KASHIMOTO Satoshi YAMANASHI MECKAL UNIVERSIY, ANESTHEOLOGY, ASSOCIATE PRCHE99OR, 医学部, 助教授 (60152633)
OGUCHI Takeshi YAMANASHI MECKAL UNIVERSIY, ANESTHEOLOGY, ASSISTANT PROTS9OR, 医学部, 講師 (60201399)
KUMAZAWA Teruo AMANASHI MECKAL UNIVERSIY, ANESTHEOLOGY, PROPESSOR, 医学部, 教授 (10092404)
|Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥2,800,000 (Direct Cost: ¥2,800,000)
Cardiovascular depression induced by propofol is rather pronounced in the elderly patients. This occurrence could be attributed to the indirect effects of propofol such as attenuated sympathetic outflow or altered baroreceptor reflex sensitivity. However, the age-related direct effects of propofol on the myocardium have not been well elucidated. This study was designed to determine whether there are differences among young, adult, and old rat hearts, in the direct action of propofol on myocardial contraction and intracellular calcium ([Ca^<2+>]).
Hearts were excised from young (6 weeks), adult (10 weeks), and old (>60 weeks) rats. The hearts were per fused with a Langendorff system at constant pressure (55 mmHg) and loaded with Fura-2/AM, as a [Ca^<2+>] I marker. The [Ca^<2+>]I was estimated by determining the ratio of the emission at 500 nm during excitation at 340 nm to the emission at 500 nm during excitation at 380 nm. Each heart was exposed to the Krebs buffer containing Intralipid
^<TM> (control) and propofol (20 μM, 50 μM, and 100 μM).
At a low concentration (20 μM), propofol did not affect left ventricular isovolemic contraction (LV dP/dt max) in young, adult, and old groups. Although 50 μM propofol produced no significant effects on the young cardiac function, LV dP/dt max was suppressed in the adult (11±4 %) and old (8±1 %) heart significantly. At the highest concentration (100 μM), decrease in LV dP/dt max was observed in all aged hearts (young hearts 14+- 3%, adult hearts 19±5%, and old hearts 17±3 %). However, propofol of all three concentrations did not produce any response in heart rate, systolic [Ca^<2+>] I and diastolic [Ca^<2+>]I levels, coronary flow, and myocardial oxygen consumption in all groups.
ge-related negative inotropic effect of propofol was demonstrated in the isolated heart at 50 μM. However,
myocardial intracellular calcium level was not influenced by animal age and doses. The present data suggest that the age-related decrease in myofilament Ca^<2+> sensitivity may cause myocardial depression by propofol. Less