Related Experiment Videos
Pharmacological mechanisms to attenuate sympathetically induced myocardial ischemia
1Abteilung für Herz-und Kreislaufphysiologie, Universität Düsseldorf, Federal Republic of Germany.
Insights
Activation of cardiac sympathetic nerves can worsen myocardial ischemia through coronary constriction. Medications like alpha-2 antagonists, nifedipine, and bradycardic agents can prevent this ischemia, offering therapeutic potential.
Area of Science:
- Cardiovascular Physiology
- Autonomic Nervous System Research
- Myocardial Ischemia Pathophysiology
Background:
- Coronary stenosis can be compensated by vasodilation and collateral flow.
- Sympathetic nerve activation can paradoxically cause coronary constriction and ischemia.
Purpose of the Study:
- To investigate the role of cardiac sympathetic nerve activation in precipitating myocardial ischemia.
- To evaluate the efficacy of pharmacological interventions in mitigating sympathetically induced ischemia.
Main Methods:
- Experimental studies in anesthetized and conscious dogs.
- Administration of alpha-2 adrenoceptor antagonists, nifedipine, atenolol, ULFS-49, procaine, and clonidine.
- Monitoring of myocardial blood flow and function under various conditions.
Main Results:
- Sympathetic nerve stimulation induced alpha-2 adrenoceptor-mediated coronary constriction and ischemia.
- Alpha-2 antagonists, nifedipine, and bradycardic agents attenuated ischemia.
- Beta-blockade was effective only with heart rate reduction; central sympathoexcitation blockade also showed benefits.
Conclusions:
- Cardiac sympathetic activation can precipitate myocardial ischemia via specific adrenoceptor pathways.
- Pharmacological interventions targeting alpha-2 adrenoceptors, calcium channels, or heart rate offer protective effects.
- Interrupting the sympathetic-ischemia feedback loop is crucial for managing myocardial ischemia.
Abstract:
Distal to a coronary stenosis, resting myocardial blood flow and function can be maintained by a compensatory dilation of the poststenotic vascular bed and an increased collateral blood flow from adjacent coronary vessels. Under this condition, electrical stimulation of cardiac sympathetic nerves, as well as their activation during sympathoexcitatory reflexes and exercise, induces a poststenotic alpha 2-adrenoceptor-mediated coronary constriction and a beta-adrenoceptor-mediated, tachycardia-related redistribution of blood flow away from the ischemia myocardium. Thus, activation of cardiac sympathetic nerves can precipitate poststenotic myocardial ischemia. In experimental studies in anesthetized, vagotomized dogs, as well as in conscious, chronically instrumented dogs, selective alpha 2-adrenoceptor antagonists and calcium-channel blockade with nifedipine were able to attenuate the sympathetically induced poststenotic myocardial ischemia. Beta-adrenoceptor blockade with atenolol was only proven beneficial as long as there was a heart-rate reduction. Conversely, a specific bradycardic agent (ULFS-49) also exerted beneficial effects. Myocardial ischemia can activate cardiac sympathetic afferents and then, by a spinal reflex, can in turn activate sympathetic efferents and aggravate the severity of myocardial ischemia. This vicious cycle could be interrupted by segmental epidural anesthesia with procaine as well as by blockade of sympathoexcitation at the central nervous level with clonidine in anesthetized dogs.