No abstract

AimsMyocardial infarction (MI) remains the commonest cause of cardiac-related death throughout the world. Adverse cardiac remodelling and progressive heart failure after MI are associated with excessive and continuous damage of the extracellular matrix (ECM). In this study, we hypothesized that implantation of hydrogel into infarcted myocardium could replace the damaged ECM, thicken the infarcted wall, and inhibit cardiac remodelling. Methods and resultsMI was induced in rabbits by coronary artery ligation; 4 days later, 200 mL Dex-PCL-HEMA/PNIPAAm gel solution was injected into the infarcted myocardium. Injection of phosphate-buffered saline served as control. Thirty days after treatment, histological analysis indicated that injection of the biomaterial prevented scar expansion and wall thinning compared with controls. Echocardiography studies showed that injection of hydrogel increased left ventricular ejection fraction and attenuated left ventricular systolic and diastolic dilatation. Haemodynamic analysis demonstrated improved cardiac function following implantation of the hydrogel. ConclusionThese results suggest that injection of thermosensitive Dex-PCL-HEMA/PNIPAAm hydrogel is an effective strategy that prevents adverse cardiac remodelling and dysfunction in MI rabbits.--

Kv1.4 encodes a slowly recovering transient outward current ( I to), which inactivates by a fast N-type (intracellular ball and chain) mechanism but has slow recovery due to C-type inactivation. C-type inactivation of the NH2-terminal deletion mutant (fKv1.4ΔN) was inhibited by 98 mM extracellular K+concentration ([K+]o), whereas N-type was unaffected. In 98 mM [K+]o, removal of intracellular K+ concentration ([K+]i) speeded C-type inactivation but had no effect on N-type inactivation, suggesting that C-type inactivation is sensitive to K+ binding to intracellular sites. C-type inactivation is thought to involve closure of the extracellular pore mouth. However, a valine to alanine mutation on the intracellular side of S6 (V561A) of fKv1.4ΔN alters recovery and results in anomalous speeding of C-type inactivation with increasing [K+]o. Extracellular pH (pHo) modulated both N- and C-type inactivation through an S5-H5 linker histidine (H508) with acidosis speeding both N- and C-type inactivation. Mutation of an extracellular lysine to a tyrosine (K532Y) slowed C-type inactivation and inhibited the pH dependence of both N- and C-type inactivation. These results suggest that mutations, [K+], and pH modulate inactivation through membrane-spanning mechanisms involving S6.

No abstract

Myocardial infarction (MI) and the subsequent heart failure remain one of the leading causes of morbidity and mortality world wide. A number of studies have demonstrated that bioderived materials improve cardiac function after implantation because of their angiogenic potential. In this study, we hypothesized that injection of biomaterials into infarcted myocardium can preserve left ventricular (LV) function through its prevention of paradoxical systolic bulging. To test this hypothesis, infarction was induced in rabbit myocardium by coronary artery ligation. After 1 week, 200-microL alpha-cyclodextrin (alpha-CD)/MPEG-PCL-MPEG hydrogel was injected into the infarcted myocardium. Injection of phosphate buffered saline (PBS) served as controls. Twenty-eight days after the treatment, histological analysis indicated that the injection of hydrogel prevented scar expansion and wall thinning compared with the control (p < 0.05) without more microvessel density in infarcted myocardium (p = 0.70). LV ejection fraction, determined by echocardiography, was significantly greater in the hydrogel-treated group (56.09% +/- 8.42%) than the control group (37.26% +/- 6.36%, p = 0.001). The LV end-diastolic and end-systolic diameters were 2.07 +/- 0.33 cm and 1.74 +/- 0.30 cm, respectively, in the control group. Smaller LV end-diastolic diameter (1.61 +/- 0.26 cm, p = 0.005) and smaller end-systolic diameter (1.17 +/- 0.23 cm, p = 0.001) were found in the hydrogel-treated group. These results suggest that alpha-CD/MPEG-PCL-MPEG hydrogel could serve as an injectable biomaterial that prevents LV remodeling and dilation for the treatment of MI.