Editorial: Defining The Relationship Between Akinesia And Dyskinesia And The Cause Of Left Ventricular Failure After Anterior Infarction And Reversal Of Remodeling To Restoration

AbstractJ Thorac Cardiovasc Surg 1998;116:47-

Left Ventricular Form and Function - Scientific Priorities and Strategic Planning for Development of New Views of Disease

Heart failure continues to be one of the most costly and prevalent medical problems. The increasing age of our population and the increased survival of patients with diseases that lead to heart failure will no doubt further magnify this very serious health problem at a staggering cost, both monetary and human. To address this public health concern, a fuller understanding of what constitutes normal cardiac function is essential to recognize optimal goals for restoration after disease disrupts stability. From micro to macro, our limited understanding of the heart’s function continues to represent an obstacle to our ability to design strategies for effective treatment of heart failure. Thus, there is a critical need to address the existing and emerging issues in this area to develop new safe and effective strategies to address the clinical challenges facing cardiologists and cardiothoracic surgeons. As a result of this need, the National Heart, Lung, and Blood Institute convened a workshop entitled “Form and Function: New Views on Development, Diseases, and Therapies for the Heart” on April 25 to 26, 2002, in Bethesda, Maryland. The objective was an effort to understand the importance of structure/function relationships of the intact ventricles from both the basic science and clinical perspectives, to define where progress is most urgently needed, and to plan research programs that will most effectively integrate understanding of functional geometry into therapy of human heart disease

Studies of hypoxemic/reoxygenation injury: With aortic clamping XIII. Interaction between oxygen tension and cardioplegiccomposition in limiting nitric oxide production and oxidant damage

AbstractThis study tests the interaction between oxygen tension and cardioplegic composition on nitric oxide production and oxidant damage during reoxygenation of previously cyanotic hearts. Of 35 Duroc-Yorkshire piglets (2 to 3 weeks, 3 to 5 kg), six underwent 30 minutes of blood cardioplegic arrest with hyperoxemic (oxygen tension about 400 mm Hg), hypocalcemic, alkalotic, glutamate/aspartate blood cardioplegic solution during 1 hour of cardiopulmonary bypass without hypoxemia (control). Twenty-nine others were subjected to up to 120 minutes of ventilator hypoxemia (oxygen tension about 25 mm Hg) before reoxygenation on CPB. To simulate routine clinical management, nine piglets underwent uncontrolled cardiac reoxygenation , whereby cardiopulmonary bypass was started at oxygen tension of about 400 mm Hg followed by the aforementioned blood cardioplegic protocol 5 minutes later. All 20 other piglets underwent controlled cardiac reoxygenation , whereby cardiopulmonary bypass was started at the ambient oxygen tension (about 25 mm Hg), and reoxygenation was delayed until blood cardioplegia was given. The blood cardioplegia solution was kept normoxemic (oxygen tension about 100 mm Hg) in 10 piglets and made hyperoxemic (oxygen tension about 400 mm Hg) in 10 others. The cardioplegic composition was also varied so that the cardioplegic solution in each subgroup contained either KCl only (30 mEq/L) or components that theoretically inhibit nitric oxide synthase by including hypocalcemia, alkalosis, and glutamate/aspartate. Function (end-systolic elastance) and myocardial nitric oxide production, conjugated diene production, and antioxidant reserve capacity were measured. Blood cardioplegic arrest without hypoxemia did not cause myocardial nitric oxide or conjugated diene production, reduce antioxidant reserve capacity, or change left ventricular functional recovery. In contrast, uncontrolled cardiac reoxygenation raised nitric oxide and conjugated diene production 19- and 13-fold, respectively ( p < 0.05 vs control), reduced antioxidant reserve capacity 40%, and contractility recovered only 21% of control levels. After controlled cardiac reoxygenation at oxygen tension about 400 mm Hg with cardioplegic solution containing KCl only, nitric oxide and conjugated diene production rose 16- and 12-fold, respectively ( p < 0.05 vs control), and contractility recovered only 43% ± 5%. Normoxemic (oxygen tension of about 100 mm Hg) controlled cardiac reoxygenation with the same solution reduced nitric oxide and conjugated diene production 85% and 71%, and contractile recovery rose to 55% ± 7% ( p < 0.05 vs uncontrolled reoxygenation). In comparison, controlled cardiac reoxygenation with an oxygen tension of about 400 mm Hg hypocalcemic, alkalotic, glutamate/aspartate blood cardioplegic solution reduced nitric oxide and conjugated diene production 85% and 62%, respectively, and contractility recovered 63% ± 4% ( p < 0.05 vs KCl only). Normoxemic delivery of this solution resulted in negligible nitric oxide and conjugated diene production and 83% ± 8% recovery of contractility ( p < 0.05 vs all other groups). These data show correlation between nitric oxide production during initial reoxygenation and the extent of oxidant damage (i.e., conjugated diene production) and link functional recovery to suppression of excessive nitric oxide production and limitation of lipid peroxidation by the interaction of oxygen tension and cardioplegic composition during initial reoxygenation. (J THORAC CARDIOVASC SURG 1995; 110:1274-86