Published descriptions of the topography of cardiac ganglia in the human heart are limited and present conflicting results. This study was carried out to determine the distribution of cardiac ganglia in adult human hearts and to address these conflicts. Hearts obtained from autopsies and heart transplant procedures were sectioned, stained, and examined. Results indicate that the largest populations of cardiac ganglia are near the sinoatrial and atrioventricular nodes. Smaller collections of ganglia exist on the superior left atrial surface, the interatrial septum, and the atrial appendage-atrial junctions. Ganglia also exist at the base of the great vessels and the base of the ventricles. The right atrial free wall, atrial appendages, trunk of the great vessels, and most of the ventricular myocardium are devoid of cardiac ganglia. These findings suggest modifications to surgical procedures involving incisions through regions concentrated with ganglia to minimize arrhythmias and related complications. Repairs of septal defects, valvular procedures, and congenital reconstructions, such as the Senning and Fontan operations, involve incisions through areas densely populated with cardiac ganglia. The current standard procedure for orthotopic heart transplantation severs cardiac ganglia and their projections to nodal and muscular tissue. One modification of the current heart transplantation procedure, involving bicaval anastomosis, preserves atrial anatomy and the cardiac ganglia. Preservation of cardiac ganglia within the donor heart may provide additional neuronal substrate for intracardiac processing and targets for regenerating nerve fibers to the donor heart.

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Aphids, among the most destructive insects to world agriculture, are mainly controlled by organophosphate insecticides that disable the catalytic serine residue of acetylcholinesterase (AChE). Because these agents also affect vertebrate AChEs, they are toxic to non-target species including humans and birds. We previously reported that a cysteine residue (Cys), found at the AChE active site in aphids and other insects but not mammals, might serve as a target for insect-selective pesticides. However, aphids have two different AChEs (termed AP and AO), and only AP-AChE carries the unique Cys. The absence of the active-site Cys in AO-AChE might raise concerns about the utility of targeting that residue. Herein we report the development of a methanethiosulfonate-containing small molecule that, at 6.0 µM, irreversibly inhibits 99% of all AChE activity extracted from the greenbug aphid (Schizaphis graminum) without any measurable inhibition of the human AChE. Reactivation studies using β-mercaptoethanol confirm that the irreversible inhibition resulted from the conjugation of the inhibitor to the unique Cys. These results suggest that AO-AChE does not contribute significantly to the overall AChE activity in aphids, thus offering new insight into the relative functional importance of the two insect AChEs. More importantly, by demonstrating that the Cys-targeting inhibitor can abolish AChE activity in aphids, we can conclude that the unique Cys may be a viable target for species-selective agents to control aphids without causing human toxicity and resistance problems.

Background-Cardiac ganglia were originally thought to contain only cholinergic neurons relaying parasympathetic information from preganglionic brain stem neurons to the heart. Accumulating evidence, however, suggests that cardiac ganglia contain a heterogeneous population of neurons that synthesize or respond to several different neurotransmitters and neuropeptides. Reports regarding monoamine and histamine synthesis and neurotransmission within cardiac ganglia, however, present conflicting information or are limited in number. Furthermore, very few studies have examined the neurochemistry of adult human cardiac ganglia. The purpose of this study was, therefore, to determine whether monoamine-and histamine-synthesizing enzymes and neurotransmitters exist within neurons of adult human cardiac ganglia. Methods and Results-Human heart tissue containing cardiac ganglia was obtained during autopsies of patients without cardiovascular pathology. Avidin-biotin complex immunohistochemistry was used to demonstrate tyrosine hydroxylase, L-dopa decarboxylase, dopamine ␤-hydroxylase, phenylethanolamine-N-methyltransferase, tryptophan hydroxylase, and histidine decarboxylase immunoreactivity within neurons of cardiac ganglia. Dopamine, norepinephrine, serotonin, and histamine immunoreactivity was also found in ganglionic neurons. Omission or preadsorption of primary antibodies from the antisera and subsequent incubation with cardiac ganglia abolished specific staining in all cases examined. Conclusions-Our results suggest that neurons within cardiac ganglia contain enzymes involved in the synthesis of monoamines and histamine and that they contain dopamine, norepinephrine, serotonin, and histamine immunoreactivity. Our findings suggest a putative role for monoamine and histamine neurotransmission within adult human cardiac ganglia. Additional, functional evidence will be necessary to evaluate what the physiological role of monoamines and histamine may be in neural control of the adult human heart. (Circulation. 1999;99:411-419.)