TY - JOUR
T1 - Use-dependent effects of lidocaine on the upper limit of vulnerability in open chest dogs
AU - Cha, Yong Mei
AU - Peters, Barry B.
AU - Chen, Peng Sheng
N1 - Funding Information:
From the Basic Arrhythmia Laboratory, Division of Cardiology, Department of Medicine, University of California, an Diego and Veterans Affairs Medical Centers, an Diego, California. This work was done during the tenure of a Clinician cientist Award (88-IU) and an Established Invesligatorship Award (93002570) to Dr. Chen from the American Heart Association and Wyeth-Ayerst, Dallas. Texas, and was supported in pan by crusts from the Whitaker Foundation. Mechanicsburg. Pennsylvania: the Department of Veterans Affairs, Washington. D.C . ; and an American Heart Association National Center Grant-in-Aid (92009825). Dallas. Texas . Dr . Chen was the recipient ofan NIH FIRT award (11129111.50259.0 1), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland . Manuscript received June 2,1993; revised manuscript received January 1 . 1994, accepted January 12, 1994 . ePre.cem address andadd-,for comcnondence:Dr. Pertheng Chen, Room 5342, Division of Cardiology, Cedars-inai Medical Center . 8700 Bevedy Boulevard, Los Angeles, California 90048.
PY - 1994/6
Y1 - 1994/6
N2 - Objectives. This study was performed to test the hypothesis that sodium channel activity is important in determining ventricular vulnerability to electric shocks. Background. It is unknown whether sodium channel activity determines the upper limit of vulnerability. Methods. The ventricles of 10 open chest dogs were paced at 300-, 500-, or 1,000-ms cycle lengths. The shock strength associated with a 50% probability of reaching the upper limit of vulnerability (ULV50) and the shock strength associated with a 50% probability of defibrillation (DFT50) were then determined by means of an up-down algorithm. Lidocaine (9.2-mg/kg body weight loading dose and 285-μg/kg per min maintenance dose) was then given, and the ULV50 and the DFT50 were redetermined after 1 h of stable infusion. Results. The mean (±SD) lidocaine concentration was 11.9 ±2.4 μg/ml. At baseline, the ULV50 tested with each S1 cycle length was not significantly different from the DFT50. During lidocaine infusion, the ULV50 determined with cycle lengths of 300 and 500 ms (18.9 ± 11.3 and 16.1 ± 8.9 J, respectively) were significantly (p < 0.05) higher than those simultaneously determined for the DFT50 (11.2 ± 4.1 and 10.9 ± 5.6 J, respectively). However, when determined with an S1 cycle length of 1,000 ms, the ULV50 (10.4 ± 4.1 J) was not found to be significantly different from the DFT50 (10.3 ± 5.3 J). Lidocaine infusion increased (p < 0.05) QRS duration and the effective refractory periods for cycle lengths of 300 and 500 ms but not 1,000 ms. Conclusions. The effect of lidocaine on the upper limit of vulnerability is use dependent. These results are compatible with the hypothesis that sodium enamel activity is important in determining ventricular vulnerability to electrical shocks.
AB - Objectives. This study was performed to test the hypothesis that sodium channel activity is important in determining ventricular vulnerability to electric shocks. Background. It is unknown whether sodium channel activity determines the upper limit of vulnerability. Methods. The ventricles of 10 open chest dogs were paced at 300-, 500-, or 1,000-ms cycle lengths. The shock strength associated with a 50% probability of reaching the upper limit of vulnerability (ULV50) and the shock strength associated with a 50% probability of defibrillation (DFT50) were then determined by means of an up-down algorithm. Lidocaine (9.2-mg/kg body weight loading dose and 285-μg/kg per min maintenance dose) was then given, and the ULV50 and the DFT50 were redetermined after 1 h of stable infusion. Results. The mean (±SD) lidocaine concentration was 11.9 ±2.4 μg/ml. At baseline, the ULV50 tested with each S1 cycle length was not significantly different from the DFT50. During lidocaine infusion, the ULV50 determined with cycle lengths of 300 and 500 ms (18.9 ± 11.3 and 16.1 ± 8.9 J, respectively) were significantly (p < 0.05) higher than those simultaneously determined for the DFT50 (11.2 ± 4.1 and 10.9 ± 5.6 J, respectively). However, when determined with an S1 cycle length of 1,000 ms, the ULV50 (10.4 ± 4.1 J) was not found to be significantly different from the DFT50 (10.3 ± 5.3 J). Lidocaine infusion increased (p < 0.05) QRS duration and the effective refractory periods for cycle lengths of 300 and 500 ms but not 1,000 ms. Conclusions. The effect of lidocaine on the upper limit of vulnerability is use dependent. These results are compatible with the hypothesis that sodium enamel activity is important in determining ventricular vulnerability to electrical shocks.
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U2 - 10.1016/0735-1097(94)90676-9
DO - 10.1016/0735-1097(94)90676-9
M3 - Article
C2 - 8195533
AN - SCOPUS:0028223694
SN - 0735-1097
VL - 23
SP - 1688
EP - 1692
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 7
ER -