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The efficacy of cardioprotective strategies can be quantified by myocardial salvage as an indicator of therapeutic benefit. Salvage is calculated as the difference between the area at risk (AAR) and the final infarct size (FIS). AAR has been quantified by angiographic assessment followed by quantification of FIS by biochemical ischaemic markers or imaging modalities such as cardiovascular magnetic resonance (CMR). Angiographical methods may overestimate AAR and since methodological differences may exist between different modalities, the use of different modalities for estimating AAR and FIS may not be recommended. 99mTechnetium (Tc)-Sestamibi single-photon emission tomography (SPECT) allows quantification of AAR and FIS by tracer injection prior to revascularization and after 1 month, respectively. SPECT provides the most validated measure of myocardial salvage and has been utilized in multiple randomized clinical trials. However, SPECT is logistically challenging, expensive, and includes radiation exposure. More recently, a large number of studies have suggested that CMR can determine salvage in a single examination by combining measures of myocardial oedema in the AAR exposed to ischaemia reperfusion with FIS quantification by late gadolinium enhancement. The T1- and T2-weighted CMR approaches for quantification of AAR utilize non-contrast, early and late gadolinium enhancement techniques. The technical progress, high spatial resolution and the potential for retrospective quantification of the AAR makes CMR the most appropriate technique for assessment of myocardial salvage. However, the optimum CMR technique for assessment of myocardial AAR remains to be defined. Consequently, we recommend a comprehensive CMR protocol to ensure reliable assessment of myocardial salvage. [ABSTRACT FROM PUBLISHER]

Abstract: Objectives: Membrane-targeted application of complement inhibitors may ameliorate ischemia/reperfusion (I/R) injury by directly targeting damaged cells. We investigated whether Mirococept, a membrane-targeted, myristoylated peptidyl construct derived from complement receptor 1 (CR1) could attenuate I/R injury following acute myocardial infarction in pigs. Methods: In a closed-chest pig model of acute myocardial infarction, Mirococept, the non-tailed derivative APT154, or vehicle was administered intracoronarily into the area at risk 5 min pre-reperfusion. Infarct size, cardiac function and inflammatory status were evaluated. Results: Mirococept targeted damaged vasculature and myocardium, significantly decreasing infarct size compared to vehicle, whereas APT154 had no effect. Cardioprotection correlated with reduced serum troponin I and was paralleled by attenuated local myocardial complement deposition and tissue factor expression. Myocardial apoptosis (TUNEL-positivity) was also reduced with the use of Mirococept. Local modulation of the pro-inflammatory and pro-coagulant phenotype translated to improved left ventricular end-diastolic pressure, ejection fraction and regional wall motion post-reperfusion. Conclusions: Local modification of a pro-inflammatory and pro-coagulant environment after regional I/R injury by site-specific application of a membrane-targeted complement regulatory protein may offer novel possibilities and insights into potential treatment strategies of reperfusion-induced injury. [Copyright &y& Elsevier]

Objective: The aim was to investigate whether ischaemic preconditioning can be obtained by a partial coronary artery occlusion without intermittent reperfusion. Methods: In seven anaesthetised open chest pigs, the flow in the proximal left anterior descending coronary artery was reduced to 30% of baseline during 30 min before the vessel was occluded completely for 60 min (60 min total coronary occlusion, TCO). After 2 h of reperfusion, the area at risk (AR) and infarct size (IS) were determined using standard procedures. Infarct sizes were compared to those observed in control animals (n = 12), which were subjected to 60 min TCO and 2 h reperfusion, and to infarct sizes determined in animals preconditioned by 10 min TCO with either 15 min (n = 10) or 60 min (n = 5) of reperfusion before the 60 min TCO and 2 h reperfusion. In the last three groups of animals, area at risk was varied by occluding the coronary artery or its branches at different sites. Results: In the control animals infarct size was linearly related (r = 0.99, p< 0.001) to the area at risk with a positive intercept on the AR axis: IS/LVmass (×100%) = 0.88 AR/LVmass (×100%)−3.6. At comparable areas at risk, the infarct size of the animals preconditioned with a 10 min TCO was less than for the control animals. For the animals preconditioned with 10 min TCO and 15 min reperfusion, the relationship between infarct size and area at risk was again linear (r = 0.88) and also had a positive intercept on the AR axis: IS/LVmass (× 100%) = 0.68 AR/LVmass (× 100%)-4.8. All animals with the flow reduction to 30% of baseline immediately preceding the 60 min TCO had infarct sizes smaller (p < 0.05) than predicted from the regression equation for the control animals, but the infarct size limitation could not be simply related to variables such as changes in regional systolic and postsystolic segment length shortening, ATP, or ADP during the partial occlusion period. Conclusions: Myocardium can be preconditioned with a flow reduction to 30% of baseline for 30 min without intermittent reperfusion (two stage Harris model). The positive intercept on the AR axis of the IS-AR relationship warrants caution of the use of IS/AR as an index for infarct size limitation.Cardiovascular Research 1994;28:1146-1151 [ABSTRACT FROM PUBLISHER]

Study objective — The aim was to evaluate the factors determining myocardial infarct size in unconscious dogs.Design — In anaesthetised open chest dogs, the left anterior descending coronary artery was occluded either by ligation or by thrombosis for different time periods (1.5 h, 4 h, 24 h), with or without reperfusion. Haemodynamic variables were recorded throughout the experiment. Radioactive microspheres (15 μm) were injected at the end of the ischaemic period to measure regional myocardial blood flow. Infarct size and area at risk were determined by the Evans blue triphenyltetrazolium staining technique followed by planimetry.Subjects — Mongrel dogs of either sex (n = 16-42 per experiment), weight 18-25 kg, were used.Measurements and main results — A large interindividual variability in infarct size was observed after occlusion of the left anterior descending coronary artery at a standardised location for a well defined period. An examination of the factors responsible for this variability was carried out in order to develop a statistical model which would make it possible to predict infarct size. Using multiple regression analysis, it was found that in most protocols (except 90 min thrombosis) more than 85% of the variability in infarct size could be explained by the size of the area at risk and the amount of collateral flow. Thus, knowing the area at risk and the collateral flow, a fairly accurate prediction can be made of the size of the infarct that the dog will develop after a defined occlusion period. Furthermore, it was found that the infarct size increased with duration of occlusion, while duration of reperfusion had no effect. In the 90 min occlusion group thrombosis induced a larger final infarct than ligature.Conclusions - A correction for baseline variables is necessary in order to compare infarct size between experimental groups. The usefulness of this procedure is shown by an example of an experimental intervention, ie, R 56 865, a drug with known cardioprotective effects. [ABSTRACT FROM PUBLISHER]

Equal reductions in heart rate (44 beats·min−1) were obtained in cats by treatment with either the beta blocking agent timolol or alinidine, an agent claimed to cause bradycardia without interfering with beta adrenoceptor function. Infarct size was measured by staining with triphenyl-tetrazolium-chloride after 5 h of coronary occlusion and related to the area of hypoperfused myocardium as measured by autoradiography. Regional myocardial blood flow was measured by 15 μm radiolabelled microspheres. Compared with the control cats, in whom 87.4 (SEM2.2)% of hypoperfused myocardium developed into necrosis, timolol reduced infarct size to 65.8 (SEM 2.6)% (p<0.001) and alinidine to 76.2 (SEM 3.1)% (p<0.01) of the hypoperfused area. Timolol reduced infarct size more than did alinidine (p<0.01). Necrosis was more extensive in the endocardium than in the epicardium in all groups. In the subendocardium timolol and alinidine reduced infarct size to the same extent, whereas timolol reduced infarct size more than alinidine in the subepicardium. Although heart rate proved to be the dominant haemodynamic predictor of infarct size, this study indicates that mechanisms other than reduced oxygen demand associated with bradycardia and cardiodepression are operating in the ischaemic myocardium during beta adrenergic blockade. [ABSTRACT FROM PUBLISHER]