Pharmacological modulation of early postinfarction remodelling
Farmacologische modulatie van vroege postinfarct remodeling
The response to acute myocardial infarction can be divided into different phases: 1. Acute myocardial infarction induces a sudden decrease of cardiac output related to the size of infarcted area. 2. CompeasatoN phase: A decreased cardiac output evokes activation of compensatory mechanisms, such as the sympathetic nervous system and reninangiotensin- aldosterone sytem. If these mechanisms cannot bring cardiac output back to acceptable levels, structural changes in the heart called hypertrophy and remodeling will follow. 3. Compensated ohase: A relatively stabile phase with (partly) restored cardiac output but with decreased left ventricular function and ejection fraction has been established; a stage compensated heart failure, in which patients are often not recognized. 4. Decompensation ohase: When symptoms of heart failure become overt, decompensation develops driven by the same mechanisms as in the previous phases, but with a very poor prognosis. Therapy during the different phases require different strategies. During phase 1 the objective of therapy is to limit infarct size by establishing reperfusion as quick as possible. Then, theoretically, phase 2 requires stimulation, phase 3 stabilization and support, and phase 4 inhibition of the same ongoing processes. Although still patients at stage 4 are clinically the most important ones, inclination towards earlier intervention is growing. The problem that may arise, however, is that earlier treatment, especially at stage 2 is aimed at the opposite direction as the later therapy. This problem is substantiated by the results of the 2 CONSENSUS trials, where delayed ACE-inhibitor ( enalapril) treatment had clearly beneficial effects (CONSENSUS I), whereas similar treatment during early phases had detrimental effects (CONSENSUS 11)91 • Pharmacological research has mainly focused on stage 4 when congestive heart failure is diagnosed and prognosis becomes very poor. Except for treatment with ACE-inhibitors, prognosis has not benefited substantially from all these research. During this stage, cardiac hypertrophy and remodeling have become a major target for therapy since they are associated with improved prognosis 112• When treatment should be started earlier, that is with ventricular dysfunction but before signs of heart failure, it implies interference with cardiac hypertrophy and remodeling, which during the early phase are regarded a pathophysiological response to compensate for the loss of contractile tissue. This indicates that treatment should therefore be selected carefully 81•91• Thus, although the importance of treatment during the comoensatorv stage is now well acknowledged, a strategy is not established yet.
|P.R. Saxena (Pramod Ranjan)|
|Erasmus University Rotterdam|
|Financial support by the Netherlands Heart Foundation (subsidienummer 2002 P028) for the publication of this thesis is gratefully acknowledged. Financial support of the following institutions and companies is gratefully acknowledged: Erasmus Medical Centre Rotterdam, Skalar Medical BV, GlaxoSmithKiine BV, Sanofi-Synthelabo Recherche Montpellier|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
van Kerckhoven, R. (2002, June 20). Pharmacological modulation of early postinfarction remodelling. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/31939