Augmented coronary blood flow response to intracoronary norepinephrine after ventricular sympathectomy

Background: Ventricular sympathetic denervation may occur as a result of myocardial infarction or heart transplantation. The present study examined the time-dependent effects of surgical ventricular sympathectomy on coronary flow and myocardial contractile responses to intracoronary norepinephrine administration in conscious dogs. Methods: Adult mongrel dogs (18-26 kg), were either ventricular sympathectomized or served as a sham-operated control. Animals were studied 2, 4, and 8 weeks after surgery. Measurements of left ventricular systolic pressure (LVSP), maximum rate of left ventricular pressure generation (dP/dt(max)), maximum negative rate of segmental shortening (-dL/dt(max)), heart rate, and mean circumflex flow velocity (CFV) were obtained before and after bolus administration of norepinephrine into the circumflex artery in doses ranging from 0.01 to 0.50 μg. Results: Intracoronary norepinephrine administration caused significant increases in LVSP, dP/dt(max), -dL/dt(max), heart rate, and CFV. After reaching a peak or maximum response, these variables returned to their respective preinjection values, except for CFV, which exhibited a biphasic response. CFV continued to decline below control levels, indicating a vasoconstrictor response to norepinephrine, before returning back to preinjection levels. With the 0.5-μg dose of intracoronary norepinephrine, the percent increases in CFV were 124%±25% and 105%±15% (P<0.05) at 2 and 4 weeks respectively, compared with the sham-operated controls, which only increased 56%±15%. The response to the 0.5-μg dose of norepinephrine at 8 weeks (61%±6%) was not significantly different from control. Elevated myocardial contractile responses in the sympathectomized hearts were also evident at 2 and 4 weeks, but not at 8 weeks. The vasoconstrictor response to norepinephrine administration was not significantly different between sympathectomized and sham-operated hearts. Finally, there was no difference in the change in LVSP, dP/dt(max), or heart rate between any of the groups at any of the doses. Conclusions: These results suggest that a supersensitivity to the coronary functional hyperemic response after intracoronary norepinephrine is present in ventricular sympathectomized hearts, but a coronary constrictor supersensitivity does not exist.