Pain and Myocardial Ischemia: the Role of Sympathetic Activation

Summary

In a first series, we tested whether the relative ischemia distal to a severe stenosis on the left circumflex coronary (CX) artery increases the activity of cardiac sympathetic (CS) nerves which, in turn, may result in a poststenotic vasoconstriction and an aggravation of ischemia. In 23 anesthetized, vagotomized dogs, an acute stenosis that reduced CX blood flow to 50% of control was produced and maintained for 20 min. The activity of postganglionic CS nerves increased by 23 ± 4% within 20 min. In parallel, poststenotic coronary resistance increased from 0.48 ± 0.03 (SEM) to 0.61 ± 0.03 mm Hg·min·100 g/ml, resulting in a net lactate production after 15 min. The selective ±₂-adrenoceptor antagonist rauwolscine (0.2 mg/kg i.V.; n = 6) and the calcium antagonist nifedipine (10μg/kg i.V.; n = 6) prevented the progressive increase in poststenotic resistance and the net lactate production, but still permitted an increase in CS activity. Segmental anesthesia of CS nerves with epidural infiltration of procaine at segments C7-T6 (n = 6) prevented the sympathetic activation, the progressive increase in poststenotic resistance and the net lactate production. In six additional dogs with intact vagus nerves, CS activation and a concomitant increase in poststenotic resistance resulting in myocardial ischemia were also found. These data suggest a vicious cycle between poststenotic coronary vasoconstriction and CS activation, resulting in severe myocardial ischemia. In a second series, stimulation of high-threshold somatic afferents (= nociceptive stimulation: NCS) was used to cause reflex CS activation. The superficial peroneal nerve was electrically stimulated in 14 anesthetized, vagotomized dogs. With intact CX arteries, a 1 min stimulation resulted in a pronounced increase in CX blood flow and perfusion pressure. In contrast, NCS in the presence of a severe stenosis on the CX artery increased end-diastolic poststenotic coronary resistance by 96 ± 15% due to a reflex activation of CS nerve fibers. This activation was markedly reduced after injection of fentanyl (27 μg/kg i.V.; n = 6). Injection of naloxone (60μg/kg) restored the original effect. Systolic wall thickening (WT; sonomicrometry) in the CX artery-perfused myocardium was increased during NCS (10.9 ± 3.9 (SD) vs. 13.6 ± 5.0%) in additional five dogs with intact coronary arteries. In the presence of a stenosis on the CX artery, systolic WT was reduced to 7.0 ± 2.5% and was further decreased to 4.6 +± 2.3% during NCS. The additional deterioration of systolic regional function during NCS was prevented after i.v.-injection of fentanyl, as was the increase in poststenotic coronary resistance. The present data suggest that CS nerve activation, both by a spinal cardiocardiac reflex and by somatic afferents, increases poststenotic coronary resistance and induces or aggravates myocardial ischemia distal to coronary stenoses.