Increased Level of Pericardial Insulin-Like Growth Factor-1 in Patients With Left Ventricular Dysfunction and Advanced Heart Failure

ObjectivesTo test the hypothesis that the cardiac insulin-like growth factor-1 (IGF-1) system is up-regulated in the failing heart, we measured the pericardial (cardiac) and plasma (circulating) IGF-1 levels in coronary artery disease patients.BackgroundLocal IGF-1 systems are regulated differently from the systemic IGF-1 system. The cardiac IGF-1 system is up-regulated by the increased left ventricular (LV) wall stress. However, it remains unknown how this system is affected in LV dysfunction and heart failure.MethodsWe measured the plasma and pericardial fluid levels of IGF-1 and brain natriuretic peptide (BNP) in 87 coronary artery disease patients undergoing cardiac surgery, and examined their relationships with LV function and heart failure severity. The expressions of IGF-1 and IGF-1 receptor proteins were examined in endomyocardial biopsies obtained from other patients with normal or impaired LV function.ResultsThe pericardial IGF-1 and BNP levels were positively correlated with the plasma BNP level (both p < 0.001). The pericardial IGF-1 level was increased in heart failure patients, whereas the plasma IGF-1 level was rather decreased. The pericardial IGF-1 level was inversely correlated with the LV ejection fraction (p < 0.001), whereas the plasma IGF-1 level was not. Positive immunostaining for IGF-1 and IGF-1 receptor proteins was enhanced in myocardial biopsies from failing hearts compared with those from nonfailing hearts.ConclusionsThe pericardial IGF-1 level was increased in patients with LV dysfunction and heart failure, whereas the plasma IGF-1 level was decreased. These results may indicate that up-regulation of the cardiac IGF-1 system serves as a compensatory mechanism for LV dysfunction

Potential crowdedness of mechanical thrombectomy and cerebral infarction mortality in Japan : Application of inverted two-step floating catchment area method

Objectives: This study aimed to evaluate a stroke medical delivery system based on population coverage and the potential crowdedness index (PCI) of mechanical thrombectomy and investigate the relationship between PCI and cerebral infarction mortality in Japan. Materials and methods: This cross-sectional study defined 662 facilities and 1605 neurointerventionalists as supply, population aged 55 years or older as demand, and set the reachable area for demand as 120 min in driving time. Multiple regression analysis adjusted for spatial autocorrelation was used to exam-ine the relationship between PCI and cerebral infarction mortality. Results: In the 2020 data, 99% of the population aged 55 years or older had access to mechanical thrombectomy (<= 120 min), and the PCI ranged from 5876 to 129838, with a median of 30426. From 2020 to 2035, the PCI is estimated to increase (30426 to 32510), decreasing after 2035 (32510 to 29469). The PCI distribution exhibited geographical heterogeneity. High PCI values emerged in eastern Japan. According to regression analysis, the increase in PCI by 1% led to an increase of 0.13% in standardized mor-tality ratio of cerebral infarction in men. However, PCI did not significantly corre-late with cerebral infarction mortality in women. Conclusions: PCI for hospitals based on supply and demand was geographically heterogeneous in Japan. Optimi-zation of PCI contributes equalization of mechanical thrombectomy provision sys-tem and may improve cerebral infarction mortality

Human Recombinant Peptide Sponge Enables Novel, Less Invasive Cell Therapy for Ischemic Stroke

Bone marrow stromal cell (BMSC) transplantation has the therapeutic potential for ischemic stroke. However, it is unclear which delivery routes would yield both safety and maximal therapeutic benefits. We assessed whether a novel recombinant peptide (RCP) sponge, that resembles human collagen, could act as a less invasive and beneficial scaffold in cell therapy for ischemic stroke. BMSCs from green fluorescent protein-transgenic rats were cultured and Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAo). A BMSC-RCP sponge construct was transplanted onto the ipsilateral intact neocortex 7 days after MCAo. A BMSC suspension or vehicle was transplanted into the ipsilateral striatum. Rat motor function was serially evaluated and histological analysis was performed 5 weeks after transplantation. The results showed that BMSCs could proliferate well in the RCP sponge and the BMSC-RCP sponge significantly promoted functional recovery, compared with the vehicle group. Histological analysis revealed that the RCP sponge provoked few inflammatory reactions in the host brain. Moreover, some BMSCs migrated to the peri-infarct area and differentiated into neurons in the BMSC-RCP sponge group. These findings suggest that the RCP sponge may be a promising candidate for animal protein-free scaffolds in cell therapy for ischemic stroke in humans