Surgical technology is now available for selective denervation of restricted portions of the heart such as the sinoatrial (SAN) or atrioventricular (AVN) nodal regions. Parasympathectomy of either of these regions has been accomplished in the canine heart. Preliminary experience with such denervation procedures indicates that such models can be prepared and instrumented permitting testing of physiologic (baroreceptor, chemoreceptor, exercise, respiratory) reflexes in the alert, conscious dog. This proposal is to implant bipolar electrodes upon the right atrium and ventricle and record activation potentials together with electrocardiogram, blood pressure, and respiratory movements while the conscious animal stands comfortably in a Pavlov Stand. Responses to graded doses of phenyleprine and nitroglycerine will be examined pre- and postoperatively, as will responses to bilateral carotid occlusion, nostril clamping, and mild to strenuous exercise. The operative procedures are intrapericardial and involve successive dissections around the superior vena cava (SVC) and its junction with the right atrium (RA), transection of the azygos vein, and dissection of the pulmonary vein complex. These procedures selectively ablate the vagal input to the SAN region. In contrast, dissection of the atrioventricular nodal (AVN) region may be accomplished by dissection of the fat pad at the junction of inferior vena cava and inferior left atrium. In both of these preparations, the sympathetic supplies to the heart remain essentially intact. Thus, it is anticipated that we shall be able to selectively isolate automatic (SAN) from conductile (AVN) regions in the chronic dog preparation and test the relative controls exerted by neural mechanisms upon these two vitally important regulatory systems. Direct implications for human cardiovascular disease control are indicated by numerous patients with neurally involved dysrhythmias, spontaneous and debilitating heart block, partial cardiac denervation related to pathophysiologic disturbances, tachdysrhythmias, atrial fibrillation, etc. Information is available for comparable sympathectomy of both SAN or AVN regions, but such preparations have not yet been achieved. They will be pursued during the tenure of this grant, and this chronic model will then become available for comparable study. It is anticipated that such conscious animals will provide valuable study models for achievement of better understanding of autonomic balance and imbalance in the mammalian heart.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Cardiovascular Study Section (CVA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Loyola University Chicago
Schools of Medicine
United States
Zip Code
Singh, Sanjay; Sayers, Scott; Walter, James S et al. (2013) Hypertrophy of neurons within cardiac ganglia in human, canine, and rat heart failure: the potential role of nerve growth factor. J Am Heart Assoc 2:e000210
Jeong, S W; Ikeda, S R; Wurster, R D (1999) Activation of various G-protein coupled receptors modulates Ca2+ channel currents via PTX-sensitive and voltage-dependent pathways in rat intracardiac neurons. J Auton Nerv Syst 76:68-74
Singh, S; Johnson, P I; Javed, A et al. (1999) Monoamine- and histamine-synthesizing enzymes and neurotransmitters within neurons of adult human cardiac ganglia. Circulation 99:411-9
Jeong, S W; Wurster, R D (1997) Muscarinic receptor activation modulates Ca2+ channels in rat intracardiac neurons via a PTX- and voltage-sensitive pathway. J Neurophysiol 78:1476-90
Jeong, S W; Wurster, R D (1997) Calcium channel currents in acutely dissociated intracardiac neurons from adult rats. J Neurophysiol 77:1769-78
Wehrmacher, W H (1995) The dual challenge of electric injury. Compr Ther 21:308-12
Xi, X; Randall, W C; Wurster, R D (1994) Electrophysiological properties of canine cardiac ganglion cell types. J Auton Nerv Syst 47:69-74
Randall, W C; Burden, S L (1992) A faculty research and training program for undergraduates in the sciences. Am J Physiol 263:S3-6
Randall, D C; Randall, W C; Brown, D R et al. (1992) Heart rate control in awake dog after selective SA-nodal parasympathectomy. Am J Physiol 262:H1128-35
Randall, W C; Kroeker, T; Hotmire, K et al. (1992) Baroreflex responses to the stress of severe hemorrhage in the rat. Integr Physiol Behav Sci 27:197-208

Showing the most recent 10 out of 39 publications