H R Schelbert

Influence of age and hemodynamics on myocardial blood flow and flow reserve.

BackgroundAging is associated with changes of the systolic blood pressure that may increase cardiac work and myocardial blood flow at rest and reduce the myocardial flow reserve. This might be misinterpreted as age-related impairment of the coronary vasodilator capacity. Methods and ResultsMyocardial blood flow was quantified at rest and after administration of intravenous dipyridamole in 40 healthy volunteers (12 women and 28 men) with 13N-ammonia and positron emission tomography. Eighteen of the normal subjects were less than and 22 were older than 50 years (31G

N-13 ammonia as an indicator of myocardial blood flow.

9 versus 64

Regional perfusion, glucose metabolism, and wall motion in patients with chronic electrocardiographic Q wave infarctions: evidence for persistence of viable tissue in some infarct regions by positron emission tomography.

9 years). The resting rate-pressure product was lower in the younger than in the older subjects (6895

Quantification of regional myocardial blood flow using 13N-ammonia and reoriented dynamic positron emission tomographic imaging.

1070 versus 8634+1890; p<0.01). Myocardial blood flow at rest averaged 0.76

Validation of [1-11C]acetate as a tracer for noninvasive assessment of oxidative metabolism with positron emission tomography in normal, ischemic, postischemic, and hyperemic canine myocardium.

0.17 mL min1 g1 in the younger volunteers and 0.92

Noninvasive quantitation of regional myocardial oxygen consumption in vivo with [1-11C]acetate and dynamic positron emission tomography.

0.25 mL. min1 g1 in the older volunteers (p< 0.05). Hyperemic blood flows did not differ between younger and older subjects (3.0+0.8 versus 2.7

Regional myocardial oxygen consumption determined noninvasively in humans with [1-11C]acetate and dynamic positron tomography.

0.6 mL* min1 g-1 p=NS); however, minimal coronary resistance was higher in the older subjects. Corrected for indexes of coronary driving pressure, hyperemic flow was lower in older than in younger normal subjects. The higher resting blood flows combined with similar hyperemic flows resulted in a lower myocardial flow reserve in the older than in the younger normal subjects (4.1

Left ventricular geometry and function in adults with Ebstein's anomaly of the tricuspid valve.

0.9 versus 3.0+0.70; p< 0.0001). The flow reserve was more closely correlated with resting than with hyperemic blood flows. ConclusionsAging does not alter significantly dipyridamole-induced hyperemic flows; although coronary vascular resistance after dipyridamole was somewhat increased in older subjects. The gradual decline of the myocardial blood flow reserve correlates with an age-related increase of baseline myocardial work and blood flow. These findings suggest that the reduced flow reserve with age is primarily due to increased cardiac work and blood flow at rest rather than to an abnormal vasodilator capacity.

Positron emission tomography detects metabolic viability in myocardium with persistent 24-hour single-photon emission computed tomography 201Tl defects.

We have characterized N-13 ammonia as a myocardial blood flow imaging agent suitable for positron-emission computed tomography. However, the mechanisms of uptake and retention of this agent in myocardium are not known, and effects of altered metabolism were not considered. Therefore, we studied the uptake and retention of N-13 ammonia in myocardium under various hemodynamic and metabolic conditions in open-chest dogs. N-13 ammonia was extracted nearly 100% during its initial capillary transit, followed by metabolic trapping that competed with flow-dependent back diffusion. At control flows, the first capillary transit extraction fraction (E) of N-13 ammonia averaged 0.82 ± 0.06. It fell with higher flows by E = 1 − 0.607 exp − 125/F. Myocardial N-13 tissue clearance half-times were similarly inversely related to blood flow, and ranged from 110–642 minutes. Cardiac work and changes in the myocardial inotropic state induced by isoproterenol and propranolol did not affect E or the tissue clearance half-times. Low plasma pH reduced E by an average of 20%, while elevated plasma pH had no effect. Decreases in flow below control also were associated with a fall in E. Inhibition of glutamine synthetase with L-methionine sulfoximine impaired metabolic trapping of N-13 ammonia and implicates the glutamic acid-glutamine reaction as the primary mechanism for ammonia fixation. The product of E times flow predicts the myocardial N-13 tissue concentrations, which increased by 70% when flow was doubled. Thus, blood flow and metabolic trapping are the primary determinants of myocardial uptake and retention of N-13 ammonia. The relative constancy of metabolic trapping over a wide range of hemodynamic and metabolic conditions demonstrates the value of N-13 ammonia as a myocardial blood flow imaging agent.

Myocardial blood flow at rest and during pharmacological vasodilation in cardiac transplants during and after successful treatment of rejection.

Positron-emission tomography with 13N-ammonia and 18F-2-deoxyglucose was used to assess regional perfusion and glucose utilization in 31 chronic electrocardiographic Q wave regions in 20 patients. With previously published criteria, regions of infarction were identified by a concordant reduction in regional perfusion and glucose utilization, and regions of ischemia were identified by preservation of glucose utilization in regions of diminished perfusion. Only 10 of the 31 regions (32%) exhibited myocardial infarction tomographically. In contrast, positron tomography revealed ischemia in six regions (20%) and was normal in 15 regions (48%). Even when Q wave regions were reassigned and consolidated to enhance the specificity of the electrocardiogram, uptake of 18F-2-deoxyglucose was noted in the majority (54%) of the regions. Neither electrocardiographic ST-T changes nor severity of associated wall motion abnormality reliably distinguished tomographically identified regions of ischemia from infarction. Thus positron tomography reveals evidence of persistent tissue metabolism in a high proportion of chronic electrocardiographic Q wave regions, and commonly used clinical tests do not reliably distinguish hypoperfused but viable regions from tomographically defined regions of myocardial infarction.