Transfusion of fresh but not old stored blood reduces infarct size and improves cardiac function after acute myocardial infarction in anemic rats*

2012 ◽  
Vol 40 (3) ◽  
pp. 740-746 ◽  
Author(s):  
Houxiang Hu ◽  
Anargyros Xenocostas ◽  
Nicolas Chin-Yee ◽  
Xiangru Lu ◽  
Ian Chin-Yee ◽  
...  
Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 661-661
Author(s):  
Anargyros Xenocostas ◽  
Houxiang Hu ◽  
Nicolas J Chin-Yee ◽  
Ian Chin-Yee ◽  
Qingping Feng

Abstract Abstract 661 Background: Anemia is a predictor of poor outcomes in acute myocardial infarction (MI) and may increase the degree of ischemia, resulting in greater tissue injury. The only existing therapeutic intervention used to acutely correct anemia is red blood cell (RBC) transfusion, although its effectiveness at improving outcomes in anemic subjects following MI remains controversial. We have previously shown that transfusion of fresh blood in anemic rats following MI decreased infarct size, and improved cardiac function and survival (Hu et al. Transfusion 2010; 50:243-251). However, it was not known if the transfusion of stored blood, which develops a series of chemical and corpuscular changes collectively known as the “storage lesion”, would be equally effective in this model. Experimental Design: Acute MI was induced by coronary artery ligation in 49 male Sprague-Dawley rats, 38 of which were made anemic (Hb = 80–90 g/L) using a combination of dietary iron deprivation and phlebotomy, and 11 with normal Hb levels. Rat blood was stored for 7 days in CPDA-1 to induce a storage lesion similar to the one seen in human blood stored under identical conditions for 28 days (d'Almeida et al. Transfusion Medicine 2000; 10:291-303). Anemic animals were randomly assigned to one of three groups: i) fresh blood transfusion (stored for <4 hours) to increase the Hb to 100 g/L, ii) transfused with stored blood to increase the Hb to 100 g/L, or iii) no transfusion. At 24 hours post-MI, infarct size, cardiac function and survival rates were determined. Results: A similar degree of left ventricular (LV) myocardial ischemia (area at risk) was induced in all groups (P=NS). In agreement with previous results, the infarct size to area at risk ratios were significantly increased in the anemic (Hb 80–90 g/L) animals compared to non-anemic MI controls, and transfusion of fresh blood to a target Hb level of 100 g/L after MI decreased infarct size (P<0.05) and improved both systolic (+dP/dtmax) and diastolic (−dP/dtmin) LV function compared to anemic animals (P<0.05). However, the transfusion of stored blood into anemic animals post-MI did not have these effects when compared to the group receiving fresh blood (P<0.05). Furthermore, survival was increased in anemic animals receiving fresh blood (9/11; P<0.05) but not stored blood (7/14; P=NS) compared to the non-transfused group (5/13). Conclusions: The prolonged storage of blood negates the beneficial effects of fresh blood transfusion, which include reductions in infarct size, and improvements in cardiac function and short-term survival following acute MI in this animal model. (This study was supported by the Canadian Institutes of Health Research, Canadian Blood Services and the Bayer Partnership Fund). Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Andreas Boening ◽  
Maximilian Hinke ◽  
Martina Heep ◽  
Kerstin Boengler ◽  
Bernd Niemann ◽  
...  

Abstract Background Because hearts in acute myocardial infarction are often prone to ischemia-reperfusion damage during cardiac surgery, we investigated the influence of intracellular crystalloid cardioplegia solution (CCP) and extracellular blood cardioplegia solution (BCP) on cardiac function, metabolism, and infarct size in a rat heart model of myocardial infarction. Methods Following euthanasia, the hearts of 50 rats were quickly excised, cannulated, and inserted into a blood-perfused isolated heart apparatus. A regional myocardial infarction was created in the infarction group (18 hearts) for 120 min; the control group (32 hearts) was not subjected to infarction. In each group, either Buckberg BCP or Bretschneider CCP was administered for an aortic clamping time of 90 min. Functional parameters were recorded during reperfusion: coronary blood flow, left ventricular developed pressure (LVDP) and contractility (dp/dt max). Infarct size was determined by planimetry. The results were compared between the groups using analysis of variance or parametric tests, as appropriate. Results Cardiac function after acute myocardial infarction, 90 min of cardioplegic arrest, and 90 min of reperfusion was better preserved with Buckberg BCP than with Bretschneider CCP relative to baseline (BL) values (LVDP 54 ± 11% vs. 9 ± 2.9% [p = 0.0062]; dp/dt max. 73 ± 11% vs. 23 ± 2.7% [p = 0.0001]), whereas coronary flow was similarly impaired (BCP 55 ± 15%, CCP 63 ± 17% [p = 0.99]). The infarct in BCP-treated hearts was smaller (25% of myocardium) and limited to the area of coronary artery ligation, whereas in CCP hearts the infarct was larger (48% of myocardium; p = 0.029) and myocardial necrosis was distributed unevenly to the left ventricular wall. Conclusions In a rat model of acute myocardial infarction followed by cardioplegic arrest, application of BCP leads to better myocardial recovery than CCP.


Author(s):  
Timur Yagudin ◽  
Yue Zhao ◽  
Haiyu Gao ◽  
Yang Zhang ◽  
Ying Yang ◽  
...  

Abstract Currently, there remains a great need to elucidate the molecular mechanism of acute myocardial infarction in order to facilitate the development of novel therapy. Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is a member of the ASPP family proteins and an evolutionarily preserved inhibitor of p53 that is involved in many cellular processes, including apoptosis of cancer cells. The purpose of this study was to investigate the possible role of iASPP in acute myocardial infarction. The protein level of iASPP was markedly reduced in the ischemic hearts in vivo and hydrogen peroxide-exposed cardiomyocytes in vitro. Overexpression of iASPP reduced the infarct size and cardiomyocyte apoptosis of mice subjected to 24 h of coronary artery ligation. Echocardiography showed that cardiac function was improved as indicated by the increase in ejection fraction and fractional shortening. In contrast, knockdown of iASPP exacerbated cardiac injury as manifested by impaired cardiac function, increased infarct size, and apoptosis rate. Mechanistically, overexpression of iASPP inhibited, while knockdown of iASPP increased the expressions of p53 and Bax, the key regulators of apoptosis. Taken together, our results suggested that iASPP is an important regulator of cardiomyocyte apoptosis, which represents a potential target in the therapy of myocardial infarction.


2006 ◽  
Vol 48 (11) ◽  
pp. 2192-2194 ◽  
Author(s):  
Henning Steen ◽  
Evangelos Giannitsis ◽  
Simon Futterer ◽  
Constanze Merten ◽  
Claus Juenger ◽  
...  

Heart ◽  
1974 ◽  
Vol 36 (3) ◽  
pp. 271-279 ◽  
Author(s):  
D Mathey ◽  
W Biefield ◽  
P Hanrath ◽  
S Effert

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 454-454
Author(s):  
Anargyros Xenocostas ◽  
Houxiang Hu ◽  
Xiangru Lu ◽  
Ian Chin-Yee ◽  
Qingping Feng

Abstract Background: The optimal hemoglobin (Hb) in the setting of acute myocardial infarction (MI) is unknown. Anemia reduces the oxygen carrying capacity of blood and may theoretically exacerbate ischemia increasing myocardial injury. The benefit of transfusion to correct anemia in acute coronary syndromes is also controversial. The goal of this study was to determine the optimal Hb in the setting of acute MI and whether transfusion reduces myocardial injury and improves outcome. Experimental design: Ninety-two male Sprague-Dawley rats (170–190g) were divided into 8 groups: 1: Normal Hb, sham operation; 2: Normal Hb, MI; 3: Hb 80–90g/L, sham; 4: Hb 80–90g/L, MI; 5: Hb 70–80g/L, sham; 6: Hb 70–80g/L, MI; 7: Hb 80–90g/L, MI with transfusion to 100g/L; 8: Hb 80–90g/L, MI with transfusion to 120g/L. To determine the effect of blood transfusion, fresh blood was immediately transfused following MI. Induction of myocardial infarction was preformed by left coronary artery ligation. Sham-operated rats underwent the same surgical procedure without ligation. At 24 hours post-MI, rats were re-anaesthetized and hemodynamic measurements preformed. Area at risk and infarct size was measured by Evans blue and triphenyltetrazolium chloride, respectively. Results: In the normal Hb group (140–150g/L), survival following sham or MI surgery was 100%. Reduction of Hb to 80–90 and 70–80g/L significantly decreased survival post-MI to 42% and 47%, respectively. Survival was significantly improved after transfusion of fresh blood to raise the hemoglobin from 80–90g/L to 100g/L (P<0.05). However, there was no improvement in survival when Hb was raised by transfusion to 120g/L (P=NS). Twenty-four hours post-MI, the ischemic to non-ischemic left ventricle (LV) weight ratios were not significantly different between any groups indicating similar areas of myocardial ischemia among all groups (P=NS). However, the infarct size to area at risk ratios were significantly increased in both 70–80g/L and 80–90g/L groups compared to the normal Hb group (P<0.05). Transfusion from Hb 80–90g/L to 100g/L significantly decreased infarct size compared to the Hb 80–90g/L group (P<0.05). However, transfusion to Hb 120g/L resulted in a significantly larger infarct size compared to the Hb 100g/L transfused group (P<0.05). Cardiac function was determined at 24 hours post-MI. Heart rate, MAP, LVSP and LVEDP were not significantly different among all groups but anemic groups 80–90 and 70–80g/L showed a significant decrease in LV +dP/dtmax and −dP/dtmin in both sham and MI rats (P<0.01) with the most significant decrease noted in MI rats compared to sham operated rats (P<0.05). Blood transfusion post-MI from a Hb 80–90 to 100g/L significantly improved LV +dP/dtmax (P<0.05). Transfusion to Hb 120g/L did not result in any further improvement in cardiac function. Conclusions: In the setting of acute MI, anemia increased mortality and infarct size compared to non-anemic controls. At 24 hours post-MI, anemia also impaired cardiac function. Transfusion of anemic animals up to a Hb of 100g/L with fresh RBCs reduced mortality and infarct size and improved cardiac function. However, transfusion to a Hb of 120g/L did not demonstrate any additional benefit and was associated with larger infarcts.


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