ACTH analogue in treatment of acute aortic dissection-Authors' reply.

Sir—The fact that the mortality rate inour patients who were assigned to thestandard treatment, without ACTH-(1-24) addition, was higher than thatreported in previous studies might beexplained by their severe haemodynamiccompromise. We selectedsubjects with type A aortic dissectioncomplicated by aortic rupture andcardiac tamponade, and with clinicaland laboratory signs of haemorrhagicshock.We share Olsson’s opinion thatACTH-(1-24) essentially modifies thecomplex pathophysiology of theperioperative period. Not only byimproving the cardiovascular function;indeed, several experimental datasuggest that melanocortins have also apeculiar, adrenal-independent antiinflammatoryactivity. They reduce theproduction of proinflammatorycytokines, such as interleukins 1, 1,and 6, and tumour necrosis factor(TNF) , and inhibit the activation ofthe transcription factor NF-kB, whileincreasing the production of the antiinflammatorycytokines interleukins 8and 10;1 in particular, in conditions ofhaemorrhagic shock, melanocortinsinhibit the overproduction of TNF,nitric oxide, and free radicals.2,3Moreover, melanocortins protectagainst the outcomes either of a shorttermmyocardial ischaemia followed byreperfusion or of the permanentocclusion of a coronary artery in rats.4Our patients underwent fluidreplacement en route and ventilatorysupport but no rescue surgery. Ourcardiac surgery unit is situated roughlyin the middle of a flat territory innorthern Italy, with a high populationdensity (about 1 million people), and areasonable road system. The time lapsefrom emergency call to arrival into thecasualty ward, by ambulance or byhelicopter, is 20–40 min.Our animal data suggest that thetime span of ACTH-(1-24) efficacy isbest if given within 5–15 min of shockinduction. We have fewer human data,but they suggest that treatment must bemade within 1 h of the first signs ofshock. In case of haemorrhagic shock(road or industrial accidents, &c), webelieve ACTH should be given asintravenous bolus injection at thescene, or en route in the ambulance.The effect of ACTH lasts a few hours.