Path G, Robitaille P M, Merkle H, Tristani M, Zhang J, Garwood M, From A H, Bache R J, Uğurbil K
Department of Biochemistry, University of Minnesota, Navarre 55392.
Circ Res. 1990 Sep;67(3):660-73. doi: 10.1161/01.res.67.3.660.
Spatially localized nuclear magnetic resonance spectroscopy was used to investigate with transmural differentiation the response of myocardial high energy phosphate compounds and inorganic orthophosphate (Pi) to graded reductions in coronary blood flow caused by sustained coronary stenosis. In an open-chest model, localized 31P nuclear magnetic resonance spectra from five layers across the left ventricular wall were obtained simultaneously with transmural blood flow measurements during control conditions and during sustained graded reductions in intracoronary pressure. Both the blood flow, and high energy phosphate and Pi contents displayed transmural heterogeneity in response to decreases in intracoronary pressure. The subendocardial creatine phosphate (CP) level remained unchanged as blood flow was reduced to approximately 0.7 ml/min/g wet wt and decreased precipitously beyond this critical flow level. The relation between CP and flow in the midmyocardium and especially in the subepicardium was more complex. Subepicardial CP content did not correlate well with blood flow; however, in cases in which a coronary stenosis resulted in subendocardial hypoperfusion but subepicardial flow was near or above normal, a close correlation was present between subepicardial and subendocardial CP levels. ATP levels in all layers remained unaltered until blood flow was severely reduced. These results demonstrate that 1) the myocardial high energy phosphate and Pi levels at any transmural layer are not generally determined by O2 and blood flow limitation under basal conditions; 2) during subtotal coronary occlusion, increased oxygen extraction is able to meet myocardial needs until a critical level of stenosis is reached; 3) below a critical flow level, subendocardial CP and Pi contents are closely correlated with absolute subendocardial blood flow; and 4) in the presence of a coronary stenosis, subepicardial CP and Pi contents may change even in the absence of perfusion deficit secondary to loss of subendocardial function.
采用空间定位核磁共振波谱技术，通过透壁区分研究了心肌高能磷酸化合物和无机正磷酸盐（Pi）对持续性冠状动脉狭窄导致的冠状动脉血流分级减少的反应。在开胸模型中，在对照条件下以及冠状动脉内压力持续分级降低期间，同时获得左心室壁五层的局部31P核磁共振波谱以及透壁血流测量值。血流、高能磷酸盐和Pi含量均显示出对冠状动脉内压力降低的透壁异质性。当血流降至约0.7 ml/min/g湿重时，心内膜下肌酸磷酸（CP）水平保持不变，而超过此临界血流水平则急剧下降。心肌中层尤其是心外膜下CP与血流之间的关系更为复杂。心外膜下CP含量与血流的相关性不佳；然而，在冠状动脉狭窄导致心内膜下灌注不足但心外膜下血流接近或高于正常的情况下，心外膜下和心内膜下CP水平之间存在密切相关性。直到血流严重减少之前，所有层的ATP水平均保持不变。这些结果表明：1）在基础条件下，任何透壁层的心肌高能磷酸盐和Pi水平通常不由氧气和血流限制决定；2）在冠状动脉次全闭塞期间，增加的氧摄取能够满足心肌需求，直到达到临界狭窄水平；3）低于临界血流水平时，心内膜下CP和Pi含量与绝对心内膜下血流密切相关；4）在存在冠状动脉狭窄的情况下，即使在心内膜下功能丧失继发灌注不足的情况下不存在时，心外膜下CP和Pi含量也可能发生变化。
