Characterization of cardiac alterations in nonsedated cynomolgus monkeys

G. E. Macallum From the Parke-Davis Research Institute, Division of Warner-Lambert Canada Inc, Mississauga, Ontario L5K 1B4 Canada.

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B. J. Houston From the Parke-Davis Research Institute, Division of Warner-Lambert Canada Inc, Mississauga, Ontario L5K 1B4 Canada.

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SUMMARY

Spontaneous variations in ECG and continuous Holter monitor recordings of a colony of 31 male and 31 female cynomolgus monkeys were characterized. Electrocardiograms recorded for approximately 1 minute on 2 occasions in nonsedated monkeys were analyzed, and intervals (PR, QRS, and QT), amplitudes (P, Q, R, and T), and heart rate were determined from lead II of these tracings. In addition, Holter moniter recorders were placed on monkeys by use of carrying jackets for 16 to 24 hours of continuous recording twice during the study, and tapes were analyzed. Mean heart rate and intervals and amplitudes were similar for males and females on the first and the second recordings. Mean heart rate for males and females was 232 and 226 beats/min (bpm), respectively. The PR, QRS, and QT interval measurements, 77, 29, and 165 milliseconds, respectively, were recorded for males and 81. 30, and 162 milliseconds, respectively, were recorded for females. The P, Q, R, and T wave amplitudes were 0.16, 0.11, 0.64, and 0.28, mV respectively, for males and were 0.17, 0.10, 0.79 and 0.24 mV, respectively, for females. In addition, ventricular ectopic beats were observed in ECG from 5 females, but not in ECG from the males. Single ventricular ectopic beats were observed in 3 females for either the first or second tracing. One monkey had ectopic beats in both tracings, but in both instances, the number of ectopic beats was low (3 singles in the first and 1 in the second tracing). One monkey had runs of pairs and bigeminal beats in only the first tracing. One monkey had sporadic beats indicative of right bundle branch block morphology in both tracings. In Holter recordings, ventricular ectopic beats were identified in 47 monkeys. Ventricular ectopic beats were observed in only 1 of the 2 Holter monitor tapes for 53% of these monkeys. Most ventricular ectopic beats occurred as single beats, but pairs, ventricular tachycardia, and bigeminy also were observed. Ectopic beats were of a single morphology in 60% of the monkeys, but as many as 4 different morphologies were observed in a single tracing. Sinus arrhythmia or arrest was observed in 66% of the monkeys. Ventricular ectopic beats and sinus arrythmia can occur without apparent cause in clinically normal monkeys. Higher prevalences of these abnormalities are identified by Holter monitoring relative to routine ECG procedures. These variables should be cautiously evaluated, because the lack of proper characterization of monkeys on test may mislead investigators as to the real importance of these findings.

SUMMARY

Spontaneous variations in ECG and continuous Holter monitor recordings of a colony of 31 male and 31 female cynomolgus monkeys were characterized. Electrocardiograms recorded for approximately 1 minute on 2 occasions in nonsedated monkeys were analyzed, and intervals (PR, QRS, and QT), amplitudes (P, Q, R, and T), and heart rate were determined from lead II of these tracings. In addition, Holter moniter recorders were placed on monkeys by use of carrying jackets for 16 to 24 hours of continuous recording twice during the study, and tapes were analyzed. Mean heart rate and intervals and amplitudes were similar for males and females on the first and the second recordings. Mean heart rate for males and females was 232 and 226 beats/min (bpm), respectively. The PR, QRS, and QT interval measurements, 77, 29, and 165 milliseconds, respectively, were recorded for males and 81. 30, and 162 milliseconds, respectively, were recorded for females. The P, Q, R, and T wave amplitudes were 0.16, 0.11, 0.64, and 0.28, mV respectively, for males and were 0.17, 0.10, 0.79 and 0.24 mV, respectively, for females. In addition, ventricular ectopic beats were observed in ECG from 5 females, but not in ECG from the males. Single ventricular ectopic beats were observed in 3 females for either the first or second tracing. One monkey had ectopic beats in both tracings, but in both instances, the number of ectopic beats was low (3 singles in the first and 1 in the second tracing). One monkey had runs of pairs and bigeminal beats in only the first tracing. One monkey had sporadic beats indicative of right bundle branch block morphology in both tracings. In Holter recordings, ventricular ectopic beats were identified in 47 monkeys. Ventricular ectopic beats were observed in only 1 of the 2 Holter monitor tapes for 53% of these monkeys. Most ventricular ectopic beats occurred as single beats, but pairs, ventricular tachycardia, and bigeminy also were observed. Ectopic beats were of a single morphology in 60% of the monkeys, but as many as 4 different morphologies were observed in a single tracing. Sinus arrhythmia or arrest was observed in 66% of the monkeys. Ventricular ectopic beats and sinus arrythmia can occur without apparent cause in clinically normal monkeys. Higher prevalences of these abnormalities are identified by Holter monitoring relative to routine ECG procedures. These variables should be cautiously evaluated, because the lack of proper characterization of monkeys on test may mislead investigators as to the real importance of these findings.

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