Hoffmeister H M, Ströbele M, Beyer M E, Kazmaier S, Fischer M, Bässler A, Seipel L
Medizinische Universitätsklinik, Abt. III; Eberhard-Karls-Universität Tübingen, Germany.
Cardiovasc Res. 1998 Apr;38(1):149-57. doi: 10.1016/s0008-6363(97)00322-2.
Severely hypertrophied myocardium was described to have a reduced tolerance towards ischemia. For non-hypertrophied hearts inconclusive findings on the Ca(2+)-responsiveness are reported. Information sensitivity to reversible ischemia and on postischemic Ca(2+)-responsiveness of hearts with clinically common moderate hypertrophy is lacking. Thus, the responsiveness of hypertrophied and normal postischemic myocardium to positive inotropic stimulation should be investigated in the present study.
Hearts from spontaneously hypertensive rats (SHR, 4 months old) with significant LV-hypertrophy (+ 50%) and hearts from normotensive 4 months old Wistar rats were investigated using an isovolumic beating isolated heart model (8 hearts/each of the 8 groups). Functional recovery after 30 min of no-flow ischemia was 78 +/- 1% and 77 +/- 3% of preischemic control data in hypertrophied and non-hypertrophied hearts assessed as developed left ventricular pressure (non-ischemic controls: 95 +/- 2% in hypertrophied and 93 +/- 3% in non-hypertrophied controls). Maximum short-term stimulation with Ca2+ revealed a decreased peak left ventricular pressure of 124 +/- 4% in hypertrophied and 120 +/- 5% in non-hypertrophied postischemic hearts, as compared with non-ischemic controls 138 +/- 3% and 157 +/- 5%, respectively ( p < 0.01). A maximum dose of dopamine stimulated hypertrophied and non-hypertrophied postischemic hearts comparable to Ca2+. Analysing the dose-response curve for Ca(2+)-stimulation, the sensitivity expressed as fraction of the maximum was identical in non-ischemic and postischemic myocardium of hypertrophied and non-hypertrophied ventricles in spite of the reduced peak values.
The findings demonstrate that after moderate reversible ischemia the steady-state function is similarly decreased in hypertrophied and non-hypertrophied postischemic myocardium. The maximum response to Ca2+ is significantly reduced in both types of myocardium, while the Ca2+ sensitivity is unchanged. Identical results after maximum dopamine stimulation as after Ca2+ indicate that the releasibility of Ca2+ and the beta-adrenoceptors are not the critical causes for the postischemic dysfunction in hypertrophied or non-hypertrophied myocardium.
据描述，严重肥厚的心肌对缺血的耐受性降低。对于非肥厚性心脏，关于钙（Ca2+）反应性的研究结果尚无定论。目前缺乏关于临床上常见的中度肥厚心脏对可逆性缺血的信息敏感性以及缺血后钙（Ca2+）反应性的研究。因此，本研究应探讨肥厚性和正常缺血后心肌对正性肌力刺激的反应性。
使用等容搏动离体心脏模型（8组，每组8个心脏）研究了来自4个月大的自发性高血压大鼠（SHR，左心室肥厚显著，+50%）的心脏和来自4个月大的正常血压Wistar大鼠的心脏。以左心室舒张末压评估，肥厚性和非肥厚性心脏在无血流缺血30分钟后的功能恢复分别为缺血前对照数据的78±1%和77±3%（非缺血对照组：肥厚性心脏为95±2%，非肥厚性心脏为93±3%）。与非缺血对照组分别为138±3%和157±5%相比，缺血后肥厚性和非肥厚性心脏在最大短期钙（Ca2+）刺激下左心室压峰值分别降低至124±4%和120±5%（p<0.01）。最大剂量的多巴胺刺激缺血后肥厚性和非肥厚性心脏的效果与钙（Ca2+）相当。分析钙（Ca2+）刺激的剂量反应曲线，尽管峰值降低，但肥厚性和非肥厚性心室的非缺血和缺血后心肌中以最大值分数表示的敏感性相同。
研究结果表明，在中度可逆性缺血后，肥厚性和非肥厚性缺血后心肌的稳态功能同样降低。两种类型的心肌对钙（Ca2+）的最大反应均显著降低，而钙（Ca2+）敏感性不变。多巴胺最大刺激后的结果与钙（Ca2+）刺激后的结果相同，表明钙（Ca2+）的释放能力和β-肾上腺素能受体不是肥厚性或非肥厚性心肌缺血后功能障碍的关键原因。
