TY - JOUR
T1 - Increased protein synthesis is necessary for the development of late preconditioning against myocardial stunning
AU - Rizvi, Ali
AU - Tang, Xian Liang
AU - Yumin, Qiu
AU - Xuan, Yu Ting
AU - Takano, Hitoshi
AU - Jadoon, Asad K.
AU - Bolli, Roberto
PY - 1999/9
Y1 - 1999/9
N2 - In phase I of this study, the rate of protein synthesis was measured by the incorporation of [3H]leucine into the protein pool in the heart of conscious rabbits. At 2 h after ischemic preconditioning (PC) with six 4-min occlusion/4-min reperfusion (O/R) cycles (group II), the [3H]leucine content in the ischemic-reperfused region was increased by 82% compared with that in controls (group I), indicating increased protein synthesis. This increase was completely abrogated by pretreatment with cycloheximide (CH; group III). In phase II, rabbits underwent six O/R cycles for three consecutive days (days 1-3). Controls (group IV) exhibited late PC against myocardial stunning on days 2 and 3. In group V, which received CH 30 min before the 1st O/R cycle on day 1 (same dose as group III), late PC against stunning on day 2 was completely abrogated. In group VI, pretreatment with CH 24 h before the 1st sequence of O/R cycles had no effect on myocardial stunning on day 1, indicating that the absence of late PC on day 2 in group V cannot be ascribed to delayed toxicity of CH. Taken together, these results demonstrate that, in the conscious rabbit, ischemic PC causes a rapid increase in myocardial protein synthesis and that this increased protein synthesis (or at least a fraction of it) is necessary for the development of the protection against myocardial stunning 24 h later. The late phase of ischemic PC is therefore dependent on the formation of new proteins in intact animals.
AB - In phase I of this study, the rate of protein synthesis was measured by the incorporation of [3H]leucine into the protein pool in the heart of conscious rabbits. At 2 h after ischemic preconditioning (PC) with six 4-min occlusion/4-min reperfusion (O/R) cycles (group II), the [3H]leucine content in the ischemic-reperfused region was increased by 82% compared with that in controls (group I), indicating increased protein synthesis. This increase was completely abrogated by pretreatment with cycloheximide (CH; group III). In phase II, rabbits underwent six O/R cycles for three consecutive days (days 1-3). Controls (group IV) exhibited late PC against myocardial stunning on days 2 and 3. In group V, which received CH 30 min before the 1st O/R cycle on day 1 (same dose as group III), late PC against stunning on day 2 was completely abrogated. In group VI, pretreatment with CH 24 h before the 1st sequence of O/R cycles had no effect on myocardial stunning on day 1, indicating that the absence of late PC on day 2 in group V cannot be ascribed to delayed toxicity of CH. Taken together, these results demonstrate that, in the conscious rabbit, ischemic PC causes a rapid increase in myocardial protein synthesis and that this increased protein synthesis (or at least a fraction of it) is necessary for the development of the protection against myocardial stunning 24 h later. The late phase of ischemic PC is therefore dependent on the formation of new proteins in intact animals.
KW - Cycloheximide
KW - Myocardial ischemia
KW - Myocardial reperfusion
KW - Systolic wall thickening
KW - [H]leucine
UR - http://www.scopus.com/inward/record.url?scp=0032888667&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032888667&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.1999.277.3.h874
DO - 10.1152/ajpheart.1999.277.3.h874
M3 - Article
C2 - 10484406
AN - SCOPUS:0032888667
SN - 0363-6135
VL - 277
SP - H874-H884
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 3 46-3
ER -