Mesenchymal stem cells (MSCs) have been reported to improve
survival of cardiomyocytes (CMCs) and overall regeneration of
cardiac tissue. Despite promising preclinical results, interactions
of MSCs and CMCs, both direct and indirect, remain unclear. In
this study, porcine bone marrow MSCs and freshly isolated
porcine primary adult CMCs were used for non-contact co-culture
experiments. Morphology, viability and functional parameters of
CMCs were measured over time and compared between CMCs
cultured alone and CMCs co-cultured with MSCs. In non-contact
co-culture, MSCs improved survival of CMCs. CMCs co-cultured
with MSCs maintained CMCs morphology and viability in
significantly higher percentage than CMCs cultured alone. In
viable CMCs, mitochondrial respiration was preserved in both
CMCs cultured alone and in CMCs co-cultured with MSCs.
Comparison of cellular contractility and calcium handling,
measured in single CMCs, revealed no significant differences
between viable CMCs from co-culture and CMCs cultured alone.
In conclusion, non-contact co-culture of porcine MSCs and CMCs
improved survival of CMCs with a sufficient preservation of
functional and mitochondrial parameters.
The inotropic effects of insulin in the rat heart are still incompletely understood. In this study, the effects of insulin on cardiac contraction were studied in right ventricular papillary muscles from both control rats and rats with chronic diabetes (lasting 16 weeks). Diabetes was induced by the application of streptozotocin (STZ) and the development of diabetes was documented by increased levels of blood glucose, by reduction in body weight and by decreased plasma concentrations of insulin. The contraction was significantly smaller in diabetic rats. Insulin (80 IU/l) reduced the contraction force in both control and diabetic groups. The post-rest potentiation of contraction was not influenced by insulin in control rats, but insulin increased it in diabetic rats. The negative inotropic effect of insulin was preserved in the presence of cyclopiazonic acid (3 μmol/l), a blocker of sarcoplasmic reticulum (SR) Ca2+ pump, in both control and diabetic groups. In contrast, the negative inotropic effect of insulin was completely prevented in the presence of nifedipine (3 μmol/l), a blocker of L-type Ca2+ current. We conclude that insulin exerts a significant negative inotropic effect in rat myocardium, both control and diabetic. This effect is probably related to processes of SR Ca2+ release triggering, whereas SR Ca2+ loading is not involved.
Propofol is a short-acting hypnotic agent used in human medicine for sedation and general anesthesia. Its administration can be associated with serious cardiovascular side-effects that include decrease in arterial blood pressure and cardiac output. The aim of the present study was to evaluate propofol effects on mitochondrial respiration, myocardial contractility and electrophysiology in the same samples isolated from the heart ventricles of adult rats. Mitochondrial oxygen consumption was
measured in permeabilized samples dissected from free walls of
both ventricles using high-resolution respirometry. State LEAK was determined with malate and glutamate. Active respiration was induced by ADP (state PI) and further by succinate, a Complex II substrate (PI+II). Rotenone was injected to measure state PII. Antimycin A, a Complex III inhibitor was used to determine residual oxygen consumption (ROX). N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride and ascorbate
were injected simultaneously for respirometric assay of cytochrome c oxidase activity (CIV). Isometric contractions and membrane potentials were determined on multicellular preparations isolated from right and left ventricles. Propofol concentrations used ranged from 0.005 to 0.5 mmol/l. All
respiratory parameters were significantly higher in the left control ventricles compared to the right ones. Propofol significantly decreased Complex I activity at concentration 0.025 mmol/l and papillary muscle contraction force at 0.1 mmol/l. Propofol did not affect action potential duration at any concentration studied. Our study suggests that mechanisms contributing to the impaired myocardial contraction during propofol anesthesia might include also mitochondrial dysfunction manifested by compromised
activity of the respiratory Complex I.