3-isobutyl-1-methylxanthine (IBMX) sensitizes cardiac myocytes to anoxia.
Cardiac myocytes incubated with 3-isobutyl-1-methylxanthine (IBMX), a nonspecific cyclic nucleotide phosphodiesterase inhibitor, formed rigor complexes under anoxic conditions more readily than cells incubated with other phosphodiesterase inhibitors. Cardiac myocytes were incubated for 1 hr with either (a) no additions, (b) 150 microM zaprinast, or (c) 1 mM IBMX, and then were rendered anoxic for periods up to 60 min. Cells were >80% viable throughout the anoxic period; viability was unaffected by either drug. Rod count decreased more rapidly after the onset of anoxia in the IBMX-treated cells than in control or zaprinast-treated cells (11% rods vs. roughly 47% rods after 30 min of anoxia). IBMX-treated cell groups also formed more "contracted" myocytes (box-like rods) than their untreated or zaprinast-treated counterparts (50% contracted vs. roughly 27% contracted after 30 min of anoxia). While nucleotide degradation patterns were similar in all experimental groups, the ratio of ATP to ADP was lower in IBMX-treated cells than in control or zaprinast-treated cells. The L-type calcium channel was apparently not involved in this phenomenon; while cyclic AMP was elevated in the IBMX-incubated cells, verapamil did not protect IBMX-incubated cells from premature damage by anoxia. Incubation with 8-cyclopentyl-1,3-dipropylxanthine (CDPX), an A1 receptor antagonist, at concentrations up to 1 microM in place of 1mM IBMX did not reproduce the IBMX effect. We concluded that IBMX sensitizes cardiac myocytes to anoxia through a mechanism related to its effect on ATP/ADP, and unrelated to an elevation of intracellular calcium or preconditioning phenomena.
Geisbuhler
Timothy P
TP
Department of Physiology, Kirksville College of Osteopathic Medicine, 800 West Jefferson Street, Kirksville, MO 63501, USA. tgeisbuhler@kcom.edu
Schwager
Tammie L
TL
Ervin
Heather D
HD
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D000818:Animals; D015687:Cell Hypoxia; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats
D010726:Phosphodiesterase Inhibitors; D015056:1-Methyl-3-isobutylxanthine