Age-related decline of PCr/ATP-ratio in progressively hypertrophied heartsof spontaneously hypertensive rats

Although the ultimate cause for the myocardial dysfunction of hypertensive heart disease is still unclear, a crucial role of the myocardial energy met abolism has been suggested. Therefore, the aim of the present study was to investigate whether age-related myocardial dysfunction in hearts of spontan eously hypertensive rats (SHR) is associated with an impaired myocardial en ergy metabolism. Isolated hearts of SHR and Wistar Kyoto rats (WKY) aged ab out 40, 60, and 80 weeks, respectively teach n = 4-5), were perfused accord ing to the working heart technique. Cardiac work and coronary flow were mon itored online. Myocardial energy metabolism was evaluated by calculating th e ratio of phosphocreatine (PCr) and adenosine triphosphate (ATP) which wer e measured by nuclear magnetic resonance (P-31-NMR) spectroscopy. All heart s were subjected to work for 30min at baseline conditions (low afterload), followed by another 30 min under a moderate pressure load thigh afterload). Each SHR group showed a higher heart weight/body weight ratio than the age -matched WKY controls. The SHR showed a progressive age-dependent reduction of cardiac work (40 weeks = 5.1 +/- 0.3, 60 weeks = 4.0 +/- 0.3, 80 weeks = 3.8 0.2 (mW/g) at baseline conditions) and PCr/ATP-ratio (40 weeks = 1.82 +/- 0.06, 60 weeks = 1.69 +/- 0.05, 80 weeks = 1.59 +/- 0.09 (PCr/ ATP) at baseline conditions). Similar results were found for hearts of SHR at high afterload. In WKY no significant decline in cardiac work or PCr/ATP-ratio was found under either low or under high afterload. The cardiac work capaci ty of hearts of SHR progressively decreases with increasing age and left ve ntricular hypertrophy. This myocardial dysfunction is closely associated wi th an impaired PCr/ ATP-ratio, suggesting a decreased energy reserve.