Increased incidence of isoproterenol-induced ventricular fibrillation in aging rats

Prolonged beta-adrenergic stimulation obtained by subcutaneous injection of isoproterenol in unanesthetized, unrestrained rats elicited ventricular fibrillation in approximately 80% of animals at 10-12 months of age. Ventricular fibrillation failed to occur in 1-month-old rats and involved only 12% of rats at 2 months. Senescence appeared not to increase the frequency of ventricular fibrillation since a similar incidence was seen in rats at 10-12 and 19-21 months. In all instances, ventricular fibrillation was preceded by ECG changes consistent with acute subendocardial ischemia. To evaluate whether acute beta-adrenergic stimulation elicits comparable cardiovascular effects in animals of different age, a dose-response curve to intravenous injection of isoproterenol was performed in anesthetized rats. Changes in heart rate, systemic arterial pressure, left ventricular pressure, and dP/dt were not different among animal groups. It was concluded that the arrhythmogenic potential of isoproterenol may not be related to differences in cardiac beta-receptor sensitivity with age as suggested by the comparable changes in the inotropic and chronotropic actions of isoproterenol in the animal groups studied.     

Deficit of glucocorticoid-induced leucine zipper amplifies angiotensin-induced cardiomyocyte hypertrophy and diastolic dysfunction

Poor prognosis in heart failure and the lack of real breakthrough strategies validate targeting myocardial remodelling and the intracellular signalling involved in this process. So far, there are no effective strategies to counteract hypertrophy, an independent predictor of heart failure progression and death. Glucocorticoid-induced leucine zipper (GILZ) is involved in inflammatory signalling, but its role in cardiac biology is unknown. Using GILZ-knockout (KO) mice and an experimental model of hypertrophy and diastolic dysfunction, we addressed the role of GILZ in adverse myocardial remodelling. Infusion of angiotensin II (Ang II) resulted in myocardial dysfunction, inflammation, apoptosis, fibrosis, capillary rarefaction and hypertrophy. Interestingly, GILZ-KO showed more evident diastolic dysfunction and aggravated hypertrophic response compared with WT after Ang II administration. Both cardiomyocyte and left ventricular hypertrophy were more pronounced in GILZ-KO mice. On the other hand, Ang II–induced inflammatory and fibrotic phenomena, cell death and reduction in microvascular density, remained invariant between the WT and KO groups. The analysis of regulators of hypertrophic response, GATA4 and FoxP3, demonstrated an up-regulation in WT mice infused with Ang II; conversely, such an increase did not occur in GILZ-KO hearts. These data on myocardial response to Ang II in mice lacking GILZ indicate that this protein is a new element that can be mechanistically involved in cardiovascular pathology.     

A case of an osteolytic lesion on an Italian Neanderthal jaw

This article describes an osteolytic odontogenetic lesion found on the mandible of a Neanderthal from the Middle Paleolithic site of Riparo Mezzena near the city of Verona (Italy). A pathology was revealed through X-ray and computerized-tomodensitometric examinations. This lesion was compared to present and sub-contemporary populations and indicates that it may have been of infectious origin, resulting from a bacterial invasion of the root canal of a coronal pulp exposure. The bacterial contamination may have resulted either from a traumatic fracture, a cavity, or extensive wear on the tooth.