Neurally mediated negative inotropic effect impairs myocardial function during cholinergic coronary vasoconstriction...

Area of Science:

• Cardiology
• Neuroscience
• Physiology

Background:

• Cholinergic coronary vasospasm typically causes myocardial dysfunction attributed to ischemia.
• However, acetylcholine released from pericoronary nerves may directly depress myocardial contractility.
• This study investigates the neural contribution to ventricular dysfunction during cholinergic coronary vasoconstriction.

Purpose of the Study:

• To determine if a neurally mediated effect contributes to impaired ventricular function during cholinergic coronary vasoconstriction.
• To analyze the impact of direct neural stimulation on myocardial contractility independent of ischemia.

Main Methods:

• Left ventricular function, ECG mapping, and coronary angiography were assessed in pigs during pericoronary methacholine application.
• Effects were evaluated with and without nitroglycerin perfusion and after pericoronary nerve disruption.
• Histological analysis confirmed the presence of nerves extending into the ventricular myocardium.

Main Results:

• Methacholine induced coronary vasoconstriction, reduced coronary blood flow, and depressed left ventricular pressure, contractility (dP/dt), and segment shortening.
• These effects were reproducible, not preceded by heart rate changes, and inhibited by atropine.
• Even with attenuated blood flow reduction by nitroglycerin, ventricular function remained impaired, suggesting a direct neural mechanism.

Conclusions:

• A neurally mediated effect, distinct from ischemia, significantly impairs left ventricular function during cholinergic coronary constriction.
• Pericoronary nerves extending into the ventricles play a crucial role in this dysfunction.
• Findings highlight a dual mechanism involving ischemia and direct neural effects in cholinergic coronary vasospasm-induced cardiac dysfunction.