Effect of Vehicle on the Nasal Absorption of Epinephrine During Cardiopulmonary Resuscitation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90174/1/j.1875-9114.1996.tb03030.x.pd

Intrinsic aerobic capacity sets a divide for aging and longevity

<p><b>Rationale:</b> Low aerobic exercise capacity is a powerful predictor of premature morbidity and mortality for healthy adults as well as those with cardiovascular disease. For aged populations, poor performance on treadmill or extended walking tests indicates closer proximity to future health declines. Together, these findings suggest a fundamental connection between aerobic capacity and longevity.</p> <p><b>Objectives:</b> Through artificial selective breeding, we developed an animal model system to prospectively test the association between aerobic exercise capacity and survivability (aerobic hypothesis).</p> <p><b>Methods and Results:</b> Laboratory rats of widely diverse genetic backgrounds (N:NIH stock) were selectively bred for low or high intrinsic (inborn) treadmill running capacity. Cohorts of male and female rats from generations 14, 15, and 17 of selection were followed for survivability and assessed for age-related declines in cardiovascular fitness including maximal oxygen uptake (VO<sub>2max</sub>), myocardial function, endurance performance, and change in body mass. Median lifespan for low exercise capacity rats was 28% to 45% shorter than high capacity rats (hazard ratio, 0.06; P<0.001). VO<sub>2max</sub>, measured across adulthood was a reliable predictor of lifespan (P<0.001). During progression from adult to old age, left ventricular myocardial and cardiomyocyte morphology, contractility, and intracellular Ca<sup>2+</sup> handling in both systole and diastole, as well as mean blood pressure, were more compromised in rats bred for low aerobic capacity. Physical activity levels, energy expenditure (Vo<sub>2</sub>), and lean body mass were all better sustained with age in rats bred for high aerobic capacity.</p> <p><b>Conclusions:</b> These data obtained from a contrasting heterogeneous model system provide strong evidence that genetic segregation for aerobic exercise capacity can be linked with longevity and are useful for deeper mechanistic exploration of aging.</p&gt

Microsatellites Reveal a High Population Structure in Triatoma infestans from Chuquisaca, Bolivia

Chagas disease is a protozoan infection caused by the parasite Trypanosoma cruzi. Chagas is prevalent throughout Central and South America, and it remains a chief concern in Bolivia. A movement that began in 1991 called the Southern Cone Initiative has been successful in reducing the incidence of Chagas disease in the Southern Cone countries of Argentina, Brazil, Chile, and Uruguay; but due to socio-economic and other factors, incidence remains high in Bolivia. The most important mode of transmission of T. cruzi to humans and other mammals is through feces of triatomine bugs. Thus, disease control and transmission prevention focus on elimination of triatomine vectors, and more specifically in Bolivia, it focuses on the elimination of Triatoma infestans. This study focuses on T. infestans in the Department of Chuquisaca, Bolivia. Ten highly variable microsatellite markers were used to analyze the population structure of insects collected in different towns. Statistical analyses show that T. infestans are highly structured, which means that they colonize on a small geographic scale. The results also suggest little active dispersal. These findings should be implemented during control efforts so that insecticide spraying focuses on geographic areas of colonization and re-colonization

Brain activation patterns at exhaustion in rats that differ in inherent exercise capacity.

In order to further understand the genetic basis for variation in inherent (untrained) exercise capacity, we examined the brains of 32 male rats selectively bred for high or low running capacity (HCR and LCR, respectively). The aim was to characterize the activation patterns of brain regions potentially involved in differences in inherent running capacity between HCR and LCR. Using quantitative in situ hybridization techniques, we measured messenger ribonuclease (mRNA) levels of c-Fos, a marker of neuronal activation, in the brains of HCR and LCR rats after a single bout of acute treadmill running (7.5-15 minutes, 15° slope, 10 m/min) or after treadmill running to exhaustion (15-51 minutes, 15° slope, initial velocity 10 m/min). During verification of trait differences, HCR rats ran six times farther and three times longer prior to exhaustion than LCR rats. Running to exhaustion significantly increased c-Fos mRNA activation of several brain areas in HCR, but LCR failed to show significant elevations of c-Fos mRNA at exhaustion in the majority of areas examined compared to acutely run controls. Results from these studies suggest that there are differences in central c-Fos mRNA expression, and potential brain activation patterns, between HCR and LCR rats during treadmill running to exhaustion and these differences could be involved in the variation in inherent running capacity between lines

Correlation between relative c-Fos mRNA and distance run during treadmill tests at week 30 of HCR and LCR.

<p>Fisher protected least significant difference: * p<.05, ** p<.01, *** p<.001.</p

Brain region, abbreviation, and bregma coordinates of brain areas quantified in high capacity runners (HCR) and low capacity runners (LCR).

<p>Bregma coordinates according to <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0045415#pone.0045415-Paxinos1" target="_blank">[84]</a>.</p

Comparison of relative c-Fos mRNA levels between HCR and LCR run to exhaustion.

<p>Panel A represents brain areas where c-Fos mRNA is statistically higher in HCR versus LCR (HCR>LCR). Panel B represents brain areas where there is no statistical difference in mRNA expression between HCR and LCR (HCR = LCR). Panel C represents brain areas where c-Fos mRNA is statistically lower in HCR versus LCR (HCR</p

Comparison of relative c-Fos mRNA levels between HCR and LCR run for 15 minutes.

<p>Panel A represents brain areas where c-Fos mRNA is statistically higher in HCR versus LCR (HCR>LCR). Panel B represents brain areas where there is no statistical difference in mRNA expression between HCR and LCR (HCR = LCR). Panel C represents brain areas where c-Fos mRNA is statistically lower in HCR versus LCR (HCR</p

Treadmill tests in high and low capacity runners at week 30.

<p>Panel A represents distance run to exhaustion between HCR and LCR. Panel B represents time run to exhaustion between HCR and LCR. N = 8 animals/group. Values represent group means ± standard error of measurement. Fisher protected least significant difference: ** p<.01, *** p<.0001 with respect to LCR at respective time point.</p

C-Fos mRNA expression in HCR and LCR in response to treadmill running.

<p>Values represent average densities ± standard error of the mean. There was no significant difference in c-Fos mRNA expression across groups in nine of the 25 brain areas examined (shown here).</p