|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1994 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 1993 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1992 : ¥300,000 (Direct Cost : ¥300,000)
1.Halothane Anesthesia Suppresses Reflex Tachycardia caused by CGRP in Dogs.
The cardiovascular response to infusions of CGRP were studied in two experimental groups : halothane anesthetized (CGRP : 0.4mug・kg^<-1>, n=7 ; 4mug・kg^<-1>, n=7 ; 40mug・kg^<-1>, n=7) and pentobarbital anesthetized (CGRP : 4mu・kg^<-1>, n=8) dogs. Mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), stroke volume index (SVI), and systemic vasular resistance (SVR) responses to changes during CGRP infusion were measured.
In halothane anesthetized dogs, during infusion of CGRP at 0.4mug・kg^<-1>, when MAP was little affected. However, there was a significant reduction in SVR associated with significant increases in CI.Higher doses of CGRP produced dose-dependent decreases in MAP through a significant reduction in SVR.In addition, both CI and SVI significantly increased at 4mug・kg^<-1> of CGRP but remained unchanged at the highest infusion rate. Onthe other hand, the increase in HR was not occurred at al
l doses despite the hypotension occurring at 4 and 40 mug・kg^<-1> of CGRP.
In pentobarbital anesthetized dogs, CGRP produced qualitatively similar cardiovascular responses in the same manner as dose (4mug・kg^<-1>) of CGRP in halothane anesthetized dogs, and the magnitude of the changes was smaller. But there was an exception ; the increase in HR was significantly increased.
Therefore, the results of present study suggest that halothane anesthesia may suppress the reflex increase in heart rate elicited by CGRP.
2.Comparative Hemodynamic Effects of Hypotension induced by CGRP and PGE_1 in Dogs.
Method : Eighteen dogs were anesthetized with halothane in oxygen (1MAC). During a steady-state baseline period, the following were measured or derived : heart rate (HR), mean arterial, mean pulmonary artery and pulmonary capillary wedge pressures (MAP,MPAP,and PCWP), cardiac and stroke volume indices (CI and SVI), systemic and pulmonary vascular resistance (SVR and PVR), and left ventricular maximum dp/dt (LV dp/dt max). After the baseline period, MAP was reduced to 60mmHg for 60min by the infusion of CGRP (n=10) or PGE_1 (n=8).Results : The CGRP-induced hypotension resulted in a significant, 58-74% reduction in SVR associated with significant increases in CI and SVI but produced little change in HR and LV dp/dt max. A significant 117-137% increase in CI was observed during induced hypotension and remained at this elevated level for the duration of observation. CI presumably increased through an increase in the SVI,while HR remained unchanged. In contrast, the PGE_1-induced hypotension resulted in a significant, 49-52% reduction in SVR associated with significant increase in the SVI and was accompanied by a significant decrease in either HR or LV dp/dt max. During PGE_1-induced hypotension, there was no change observed in the CI.This unchanged cardiac output may be due to either a decrease in HR or cardiac contractility in spite of a profound reduction in SVR.CGRP did not affect MPAP and PCWP,however, PGE_1 tended to decrease these variables at levels which were not statistically significant. Conclusions : This study suggests that CGRP and PGE_1 are equally effective in decreasing afterload and in achieving induced hypotension but CGRP is more advantageous because of its more potent vasodilatory actin and increased cardiac output. It is concluded that CGRP also may be a safe agent for induced hypotension in clinical practise.
3.The Effect of CGRP-induced Hypotension on Splanchnic Organ Blood Flow during Halothane Anesthesia in Dog.
Method : Organ blood flows were determined in 18 mongrel dogs allocated randomly to one of two groups : (1) CGRP group (n=10) (2) nonhypotensive group (n=8). CGRP was infused at a rate sufficient to decrease the mean arterial pressure of 60mmHg from the baseline values for a 60min-hypotensive period. Organ blood flows were measured using the hydrogen clearance technique.
Results : No changes were observed in organ blood flows in the nonhypotensive group. In the CGRP groupo, the kindney and pancreas blood flows remained unchanged throughout the experiment. The liver blood flow remained unchanged during induced hypotension and thereafter slightly increased after induced hypotension. In contrast to the splanchnic organ blood flow, the muscle blood flow decreased during induced hypotension but the rebound phenomen observed after infusion of CGRP.Conclusion : These findings suggest that CGRP is a potent vasodialtor of the splanchnic organs and did not affect adversely splanchnic organ flows in the presence of profound hypotension, in the presence of a muscle blood flow decrease in halothane aneshetized dogs. The results of this study show that CGRP may be an useful vasodilator for induced hypotension. Less