Coronary Ischemia-reperfusion Injury Research Articles

Abstract 4124277: Resorcimoline, a Novel Free Radical Scavenger, Exhibits Cardioprotective Effects Following Coronary Ischemia-reperfusion Injury

Background: Ischemic heart disease remains the leading cause of death worldwide. Early coronary revascularization is the most important treatment. Recent findings have revealed that reactive oxygen species (ROS) can lead to tissue damage following coronary artery revascularization, known as ischemia-reperfusion injury. In this study, we focused on a novel free radical scavenger, resorcimoline (RML). Last year, we reported the scavenging activity of RML in vitro against multiple ROS, confirmed by the electron spin resonance spectrometry. Hypothesis: Resorcimoline might reduce ROS damage in cardiomyocytes, thereby exerting cardioprotective effects following coronary ischemia-reperfusion injury. Methods: Nine-to-eleven-week-old male Wistar rats were subjected to acute myocardial ischemia induced by ligation of the left anterior descending coronary artery for 30 minutes. Rats received intravenous injections of RML at 6 mg/kg before the ligation release or saline as a control. The heart sections were double-stained at 24-hour reperfusion with Evans blue and triphenyltetrazolium chloride to assess the infarct area. Cardiac function was evaluated at 2-day and 7-day reperfusion with echocardiography. Myocardial fibrosis was assessed at 7-day reperfusion by Masson’s trichrome staining. Primary cultured rat cardiomyocytes were treated with 10 μM angiotensin II for 3.5 hours and then exposed to RML for 30 minutes. Cellular ROS assay kits were used to assess the levels of ROS in the cardiomyocytes. Results: Infarct size in RML-treated animals was significantly smaller than in control animals (41.8±19.4% vs. 60.8±12.9%, p=0.03, Fig. 1A). Apoptotic cells in the border zone were significantly reduced in RML-treated animals (32.0±11.7% vs. 55.1±16.9%, p=0.01, Fig. 1B). Troponin I level in RML-treated animals was significantly lower than in control animals (p=0.04, Fig. 1C). Ejection fraction in RML-treated animals was significantly preserved at 2-day reperfusion and 7-day reperfusion when compared to control animals (p=0.001, p=0.003, Fig. 2A). Myocardial fibrosis area in RML-treated animals was significantly smaller than in control animals (23.9±11.7% vs. 40.6±15.6%, p=0.01, Fig. 2B). RML significantly reduced angiotensin II-induced ROS in cardiomyocytes in a concentration-dependent manner (Fig. 3A,B,C). Conclusion: Resorcimoline exhibits cardioprotective effects following coronary ischemia-reperfusion injury by reducing the infarct size and ROS damage in cardiomyocytes.

Positive charged mannose polymer increases myocardial damage induced by coronary ischemia reperfusion injury on in vivo model

Endothelial membrane (EnM) at the coronary vessels is a key element in the pathway involved in the coronary ischemia/reperfusion injury (cIRI). We demonstrated the presence of the mannose receptor (MR) in the coronary EnM. MR mediates a positive (+) inotropic and dromotropic effects in isolated guinea pig hearts. We used mannose polymer (Man‐pol) that has + charge, this polymer was synthesized with a high MW dextran, divinyl sulfone (DVS) as linker for mannose and ethylene diamine to inactivate unbound DVS residues. EnM glycocalyx (Gcx) has been involved in the pathway of the IRI, and its homeostasis is required to down modulate the cIRI. + Charged macromolecules damage the Gcx and exacerbates IRI. Therefore, we evaluated the effect of the +Man‐pol on in vivo cIRI models. We determinate myocardial viability on rat hearts 4 hrs after the cIRI with tetrazolium, and reported as ratio between infarcted area (IA) and total area (TA). +Man‐pol treated hearts 15 min prior reperfusion, significantly increases the damage induced by the cIRI when compared with vehicle treated hearts, IA/TA was 1.7 fold. Detrimental effect of the + charge on the Man‐pol suggests the role of the Gcx on the response against the cIRI. On the other hand, uncharged Man‐pol treated hearts decreased IA/TA by half when compared with vehicle treated hearts; this effect could be induced by the beneficial interaction between Gcx and MR. CONACyT # 46187‐A.

Changes in Plasma Levels of ET-1 and its Precursor, Big ET-1, in the Arterial and Venous Circulation Following Double Myocardial Ischemia—Reperfusion Injury In Dogs

Upregulation of the endothelin (ET) system, following coronary ischemia-reperfusion injury, may contribute to coronary vasospasm and congestive heart failure. Because endothelin-1 (ET-1) is rapidly cleared from the circulation, the levels of its inactive precursor big ET-1 and the ET-1/big ET-1 ratio may constitute better ways to assess the activation of the ET system in both venous and arterial beds. Anesthetized dogs (n = 6-12) were subjected to two successive coronary artery occlusions (with intervening 60 min reperfusion) over 6 h. Cardiac hemodynamics and electrocardiogram (ECG) were recorded and blood samples were drawn simultaneously from the internal thoracic artery and coronary sinus (venous blood). Under basal conditions at t = -20 min, arterial plasma levels of ET-1 and big ET-1 were 2.05 +/- 0.21 and 2.00 +/- 0.51 pg/ml (ratio: 1.00; n = 12); venous values were 2.29 +/- 0.25 and 3.14 +/- 0.77, respectively (ratio: 0.73, n = 12). Both arterial and venous plasma levels of ET-1 increased (by 46 and 56%) after 5 and 15 min of reperfusion, respectively, following the initial 120 min ischemic period compared to baseline values, and returned to near baseline values after 60 min reperfusion. Both arterial and venous values for big ET-1 increased steadily by 2.2 and 2.3 times maximum, respectively, during the initial 60 min reperfusion period; these values increased by 3.4 and 3.2 times, respectively by the end of the second 120 min reperfusion period. ET-1/big ET-1 ratios dropped to 0.39, in arterial, and 0.21, in venous plasma, at the end of the second reperfusion period. In conclusion, plasma ET-1 levels increase significantly but transiently after the first ischemic injury; the increased plasma big ET-1 levels were more pronounced in both the arterial and venous circulation along with ischemia-reperfusion injuries. These results suggest an upregulation of the ET system that was easily monitored by increased production of big ET-1. During ischemia-reperfusion injuries, the conversion to the active mature peptide ET-1 is either impaired, or ET-1 is more rapidly degraded.