Effect of calcium to reverse the electrocardiographic effects of hyperkalemia in the isolated rat heart: a prospective, dose-response study.
OBJECTIVE
To determine: a) any heart site or tissue-specific differences in the response to increased perfusion potassium concentrations, and b) the cellular site (intracellular vs. extracellular) of the effect of calcium on reversing electrocardiographic effects of hyperkalemia.


METHODS
In vitro prospective, repeated-measures, dose-response study.


METHODS
University/medical school experimental physiology laboratory.


METHODS
Adult male Sprague-Dawley rats whose hearts were studied in an in vitro perfusion preparation.


METHODS
One group of hearts was perfused with modified Krebs-Henseleit physiologic salt solution onto which were superimposed infusions of concentrated potassium and/or calcium solutions. Infusion rates increased stepwise the respective ions in order to calculate increased concentrations through the course of the experiment. Calcium concentration was at either 4.0 or 5.4 mEq/L (2.0 or 2.7 mmol/L); potassium concentration was increased from 5.8 to 7.3, 8.0, 8.8, 10.2 and 11.8 mmol/L. Two more groups of hearts were perfused with Krebs-Henseleit solution containing the lower calcium concentration to which was added the calcium ionophore A23187 in one of two doses. A fourth group of hearts was perfused with Krebs-Henseleit solution containing the higher calcium concentration to which was added the a single dose of the calcium-channel blocking agent verapamil.


RESULTS
We tested the effects of a series of ion and drug concentrations on epicardial EKG variables (atrial and ventricular rates, P-wave amplitude, PR interval, QRS complex amplitude and duration, and T-wave amplitude and duration). The effects of these variables were tested by increasing the ionized calcium in the perfusate of isolated rat hearts from 4.0 mEq/L (2.0 mmol/L) to 5.4 mEq/L (2.7 mmol/L) as perfusate potassium was increased stepwise from normal (5.8 mEq/L or mmol/L) to as high as 11.8 mEq/L (mmol/L). In addition, we studied the effect of adding the calcium ionophore A23187 to the perfusate with the lower ionized calcium concentration, and we also studied the effect of adding the calcium-channel blocking agent verapamil to the perfusate containing the higher ionized calcium while increasing the perfusate potassium concentration in a stepwise manner in each of the series. The higher calcium concentration (5.4 mEq/L or 2.7 mmol/L) prevented most of the adverse effects of the highest potassium concentration in the first drug-free series of experiments. When the calcium ionophore A23187 was added to the perfusate, most electrocardiographic variables remained normal even in the presence of a lower ionized calcium concentration. However, the higher ionized calcium concentration was not able to prevent electrical abnormalities in hearts perfused with high potassium when verapamil was in the solution.


CONCLUSIONS
We conclude that the mechanism whereby calcium reverses the clinically observable electrocardiographic effects of hyperkalemia is an intracellular one.
Bisogno
J L
JL
Wright State University, Dayton, OH.
Langley
A
A
Von Dreele
M M
MM
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate; D006947:Hyperkalemia / Q000378:metabolism*; D007260:Infusion Pumps; D008297:Male; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D014700:Verapamil / Q000494:pharmacology
D000001:Calcimycin; D014700:Verapamil; D002118:Calcium