Nitrates and Left Ventricular Remodeling
Section snippets
Pathophysiology of Ventricular Remodeling
Ventricular remodeling refers to the changes in structure and shape associated with myocardial damage. Left ventricular remodeling after myocardial infarction is a complex and dynamic process. It involves progressive changes in shape, volume, and mass, which frequently aggravate dysfunction, especially after large anterior transmural or Q-wave infarction.11, 14, 15, 26, 27, 28, 29, 30Evidence from several laboratories1, 2, 22underscores 5 important points about ventricular remodeling. First, it
Limitation of Ventricular Remodeling
The major determinants of ventricular remodeling (Table III ) include infarct size, loading conditions (mechanical deformation forces and wall stress), integrity of the supporting collagen framework, and adequacy of the healing process. Several potential therapies (Table IV ) can be directed at the determinants (Fig. 2) .1, 2, 9Appropriate timing and choice of the therapies according to the stage of progression2, 22can potentially interrupt, prevent, or reverse the vicious cycle of remodeling.
Nitrates for Limitation of Early Ventricular Remodeling
The mechanisms for the cardioprotective effects of nitrates have been reviewed elsewhere.23, 24, 103Briefly, nitrate-induced vasodilation of venous, arterial, and coronary beds results in decreased preload, afterload, and impedance, and enhanced myocardial perfusion that leads to improved ventricular geometry and myocardial energetics in acute infarction.
Nitrate-induced increase in prostacyclin and decrease in platelet adhesiveness contribute in improving perfusion. Several experimental3, 4, 104
Nitrates for Limitation of Late Ventricular Remodeling
Although prolonged vasodilator therapy is a logical approach for preventing progressive ventricular remodeling after myocardial infarction, the development of tolerance with chronic application of nitrates is a major limitation. However, tolerance can be minimized by intermittent or eccentric administration of nitrates, or use of less tolerance-prone preparations such as isosorbide-5-mononitrate.129, 130Using these approaches, cardioprotection and antiremodeling effects were achieved during
Conclusions
The prevention or limitation of left ventricular remodeling and preservation of left ventricular function are primary goals of antiremodeling therapy. During acute myocardial infarction, nitrates, alone or as an adjunct to thrombolytic therapy, can effectively limit early left ventricular remodeling. Prolonged vasodilator therapy after myocardial infarction can prevent late remodeling. However, the effectiveness of prolonged nitrate administration for preventing late ventricular remodeling is
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