title: Nonischemic myocardial acidosis adversely affects microvascular and myocardial function and triggers apoptosis during cardioplegia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass 02215, USA.
authors.forename: Kamal R
authors.initials: KR
authors.lastname: Khabbaz
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.forename: Munir
authors.initials: M
authors.lastname: Boodhwani
authors.forename: Richard T
authors.initials: RT
authors.lastname: Clements
authors.forename: Cesario
authors.initials: C
authors.lastname: Bianchi
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D017209:Apoptosis; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D003326:Coronary Circulation / Q000502:physiology; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D008833:Microcirculation / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011817:Rabbits; D020127:Recovery of Function; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2