Allan G, Chapple D J, Hughes B
Br J Pharmacol. 1986 Sep;89(1):183-90. doi: 10.1111/j.1476-5381.1986.tb11134.x.
The effects of BW12C on myocardial function in the erythrocyte-perfused rabbit heart and on myocardial infarct size in the anaesthetized dog have been evaluated. Perfusion of rabbit hearts with erythrocytes pretreated with BW12C (10(-3) M-4 X 10(-3) M) produced concentration-dependent decreases in left ventricular pressure (LVP), LVP dP/dt and coronary perfusion pressure. A concomitant decrease in PO2 and an increase in lactate production by the myocardium was also observed. Perfusion of rabbit hearts with Krebs Henseleit buffer containing BW12C (10(-5)-10(-4) M) caused no change in measured variables. Although BW12C (10(-3) M) caused a small decrease in LVP, coronary perfusion pressure and heart rate, these changes were not significant. In anaesthetized dogs, an infusion of BW12C (total dose 50 mg kg-1, i.v.) caused small, but significant, changes in haemodynamic status. The oxygen saturation curve was shifted to the left and relative % oxygenation (P20) was shifted to the left throughout the course of the experiment. (P20, control 16.3 +/- 0.4 mmHg; after BW12C 7.9 +/- 1.4 mmHg). Pretreatment with BW12C (total dose 50 mg kg-1) caused no change in area at risk but significantly increased the myocardial infarct size by 410%. These studies with BW12C demonstrate that alteration in haemoglobin-oxygen affinity can induce adaptive physiological changes in tissue function and metabolism and can assume a critical role when oxygen supply may be impaired due to a flow-limiting stenosis.
已评估了BW12C对红细胞灌注兔心脏心肌功能以及对麻醉犬心肌梗死面积的影响。用经BW12C（10⁻³M - 4×10⁻³M）预处理的红细胞灌注兔心脏，可使左心室压力（LVP）、LVP dP/dt和冠状动脉灌注压力呈浓度依赖性降低。同时还观察到心肌的PO₂降低以及乳酸生成增加。用含BW12C（10⁻⁵ - 10⁻⁴M）的Krebs Henseleit缓冲液灌注兔心脏，所测变量未发生变化。尽管BW12C（10⁻³M）使LVP、冠状动脉灌注压力和心率略有降低，但这些变化并不显著。在麻醉犬中，静脉输注BW12C（总剂量50 mg kg⁻¹）引起血流动力学状态出现小但显著的变化。在整个实验过程中，氧饱和度曲线向左移动，相对氧合百分比（P20）也向左移动。（P20，对照组为16.3±0.4 mmHg；BW12C处理后为7.9±1.4 mmHg）。用BW12C（总剂量50 mg kg⁻¹）预处理对危险面积无影响，但使心肌梗死面积显著增加了410%。这些关于BW12C的研究表明，血红蛋白 - 氧亲和力的改变可诱导组织功能和代谢的适应性生理变化，并且当由于限流性狭窄导致氧供应可能受损时，这种改变可能起关键作用。
