Cardiac Energetics and Function in Normal Human Ageing

• Vascular Stiffness [ Time Frame: 2 Hours - Acute study with no follow-up ] [ Designated as safety issue: No ]
  There are 3 principal measures of vascular stiffness, and these are central pulse pressure, central systolic pressure, and the augmentation index. These are correlated against the 3 principal measures of left ventricular function and energetics that are known to change with age: torsion to shortening ratio, early to late diastolic filling ratio, and the ratio of phosphocreatine to adenosine triphosphate (listed as separate Primary Outcome Measures).
  
  
• Left Ventricular Energetics [ Time Frame: 2 hours - Acute Study, no follow-up ] [ Designated as safety issue: No ]
  Left ventricular energetics is measured as the ratio of phosphocreatine to adenosine triphosphate
  
  
• Left Ventricular Function [ Time Frame: 2 hours - Acute Study, no follow-up ] [ Designated as safety issue: No ]
  Left ventricular function is measured with the 2 parameters that are known to change with age: ratio of early to late diastolic filling, and ratio of torsion to shortening ratio.
  
  

• Effects of ACE inhibitor on left ventricular energetics and function in those subjects aged 40 and over [ Time Frame: 6 hours - Acute study, no follow-up ] [ Designated as safety issue: No ]
  A single dose of ACE inhibitor is given to reduce vascular stiffness, and we then measure the effects of this on the measures of left ventricular function and energetics which are the torsion to shortening ratio, diastolic early to late filling ratio, and the phosphocreatine to adenosine triphosphate ratio.
  
  

Normal aging is characterized by altered cardiovascular function. Our preliminary data with MR imaging and spectroscopy in normal subjects without cardiovascular disease or hypertension show that age-related cardiac dysfunction is characterized initially by diastolic dysfunction (40 - 60 years), and then at > 60 years altered systolic strains and impaired myocardial energetics. The investigators propose to study the mechanism of these findings in subjects with normal aging without any cardiovascular disease, hypothesizing that increased vascular stiffening contributes to impaired energetics and left ventricular function. For the first time, the investigators will test whether the functional and energetic effects of normal aging can be reversed by acutely reducing afterload using an ACE inhibitor. This will be tested at 2 ages (40-60 and > 60 years), so that the intervention tests the hypothesis soon after the abnormalities develop (40-60 years - diastolic dysfunction; > 60 years energetics and altered strains). This will potentially have important insights into how normal aging affects the heart, and how potential treatments could be used to attenuate this process.