Khabbaz Kamal R, Feng Jun, Boodhwani Munir, Clements Richard T, Bianchi Cesario, Sellke Frank W
Division of Cardiothoracic Surgery, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass 02215, USA.
J Thorac Cardiovasc Surg. 2008 Jan;135(1):139-46. doi: 10.1016/j.jtcvs.2007.07.035.
We investigated whether the degree of nonischemic myocardial acidosis during a period of cardioplegic arrest differentially affects the recovery of microvascular/left ventricular function, the profile of Bcl2-family protein expression, and the occurrence of apoptosis.
Isolated hearts from donor rabbits were perfused with oxygenated diluted blood on a modified Langendorff apparatus. The hearts were arrested for 60 minutes with cold (15 degrees C +/- 0.5 degrees C) diluted-blood cardioplegic solution (hematocrit: 18%-25%) administered continuously under nonischemic conditions (flow rate; 10 mL/min). The myocardial pH was adjusted and measured continuously with a glass electrode system. Myocardial pH was maintained at 7.2, 6.5, or 6.2, respectively (n = 6 per group) during 60 minutes of arrest. Hearts were then reperfused for 120 minutes with oxygenated diluted blood.
Recovery of left ventricular and microvascular endothelial function was better with a myocardial pH of 7.2 than with a pH of 6.5 or 6.2 (P < .05). There were no significant differences in total Bcl2, phospho-Bcl2-serine 70, phospho-Bad-serine 112, and phospho-Bad-serine 136 levels among groups. Myocardial pH of 7.2 also induced less caspase 3 activation and apoptotic cells (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) than a pH of 6.5 or 6.2 (P < .05). Regression analysis demonstrated that a significant relationship existed between the recovery of endothelial microvascular (r2 = 0.38, P =.004) or left ventricular (r2 = 0.37, P =.007) function and myocardial pH.
Severe acidosis during cardioplegic arrest, independent of ischemia, adversely affects recovery of microvascular and left ventricular function and increases indices of apoptosis. This effect on apoptosis may influence long-term outcome after cardiac surgery.
我们研究了心脏停搏期间非缺血性心肌酸中毒的程度是否会对微血管/左心室功能的恢复、Bcl2家族蛋白表达谱以及细胞凋亡的发生产生不同影响。
从供体兔获取离体心脏，在改良的Langendorff装置上用氧合稀释血液进行灌注。心脏在非缺血条件下（流速：10 mL/min），用冷（15℃±0.5℃）稀释血液心脏停搏液（血细胞比容：18% - 25%）持续灌注60分钟使其停搏。用玻璃电极系统连续调节并测量心肌pH值。在停搏的60分钟内，心肌pH值分别维持在7.2、6.5或6.2（每组n = 6）。然后用氧合稀释血液对心脏再灌注120分钟。
心肌pH值为7.2时左心室和微血管内皮功能的恢复比pH值为6.5或6.2时更好（P < 0.05）。各组之间总Bcl2、磷酸化Bcl2丝氨酸70、磷酸化Bad丝氨酸112和磷酸化Bad丝氨酸136水平无显著差异。与pH值为6.5或6.2相比，心肌pH值为7.2时诱导的半胱天冬酶3激活和凋亡细胞（末端脱氧核苷酸转移酶介导的dUTP缺口末端标记）也更少（P < 0.05）。回归分析表明，内皮微血管（r2 = 0.38，P = 0.004）或左心室（r2 = 0.37，P = 0.007）功能的恢复与心肌pH值之间存在显著关系。
心脏停搏期间的严重酸中毒，与缺血无关，会对微血管和左心室功能的恢复产生不利影响，并增加细胞凋亡指标。这种对细胞凋亡的影响可能会影响心脏手术后的长期预后。
