Search

Regional differences in cholinergic activity in the cardiac conduction system have been difficult to study. We tested the utility of (+)-m-[125I]iodobenzyl)trozamicol(+)-[125I]MIBT), a novel radioligand that binds to the vesamicol receptor located on the synaptic vesicle in presynaptic cholinergic neurons, as a functional marker of cholinergic activity in the conduction system. The (+)-[125I]MIBT was injected intravenously into four rats. Three hours later, the rats were killed and their hearts were frozen. Quantitative autoradiography was performed on 20-micron-thick sections that were subsequently stained for acetylcholinesterase to identify specific conduction-system elements. Marked similarities existed between (+)-[125I]MIBT uptake and acetylcholinesterase-positive regions. Optical densitometric analysis of regional (+)-[125I]MIBT uptake revealed significantly greater (+)-[125I]MIBT binding (nCi/mg) in the atrioventricular node (AVN) and His bundle regions compared with other conduction and contractile elements (AVN: 3.43 +/- 0.37; His bundle: 2.16 +/- 0.30; right bundle branch: 0.95 +/- 0.13; right atrium: 0.68 +/- 0.05; right ventricle: 0.57 +/- 0.03; and left ventricle: 0.57 +/- 0.03; p < 0.05 comparing conduction elements with ventricular muscle). This study demonstrates that (+)-[125I]MIBT binds avidly to cholinergic nerve tissue innervating specific conduction-system elements. Thus, (+)-[125I]MIBT may be a useful functional marker in studies on cholinergic innervation in the cardiac conduction system.

Although previous studies have suggested that aging results in an increase in vascular stiffness, diseases that increase in prevalence with advanced age may have confounded the results of some of this past research. The purpose of this investigation was to determine whether aging per se results in reduced arterial compliance by using animals that are resistant to atherosclerosis and do not develop hypertension or hyperlipidemias with advanced age. We evaluated systemic and regional (femoral) arterial compliance in older (110 ± 8 months old) and in younger (27 ± 2 months old) female beagle dogs by using a computer-based assessment of the diastolic decay of arterial pressure waveforms and a modified Windkessel model of the circulation. Although systemic arterial pressure was very similar in both age groups, cardiac output was 29% lower ( p = 0.03) and systemic vascular resistance was 24% higher ( p = 0.02) in the older dogs. Moreover, there was an age-related reduction in systemic arterial compliance, derived both from the exponential decay in the arterial pulse (C 1 ) ( p = 0.05) and that derived from the oscillatory component of the diastolic pulse wave (C 2 ) ( p = 0.04). By contrast, although femoral vascular resistance was 25% higher in the older dogs ( p = 0.04), regional (femoral) vascular compliance measured after femoral arterial occlusion was also 25% reduced but was not significantly changed with age ( p = 0.14). These results demonstrate that systemic arterial compliance is reduced with age in dogs, extending this finding to animals without age-related diseases that frequently occur in older human beings. Regional compliance, evaluated in the isolated femoral vascular bed, also tends to be reduced with age, but variability in this parameter in dogs reduces the significance of this finding.

Aging significantly affects reflex cardiovascular (CV) responses to induced muscular contraction in anesthetized dogs. To further investigate whether age-related changes in beta-adrenergic responsiveness contribute to these previously reported changes in reflex CV responses associated with advanced age, hemodynamic and regional blood flow (BF) responses to static hindlimb contraction (HLC) were evaluated during alpha-chloralose anesthesia before and after beta-adrenergic blockade (AB) in younger (2-3 years) and older (8-14 years) beagles. AB with propranolol resulted in significant (Por = 0.05) reductions in cardiac output, heart rate and mean arterial pressure at baseline, regardless of age. However, baseline stroke volume and systemic vascular resistance were only changed by AB in the older dogs. During HLC, AB had a similar effect (or lack of effect) on each of the five hemodynamic responses evaluated in both age groups. AB did not significantly change baseline BF (microspheres) to any of the individual abdominal organs evaluated in the younger dogs, but resulted in a reduction in baseline BF to five of eight abdominal organs in the older dogs. By contrast, AB resulted in attenuated, rather than accentuated, BF reductions during HLC to six of eight abdominal organs in the younger dogs but in only one of eight abdominal organs in the older dogs. Likewise, the combined BF reduction to all eight abdominal regions during HLC was attenuated only in the younger dogs, probably reflecting age-related changes in reflex sympathetic nerve responses to HLC rather than the effects of age on beta-adrenergic mediated CV responses. Baseline BF was reduced in three of eight muscles after AB only in the older beagles. However, the BF response to three of four contracting muscles was unchanged after AB, regardless of age. These results demonstrate that baseline differences in the level of beta-adrenergic stimulation and/or function in younger and older dogs are generally not associated with age-related differences in CV responses to HLC initiated in contracting muscles and mediated by reflex beta-adrenergic CV stimulation.