Cardiomyocytes of adult myocardium increase their cellular mass in response to growth stimuli. They undergo hypertrophic growth but they do not proliferate in contrast to immature cardiomyocytes. Growth stimuli of the adult cardiomyocytes include classical growth hormones, various neuroendocrine factors, and the increase in mechanical load. The signal transduction of alpha1-adrenoceptor stimulation has been investigated in greatest detail and may therefore be taken as a reference for other humoral stimuli. It involves the activation of protein kinase C (PKC) and, downstream of PKC activation, of two separate signaling pathways, one including the mitogen-activated protein kinase and another including PI3-kinase and p70(s6k) as key steps. Activation of the first pathway leads to re-expression of fetal genes, activation of the second pathway to a general activation of protein synthesis, and cellular growth. In neonatal cardiomyocytes, mechanical stretch causes growth by an activation of an autocrine mechanism including angiotensin II and endothelin. This mechanism does not operate, however, in adult cardiomyocytes. A mechanism of mechanotransduction has not yet been identified on adult cardiomyocytes but integrins may play a part. In microgravity, the scenario of myocardial growth stimulation is altered. On the systemic level, there are changes in hemodynamic and neuroendocrine regulation that exert indirect effects on the myocardium. Microgravity may also exert a direct cellular effect by the absence of a constant gravitational load component.
Objective: We compared the hemodynamic performance, protein expression, phosphorylation and mRNA levels of apoptosis-related genes in young and old rat hearts after application of Buckberg's blood cardioplegia (BCP) to evaluate differences between the age groups regarding postischemic myocardial function and cellular survival.
Abstract —Ventricular cardiomyocytes have previously been identified as potential target cells for parathyroid hormone–related peptide (PTHrP). Synthetic PTHrP peptides exert a positive contractile effect. Because systemic PTHrP levels are normally negligible, this suggests that PTHrP is expressed in the ventricle and acts as a paracrine mediator. We investigated the ventricular expression of PTHrP and its expression in cultured cells isolated from the ventricle, studied the release of PTHrP from hearts and cultures, and investigated whether this authentic PTHrP mimics the biological effects previously described for synthetic PTHrP on ventricular cardiomyocytes. We found PTHrP expressed in ventricles of neonatal and adult rat hearts. In cells isolated from adult hearts, we found PTHrP expression exclusively in coronary endothelial cells but not in cardiomyocytes. The latter, however, are target cells for PTHrP. PTHrP was released from isolated perfused hearts during hypoxic perfusion and from cultured coronary endothelial cells under energy-depleting conditions. This PTHrP was biologically active; ie, it exerted a positive contractile and lusitropic effect on cardiomyocytes. Authentic PTHrP was glycosylated and showed a slightly higher potency than synthetic PTHrP. These results suggest that PTHrP is an endothelium-derived modulator of ventricular function.
Calcium plays a pivotal role in excitation-contraction coupling of cardiomyocytes and many other cellular re- sponses observed in cardiovascular cells. Thus maintaining a healthy status requires very strict regulation of cytoplasmatic but also plasma ionized calcium concentration. Plasma ionized calcium is regulated by calcium sensing and the regulation of calcium uptake and secretion. Under conditions of heart failure, however, electrolyte deregulation occurs due to an ac- tivation of the sympathetic nervous system and the renin-angiotensin-aldosterone system because both systems are cou- pled calcium regulation and thereby also to the regulation of hormones controlling calcium homeostasis such as parathy- roid hormone, parathyroid hormone-related protein, and vitamin D that are activated in a calcium-dependent way. Of note, these hormones and receptors have also direct cardiac effects that modulate cardiac and renal function. Therefore, they play not only a role in end-stage heart failure but also in essential hypertension and reno-cardiovascular complications. In this review we summarize our current understanding about the role of calcium deregulation in heart failure and discuss the consequences from these observations. In conclusion, controlling plasma ionized calcium, plasma parathyroid hormone, and vitamin D status are pivotal in successful pharmacotreatment of patients with heart failure.
Objective: We compared the hemodynamic performance of young rat hearts after application of blood cardioplegia (BCP) in two different temperatures to evaluate differences regarding postischemic myocardial function.
Objectives Antithrombin (AT) has been proven to have major impact on perioperative activation of the coagulation system.The aim of this prospective, controlled, single-blind clinical trial was to determine the impact of AT substitution on perioperative thrombin formation.Methods Forty male coronary artery bypass graft patients participated in the trial.Prior to skin incision, 30 patients received AT according to a formula targeted at 120% AT activity before extracorporeal circulation (ECC), plus an additional 1000 U (group A, n = 10), 2000 U (group B, n = 10) or 3000 U (group C, n = 10) of AT in order to compensate for increased consumption during ECC.Control patients did not receive any AT substitution (group D, n = 10).The following parameters were determined perioperatively and until the fifth postoperative day: AT levels, parameters of coagulation activation (prothrombin fragment F 1.2 , thrombin-antithrombin complex, D-dimer), inflammation (IL-6) and myocardial perfusion (troponin).Statistical comparison between groups was performed using analysis of variance, followed by Fisher's PLSD (P < 0.05) after ECC.
In ischemic-reperfused myocardium, myocardial cells are jeopardized not only by reoxygenation-induced hypercontracture but also by the development of a transsarcolemmal osmotic gradient. Here the question of whether osmotic fragility of cardiomyocytes can be reduced by interventions during reoxygenation was addressed. Isolated ventricular cardiomyocytes (from adult rats), exposed to 120 min of hypoxia and subsequent reoxygenation, were used as model. With reoxygenation, medium osmolarity was reduced from 270 to 80 mosM. Loss of sarcolemmal integrity was characterized by enzyme loss from cells (creatine kinase and lactate dehydrogenase). Cardiomyocytes reoxygenated after 120 min of hypoxia hypercontracted, but enhanced enzyme loss was observed only at 80 mosM. The nitric oxide (NO) donors 3-morpholinosydnonimine (10 mM), sodium nitroprusside (10 mM), S-nitroso-N-acetyl-DL-penicillamine (100 microM), and the antilipid peroxidant diphenylphenylenediamine (DPPD, 2.5 microM) reduced enzyme loss with hyposmolar reoxygenation. Agents activating guanosine 3',5'-cyclic monophosphate (cGMP)-dependent pathways [atrial natriuretic peptide (1 microM), urodilatin (1 microM), and 8-bromo-cGMP (10 mM)], the contractile inhibitor 2,3-butanedione monoxime (10 mM), and the SIN-1 metabolite SIN-1C (10 mM) did not protect cardiomyocytes against osmotic fragility. The results show that increased osmotic fragility of isolated adult rat cardiomyocytes can be prevented at the time of reoxygenation by NO donors and DPPD in a cGMP-independent way.
