An injectable hydrogel was applied to regenerate a myocardial infarction and functional recovery of the heart. A myocardial infarction was induced in rat by circumflex artery ligation. A hyaluronic acid-based hydrogel was injected into the epicardium of the infarcted area. Then, cardiac functions and regeneration of the myocardium in sham-operated (SHAM), myocardial infarction (MI), and gel-injected group (GEL) (n = 6) were evaluated 4 weeks after the injection. Measurements of the thickness of the wall showed that the thickness in the GEL group increased by up to 200% compared with that in the MI group (p < 0.001). The infarcted area of the left ventricular in the GEL group decreased by 53% compared with the MI group (p < 0.001). The number of arterioles and capillaries in the border zone of the GEL group increased by 152% and 148%, whereas the apoptotic index decreased by 42% (p < 0.05). Measurement of the heart functions, such as ejection fraction, arterial elastance (Ea), dP/dt max, and dP/dt min, indicated that the injection of a hydrogel significantly facilitated the functional recovery compared with the MI group. Because of its simplicity, easy applicability, and a great regenerating potential, this injectable hydrogel promises as a treatment for myocardial infarction.

BackgroundRemote ischemic preconditioning (RIPC) and postconditioning (RpostC) have protective effects on ischemia and reperfusion injury. The effects have been reported to activate heme oxygenase-1 (HO-1) and attenuate nuclear factor kappa B (NF-κB) and subsequently reduce systemic inflammation. Ischemic preconditioning prevented inflammatory responses by modulating HO-1 expression in endotoxic shock model. Therefore, we investigated whether RpostC could have protective effects on lipopolysaccharide (LPS)-induced systemic inflammation.MethodsThe LPS-induced sepsis mice received LPS (20 mg/kg) intraperitoneally. Remote ischemic conditioning was induced with three 10-min ischemia/10-min reperfusion cycles of the right hind limbs using tourniquet before LPS injection (RIPC) or after LPS injection (RpostC). The effects of RIPC and RpostC were examined for the survival rate, serum cytokines, NF-κB, HO-1 and liver pathology in the LPS injected mice.ResultsSurvival rate within 120 hours significantly increased in the LPS injected and remote ischemic conditioned mice than in LPS only injected mice (60-65% vs 5%, respectively, p < 0.01). Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) increased markedly in the LPS only injected mice, however, remote ischemic conditioning suppressed the changes (p < 0.05). Interleukin-10 (IL-10) level was significantly higher in the LPS injected and RpostC treated mice than in the LPS only injected mice (p = 0.014). NF-κB activation was significantly attenuated (p < 0.05) and HO-1 levels were substantially higher in the LPS injected and remote ischemic conditioned mice than in the LPS only injected mice. Neutrophil infiltration was significantly attenuated in the LPS injected and remote ischemic conditioned mice than in the only LPS injected mice (p < 0.05).ConclusionsRpostC attenuated inflammatory responses and improved survival outcomes of mice with LPS-induced systemic inflammation. The mechanism may be caused by modifying NF-κB mediated expression of cytokines.

The aim of this meta-analysis was to determine whether pulsatile perfusion during cardiac surgery has a lesser effect on renal dysfunction than nonpulsatile perfusion after cardiac surgery in randomized controlled trials. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were used to identify available articles published before April 25, 2014. Meta-analysis was conducted to determine the effects of pulsatile perfusion on postoperative renal functions, as determined by creatinine clearance (CrCl), serum creatinine (Cr), urinary neutrophil gelatinase-associated lipocalin (NGAL), and the incidences of acute renal insufficiency (ARI) and acute renal failure (ARF). Nine studies involving 674 patients that received pulsatile perfusion and 698 patients that received nonpulsatile perfusion during cardiopulmonary bypass (CPB) were considered in the meta-analysis. Stratified analysis was performed according to effective pulsatility or unclear pulsatility of the pulsatile perfusion method in the presence of heterogeneity. NGAL levels were not significantly different between the pulsatile and nonpulsatile groups. However, patients in the pulsatile group had a significantly higher CrCl and lower Cr levels when the analysis was restricted to studies on effective pulsatile flow (P < 0.00001, respectively). The incidence of ARI was significantly lower in the pulsatile group (P < 0.00001), but incidences of ARF were similar. In conclusion, the meta-analysis suggests that the use of pulsatile flow during CPB results in better postoperative renal function.

The Twin-Pulse Life Support System (T-PLS) is a novel pulsatile extracorporeal life support system developed in Korea. It has been reported that the T-PLS achieves higher levels of tissue perfusion of the kidney during short-term extracorporeal circulation and provides more blood flow to coronary artery than nonpulsatile blood pumps. However, these results lack pulsatility quantifications and thus make it hard to analyze the effects of pulsatility upon hemodynamic performance. We have adopted the concepts of hemodynamic energy, energy equivalent pressure (EEP), and surplus hemodynamic energy (SHE) to evaluate pulsatility performance in the different circuit configurations of the T-PLS and a membrane oxygenator (MO) in vitro. In a mock system, three different circuits were constructed depending on the location of an MO: pump-MO-pump (serial), MO-pumps (parallel A), and pumps-MO (parallel B). In parallel A, a low-resistance MO was used to preserve the pulsatility from the pump. All circuits showed good pulsatility in terms of EEP (serial: 13.2% +/- 3.2%, parallel A: 10.0% +/- 1.6%, parallel B: 7.00% +/- 1.1%; change from aortic pressure to EEP; p < 0.003). The SHE levels were 17,404 +/- 3750 ergs/cm3, 13,170 +/- 1486 ergs/cm3, and 9192 +/- 1122 ergs/cm3 in each circuit setup (p < 0.001). Although EEP levels were somewhat lower, both parallel types provided higher pump output compared with the serial type (serial: 1.87 +/- 0.29 l/min, parallel A: 3.09 +/- 0.74 l/min, parallel B: 3.06 +/- 0.56 l/min; p < 0.003 except parallel A vs. parallel B, p = 0.90). Conclusively, the precise quantifications of pressure flow waveforms, EEP, and SHE are valuable tools for evaluating pulsatility of the mechanical circulatory devices, and are expected to be used as additional performance indexes of a blood pump. The pulsatility performances are different according to circuit setups. However, the parallel A circuit could achieve higher pump output and generate adequate pulsatility level. Thus, the parallel A circuit is suggested as the optimal configuration in T-PLS applications.

The aim of this study was to determine whether pulsatile or nonpulsatile perfusion had a greater effect on pulmonary dysfunction in randomized controlled trials. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were used to identify available articles published before April 13, 2013. A meta-analysis was conducted on the effects of pulsatile perfusion on postoperative pulmonary function, intubation time, and the lengths of intensive care unit (ICU) and hospital stays. Eight studies involving 474 patients who received pulsatile perfusion and 496 patients who received nonpulsatile perfusion during cardiopulmonary bypass (CPB) were considered in the meta-analysis. Patients receiving pulsatile perfusion had a significantly greater PaO2 /FiO2 ratio 24 h and 48 h post-operation (P < 0.00001, both) and significantly lower chest radiograph scores at 24 h and 48 h post-operation (P < 0.00001 and P = 0.001, respectively) compared with patients receiving nonpulsatile perfusion. The incidence of noninvasive ventilation for acute respiratory insufficiency was significantly lower (P < 0.00001), and intubation time and ICU and hospital stays were shorter (P = 0.004, P < 0.00001, and P < 0.00001, respectively) in patients receiving pulsatile perfusion during CPB compared with patients receiving nonpulsatile perfusion. In conclusion, our meta-analysis suggests that the use of pulsatile flow during CPB results in better postoperative pulmonary function and shorter ICU and hospital stays.