Progressive cardiac dysfunction with repeated pacing-induced ischemia: protection by AICA-riboside.
The effects of repeated episodes of demand-induced ischemia on regional myocardial wall thickening, endocardial electrogram, and regional myocardial blood flow are not well delineated. We studied the cumulative effects of six periods of pacing-induced ischemia in 35 chloralose-anesthetized dogs with circumflex coronary stenosis. Repetitive ischemia of the posterior left ventricular free wall was induced with six 5-min pacing periods separated by 15-min recovery periods. The three groups of dogs studied were 1) saline control, 2) the purine precursor 5-aminoimidazole 4-carboxamide riboside (AICA-r), and 3) nitroglycerin (NTG). During the initial pacing period (before treatment), thickening of the posterior wall declined in the saline group (43 +/- 5% of control), the AICA-r group (47 +/- 8% of control), and the NTG group (55 +/- 3% of control), associated with endocardial S-T segment elevation and a decrease in subendocardial blood flow. Wall thickening continued to decrease in each group with each successive pacing episode. However, during the sixth pacing period wall thickening was significantly (P less than 0.05) less in the saline group (2 +/- 5% of control) than in the AICA-r (31 +/- 7% of control) or NTG (61 +/- 7% of control) group. The progressive decline in wall thickening was accompanied by a further decrease in subendocardial blood flow and a rise in S-T segment in the saline group but not in the AICA-r or NTG group (P less than 0.05). These results demonstrate that sequential periods of ischemia and reperfusion cause a progressive decline in regional wall motion, coincident with a progressive decrease in subendocardial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)
Young
M A
MA
Research Department, Gensia Pharmaceuticals, San Diego, California 92121.
Mullane
K M
KM
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation; D003327:Coronary Disease / Q000503:physiopathology* / Q000517:prevention & control; D004285:Dogs; D004699:Endocardium / Q000187:drug effects / Q000503:physiopathology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D012265:Ribonucleotides / Q000494:pharmacology*
D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C031143:AICA ribonucleotide; D005996:Nitroglycerin