钙敏化剂EMD 57033对开胸麻醉的局部心肌顿抑猪的心血管作用

Cardiovascular profile of the calcium sensitizer EMD 57033 in open-chest anaesthetized pigs with regionally stunned myocardium.

作者信息

de Zeeuw S, Trines S A, Krams R, Verdouw P D, Duncker D J

机构信息

Experimental Cardiology, Thoraxcenter, Cardiovascular Research Institute COEUR, Erasmus University Rotterdam, Rotterdam, The Netherlands.

出版信息

Br J Pharmacol. 2000 Apr;129(7):1413-22. doi: 10.1038/sj.bjp.0703231.

DOI:10.1038/sj.bjp.0703231

PMID:10742297

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1571982/

Abstract

Ca(2+) sensitizers enhance systolic function, but may impair relaxation in vitro; these effects may differ in stunned and normal myocardium. We therefore studied the effect of EMD 57033 on systolic and diastolic function of normal and stunned porcine myocardium in vivo. 2. Myocardial stunning by 15 min coronary occlusion and 30 min reperfusion abolished systolic shortening (SS) (baseline 13+/-1%) and decreased end-systolic elastance (E(es)) from 67+/-7 to 47+/-5 mmHg mm(-1) (both P<0.05). Maximum rate of fall of myocardial elastance (dE/dt(min)) decreased from -850+/-100 to -320+/-30 mmHg mm(-1) s(-1), while the time constant tau(e) of the decay of elastance increased from 58+/-3 to 68+/-6 ms (both P<0.05). End-diastolic elastance (E(ed)) was unchanged although the zero pressure intercept (L(0,ed)) had increased. 3. In the stunned region, EMD 57033 (0.2 mg kg(-1) min(-1) for 60 min, i.v., n=7) increased SS to 19+/-2%, E(es) to 287+/-40 mmHg mm(-1), dE/dt(min) to -3630+/-640 mmHg mm(-1) s(-1) and decreased tau(e) to 50+/-3 ms, while E(ed) remained unchanged. In the normal region, 4. EMD 57033 increased SS from 14+/-2 to 18+/-3%, E(es) from 59+/-4 to 263+/-23 mmHg mm(-1), dE/dt(min) from -480+/-70 to -2280+/-700 mmHg mm(-1) s(-1) and decreased tau(e) from 91+/-12 to 61+/-3 ms (all P<0.05), while E(ed) remained unchanged. These responses were minimally affected by adrenoceptor blockade (n=7). Vehicle (n=7) had no effect on either region. EMD 57033 increased cardiac output (up to 27+/-8%) and LVdP/dt(max) (86+/-19%). Mean aortic pressure decreased (19+/-7%) due to systemic vasodilation that was not amenable to blockade of adrenoceptors or NO synthesis. 5. In conclusion, EMD 57033 restored systolic and diastolic function of stunned myocardium, and produced similar improvements in systolic and diastolic function in normal myocardium.

摘要

钙敏化剂可增强收缩功能，但在体外可能会损害舒张功能；这些效应在顿抑心肌和正常心肌中可能有所不同。因此，我们研究了EMD 57033对正常和顿抑猪心肌在体收缩和舒张功能的影响。2. 15分钟冠状动脉闭塞和30分钟再灌注导致的心肌顿抑消除了收缩期缩短（SS）（基线为13±1%），并使收缩末期弹性（E(es)）从67±7降至47±5 mmHg·mm⁻¹（两者P<0.05）。心肌弹性下降的最大速率（dE/dt(min)）从-850±100降至-320±30 mmHg·mm⁻¹·s⁻¹，而弹性衰减的时间常数tau(e)从58±3增加至68±6 ms（两者P<0.05）。舒张末期弹性（E(ed)）未改变，尽管零压力截距（L(0,ed)）增加。3. 在顿抑区域，EMD 57033（0.2 mg·kg⁻¹·min⁻¹，静脉注射60分钟，n = 7）使SS增加至19±2%，E(es)增加至287±40 mmHg·mm⁻¹，dE/dt(min)增加至-3630±640 mmHg·mm⁻¹·s⁻¹，并使tau(e)降至50±3 ms，而E(ed)保持不变。在正常区域，4. EMD 57033使SS从14±2增加至18±3%，E(es)从59±4增加至263±23 mmHg·mm⁻¹，dE/dt(min)从-480±70增加至-2280±700 mmHg·mm⁻¹·s⁻¹，并使tau(e)从91±12降至61±3 ms（均P<0.05），而E(ed)保持不变。这些反应受肾上腺素能受体阻断的影响最小（n = 7）。溶剂对照组（n = 7）对两个区域均无影响。EMD 57033使心输出量增加（最高达27±8%）和左心室压力变化最大速率（LVdP/dt(max)）增加（86±19%）。平均主动脉压下降（19±7%），原因是全身血管舒张，这不受肾上腺素能受体阻断或一氧化氮合成阻断的影响。5. 总之，EMD 57033恢复了顿抑心肌的收缩和舒张功能，并在正常心肌的收缩和舒张功能方面产生了类似的改善。