The In Vitro Effects of Phosphodiesterase Inhibitors on the Human Internal Mammary Artery

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Abstract
The internal mammary artery (IMA) is the preferred conduit for myocardial revascularization, but it changes diameter in response to injury or thromboxane release to decrease myocardial blood supply.Papaverine, a phosphodiesterase (PDE) inhibitor, is injected in the IMA bed during surgery to prevent spasm. We evaluated the ability of papaverine and cyclic adenosine monophosphate PDE Type III (cAMP-PDE) inhibitors (amrinone, enoximone, and milrinone) in vitro to reverse the constriction of human IMA rings, induced by a thromboxane A2 analog, U46619, and evaluated amrinone's ability to modify the constricting effect of norepinephrine (NE). All cAMP-PDE inhibitors produced complete relaxation of U46619-induced contractions. The concentrations necessary to produce 50% relaxation (EC50) were within therapeutic ranges. The vasodilatory potency of amrinone was greater after NE than after U46619 (EC50, 1.9 +/- 0.5 vs 4.3 +/- 2.2 times 10-5 M; mean +/- SD; P < 0.05). Response to constriction after a submaximal dose of NE was attenuated to 38% (P < 0.001) from that observed in the control rings by a pretreatment with amrinone. These results suggest that cAMP-PDE inhibitors have the potential utility to reverse IMA spasm, and represent a potential therapeutic modality for IMA spasm after myocardial revascularization. (Anesth Analg 1996;82:954-7)