The effects of chronic calcium channel blocker treatment on action potential of heart

Hypertension is a very common disease and calcium channel blockers are frequently used to regulate blood pressure in these patients, however, little is known about the long-term cardiac effects of these drugs. The specific aim of my work was to study the effect of chronic nifedipine, a calcium channel antagonist treatment on the electrophysiological properties of canine cardiac muscle cells.
Adult dogs were treated with 1 tabl/day Adalat GITS 60 retard pills. This pill releases nifedipine evenly and continuously. The nifedipine concentration of the blood was monitored during the 1 month treatment. The action potential of isolated canine cardiac cells was measured by sharp microelectrodes at 37 oC. Isolated ventricular cells were obtained by collagenase digestion. At the end of digestion the cells from the different layers of the ventricular wall (epi-, mid-, and endo-cardium) were handled separately.
During the analysis the main parameters of the action potentials were determined (maximal slope of rising phase, amplitude, duration of action potential). We have observed that the chronic nifedipine treatment had no effect on the parameters of epi- and endo-cardial action potentials. In mid-myocardial cells the chronic nifedipine treatment significantly increased the duration of action potentials measured at 50% (APD50) and 90% (APD90) repolarization. The differences were significant at stimulation frequencies lower than 1 Hz. At 0.5 Hz stimulation frequency the APD50 and APD90 values were 205±8 ms and 244±10 ms at non-treated animals, while these parameters were obtained to 227±6 ms and 269±7 ms after the chronic nifedipine treatment (n=16, p<0.05).
In conclusion, chronic nifedipine treatment changes the dispersion of action potential across the ventricular wall and it may increase the possibility of the development of arrhythmias. Although our previous results show that the nifedipine alters the calcium homeostasis of ventricular cells, it manifests only on the action potential parameters of mid-myocardial cells.