ISSN:
1435-1803
Keywords:
Adenosine deaminase
;
microdialysis
;
micropig
;
myocardial blood flow
;
pentostatin
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract In order to examine the relationship between local adenosine concentrations before, during, and after ischemia and the extent of ischemic myocardial damage, measurements of interstitial fluid (ISF) nucleosides were made using microdialysis probes implanted in the ischemic region of isoflurane anesthetized Micropigs undergoing 60′ coronary artery occlusion (CAO) and 3h of reperfusion (REP). Nucleoside concentrations in the dialysate collected from the microdialysis probes were used as an index of ISF levels. Dialysate nucleoside concentrations (ADO, inosine and hypoxanthine), myocardial infarct size, and myocardial blood flow (MBF) were determined in control animals (n=6), animals preconditioned with a single 10′ cycle of CAO and REP (PC, n=6), and those treated with the adenosine deaminase inhibitor pentostatin (n=6, 0.2 mg/Kg IV 30′ prior to CAO). The brief PC occlusion resulted in a transient but significant increase in dialysate ADO (6.7±1.8 μM vs. 0.67±0.1 μM at baseline). Pentostatin administration had no significant effect on either dialysate nucleosides or MBF at baseline. During the 60′ CAO, dialystate ADO increased in control animals. In PC animals, however, dialysate ADO during CAO was lower than control. Pretreatment with pentostatin resulted in a six-fold augmentation in dialysate ADO during the 60 min CAO when compared to the control values (110.62±30.2 μM vs. 16.31±2.1 μM at 60 min of ischemia). Pentostatin also resulted in a significant reduction in the accumulation of inosine and hypoxanthine, indicating inhibition of adenosine deaminase activity. There were no significant differences in MBF between groups at any time point. Following 3 h REP, infarct size was 35.4±5.5%, 8.1±1.5% and 8.3±1.8% of the region at control, PC, and pentostatin groups, respectively. These data suggest that marked increase in ISF ADO during CAO, may be as effective in reducing INF as a modest increase in ISF ADO prior to prolonged CAO.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00788519
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