Variations in atrioventricular valve innervation in four species of mammals

Abstract In this series of studies, the innervation patterns of whole‐mount preparation of bicuspid and tricuspid valves were studied by light microscopy in the mouse, rat, guinea pig, and opossum. The acetylcholinesterase‐positive networks of nerve fibers showed many similarities in the basic patterns of valve innervation in all of the species studied, but several interspecies variations were observed. The basal zone of the valve adjacent to the fibromuscular atrioventricular ring displayed the most dense plexus of nerves, with acetylcholinesterase‐positive fibers being seen across the width of the valve. In the intermediate zone of the valve, less dense plexuses of nerve fibers were found; and these were more numerous in the cuspal areas and less numerous in the intervening commissural areas. In the distal portions of the valve, nerve networks arborized extensively, with some of their nerve fibers extending toward the chordae tendineae and the free edges of the valve cusps. Only in the guinea pig and opossum did these fibers reach the free margin of the valve cusp, where they either ended directly as free nerve endings or lay parallel to the free edge of the cusp, often running between adjacent chordae tendineae. Although the patterns of innervation were similar in both bicuspid and tricuspid valves, the innervation density of the bicuspid valve was greater than that of the tricuspid valve for each species examined. A distinguishing feature of guinea pig and opossum tricuspid valves was that their chordae tendineae were relatively more prominent and more densely innervated than the bicuspid chordae tendineae. Free nerve endings with no light microscopic evidence of specialization were present throughout the bicuspid and tricuspid valves of all species studied. Some nerve endings in the opossum showed evidence of specialization, with brush‐like arborizations leading to presumed free terminals seen chiefly in the distal zone of the valve cusps. Although some general tendencies were apparent, we have demonstrated that interspecies heterogeneity exists in the terminal networks of the atrioventricular valves of mouse, rat, guinea pig, and opposum. In spite of the questions raised regarding the significance of valve innervation in light of the success of valve prostheses, there is relatively high morbidity and mortality associated with heart valve replacement, partly due to deterioration in ventricular function. We and other investigators have reported that valvar nerves extend to the chordae and papillary muscles, varying with valve and species. This anatomical information about normal valves helps to lay the foundation for future studies of the role of valve innervation in the regulation of cardiac function and dysfunction. Such knowledge should be applicable for the control and management of myocardial infarction, valve disease, valve replacement, valvuloplasty, cardiac transplantation, administration of drugs, etc.