Related Experiment Videos
[Transition of myocardial ischemia to heart failure]
G Ertl1, D Fraccarollo, P Gaudron
1II. Medizinische Klinik, Fakultät für Klinische Medizin Mannheim, Universität Heidelberg. georg.ertl@med2.ma.uni-heidelberg.de
Insights
Myocardial ischemia causes heart dysfunction, leading to heart failure through stunning, hibernation, or necrosis. Adaptive changes in the heart involve hemodynamic, neurohumoral, and structural alterations.
Area of Science:
- Cardiology
- Pathophysiology
- Molecular Biology
Context:
- Myocardial ischemia leads to impaired heart function, progressing to chronic heart failure.
- Adaptive cardiac remodeling, including hypertrophy and dilatation, occurs in response to ischemia.
- The interplay between hemodynamic, neurohumoral, and structural changes is central to heart failure development.
Purpose:
- To elucidate the complex pathophysiology of myocardial ischemia and its contribution to chronic heart failure.
- To highlight the interconnectedness of hemodynamic, neurohumoral, and structural cardiac modifications.
- To underscore the significance of molecular mechanisms in cardiac adaptation and disease progression.
Summary:
- Myocardial ischemia induces dysfunction, potentially leading to stunning, hibernation, or necrosis, all contributing to heart failure.
- Adaptive processes like hypertrophy and dilatation in non-ischemic myocardium also drive chronic left heart failure.
- Heart failure involves interrelated hemodynamic (e.g., increased filling pressure, reduced ejection fraction), neurohumoral (e.g., catecholamines, renin-angiotensin-system activation), and structural changes (e.g., cardiac remodeling).
- Impaired vascular endothelium function and elevated endothelin-1 levels are observed in heart failure.
- Research into the molecular control of these cellular processes, involving cardiomyocytes and cardiofibroblasts, holds therapeutic potential.
Impact:
- Provides a comprehensive overview of the pathophysiology of ischemic heart disease and heart failure.
- Identifies key molecular and cellular targets for future therapeutic interventions.
- Enhances understanding of the progression from myocardial ischemia to chronic heart failure.
Abstract:
Myocardial ischemia results in myocardial dysfunction. Recovery may be delayed ("stunning"), or persistent if perfusion remains reduced ("hibernation") and ischemia may go on to necrosis, thus, contributing to chronic heart failure. In addition, myocardium not directly affected by ischemia may undergo adaptive processes like hypertrophy and dilatation, which may result in chronic left heart failure. This process is characterized by hemodynamic, neurohumoral, and progressive morphologic changes of the heart which are closely interrelated. Hemodynamic changes basically consist of an increase in left ventricular filling pressure and a decrease in global ejection fraction, and, in most cases years after myocardial infarction, in an increase in systemic vascular resistance and right atrial pressure. Neurohumoral changes consist of an increase in plasma catecholamines, atrial natriuretic factor and vasopressin, and in an activation of the renin-angiotensin-system. Plasma endothelin-1 was recently reported to be increased in patients with heart failure, and prognosis was related to endothelin levels. Diminished response of vessels to endothelium (EDRF/NO) dependent vasodilatation suggests impairment of vascular endothelium in heart failure. Local changes of cardiac neurohumoral systems could contribute to structural changes of the heart, e.g., systemic activation to hemodynamic changes. Structural changes of the heart are characterized by an increase in volume and thickness of surviving myocardium and an expansion of ischemic and necrotic myocardium. Molecular control of these processes which include various cell types, such as cardiomyocytes and cardiofibroblasts, are currently an issue of intense research and could result in specific therapeutic importance.