Augmented coronary blood flow response to intracoronary norepinephrine after ventricular sympathectomy

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.

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/dtmax), maximum negative rate of segmental shortening (-dL/dtmax), 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 microgram.

Intracoronary norepinephrine administration caused significant increases in LVSP, dP/dtmax, -dL/dtmax, 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-microgram 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-microgram 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/dtmax, or heart rate between any of the groups at any of the doses.

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.