Taurine (2-aminoethanesulfonic acid) is a potent antioxidant and inhibits cell apoptosis in ischemic reperfusion injury. In this study we evaluated whether addition of taurine to St. Thomas' cardioplegic solution enhances its myocardial protective effects in prolonged hypothermic heart preservation in rats. Hearts isolated from male Sprague-Dawley rats were mounted on a Langendorff apparatus to estimate baseline cardiac function, then arrested and stored in St. Thomas' cardioplegic solution, with taurine (10 mM; taurine group, n = 8) or without taurine (control group, n = 8), for 6 h at 4 degrees C. After storage, the hearts were reperfused and heart rate (HR), coronary flow (CF), left ventricular developed pressure (LVP), and positive maximum left ventricular developing pressure (max LV dp/dt) were measured. The LV tissue was examined immunohistochemically for determining DNA oxidative stress and cell apoptosis. Compared with control groups, recovery of LVP (P < 0.001), max LV dp/dt (P < 0.001), and coronary flow (P < 0.001) were significantly enhanced, whereas glutamic oxaloacetic transaminase (P < 0.01), lactate dehydrogenase (P < 0.05), creatine phosphate kinase (P < 0.01), 8-hydroxy-2'-deoxyguanosine index (P < 0.01), caspase-3 mRNA expression (P < 0.05), and percentage of TUNEL-positive cardiomyocytes (P < 0.05) were reduced in the taurine group. Addition of taurine to St. Thomas' cardioplegic solution improved cardiac function recovery for prolonged hypothermic rat heart preservation by suppressing DNA oxidative stress and cell apoptosis.
The combined growth factor therapy with an omental flap induced arteriogenesis and provided additional perfusion via the gastroepiploic artery to ameliorate regional dysfunction in the chronically ischemic myocardium.
The decrease in contractility in myocardium adjacent (border zone; BZ) to a myocardial infarction (MI) is correlated with an increase in reactive oxygen species (ROS). We hypothesized that injection of a thermoresponsive hydrogel, with ROS scavenging properties, into the MI would decrease ROS and improve BZ function. Fourteen sheep underwent antero‐apical MI. Seven sheep had a comb‐like copolymer synthesized from N‐isopropyl acrylamide (NIPAAm) and 1500 MW methoxy poly(ethylene glycol) methacrylate, (NIPAAm‐PEG1500), injected (20 × 0.5 mL) into the MI zone 40 min after MI (MI + NIPAAm‐PEG1500) and seven sheep were MI controls. Cardiac MRI was performed 2 weeks before and 6 weeks after MI + NIPAAm‐PEG1500. BZ wall thickness at end systole was significantly higher for MI + NIPAAm‐PEG1500 (12.32 ± 0.51 mm/m2 MI + NIPAAm‐PEG1500 vs. 9.88 ± 0.30 MI; p = .023). Demembranated muscle force development for BZ myocardium 6 weeks after MI was significantly higher for MI + NIPAAm‐PEG1500 (67.67 ± 2.61 mN/m2 MI + NIPAAm‐PEG1500 vs. 40.53 ± 1.04 MI; p < .0001) but not significantly different from remote myocardium or BZ or non‐operated controls. Levels of ROS in BZ tissue were significantly lower in the MI + NIPAAm‐PEG1500 treatment group (hydroxyl p = .0031; superoxide p = .0182). We conclude that infarct injection of the NIPAAm‐PEG1500 hydrogel with ROS scavenging properties decreased ROS and improved contractile protein function in the border zone 6 weeks after MI.
After myocardial infarction, a poorly contracting nonischemic border zone forms adjacent to the infarct. The cause of border zone dysfunction is unclear. The goal of this study was to determine the myofilament mechanisms involved in postinfarction border zone dysfunction. Two weeks after anteroapical infarction of sheep hearts, we studied in vitro isometric and isotonic contractions of demembranated myocardium from the infarct border zone and a zone remote from the infarct. Maximal force development (Fmax) of the border zone myocardium was reduced by 31 ± 2% versus the remote zone myocardium (n = 6/group, P < 0.0001). Decreased border zone Fmax was not due to a reduced content of contractile material, as assessed histologically, and from myosin content. Furthermore, decreased border zone Fmax did not involve altered cross-bridge kinetics, as assessed by muscle shortening velocity and force development kinetics. Decreased border zone Fmax was associated with decreased cross-bridge formation, as assessed from muscle stiffness in the absence of ATP where cross-bridge formation should be maximized (rigor stiffness was reduced 34 ± 6%, n = 5, P = 0.011 vs. the remote zone). Furthermore, the border zone myocardium had significantly reduced phosphorylation of myosin essential light chain (ELC; 41 ± 10%, n = 4, P < 0.05). However, for animals treated with doxycycline, an inhibitor of matrix metalloproteinases, rigor stiffness and ELC phosphorylation were not reduced in the border zone myocardium, suggesting that doxycycline had a protective effect. In conclusion, myofilament dysfunction contributes to postinfarction border zone dysfunction, myofilament dysfunction involves impaired cross-bridge formation and decreased ELC phosphorylation, and matrix metalloproteinase inhibition may be beneficial for limiting postinfarct border zone dysfunction.
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