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Attenuation of the responses to repeated cholinergic interventions in the isolated dog atrium
Abstract:
In the isolated, blood-perfused canine right atrium, which was pretreated with propranolol, negative chronotropic and inotropic responses were evoked by stimulation of the intramural parasympathetic nerve fibers or by intra-arterial infusion of acetylcholine (ACh). Successive cholinergic interventions were applied; first, a conditioning intervention for 2 min was given, then this was followed by a test intervention for 4 min. The two interventions were separated by a rest period that varied from 15 to 240 s. The cardiac responses to the conditioning parasympathetic nerve stimulation quickly reached maximum levels, and then they "faded" or progressively diminished back toward the control level. The inotropic responses to the conditioning infusion of ACh (1 microgram/min) faded slightly but the chronotropic response did not. After the rest period, the test nerve stimulation evoked responses that also gradually faded with time. The maximal amplitude of the responses to the test stimuli were less than those to the conditioning stimuli. This reduction in the maximal amplitude of the cardiac responses to the test stimuli was more pronounced with high frequency stimulation (30 Hz) than with low frequency stimulation (5 Hz). The decrement was also more pronounced the shorter the rest period, and it was greater at earlier times after beginning the stimulation. Conversely, the maximal cardiac responses to test infusions of ACh were not appreciably less than the responses to the conditioning infusions. We conclude, therefore, that the diminution of the cardiac responses to the second test stimulation of the parasympathetic nerve fibers was mainly ascribable to a prejunctional rather than to a postjunctional mechanism.
Insights
Parasympathetic nerve stimulation caused cardiac responses that faded over time. This fading was primarily due to prejunctional mechanisms, not postjunctional ones, affecting nerve fiber function.
Area of Science:
- Cardiovascular Physiology
- Autonomic Nervous System Function
Background:
- The autonomic nervous system regulates heart rate and contractility.
- Cholinergic signaling via acetylcholine (ACh) plays a key role in cardiac function.
Purpose of the Study:
- To investigate the mechanisms underlying the fading of cardiac responses to repeated parasympathetic nerve stimulation.
- To differentiate between prejunctional and postjunctional contributions to response decrement.
Main Methods:
- Isolated, blood-perfused canine right atrium preparation.
- Propranolol pretreatment to block beta-adrenergic effects.
- Stimulation of intramural parasympathetic nerve fibers and intra-arterial infusion of acetylcholine (ACh).
- Application of conditioning and test stimuli with varying rest periods.
Main Results:
- Cardiac responses to parasympathetic nerve stimulation exhibited fading, diminishing toward control levels.
- Responses to test nerve stimulation were less maximal than conditioning stimulation, especially at higher frequencies and shorter rest periods.
- Cardiac responses to acetylcholine infusion showed minimal fading, indicating a prejunctional mechanism for nerve stimulation response decrement.
Conclusions:
- The reduction in cardiac responses to repeated parasympathetic nerve stimulation is primarily mediated by prejunctional mechanisms.
- Postjunctional mechanisms do not significantly contribute to the observed fading of chronotropic and inotropic responses.