We have greatly appreciated the interest by Dr Vinten-Johansen [1] in our paper investigating the beneficial impact of polarizing microplegia on biochemical, hemodynamic, echocardiographic and clinical outcomes of patients undergoing CABG for unstable angina [2]. We are really intrigued about his comments, related to the potential underestimation of the beneficial effects of our microplegia in terms of postoperative clinical outcome. Indeed, we were really impressed by our biochemical results, showing a significantly attenuated perioperative release of troponin I —which was our primary endpoint [2]. Accordingly, we have underscored also the significant amelioration of the entire “hemodynamic pattern” of patients treated with microplegia during the postoperative course, because of the better systo-diastolic left ventricular function at echocardiography, and the better hemodynamic indices of cardiac function,myocardial oxygenconsumption, andventricular–arterial coupling at PRAM monitoring [2]. However, when clinical outcome was considered, we were able to demonstrate only a significant reduction of blood products usage and a significantly shortened hospitalization. However, the level of statistical significance of our secondary clinical outcome “proxies” was significantly augmented by the Bonferroni correction, so that only a “trend” towards a shorter/lower needof inotropic support and a shorter ICU-length of stay could be detected.Whether these “preliminary” beneficial effects will translate in statistical significant differencesneed tobeascertainedonhighernumberof patients and future clinical studies. However, we agree with Dr Vinten-Johansen that improvements in length of hospitalization and usage of blood products are still sufficient to ameliorate patient's outcome and hospital costs [3]. When the risk for potential bias related to the complex combinations of substrates in both groups (Buckberg andMicroplegia) was considered, we completely agree that it is difficult at the moment to attribute the overall beneficial effect of microplegia to one or other substrate composing our “microplegic milieu”. However, we have tried to avoid all the potential biases by either strict enrollment criteria or standardized perioperative care. As example, tight glycemic control was always guaranteed by the application of Portland protocol either intraoperatively and postoperatively [4], so that only slight oscillations in glycemia could happen. Furthermore, the role of insulin in myocardial protection can be considered a “never-ending story” which has actually no data demonstrating its beneficial effect [5,6]. Furthermore, when microplegia is routinely used in clinical practice (as we do in our institution following that experimental study), thefirst “impressive” result– compared toother cardioplegic solutions – is the extremely rare need for internal cardioversion after aortic declamping, a well-known sign of adequacy of myocardial protection for cardiac surgeons. According to the pioneering studies by Dobson et al. proving the anti-ischemic, antiinflammatory and pre-conditioning effects of adenosine–lidocaine– magnesium (ALM) solutions [7,8], we think that our data can only be attributed to a better myocardial protection achieved with the entire “ALM”milieu. According to that, our results – although achieved with a lower concentration of ALM reported in other preliminary clinical experiences [1] and animal studies [7,8] – can only be the consequence of anattenuated ischemia–reperfusion injury (IRI) in a cohortof patients at high risk, because of unstable angina, for severe IRI following aortic declamping [2]. Similarly, we cannot exclude that our blood product saving can be related either to the lower hemodilution (all-blood cardioplegia vs 4:1 crystalloid dilution of our Buckberg solutions) and the higher anti-inflammatory/anti-fibrinolytic effect (a direct consequence of IRI-attenuation) of microplegia. Certainly future studies on the topic are needed for definitive conclusions. Finally,weperfectlyagreewithDrVinten-Johansenon theurgentneed for future clinical and laboratory investigations on the potential multiorgan effects of ALM in cardiac surgery. As examples, other intriguing issues needing future clinical investigations are the comparison between continuous and intermittent ALM administrations [9] and between “warm” and “cold” ALM administrations [10]. Certainly, the time to move from bench to bed has come!
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