MONOAMINERGIC INNERVATION IN NORM VOLUNTEERS STUDIED W/ MYOCARDIAL PET IMAGING

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In the left ventricular wall of the human heart, large numbers of nerve fibers are interspersed between the heart's muscle cells. Impulses from the brain cause the nerves to release the neurotransmitter molecule norepinephrine from the nerve endings. When the norepinephrine molecules that are released from the nerves bind to special proteins in the heart muscle cells (called "receptors"), it causes the muscle cells to contract more rapidly and with greater force, leading to an increase in the amount of blood being pumped by the heart. After binding to the receptors, norepinephrine molecules are taken back up by the nerves for reuse, by another class of proteins called "transporters". The radioactive molecule [11C]meta-hydroxyephedrine (HED) is structurally similar to norepinephrine, so similar in fact that the transporters on the nerve endings also will take up HED molecules into the nerve endings. By injecting HED into a patient's bloodstream, and taking pictures of its accumulation into the nerves of the heart with a special imaging device known as a positron emission tomography (PET) camera, clinicians can obtain images that show whether the nerves of the heart have been damaged by disease. HED uptake in the heart will be high in regions where the nerves are normal and low in regions where the nerves have been damaged or destroyed. Many heart and neurological diseases have been found to cause damage to the nerves of the heart, including diabetes, congestive heart failure, myocardial infarction, and Parkinson's disease. Also, there is increasing evidence that damaged cardiac nerves may be an underlying cause to sudden cardiac death. Therefore there is great interest in increasing our understanding of the changes that occur to cardiac nerves in many different diseases. The primary objectives of this study are (1) to better characterize the uptake and retention of HED in normal healthy subjects; and (2) to investigate the dependence of HED on the age of the subject. By establishing a database of "normal" HED uptake levels in the hearts of healthy volunteers over a wide range of subject ages, we will be able to more accurately characterize the damage to cardiac nerves that is seen in many different diseases. Ultimately, a better understanding of the nerve damage in these diseases may lead to improved therapies for halting the progression of the disease, and possibly reversing the damage to cardiac nerve populations.'