title: Formation of S-adenosylhomocysteine in the heart. II: A sensitive index for regional myocardial underperfusion.
abstract: Rate of accumulation of myocardial S-adenosylhomocysteine (SAH) was used in an open-chest dog preparation as an index of free cytosolic adenosine levels. Following 30 minutes of coronary artery ligation and infusion of L-homocysteine thiolactone (10 mumol/kg/min i.v.) SAH levels increased from 1.3 (control) to 3.3 nmoles/g in the nonischemic and to values over 100 nmoles/g in the ischemic region. Compared with regional myocardial blood flow the enhanced rate of SAH accumulation was strictly confined to the ischemic area. As long as blood flow was 0.6-1.2 ml/min/g, SAH levels remained unchanged. However, they steeply increased when regional myocardial blood flow decreased below 60% of control. Tissue levels of adenine nucleotides, adenosine, and lactate were not significantly affected in the flow range of 0.4-0.6 ml/min/g but rate of SAH accumulation was enhanced by 400%. In the nonischemic myocardium, SAH accumulation was 60% higher in the subendocardium than in the subepicardium. Decreasing coronary perfusion pressure from 110 to 60, 45, and 35 mm Hg was associated with an exponential increase in coronary venous adenosine release only when perfusion pressure was below 60 mm Hg. Transmural mapping of SAH revealed that at 110 mm Hg SAH was homogeneously distributed, while at a perfusion pressure of 60 mm Hg SAH accumulation was enhanced only in the subendocardial layers. Decreasing perfusion pressure further to 40 and 30 mm Hg not only enhanced subendocardial SAH levels to 120 and 170 nmoles/g, respectively, but also considerably steepened the transmural gradient of SAH. SAH-hydrolase exhibited a broad pH-optimum and its activity in different parts of ventricular myocardium was identical. Our findings provide evidence that 1) measurement of SAH accumulation is a sensitive metabolic index for the assessment of regional myocardial ischemia, 2) significant formation of SAH occurs only when regional myocardial blood flow is less than 0.6 ml/min/g, and 3) transmural SAH gradient, a measure of free cytosolic adenosine, and coronary venous adenosine release significantly increase only when the autoregulatory reserve is exhausted.
authors: Zentrum für Physiologie, Universität Düsseldorf, FRG.
authors: A
authors: A
authors: Deussen
authors: M
authors: M
authors: Borst
authors: K
authors: K
authors: Kroll
authors: J
authors: J
authors: Schrader
mesh_terms: D000241:Adenosine / Q000032:analysis / Q000097:blood; D043383:Adenosylhomocysteinase; D000818:Animals; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism; D004285:Dogs; D004699:Endocardium / Q000201:enzymology; D006710:Homocysteine / Q000031:analogs & derivatives*; D006863:Hydrogen-Ion Concentration; D006867:Hydrolases / Q000378:metabolism; D009206:Myocardium / Q000032:analysis / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion; D012435:S-Adenosylhomocysteine / Q000096:biosynthesis*
chemical_list: D006710:Homocysteine; D012435:S-Adenosylhomocysteine; D006867:Hydrolases; D043383:Adenosylhomocysteinase; D000241:Adenosine