Canine coronary vasodepressor responses to hypoxia are attenuated but not abolished by 8-phenyltheophylline.

The purpose of this study was twofold: 1) to verify a report that a suspension of 8-phenyltheophylline (8-PT) completely abolished hypoxia-induced coronary vasodilation [H. M. Wei, Y. H. Kang, and G. F. Merrill. Am. J. Physiol. 257 (Heart Circ. Physiol. 26): H1043-H1048, 1989] and 2) to determine the effect of dissolved 8-PT on hypoxic hyperemia. The left anterior descending coronary artery of anesthetized dogs was cannulated and perfused at either constant flow or constant pressure. An 8-PT suspension (40 micrograms.kg-1.min-1) produced a twofold elevation of coronary perfusion pressure at constant flow, a 97% decrease in coronary flow at constant pressure, and regional akinesia in both conditions. The coronary vasculature was unresponsive to 60-s coronary occlusion, exogenous adenosine, and hypoxia after infusion of the 8-PT suspension. These findings are consistent with obstruction of the coronary microvasculature by the 8-PT suspension. An 8-PT solution (40 micrograms.kg-1.min-1) produced 95 +/- 3% (P less than 0.001, n = 6) attenuation of exogenous adenosine-induced vasodilation at constant pressure, a 28 +/- 5% (P less than 0.01, n = 6) attenuation of reactive hyperemia, and a 24 +/- 6% (P less than 0.05, n = 6) decrease in hypoxia-induced vasodilation. An 8-PT solution had no effect on systolic segment length shortening and myocardial oxygen consumption. We conclude that 8-PT, when in solution, attenuates but does not abolish the coronary vasodilatory response to hypoxia. Hence, adenosine appears to contribute to hypoxia-induced vasodilation but is not uniquely responsible for the hyperemic response.
AuthorsS C Lee, R T Mallet, Y Shizukuda, A G Williams Jr, H F Downey
JournalThe American journal of physiology (Am J Physiol) Vol. 262 Issue 4 Pt 2 Pg. H955-60 (Apr 1992) ISSN: 0002-9513 [Print] UNITED STATES
PMID1566915 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Solutions
  • 8-phenyltheophylline
  • Theophylline
  • Adenosine
  • Adenosine (pharmacology)
  • Animals
  • Anoxia (physiopathology)
  • Coronary Circulation (drug effects)
  • Dogs
  • Heart (drug effects, physiopathology)
  • Hemodynamics (drug effects)
  • Pressure
  • Solutions
  • Theophylline (analogs & derivatives, pharmacology)
  • Vasodilation (drug effects)

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