Abstract 15780: Sinoatrial Node Mapping and the Mechanisms of Sinus Rate Acceleration
Background: Studies using isolated sinoatrial node (SAN) cells indicate that rhythmic spontaneous sarcoplasmic reticulum Ca release (Ca clock) plays an important role in SAN automaticity. However, it is difficult to translate these findings into intact SAN because the SAN is embedded in the right atrium (RA). Cross contamination of the optical signals between SAN and RA prevents the definitive testing of Ca clock hypothesis in intact SAN.
Hypothesis: We hypothesized that high potassium concentration can block electrical conduction from the SAN to RA and is useful for estimating Ca clock in intact SAN. The purpose of the present study was to use a novel approach to selectively map intact SAN to examine the Ca clock function in intact RA.
Methods: We simultaneously mapped intracellular Ca (Cai) and membrane potential (Vm) in 7 isolated, Langendorff perfused normal canine RA. Electrical conduction from the SAN to RA was inhibited with high potassium (10 mmol/L) Tyrode's solution, allowing selective optical mapping of Vm and Cai of the SAN. Isoproterenol (ISO), ryanodine and ZD7288 were given after baseline recordings.
Results: With high potassium concentration (10 mmol/L), conduction block from the SAN to the surrounding RA was reliably induced in all 7 preparations. The cycle length of SAN activity was 609±66 ms at baseline and 586±17 ms (P=0.77) when the RA was perfused with 10 mmol/L potassium. The leading pacemaker sites were located in the middle and inferior SANs in 4 and 3 preparations, respectively. ISO (0.03 μmol/L) treatment significantly decreased cycle length of the sinus beats from 586±17 ms at baseline to 366±32 ms (P<0.01), and shifted the leading pacemaker site from the middle or inferior SAN to the superior SAN in all RAs. The Cai upstroke preceded the Vm in the leading pacemaker site by up to 18±2 ms. ISO-induced changes to SAN were inhibited by ryanodine (3 μmol/L), but not ZD7288 (3 μmol/L), a selective I f blocker.
Conclusions: We conclude that a high extracellular potassium concentration results in intermittent SAN-RA conduction block, allowing selective optical mapping of the intact SAN. Acceleration of Ca cycling in the superior SAN underlies the mechanism of sinus tachycardia during sympathetic stimulation.
- © 2010 by American Heart Association, Inc.