Initial Outcomes for the NHLBI K99/R00 Pathway to Independence Program in Relation to Long-Standing Career Development Programs: Implications for Trainees, Mentors, and Institutions.

Sufficient history now exists to assess the NIH Pathway to Independence Award (K99/R00), first offered in 2007 to support the career development of biomedical researchers. The success of K99 principal investigators (PIs) in obtaining subsequent grant support was compared to PIs supported by the long-standing K08 and K23 programs. For cardiovascular K awards initiated in fiscal years 2007–2009, K99 PIs were more successful in obtaining subsequent grant support than the other groups.

National Institutes of Health Career Development Awards for Cardiovascular Physician-Scientists: Recent Trends and Strategies for Success.

Nurturing the development of cardiovascular physician-scientist investigators is critical for sustained progress in cardiovascular science and improving human health. The transition from an inexperienced trainee to an independent physician-scientist is a multifaceted process requiring a sustained commitment from the trainee, mentors, and institution. A cornerstone of this training process is a career development (K) award from the National Institutes of Health (NIH).

Messenger RNA for neuropeptide Y in the arcuate nucleus increases in parallel with plasma adrenocorticotropin during sepsis in the rat.

Loss of appetite occurs in the cecal ligation and puncture (CLP) model of sepsis in conjunction with the activation of central neural stress pathways. Neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus is upregulated by several stressors and is stimulatory to feeding. To examine the response of NPY messenger RNA in the arcuate nucleus to sepsis, we used biotinylated RNA probes and a quantitative non-isotopic in situ hybridization approach in cryo-preserved sections from rats made septic by CLP.

The absence of circadian cues during recovery from sepsis modifies pituitary-adrenocortical function and impairs survival.

Lighting and other environmental cues in the intensive care unit rarely adhere to a consistent daily pattern. To determine the influence of the daily light/dark (LD) cycle on recovery from sepsis, male Sprague Dawley rats were acclimated to lights-on condition at 6 AM and lights-off condition at 6 PM for 6 to 14 days. Catheter placement and cecal ligation and puncture (CLP) were performed under ketamine and xylazine.

Central neural distribution of immunoreactive Fos and CRH in relation to plasma ACTH and corticosterone during sepsis in the rat.

Although brain pathways activated by sepsis may respond acutely to endotoxin administration, the long-term central response to sepsis is not known. We prepared male rats for hormonal sampling at the circadian nadir (AM) and peak (PM) after cecal ligation and puncture (CLP) or sham surgery. Diurnal variation of corticosterone was present on postoperative day (D) 3 and D4 after sham surgery but not after CLP.

Hypotensive hemorrhage increases calcium uptake capacity and Bcl-XL content of liver mitochondria.

We tested the hypothesis that the response of mitochondrial uptake of calcium and content of Bcl proteins to reversible hemorrhagic shock increases the vulnerability for hepatocellular death. Pentobarbital-anesthetized rats were bled to a mean arterial pressure of 30 to 40 mmHg for 1 h. A subset was then resuscitated (isotonic sodium chloride solution, three times shed volume).

Cecal ligation and puncture in rats interrupts the circadian rhythms of corticosterone and adrenocortical responsiveness to adrenocorticotrophic hormone.

Objective: To determine the altered patterns of pituitary-adrenal activity and impaired adrenocortical sensitivity to adrenocorticotrophic hormone (ACTH) in the cecal ligation and puncture (CLP) model of sepsis.

Design: Prospective, controlled experiment.

Setting: Basic science laboratory.

ATP accelerates respiration of mitochondria from rat lung and suppresses their release of hydrogen peroxide.

Lung mitochondria were isolated by differential centrifugation from pentobarbital-anesthetized male rats. One to three millimolar Mg2+-ATP increased the consumption of oxygen of lung mitochondria oxidizing 10 mM succinate > fourfold (P < 0.01) whereas ATP increased the respiration of liver mitochondria by < 35%.

G-CSF, but not corticosterone, mediates circulating neutrophilia induced by febrile-range hyperthermia.

We previously showed that sustained exposure to febrile-range hyperthermia (FRH) for 24 h caused an increase in circulating granulocyte colony-stimulating factor (G-CSF) levels and a peripheral neutrophilia in mice (Hasday J, Garrison A, Singh I, Standiford T, Ellis G, Rao S, He JR, Rice P, Frank M, Goldblum S, and Viscardi R. Am J Pathol 162: 2005-2017, 2003). In this study, we utilized a conscious temperature-clamped mouse model to analyze the kinetics of G-CSF expression and peripheral neutrophil expansion and the contributions of FRH-induced G-CSF expression, glucocorticoid generation, and catecholamine-induced neutrophil demargination.

Detrimental effects of rapid fluid resuscitation on hepatocellular function and survival after hemorrhagic shock.

Because end-organ injury can occur with reperfusion following hemorrhage or ischemia, we hypothesized that aggressive intravenous fluid resuscitation would aggravate tissue injury in a fixed-volume model of hemorrhagic shock. Unanesthetized chronically prepared male rats were hemorrhaged 33-36 mL/kg for 2.5 h.