Reduced mechanical efficiency in left-ventricular trabeculae of the spontaneously hypertensive rat.

Long-term systemic arterial hypertension, and its associated compensatory response of left-ventricular hypertrophy, is fatal. This disease leads to cardiac failure and culminates in death. The spontaneously hypertensive rat (SHR) is an excellent animal model for studying this pathology, suffering from ventricular failure beginning at about 18 months of age. In this study, we isolated left-ventricular trabeculae from SHR-F hearts and contrasted their mechanoenergetic performance with those from nonfailing SHR (SHR-NF) and normotensive Wistar rats. Our results show that, whereas the performance of the SHR-F differed little from that of the SHR-NF, both SHR groups performed less stress-length work than that of Wistar trabeculae. Their lower work output arose from reduced ability to produce sufficient force and shortening. Neither their heat production nor their enthalpy output (the sum of work and heat), particularly the energy cost of Ca(2+) cycling, differed from that of the Wistar controls. Consequently, mechanical efficiency (the ratio of work to change of enthalpy) of both SHR groups was lower than that of the Wistar trabeculae. Our data suggest that in hypertension-induced left-ventricular hypertrophy, the mechanical performance of the tissue is compromised such that myocardial efficiency is reduced

Association between infection early in life and mental disorders among youth in the community: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to examine the association between infection early in life and mental disorders among youth in the community.</p> <p>Methods</p> <p>Data were drawn from the MECA (Methods in Epidemiology of Child and Adolescent psychopathology), a community-based study of 1,285 youth in the United States conducted in 1992. Multiple logistic regression analyses were used to investigate the association between parent/caregiver-reported infection early in life and DSM/DISC diagnoses of mental disorders at ages 9-17.</p> <p>Results</p> <p>Infection early in life was associated with a significantly increased odds of major depression (OR = 3.9), social phobia (OR = 5.8), overanxious disorder (OR = 6.1), panic disorder (OR = 12.1), and oppositional defiant disorder (OR = 3.7).</p> <p>Conclusions</p> <p>These findings are consistent with and extend previous results by providing new evidence suggesting a link between infection early in life and increased risk of depression and anxiety disorders among youth. These results should be considered preliminary. Replication of these findings with longitudinal epidemiologic data is needed. Possible mechanisms are discussed.</p

Differential Regulation of PDE5 Expression in Left and Right Ventricles of Feline Hypertrophy Models

Though long known to affect smooth muscle biology, recent studies indicate that phosphodiesterase 5 (PDE5) is also expressed in myocardium. Recognizing that the regulation of PDE5 in hypertrophy is not well understood, we assessed the response of PDE5 expression and the level of cGMP-dependent kinase I (cGKI) in the left and right ventricles of feline hypertrophy models.Using a cDNA library of feline aortic smooth muscle cells, we identified and cloned PDE5 cDNA for the first time in this species. The sequence shares 98% identity with its human orthologue at the amino acid level. E. coli expression of the cloned allele allowed selection of antibodies with appropriate specificity, facilitating the analysis of PDE5 expression in feline models created by selective proximal aortic (Ao) or pulmonary artery (PA) banding that resulted in hypertrophy of the left ventricle (LV) and right ventricle (RV), respectively. We demonstrated that PDE5 expression responded differentially with a decreased expression in the LV and an increased expression in the RV in the Ao-banded model. Similarly, in the PA-banded model, LV showed reduced expression while the RV expression was unaltered. In addition, the expression of cGKI was significantly decreased in the RV of Ao-banded group, correlating inversely with the increase in PDE5 expression.The differential regulation of PDE5 and cGKI expression suggests that the mechanisms involved in hypertrophy could be different in RV vs. LV. Reciprocal PDE5 and cGKI expression in the RV of Ao-banded model suggests functional significance for PDE5 up-regulation

No behavioural response to kin competition in a lekking species

The processes of kin selection and competition may occur simultaneously if limited individual dispersal i.e. population viscosity, is the only cause of the interactions between kin. Therefore, the net indirect benefits of a specific behaviour may largely depend on the existence of mechanisms dampening the fitness costs of competing with kin. In lekking species, males may increase the mating success of their close relatives (and hence gain indirect fitness benefits) because female prefer large leks. At the same time, kin selection may also lead to the evolution of mechanisms that dampen the costs of kin competition. As this mechanism has largely been ignored to date, we used detailed behavioural and genetic data collected in the black grouse Lyrurus tetrix to test whether males mitigate the costs of kin competition through the modulation of their fighting behaviours according to kinship and the avoidance of close relatives when establishing a lek territory. We found that neighbouring males’ fighting behaviour was unrelated to kinship and males did not avoid settling down with close relatives on leks. As males’ current and future mating success are strongly related to their behaviour on the lek (including fighting behaviour and territory position), the costs of kin competition may be negligible relative to the direct benefits of successful male-male contests. As we previously showed that the indirect fitness benefits of group membership were very limited in this black grouse population, these behavioural data support the idea that direct fitness benefits gained by successful male-male encounters likely outbalance any indirect fitness benefits

Dependence of Muscle Fatigue On Stimulation Protocol - Effect of Hypocaloric Diet

This study tested the hypothesis that the decreased resistance of skeletal muscles to fatigue after a period of inadequate nutrition is a consequence of the type of fatigue test employed. Rats (n = 8) were fed hypocalorically for 10 days, resulting in a 33.5 ± 3.0% (SE) reduction in body weight. The fatigue resistance of muscles was assessed with use of isolated soleus muscles at a temperature of 25°C. Fatigue resistance was determined from the decline in isometric force during a series of tetanic contractions. Two contrasting contraction protocols were devised to test the susceptibility of muscles to fatigue. One protocol was designed to require high rates of energy supply and hence force a dependence on glycolytic energy supply pathways. The second protocol required much lower rates of energy supply that could be entirely met by oxidative energy supply processes. During the high energy demand (glycolytic) protocol, the force produced by muscles from a control group of rats decreased to 78.7 ± 0.8% (n = 12 muscles) of the initial value. Hypocaloric feeding significantly reduced the resistance of muscles to fatigue: force declined to 61.3 ± 3.5% (n = 16 muscles) during the contraction protocol. In contrast, when fatigue was quantified using the low energy demand (oxidative) contraction protocol, the effect of nutritional status on fatigue resistance was entirely abolished. This result supports the hypothesis that resistance to fatigue is critically dependent on the fatigue test employed

Regulation of cardiac cellular bioenergetics: mechanisms and consequences

The regulation of cardiac cellular bioenergetics is critical for maintaining normal cell function, yet the nature of this regulation is not fully understood. Different mechanisms have been proposed to explain how mitochondrial ATP production is regulated to match changing cellular energy demand while metabolite concentrations are maintained. We have developed an integrated mathematical model of cardiac cellular bioenergetics, electrophysiology, and mechanics to test whether stimulation of the dehydrogenase flux by Ca(2+) or Pi, or stimulation of complex III by Pi can increase the rate of mitochondrial ATP production above that determined by substrate availability (ADP and Pi). Using the model, we show that, under physiological conditions the rate of mitochondrial ATP production can match varying demand through substrate availability alone; that ATP production rate is not limited by the supply of reducing equivalents in the form of NADH, as a result of Ca(2+) or Pi activation of the dehydrogenases; and that ATP production rate is sensitive to feedback activation of complex III by Pi. We then investigate the mechanistic implications on cytosolic ion homeostasis and force production by simulating the concentrations of cytosolic Ca(2+), Na(+) and K(+), and activity of the key ATPases, SERCA pump, Na(+)/K(+) pump and actin-myosin ATPase, in response to increasing cellular energy demand. We find that feedback regulation of mitochondrial complex III by Pi improves the coupling between energy demand and mitochondrial ATP production and stabilizes cytosolic ADP and Pi concentrations. This subsequently leads to stabilized cytosolic ionic concentrations and consequentially reduced energetic cost from cellular ATPases