Mechanisms of action of various ATP-sensitive potassium channel openers.

Dr. Grover’s very kind and complimentary remarks about the recent review [l] on ATP-sensitive potassium channel openers during ischemia and reperfusion are much appreciated. One point, however, causes Dr. Grover considerable concern-this is the citation of (and by implication a presumed agreement with) the comments in the paper by Richer et al. [2]. This paper was critical of the conclusions of a study [3] by Dr. Grover and colleagues in which the authors compared intravenous versus intracoronary administration of nicorandil versus cromakalim. This reply to Dr. Grover is from the author of the review [ 1 ] and the senior co-author of the contentious paper [2]. Dr. Grover states that “Professor Hearse criticised this study based on the lOO-fold lower dose of nicorandil given into the coronary”. Dr. Grover then goes on to justify the choice of this dose on the basis of the fact that the coronary bed supplies a very small mass of tissue and therefore a much lower absolute dose is required than with intravenous administration. We filly accept this and indeed, neither the review El] nor the Richer article [2] took specific issue with this aspect of Dr. Grover’s protocol design. The criticism that was intended related not to the choice of dose between intravenous and intracoronary studies but to the fact that Grover et al. [3] used a dose of nicorandil that was only 3 times higher than that selected for cromakalim. What Professor Hearse actually stated in his concluding synopsis of the Richer paper was that “they argued that, since nicorandil was ten times less potent than cromakalim, any study designed to compare the two drugs and the two routes of administration should have employed a larger dose of nicorandil.” The choice of intravenous versus intracoronary dose was not actually contested by the author of the review. The point at issue (which has been made on a previous occasion [4] by the co-signatory of this letter) is quite straight forward: namely, that because nicorandil is at least 10 times less potent than