AJP - Heart and Circulatory Physiology, Vol 253, Issue 5 1224-H1233, Copyright © 1987 by American Physiological Society
Inosine preserves ATP during ischemia and enhances recovery during reperfusion
Sr. Devous MD and E. D. Lewandowski
Nuclear Medicine Center, University of Texas Health Science Center at Dallas 75235.
The effects of exogenous inosine (IN) on high-energy phosphate metabolism
and function in isolated, working rabbit hearts were monitored with
31P-nuclear magnetic resonance spectroscopy. Dynamic measurements of ATP
and phosphocreatine (PCr) were made along with concomitant functional
recordings during normal perfusion, global ischemia (IS), and reperfusion
(RE). We found that 0.1 mM IN enhanced the rate of pressure development
(dP/dt) within the left ventricle by 10 +/- 5% (n = 7). Although IN levels
in treated hearts were elevated during normal perfusion, no effect was
observed on ATP or PCr levels. However during IS, pretreatment with IN
minimized ATP loss for the first 20 min relative to untreated controls
(UNT, P less than 0.05). Both IN and UNT hearts that were ischemic for only
13.5 min regained function during a 60-min RE period. However, at the end
of IS, IN hearts (n = 8) displayed 88 +/- 10% of the pre-IS ATP levels,
whereas UNT hearts (n = 7) retained only 60 +/- 10%. With RE, ATP in IN
hearts remained elevated over that of UNT hearts for the entire 60 min. IN
treatment also increased the rate of recovery of dP/dt and maintained
improved function over 60 min of RE. No correlation was found between
post-IS ATP levels and dP/dt values during RE in either IN or UNT hearts.
These data indicate that IN was protective against ATP loss during IS and
improved functional recovery on RE.
