Positron emission tomography and the changing paradigm in coronary artery disease.

While lowering cholesterol with HMG-CoA reductase inhibitors appears to affect little if at all the severity of coronary artery stenoses, at least over the time periods studied, it markedly reduces cardiac morbidity and mortality. The beneficial effects of these agents have therefore been attributed to plaque stabilization and improved coronary vasomotor function. This then has shifted the emphasis of detection and treatment of coronary artery disease from the assessment of structural to functional alterations.

Effects of dobutamine stimulation on myocardial blood flow, glucose metabolism, and wall motion in normal and dysfunctional myocardium.

Background: This investigation examines the effects of inotropic stimulation on myocardial blood flow (MBF) and glucose metabolism (MRGlc) in dysfunctional myocardium through the use of positron emission tomography (PET).

Methods And Results: Nineteen patients with chronic coronary artery disease and 12 normal volunteers were studied with 13N-ammonia, 18F-deoxyglucose, and PET and with two-dimensional echocardiography at baseline and during intravenous dobutamine (5 to 10 micrograms/kg per minute). At rest, MBF in mismatch regions (n = 10) averaged 0.

Coronary vasodilatory capacity is impaired in patients with dilated cardiomyopathy.

Increases in wall stress because of left ventricular enlargement and/or alterations in coronary vasomotor tone might affect myocardial blood flow and vasodilatory capacity in patients with dilated cardiomyopathy. To test this hypothesis myocardial blood flow was measured at rest and during intravenous administration of dipyridamole (0.56 mg/kg) using dynamic nitrogen 13-ammonia positron emission tomography (two-compartment model) in 10 patients with dilated cardiomyopathy (mean left ventricular ejection fraction 28 +/- 8% 1 woman, 9 men; 47 +/- 13 years of age).

Noninvasive quantification of myocardial blood flow in humans. A direct comparison of the [13N]ammonia and the [15O]water techniques.

Background: [13N]Ammonia has been validated in dog studies as a myocardial blood flow tracer. Estimates of myocardial blood flow by [13N]ammonia were highly linearly correlated to those by the microsphere and blood sample techniques. However, estimates of myocardial blood flow with [13N]ammonia in humans have not yet been compared with those by an independent technique.

6-[18F]fluoro-L-DOPA-PET studies show partial reversibility of long-term effects of chronic amphetamine in monkeys.

The acute and long-term effects of chronic amphetamine administration on the striatal dopamine system in monkeys were assessed with 6-[18F]fluoro-L-DOPA (FDOPA) and positron emission tomography (PET). Vervet monkeys (Cerecopithecus aethiops) were administered amphetamine doses, i.m.

The influence of aging on whole body choline release and clearance.

We have confirmed that hypoxia elicits a substantial rise in blood choline levels in young adult rats. An intravenous infusion of tracer quantities of [2H4]-Ch, serial measurements of blood [2H0]-Ch and [2H4]-Ch, and a simple pharmacokinetic model were used to assess the bidirectional flux of choline between the central pool and peripheral pools before, during and after a period of imposed hypoxia, in rats ranging from 56 to 780 days of age. The results indicate that the age-dependence of the hypercholinemic response to hypoxia is predominantly due to an increase in the amount of choline released in response to hypoxia, and that changes in its clearance are relatively unimportant.

Oxidation of N-hydroxyguanidine by nitric oxide and the possible generation of vasoactive species.

It has been reported previously that the N-hydroxyguanidine function of N-hydroxy-L-arginine can react with nitric oxide (NO) to generate other species that can act as potent vasodilators with different biological lifetimes than NO. The identities of these species have yet to be determined. Therefore, we have studied the reaction between NO and N-hydroxyguanidine and determined that N-hydroxyguanidine is capable of reducing NO to yield nitrous oxide (N2O) and possibly other nitroso species.

Effect of caffeine on myocardial blood flow at rest and during pharmacological vasodilation.

Unlabelled: Stress testing with intravenous injection of dipyridamole is frequently used for noninvasive detection of coronary artery disease (CAD) with PET or SPECT. Dietary intake of caffeinated food, beverages or medication might alter both resting and dipyridamole-induced hyperemic blood flow, thereby compromising the diagnostic sensitivity of dipyridamole stress testing.

Methods: To quantify the effect on myocardial blood flow at rest and during intravenous injection of dipyridamole, 12 healthy volunteers (mean age 27 +/- 6 yr) with low risk for CAD were studied with dynamic PET and a tracer kinetic model for 13N-ammonia after 24 hr of caffeine abstinence and after caffeine intake.