Organ-specific model of simulated ischemia/reperfusion and hyperglycemia based on engineered heart tissue

Vascul Pharmacol. 2023 Aug 10:107208. doi: 10.1016/j.vph.2023.107208. Online ahead of print.ABSTRACTHere we aimed to establish an in vitro engineered heart tissue (EHT) co-morbidity mimicking model of ischemia-reperfusion injury and diabetes. EHTs were generated from primary neonatal rat cardiomyocytes. Hyperglycemic conditions or hyperosmolar controls were applied for one day to model acute hyperglycemia and for seven days to model chronic hyperglycemia. 120 min' simulated ischemia (SI) was followed by 120 min' reperfusion (R) and 1-day follow-up reperfusion (FR). Normoxic controls (N) were not subjected to SI/R. Half of the EHTs was paced, the other half was left unpaced. To assess cell injury, lactate-dehydrogenase (LDH) concentration was measured. Beating force and activity (frequency) were monitored as cardiomyocyte functional parameters. LDH-release indicated relevant cell injury after SI/N in each experimental condition, with much higher effects in the chronically hyperglycemic/hyperosmolar groups. SI stopped beating of EHTs in each condition, which returned during reperfusion, with weaker recovery in chronic conditions than in acute conditions. Acutely treated EHTs showed small LDH-release and ~ 80% recovery of force during reperfusion and follow-up, while chronically treated EHTs showed a marked LDH-release, only ~30% recovery with reperfusion and complete loss of beating activity during 24 h follow-up reperfusion. We conclude that EHTs respond differently to SI/R in...
Source: Vascular Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research