Can We Improve Myocardial Protection during Ischaemic Injury?

Ferrari, Roberto; Biscaglia, Simone; Malagù, Michele; Bertini, Matteo; Campo, Gianluca

doi:10.1159/000444847

Cited by 11 publications

(11 citation statements)

References 59 publications

(73 reference statements)

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“…Unfortunately, despite strong logic, both animal and clinical studies examining the cardioprotective effect of different antioxidants have always been inconclusive. 1 As oxidative stress reduces the availability of nitric oxide (NO), it was also thought that the administration of NO donors could be cardioprotective. When tested in the clinic and administered to reperfused STEMI patients, nicorandil, an NO donor, and trimetazidine, a metabolic modulator with antioxidant properties, failed to limit the infarct size.…”

Section: Calcium Paradoxmentioning

confidence: 99%

“…That reperfusion itself might contribute to the damage during AMI seems a paradox as, unquestionably, timely revascularization either by thrombolytic therapy or primary percutaneous coronary angioplasty (PCA) is, at present, the most effective therapy for limiting infarct size, reducing the healing pattern of the infarcted zone, preserving left ventricular systolic function and delaying the onset of remodeling and heart failure. [1][2][3][4] In the present review we analyze the "two-faced aspect" of reperfusion itself, we highlight the progress and the failure of each of the 4 lines of research, trying to summarize the most important and probable physiopathologic aspects of RI, as well as the evolving therapies targeting ischemic/reperfusion injury.…”

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confidence: 99%

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Reperfusion Damage　― A Story of Success, Failure, and Hope ―

Ferrari

Balla

Malagù

et al. 2017

Circ J

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wrong, an error that was confirmed by a number of completely unsuccessful clinical trials that failed to show the benefits with a range of putative infarct-reducing agents. The main reason for this discrepancy lay in the time of administration of the compounds (i.e., before the onset of ischemia in the experimental setting, after the infarct in the clinical one).It then became apparent that early reperfusion was a prerequisite for the salvage of ischemic tissue. At the same time, it became also evident that reperfusion per se can be, paradoxically, dangerous, increasing rather than reducing the extension of the infarct.The second line of research related to cardiac surgery. Quickly, coronary artery bypass became a standard procedure for patients with angina and, with the time, this was extended, although with poor results, to evolving myocardial infarction (MI). No doubt that the surgeons had the monopoly of reperfusion and indeed they managed to develop techniques such as cardioplegia and hypothermia able to protect against the damage induced by reperfusion. Once again, the success of these techniques relies on their application before induction of ischemia.The third line of research is linked to pharmacologists who, in parallel with surgeons and pathologists, questioned that the thrombus was the result of an infarct. They proved that, actually, it is the cause of the infarct and started to look at measures to dissolve the infarct-initiating thrombi. Medicine has been undergoing constant changes, with cardiology being arguably the fastest changing field of all. The evolution -or should we say the revolution -of reducing the progression of coronary atherosclerosis with aspirin, angiotensin enzyme inhibitors and cholesterol-lowering drugs had a remarkable effect on the treatment of coronary artery disease. But perhaps one of the most important changes in cardiology is the ability to reperfuse the ischemic myocardium and consequently to reduce the deleterious effects of acute ischemia. Interestingly, during the second half of the century, 4 independent and different streams of research were initiated and would culminate in the ability to reperfuse the ischemic human heart.The first line of research related to pathophysiology. The 1960 s witnessed a remarkable increase in the systematic study of (1) the nature of atheroma and thrombosis and (2) the metabolic, contractive, ultrastructural and electrophysiological consequences of myocardial ischemia. Later, in part because of the relative ease of restoring coronary flow, investigators, including the authors of this review, turned their attention to the effects of reperfusion. 1-4 The idea of protecting the ischemic myocardium soon attracted a lot of enthusiasm and a cornucopia of compounds such as β-blockers, calcium antagonists, antiinflammatory drugs, and vasodilators were administered to animals with results that appeared dramatically successful. In the 1970 s and 1980 s, however, it became clear that this approach was Tissue salvage of severely ischemic myocardiu...

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Section: Calcium Paradoxmentioning

confidence: 99%

mentioning

confidence: 99%

Reperfusion Damage　― A Story of Success, Failure, and Hope ―

Ferrari

Balla

Malagù

et al. 2017

Circ J

Self Cite

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show abstract

“…In the first part of this review in Cardiology , we elaborated the concept that early interventions to open occluded coronary arteries may limit infarct size and subsequent remodelling, but late opening of coronary occlusions may do more harm than good [1]. Although myocardial infarction in humans is a complex process, it usually evolves areas of acute myocardial necrosis and adjacent regions, where viable and/or stunned myocytes exist.…”

Section: Remodelling After Myocardial Infarctionmentioning

confidence: 99%

“…Also, clinical studies show that it is not always progressive, as in the conventional picture of the so-called ‘cardiovascular continuum', implying that once the LV dilatation starts, it inexorably leads to further worsening of cardiac function, HF and, ultimately, death, either by triggering arrhythmias or by end-stage congestion and pump failure [1]. This may have been true in the past, but, likely due to the benefits of modern therapy, is no longer the case for every patient.…”

Section: Remodelling After Myocardial Infarctionmentioning

confidence: 99%