Wangler R D, Peterson W P, Sparks H V
Department of Physiology, Michigan State University, East Lansing 48824.
Am J Physiol. 1989 Mar;256(3 Pt 2):H772-8. doi: 10.1152/ajpheart.1989.256.3.H772.
d-Propranolol eliminates the increased adenine nucleoside release from hypoperfused hearts [R. D. Wangler, D. F. DeWitt, and H. V. Sparks, Am. J. Physiol. 247 (Heart Circ. Physiol. 16): H330-H336, 1984]. To determine whether d-propranolol reduces adenosine formation or adenosine release into the vascular compartment, we measured myocardial tissue adenosine (TADO). Decreased formation would lower TADO, whereas decreased release would elevate TADO. Reduction of perfusion pressure by 50% reduced coronary flow (CF), venous oxygen tension (PVO2), and myocardial oxygen consumption (MVO2) by approximately 40, 25, and 35%, respectively. Total adenosine and inosine released during 30 min of hypoperfusion increased 10- and 5-fold, respectively. Also, TADO increased from 2.68 +/- 0.37 to 5.17 +/- 0.67 nmol/g (P less than 0.05). In the presence of d-propranolol, the same reduction in perfusion pressure caused a similar decrease in CF and MVO2. d-Propranolol eliminated the release of adenosine and inosine associated with hypoperfusion. TADO after 30 min of hypoperfusion plus d-propranolol was not significantly increased (3.27 +/- 0.40 nmol/g) and was significantly less than hypoperfused hearts. When severe hypoperfusion was created by reducing perfusion pressure 75%, adenosine release still did not increase if d-propranolol was present. When adenosine release was plotted as a function of oxygen supply-consumption, they were related in a hyperbolic fashion. Despite the severity of hypoperfusion, in the presence of d-propranolol the supply-to-consumption ratio was similar to that of the control perfusion group (no drug). We conclude that d-propranolol blocks nucleoside formation during hypoperfusion by reducing oxygen demand such that a reduction of oxygen supply no longer stimulates adenosine formation.
右旋普萘洛尔可消除灌注不足心脏中腺嘌呤核苷释放的增加[R.D. 万勒、D.F. 德威特和H.V. 斯帕克斯，《美国生理学杂志》247(心脏循环生理学16):H330 - H336, 1984]。为了确定右旋普萘洛尔是否减少腺苷的形成或减少腺苷向血管 compartment 的释放，我们测量了心肌组织腺苷(TADO)。形成减少会降低TADO，而释放减少会升高TADO。灌注压力降低50%分别使冠状动脉血流量(CF)、静脉血氧张力(PVO2)和心肌耗氧量(MVO2)降低约40%、25%和35%。低灌注30分钟期间释放的总腺苷和肌苷分别增加了10倍和5倍。此外，TADO从2.68±0.37增加到5.17±0.67 nmol/g(P<0.05)。在右旋普萘洛尔存在的情况下，相同的灌注压力降低导致CF和MVO2出现类似程度的降低。右旋普萘洛尔消除了与低灌注相关的腺苷和肌苷的释放。低灌注30分钟加右旋普萘洛尔后的TADO没有显著增加(3.27±0.40 nmol/g)，且显著低于灌注不足的心脏。当通过将灌注压力降低75%造成严重低灌注时，如果存在右旋普萘洛尔，腺苷释放仍不会增加。当将腺苷释放作为氧供应 - 消耗的函数作图时，它们呈双曲线关系。尽管低灌注严重，但在右旋普萘洛尔存在的情况下，供应与消耗的比率与对照灌注组(无药物)相似。我们得出结论，右旋普萘洛尔通过降低氧需求来阻断低灌注期间核苷的形成，从而使氧供应的减少不再刺激腺苷的形成。
