Because sympathetic fibers travel in the subepicardium and generally follow the coronary arteries in a basal to apical course, we tested the hypothesis that transmural myocardial infarction that involves this subepicardial region interrupts sympathetic axons traveling through the infarct and produces sympathetic denervationat noninfarcted sites apical to the infarction. A rapidly hardening vinyl latex solution injected into the first diagonal branch of the left anterior descending coronary artery produced the transmural myocardial infarction by embolizing the vasculature. Ten dogs were studied 90 minutes after coronary artery embolization (acute) and 12 dogs were studied 7-21 days after infarction (chronic). The integrity of the sympathetic innervation was tested in an open-chest preparation of the acutely and chron-ically infarcted dogs by measuring endocardial and epicardial effective refractory period changes during left and right stellate stimulation. Additionally, regional myocardial norepinephrine content and fluores-cence were examined in the chronically infarcted dogs. Transmural infarction was verified using nitroblue tetrazolium staining. In the 10 acutely infarcted dogs, left and right stellate stimulation shortened the effective refractory period at all 56 sites examined before infarction and at 30 sites basal or lateral to the infarction after embolization. Twenty-six noninfarcted sites apical to, but not within, the zone of infarction did not respond to left or right stellate stimulation after infarction. In the 12 chronically infarcted dogs, left and right stellate stimulation shortened the effective refractory period at all 20 sites basal to infarction. In noninfarcted sites apical to the infarction, left stellate stimulation didnot shorten the eifective refractory period at 23 of41 sites, while right stellate stimulation was ineffective at 24 of 41 sites. Both left and right stellate stimulation were ineffective at 18 of 41 sites. Twelve of 41 sites apical to the infarct had normal effective refractory period shortening during left and right stellate stimulation. In both groups of dogs, norepinephrine infusion, 0.05, ug/kg/min, iv, shortened the refractory period at all sites apical to the infarct that did not shorten refractory period in response to stellatestimulation. In chronically infarcted dogs, myocardial norepinephrine content was reduced at the denervated sites, and histologically reduced norepinephrine fluorescence in noninfarcted, denervated myocardium was found. We conclude that transmural myocardial infarction produces heterogeneous sympathetic denervation in noninfarcted sites apical to the area of necrosis. This denervation is probably the result of interrupting sympathetic nerves coursing from base to apex.

ALTHOUGH some sympathetic nerves innervate relatively specific and localized sites in the ventricle,'sev-eral studies'-'have shown that the anterior leftventricle receives its major efferent sympathetic nerve supply from nerves that course in the superficial subepicardium, most likely within the upper 0.25-0.50 mm. These nerves travel from base to apex along the coronary arteries," 2 probably dive transmurally to in-nervate the endocardium, 3 and modulate a variety of myocardial functions.'-It is known that myocardial ischemia disrupts autonomic neurotransmissionwithin a region of developing infarction; 5 but it is not known