Clive S. Lawson

Ischemic Preconditioning against Arrhythmias: An Anti-Arrhythmic or an Anti-Ischemic Phenomenon?

Experimental studies have shown that the resistance of the heart to a prolonged episode of ischemia is transiently but substantially increased after one or more brief (<5 min) episodes of ischemia and reperfusion. 132 This phenomenon, “ischemic preconditioning,” reliably reduces the extent of myocardial necrosis in all species studied to date.2-5 The limitation in infarct size is achieved by delaying the development of necrosis thereby allowing enhanced tissue salvage on reperfusion.2 Sudden death in acute myocardial infarction is usually due to the development of malignant ventricular arrhythmias6 and experimental studies have indicated that preconditioning can also reduce the severity of those induced by both ischemia and repe r fu~ ion .~ -~ The delaying effect of preconditioning on myocardial necrosis might suggest that its anti-arrhythmic protection would be due to an alteration ( e g , delay) in the time-dependent characteristics of the arrhythmias. It is possible, however, that preconditioning has a true anti-arrhythmic action and is capable of producing an absolute reduction in arrhythmia severity irrespective of the duration of ischemia or reperfusion. Previous studies have failed to distinguish between these possibilities, in part because they were performed in viva and were associated with significant data censoring as a consequence for non-arrhythmic animal mortality. Protection against myocardial necrosis can be achieved with a single cycle of preconditioning ischemia and reperfusionlo but conflicting data have been reported as to whether additional benefit can be gained from additional cycles.10-12 Although previous studies investigating preconditioning and arrhythmogenesis have generally employed multiple preconditioning cycle~32~.~ none has addressed whether the additional cycles are necessary for maximum anti-arrhythmic protection. In the present studies isolated, blood-perfused rat hearts have been employed to examine whether the protective effect of preconditioning against ischemiaand reperfusion-induced arrhythmias is due to an alteration in their temporal profile or to an absolute reduction in their severity. In addition, we have investigated whether multiple cycles of preconditioning ischemia and reperfision are associated with a cumulative anti-arrhythmic benefit.

Preconditioning and Ischemia- and Reperfusion-Induced Arrhythmias

The term preconditioning is currently employed primarily to describe the enhanced resistance to ischemia-induced myocardial necrosis afforded by one or more brief preceding episodes of ischemia and reperfusion. Indeed, some investigators believe that the term should be reserved strictly for studies where myocardial protection is expressed as a limitation of myocardial infarct size. Quite why such a limited usage should be suggested is, in our opinion, not clear. Historically, of course, the term preconditioning with ischemia was first coined in the context of infarct size limitation in dogs [1]. That report, and the many subsequent confirmations of the potency of preconditioning (for review, see reference [2]), generated a great deal of excitement, principally because, with the exception of reperfusion, no previous intervention had proven able to afford a sustained limitation of infarct size under carefully controlled experimental conditions. Myocardial protection, however, can be manifest in a number of different ways, and the study by Murry et al. [1] was by no means the first to document altered myocardial responses to serial challenges. Two years earlier Neely and Grotyhan [3] had described the protective effect of a period of hypoxic perfusion on contractile dysfunction and the accumulation of metabolic products following an ischemic challenge. The first indications of the antiarrhythmic properties of what might now be considered ischemic preconditioning, however, were published even earlier [4] and predate Murry’s classical paper [1] by more than 30 years.

Giant sinus of Valsalva aneurysm: the role of multimodality imaging

An 82-year-old man presented with severe exertional breathlessness to the outpatient clinic. Previous medical history included hypertension and transient ischaemic attack. During routine workup, transthoracic echocardiography was performed. A large defect (*) in the anterior wall of the aortic sinus of Valsalva was identified (figure 1A) which extended into a cavity containing spontaneous echo-contrast (see online supplementary data video S1). Further imaging by CT with three-dimensional reconstruction (figure 1B,C) and cardiac magnetic …