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BACKGROUND - The determinants of pulmonary artery systolic pressure (PASP) are not fully understood. It is unknown whether racial differences in PASP exist or if other population characteristics are associated with pulmonary pressure in humans. We examined echocardiographically estimated PASP in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a middle-aged, biracial community-based cohort.
METHODS AND RESULTS - At the CARDIA year-25 examination, 3469 participants underwent echocardiography, including measurement of tricuspid regurgitant jet velocity to estimate PASP. Clinical features, laboratory values, pulmonary function tests, and measurement of adipose depot volume were analyzed for association with PASP. PASP was estimated in 1311 individuals (61% female, 51% white). Older age, higher blood pressure, and higher body mass index were associated with higher PASP. Black race was associated with higher PASP after adjustment for demographics and left and right ventricular function (β 0.94, 95% CI 0.24-1.64; =0.009), but this association was no longer significant after further adjustment for lung volume (β 0.42, 95% CI -0.68 to 0.96; =0.74). Insulin resistance, inflammation (C-reactive protein and interleukin-6), and visceral adipose volume were independently associated with higher PASP after adjustment for relevant covariates. PASP rose with worsening diastolic function (ratio of early transmitral Doppler velocity to average mitral annular tissue Doppler velocity [E/e'] and left atrial volume index).
CONCLUSIONS - In a large biracial cohort of middle-aged adults, we identified associations among black race, insulin resistance, and diastolic dysfunction with higher echocardiographically estimated PASP. Further studies are needed to examine racial differences in PASP and whether insulin resistance directly contributes to pulmonary vascular disease in humans.
© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
AIMS - Recombinant Neuregulin (NRG)-1β has multiple beneficial effects on cardiac myocytes in culture, and has potential as a clinical therapy for heart failure (HF). A number of factors may influence the effect of NRG-1β on cardiac function via ErbB receptor coupling and expression. We examined the effect of the NRG-1β isoform, glial growth factor 2 (GGF2), in rats with myocardial infarction (MI) and determined the impact of high-fat diet as well as chronicity of disease on GGF2 induced improvement in left ventricular systolic function. Potential mechanisms for GGF2 effects on the remote myocardium were explored using microarray and proteomic analysis.
METHODS AND RESULTS - Rats with MI were randomized to receive vehicle, 0.625 mg/kg, or 3.25 mg/kg GGF2 in the presence and absence of high-fat feeding beginning at day 7 post-MI and continuing for 4 weeks. Residual left ventricular (LV) function was improved in both of the GGF2 treatment groups compared with the vehicle treated MI group at 4 weeks of treatment as assessed by echocardiography. High-fat diet did not prevent the effects of high dose GGF2. In experiments where treatment was delayed until 8 weeks after MI, high but not low dose GGF2 treatment was associated with improved systolic function. mRNA and protein expression analysis of remote left ventricular tissue revealed a number of changes in myocardial gene and protein expression altered by MI that were normalized by GGF2 treatment, many of which are involved in energy production.
CONCLUSIONS - This study demonstrates that in rats with MI induced systolic dysfunction, GGF2 treatment improves cardiac function. There are differences in sensitivity of the myocardium to GGF2 effects when administered early vs. late post-MI that may be important to consider in the development of GGF2 in humans.
OBJECTIVE - This study evaluated the smooth muscle functional response and viability of human saphenous vein (HSV) grafts after harvest and explored the effect of mechanical stretch on contractile responses of porcine saphenous vein (PSV).
METHODS - The contractile responses (stress, 10(5) N/m(2)) of deidentified, remnant HSV grafts to depolarizing potassium chloride and the agonist norepinephrine were measured in a muscle organ bath. Cellular viability was evaluated using a methyl thiazole tetrazolium (MTT) assay. A PSV model was used to evaluate the effect of radial, longitudinal, and angular stretch on smooth muscle contractile responses.
RESULTS - Contractile responses varied greatly in HSV harvested for autologous vascular and coronary bypass procedures (0.04198 ± 0.008128 × 10(5) N/m(2) to 0.1192 ± 0.02776 × 10(5) N/m(2)). Contractility of the HSV correlated with the cellular viability of the grafts. In the PSV model, manual radial distension of ≥ 300 mm Hg had no impact on the smooth muscle responses of PSV to potassium chloride. Longitudinal and angular stretch significantly decreased the contractile function of PSV by 33.16% and 15.26%, respectively (P < .03).
CONCLUSIONS - There is considerable variability in HSV harvested for use as an autologous conduit. Longitudinal and angular stretching during surgical harvest impairs contractile responsiveness of the smooth muscle in saphenous vein. Avoiding stretch-induced injuries to the conduits during harvest and preparation for implantation may reduce adverse biologic responses in the graft (eg, intimal hyperplasia) and improve patency of autologous vein graft bypasses.
Published by Mosby, Inc.
BACKGROUND - Deficiency of the PERK eIF2 alpha kinase in humans and mice results in postnatal exocrine pancreatic atrophy as well as severe growth and metabolic anomalies in other organs and tissues. To determine if the exocrine pancreatic atrophy is due to a cell-autonomous defect, the Perk gene was specifically ablated in acinar cells of the exocrine pancreas in mice.
RESULTS - We show that expression of PERK in the acinar cells is required to maintain their viability but is not required for normal protein synthesis and secretion. Exocrine pancreatic atrophy in PERK-deficient mice was previously attributed to uncontrolled ER-stress followed by apoptotic cell death based on studies in cultured fibroblasts. However, we have found no evidence for perturbations in the endoplasmic reticulum or ER-stress and show that acinar cells succumb to a non-apoptotic form of cell death, oncosis, which is associated with a pronounced inflammatory response and induction of the pancreatitis stress response genes. We also show that mice carrying a knockout mutation of PERK's downstream target, ATF4, exhibit pancreatic deficiency caused by developmental defects and that mice ablated for ATF4's transcriptional target CHOP have a normal exocrine pancreas.
CONCLUSION - We conclude that PERK modulates secretory capacity of the exocrine pancreas by regulating cell viability of acinar cells.
The gastrointestinal tract possesses an omnipresent electrical slow wave called the basic electrical rhythm (BER). It has been shown that the frequency of the BER falls during intestinal ischaemia. The correlation between changes in the BER and pathology that occur during acute ischaemia are not completely understood. To study this, the electrical activity of the ileum in 14 adult male rabbits was recorded during ischaemia. At baseline, 60, 120 and 210 minutes of ischaemia, segments of bowel were resected for histopathologic evaluation. The BER frequency was determined using the Fast Fourier Transformation (FFT) spectral analysis. The BER amplitude and FFT spectral power were also determined. The results showed significant decrease (p<0.05, Student's T-test) in the BER frequency, amplitude, and spectral power at all time points. Between 60 and 120 minutes, while there was a decrease in BER activity the pathologic grade remained the same (focal loss of surface epithelium). By 210 minutes of ischaemia when the BER could not be recorded, there was diffuse mucosal infarction. The results indicate that changes in the electrical activity of the bowel during acute mesenteric ischaemia occurred prior to the pathologic changes. The presence of electrical activity indicates that there was viable bowel. Thus it should be possible to use recordings of electrical activity to evaluate bowel viability during acute ischaemia.