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.
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