Time course of sympathetic denervation supersensitivity in canine ventricular recovery

We studied the timing of the electrophysiological effects of sympathetic supersensitivity with chronically implanted electrodes in the anterior and posterior left ventricular free wall in 10 dogs. We produced denervation of the anterior wall in six dogs by application of phenol surrounding the anterior electrode. Drug infusions that were performed under pentobarbital sodium anesthesia included norepinephrine, isoproterenol, and methoxamine. In four controls there was no difference in response of the two sites. Presynaptic supersensitivity was manifest as early as 2 days and as late as 64 days by a parallel left shift (greater than or equal to 8.3 ms) in the norepinephrine dose to effective refractory period shortening response curve in the anterior compared with posterior left ventricle, P less than 0.01. The isoproterenol dose-response curve was also shifted to the left by 5.6 ms (P less than 0.01) but was manifest only after 10 days and only until 28 days from the denervation procedure. Local repolarization in the denervated areas shortened more than the innervated areas with both drugs. The methoxamine dose-response curve was flat, and the anterior-denervated area was not different than the posterior-innervated area. We conclude that recovery properties in ventricular muscle demonstrate evidence of supersensitivity, which is neurotransmitter and beta- but not alpha-receptor specific.