MYOCARDIAL IRRITABILITY— I lEGNAUER and COVINO d>Z7 



llhrillation following calciuni chloride infusions. The remaining 35 per cent escape 

 fibrillation and terminate in asystole (cardiac contracture). The amount of calcium 

 chloride necessary to produce asystole in the latter is almost twice that required to 

 cause fibrillation in the former. These results on normothermic dogs are in agree- 

 ment with those previously reported for similar experiments by Hoff et al.'-- In 

 contrast to the normothermic dogs, calcium infusions produce ventricular fibrilla- 

 tion in all hypothermic dogs. And, furthermore, tlie amount of calcium required to 

 produce fibrillation diminishes as hypothermia progresses, such that at 25° fibrilla- 

 tion may be caused by one-ninth the amount required at normal temperature. Ter- 

 minal plasma calcium levels (heart samples) in the normothermic group are greater 

 than the pre-in fusion levels by a factor of 5, and in the hypothermic group by a 

 factor of 2 .These results indicate clearly that at 25° the dog's heart is several times 

 more sensitive to exogenous calcium than at normal temperature, and from the 

 available data the increased sensitivity is a progressive phenomenon. 



Investigation of the pH factor on sensitivity to exogenous calcium in hypo- 

 thermia reveals that if such a factor exists it is of a magnitude not revealed by the 

 relatively crude technicjue employed. The artificially respired dogs with terminal 

 pH levels in the normal range are no less sensitive than acidotic dogs. The mean 

 pH of 7.26 represents a less extreme degree of acidosis in the hypothermic state 

 than was encountered in earlier experiments where spontaneous respiration pre- 

 vailed, but despite this the most acidotic dog (pH 7.12) required the largest in- 

 fusion to produce fibrillation of any dog in the group. Thus maintenance of an 

 approximately normal pH throughout cooling is without apparent efi'ect on the 

 sensitivity of hypothermic dogs to exogenous calcium (last group shown in table 

 III). Similarly when calcium chloride is administered to normothermic dogs previ- 

 ously rendered acidotic by administration of COo to the inspired air (mean 

 pH<6.9) it is found that such animals do not differ in sensitivity to calcium from 

 the normothermic controls. It appears therefore that blood pH is not a factor de- 

 termining the amount of calcium required to produce fibrillation in either normo- 

 or hypothermic dogs. 



The electrocardiographic changes following calcium infusions in both normo- and 

 hypothermic dogs are similar to those described by Hofif ct al.," and here shown 

 in figures 5 and 6. It is of interest that one of the early changes in normal animals 

 is the appearance of an upward deflection of the earliest portion of the S-T seg- 

 ment, similar to that described for some hypothermic dogs and resembling injury 

 potentials. In hypothermic dogs possessing such an ECG the early S-T elevation 

 is immediately augmented by calcium infusions. The significance of these observa- 

 tions remains obscure. 



That the myocardial responses to exogenous calcium as just described are specific 

 for calcium is substantiated in part, at least, by substitution of isotonic saline or iso- 

 tonic potassium chloride. Volumes of the former in excess of any calicum chloride 

 infusions employed produced no distinct ECG changes. Potassium chloride in- 

 fusions in small series of normo- and hypothermic animals yielded different char- 

 acteristic responses from those described for calcium. The average lethal dose was 

 2.7 niEq. of potassium per kg. for normothermic, and 1.8 mEq. per kg. for hypo- 

 thermic dogs. The difference is not statistically significant for these small groups. 



