Ann Thorac Surg 1996;61:1688
© 1996 The Society of Thoracic Surgeons
Discussion
Discussion
See also page 1680.
DR ALDEN H. HARKEN (Denver, CO):I find this very exciting material. This hyperpolarized concept is a very real adjunct to our standard cardioplegic techniques. I have several questions. First, with doses of pinacidil greater than 50 µmol/L, why does there seem to be a decrease in mechanical function? Second, do you have a putative mechanism for the increase in coronary blood flow? And third, during ischemia, if the ventricular electrical activity persists, then it is counterintuitive that that would preserve high-energy phosphates. Could you explain this for me?
DR LAWTON:
Thank you, Dr Harken. To answer your first question, we do not know the reason for toxicity at high and low doses of pinacidil. Previous work from our laboratory demonstrated a similar pattern of toxicity with the potassium channel opener aprikalim. The best dose of aprikalim was 100 µmol/L, with toxicity at higher doses. The decrease in mechanical function may be due to a specific effect of the drug on the potassium channel or other ion channels, or it may be due to some unrelated effect of the drug that has yet to be determined.
To answer your second question, we do not believe that the increased coronary blood flow seen with pinacidil on reperfusion was an exaggerated hyperemic response, as we noted a better recovery of ventricular function in the group with the highest coronary blood flow on reperfusion. The increased blood flow may be due to the potent vasodilator effect that these drugs are known to have. Other investigators have shown this vasodilator effect to be unrelated to the cardioprotective effects, as they demonstrated an improved recovery of ventricular function after ischemia while reperfusion coronary blood flow was held constant.
To answer your third question, the limited persistence of electrical activity in these hearts does not appear to be detrimental. It has been demonstrated that electrical activity constitutes less than 1% of myocardial oxygen consumption. In addition, previous work from our laboratory has demonstrated that inhibition of persistent electrical activity with procaine during myocardial ischemia protected with the potassium channel opener aprikalim does not improve ATP preservation.
Related Article
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Myocardial Protection With Pinacidil Cardioplegia in the Blood-Perfused Heart
- Jennifer S. Lawton, Gary C. Harrington, Cynthia T. Allen, Peng-Wie Hsia, and Ralph J. Damiano, Jr
Ann. Thorac. Surg. 1996 61: 1680-1688.
[Abstract]
[Full Text]
