Inferior vena cava collapsibility loses correlation with internal jugular vein collapsibility during increased thoracic or intra-abdominal pressure

Purpose

Point-of-care ultrasound evaluates inferior vena cava (IVC) and internal jugular vein (IJV) measurements to estimate intravascular volume status. The reliability of the IVC and IJV collapsibility index during increased thoracic or intra-abdominal pressure remains unclear.

Methods

Three phases of sonographic scanning were performed: spontaneous breathing phase, increased thoracic pressure phase via positive pressure ventilation (PPV) phase, and increased intra-abdominal pressure (IAP) phase via laparoscopic insufflation to 15 mmHg. IVC measurements were done at 1–2 cm below the diaphragm and IJV measurements were done at the level of the cricoid cartilage during a complete respiratory cycle. Collapsibility index was calculated by (max diameter − min diameter)/max diameter × 100 %. Chi square, t test, correlation procedure (CORR) and Fisher’s exact analyses were completed.

Results

A total of 144 scans of the IVC and IJV were completed in 16 patients who underwent laparoscopic surgery. Mean age was 46 ± 15 years, with 75 % female and 69 % African-American. IVC and IJV collapsibility correlated in the setting of spontaneous breathing (r² = 0.86, p < 0.01). IVC collapsibility had no correlation with the IJV in the setting of PPV (r² = 0.21, p = 0.52) or IAP (r² = 0.26, p = 0.42). Maximal IVC diameter was significantly smaller during increased IAP (16.5 mm ± 4.9) compared to spontaneous breathing (20.6 mm ± 4.8, p = 0.04) and PPV (21.8 mm ± 5.6, p = 0.01).

Conclusion

IJV and IVC collapsibility correlated during spontaneous breathing but there was no statistically significant correlation during increased thoracic or intra-abdominal pressure. Increased intra-abdominal pressure was associated with a significant smaller maximal IVC diameter and cautions the reliability of IVC diameter in clinical settings that are associated with intra-abdominal hypertension or abdominal compartment syndrome.     

HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes

Endothelial progenitor cells (EPCs) play an important role in postnatal neovascularization of ischemic tissue. Ex vivo expansion of EPCs might be useful for potential clinical cell therapy of myocardial ischemia. However, cultivation of primary cells leads to cellular aging (senescence), thereby severely limiting the proliferative capacity. Therefore, we investigated whether statins might be able to prevent senescence of EPCs. EPCs were isolated from peripheral blood and characterized. After ex vivo cultivation, EPCs became senescent as determined by acidic beta-galactosidase staining. Atorvastatin or mevastatin dose-dependently inhibited the onset of EPC senescence in culture. Moreover, atorvastatin increased proliferation of EPCs as assessed by BrdU incorporation and colony-forming capacity. Whereas geranylgeranylpyrophosphate or farnesylpyrophosphate reduced the senescence inhibitory effect of atorvastatin, NO synthase inhibition, antioxidants, or Rho kinase inhibitors had no effect. To get further insights into the underlying downstream effects of statins, we measured telomerase activity and determined the expression of various cell cycle regulatory genes by using a microarray assay. Whereas telomerase activity did not change, atorvastatin modulated expression of cell cycle genes including upregulation of cyclins and downregulation of the cell cycle inhibitor p27Kip1. Taken together, statins inhibited senescence of EPCs independent of NO, reactive oxygen species, and Rho kinase, but dependent on geranylgeranylpyrophosphate. Atorvastatin-mediated prevention of EPC senescence appears to be mediated by the regulation of various cell cycle proteins. The inhibition of EPC senescence and induction of EPC proliferation by statins in vitro may importantly improve the functional activity of EPCs for potential cell therapy.     

Enzyme functional evolution through improved catalysis of ancestrally nonpreferred substrates

In this study, we investigated the role for ancestral functional variation that may be selected upon to generate protein functional shifts using ancestral protein resurrection, statistical tests for positive selection, forward and reverse evolutionary genetics, and enzyme functional assays. Data are presented for three instances of protein functional change in the salicylic acid/benzoic acid/theobromine (SABATH) lineage of plant secondary metabolite-producing enzymes. In each case, we demonstrate that ancestral nonpreferred activities were improved upon in a daughter enzyme after gene duplication, and that these functional shifts were likely coincident with positive selection. Both forward and reverse mutagenesis studies validate the impact of one or a few sites toward increasing activity with ancestrally nonpreferred substrates. In one case, we document the occurrence of an evolutionary reversal of an active site residue that reversed enzyme properties. Furthermore, these studies show that functionally important amino acid replacements result in substrate discrimination as reflected in evolutionary changes in the specificity constant (k(cat)/K(M)) for competing substrates, even though adaptive substitutions may affect K(M) and k(cat) separately. In total, these results indicate that nonpreferred, or even latent, ancestral protein activities may be coopted at later times to become the primary or preferred protein activities.