrhythmia in animal models of myocardial infarction, albeit through uncertain mechanisms. 4,5 Unfortunately, our study was not specifically designed to address this question, and a carefully designed experiment within a suitable animal model of AN would be required to determine this definitively.…”

Section: In Responsementioning

confidence: 99%

Response by Padfield and Krahn to Letter Regarding Article, “Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa”

Padfield

Krahn

2016

Circulation

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In Response:We thank Aparci et al for their interest in our article 1 and for the interesting points they raise. We agree that the pathogenesis of ventricular arrhythmias in anorexia nervosa (AN) is likely to be multifactorial; however, the argument that excess growth hormone (GH) may be responsible for arrhythmogenesis in AN is not particularly convincing. The ability of growth hormone to increase muscle mass is well described, and myocyte hypertrophy is a characteristic finding in acromegaly. The observation of late potentials in acromegaly 2 is consistent with the action of GH on myocyte physiology and a plausible arrhythmogenic effect in this context. In contrast to acromegaly, myocardial muscle mass is characteristically decreased in AN because of malnutrition and hypotrophy. Although GH may be increased in AN, this is as a consequence of GH resistance 3 ; therefore, the biologic action of GH in this context is blunted. The theory that GH is exerting an arrhythmogenic effect in the absence of myocyte hypertrophy seems uncertain, and, indeed, administration of GH has been associated with a reduced susceptibility to arrhythmia in animal models of myocardial infarction, albeit through uncertain mechanisms.4,5 Unfortunately, our study was not specifically designed to address this question, and a carefully designed experiment within a suitable animal model of AN would be required to determine this definitively. DISCLOSURESNone. AFFILIATIONFrom University of British Columbia, Vancouver, BC, Canada.

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Antiarrhythmic effects of growth hormone—in vivo evidence from small-animal models of acute myocardial infarction and invasive electrophysiology

Cited by 7 publications

References 33 publications

Modified Technique for Coronary Artery Ligation in Mice

Modified Technique for Coronary Artery Ligation in Mice

Electrophysiologic Effects of Growth Hormone Post-Myocardial Infarction

Response by Padfield and Krahn to Letter Regarding Article, “Characterization of Myocardial Repolarization Reserve in Adolescent Females With Anorexia Nervosa”

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