Sympathetic activity and myocardial damage after stimulation of dorsal medulla and vagotomy in a novel animal model.
Many kinds of brain lesions cause sympathetic hyperexcitation and myocardial damage. A novel animal model was developed for the correlation of sympathetic excitation with ventricular dysfunction and myocardial damage. Six cats (3.23+/-0.26 kg) under intraperitoneal urethane-chloralose anesthesia were artificially ventilated and bilaterally vagotomized. They underwent an electrical stimulation of unilateral dorsal medulla for 180 min (monopolar square-wave pulses, 10 Hz, 10 V, 0.5 ms). Mean blood pressure, heart rate plasma concentration of norepinephrine and left ventricular size and ejection fraction were measured at 0, 5, 15, 30, 60, 90, 120 and 180 min. Mean blood pressure (mm Hg), heart rate (beats/min) and norepinephrine (pg/ml) increased abruptly from 128+/-15, 203+/-22 and 353+/-123 to 234+/-26, 240+/-13 and 4727+/-2159 at 5 min after electrical stimulation (all p<0.01). The left ventricles showed significant dilatation (end-diastolic diameter: from 1.35+/-0.13 to 1.84+/-0.21 cm, p=0.006; end-systolic diameter: from 0.65+/-0.20 to 1.54+/-0.24 cm, p=0.002) and hypokinesia (ejection fraction: from 88.9+/-6.4% to 37.3+/-8.7%, p<0.001). Cardiac pathology revealed myocardial hemorrhage, cardiomyocyte apoptosis and coagulative myocytolysis (contraction band necrosis), characterized by sarcoplasmic coagulation, granulation and disruption. In conclusions, the present experiment develops a novel animal model in which stimulation of the pressor area in the dorsal medulla in vagotomized cats produces sympathetic hyperexcitation accompanied with myocardial dysfunction and damage. This model may be applicable for studying protective effect of drugs on myocardial dysfunction and damage caused by sympathetic hyperexcitation occurring in brain diseases.
Chiu
Yung-Tsung
YT
Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.
Chen
Ying-Tsung
YT
Lin
Nai-Nu
NN
Cheng
Ching-Chang
CC
Gong
Chi-Li
CL
Cheng
Fu-Chou
FC
Hsu
Shih-Lan
SL
Chi
Ching-Shiang
CS
Fu
Yun-Ching
YC
D000818:Animals; D002415:Cats; D004108:Dilatation, Pathologic; D004558:Electric Stimulation; D006321:Heart / Q000294:innervation*; D008526:Medulla Oblongata / Q000503:physiopathology*; D023421:Models, Animal; D009206:Myocardium / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D009336:Necrosis; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D014628:Vagotomy; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*