Conventional Hemodynamic Resuscitation May Fail to Optimize Tissue Perfusion: An Observational Study on the Effects of Dobutamine,Enoximone, and Norepinephrine in Patients with Acute Myocardial Infarction Complicated by Cardiogenic Shock

Aim

To investigate the effects of inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock.

Methods and Results

Thirty patients with cardiogenic shock were included. Patients received dobutamine, enoximone, or norepinephrine. We performed hemodynamic measurements at baseline and after titration of the inotropic agent until cardiac index (CI) ≥2.5 L.min⁻¹.m⁻² or mixed-venous oxygen saturation (SvO₂) ≥70% (dobutamine or enoximone), and mean arterial pressure (MAP) ≥70 mmHg (norepinephrine). As parameters of tissue perfusion, we measured central-peripheral temperature gradient (delta-T) and sublingual perfused capillary density (PCD). All patients reached predefined therapeutic targets. The inotropes did not significantly change delta-T. Dobutamine did not change PCD. Enoximone increased PCD (9.1 [8.9–10.2] vs. 11.4 [8.4–13.9] mm.mm⁻²; p<0.05), and norepinephrine tended to decrease PCD (9.8 [8.5–11.9] vs. 8.8 [8.2–9.6] mm.mm⁻², p = 0.08). Fifteen patients (50%) died within 30 days after admission. Patients who had low final PCD (≤10.3 mm.mm⁻²; 64%) were more likely to die than patients who had preserved PCD (>10.3 mm.mm⁻²; mortality 72% vs. 17%, p = 0.003).

Conclusion

This study demonstrates the effects of commonly used inotropic agents on parameters of tissue perfusion in patients with cardiogenic shock. Despite hemodynamic optimization, tissue perfusion was not sufficiently restored in most patients. In these patients, mortality was high. Interventions directed at improving microcirculation may eventually help bridging the gap between improved hemodynamics and dismal patient outcome in cardiogenic shock.     

Predictors of long-term weight loss in adults with modest initial weight loss, by sex and race

Effective weight management interventions could reduce race-sex disparities in cardiovascular disease (CVD), yet little is known about factors associated with successful weight loss maintenance in race-sex subgroups. In the Weight Loss Maintenance trial (WLM), overweight/obese (BMI 25-45 kg/m(2)) adults who lost ≥4 kg in a 6-month behavioral weight loss intervention (phase I) were randomized into one of three 30-month maintenance interventions (phase II). To investigate predictors in subgroups, randomized groups were combined for this analysis. Of 1,685 phase I participants, 1,032 (61%) entered phase II, including 12% black men (BM), 26% black women (BW), 25% white men (WM), and 37% white women (WW). Weight change over the 36-month study ranged from -2.3% (95% confidence interval = -3.1 to -1.5%) in BW to -4.5% (95% confidence interval = -5.7 to -4.0%) in WM, the result of differential weight loss during phase I. Within race, men lost significantly more weight than women, but within sex group, weight loss did not differ significantly between races. Although participants regained weight during phase II, regain did not differ by race-sex group, and mean weight at the end of the study was significantly lower than phase I entry weight for each subgroup. In regression models, phase I weight loss predicted overall 36-month weight loss in all race-sex groups. Healthy dietary pattern at entry, improvement in dietary pattern, or both were predictive in three of four race-sex groups. Few other variables other than initial weight loss and dietary pattern were predictive. Future research should identify additional modifiable influences on long-term maintenance after a modest weight loss.     

Quantification of viability in organotypic multicellular spheroids of human malignant glioma using lactate dehydrogenase activity: a rapid and reliable automated assay.

Organotypic spheroids from malignant glioma resemble the biological complexity of the original tumor and are therefore appealing to study anticancer drug responses. Accurate and reproducible quantification of response effect has been lacking to determine drug responses in this three-dimensional tumor model. Lactate dehydrogenase (LDH) activity was demonstrated in cryostat sections of spheroids using the tetrazolium salt method. Calibrated digital image acquisition of the stained cryostat sections enables quantification of LDH activity. Fully automated image cytometry reliably demarcates LDH-active and LDH-inactive tissue areas by thresholding at specific absorbance values. The viability index (VI) was calculated as ratio of LDH-active areas and total spheroid tissue areas. Duplicate staining and processing on the same tissue showed good correlation and therefore reproducibility. Sodium azide incubation of spheroids induced reduction in VI to almost zero. We conclude that quantification of viability in cryostat sections of organotypic multicellular spheroids from malignant glioma can be performed reliably and reproducibly with this approach.     

Effect of group racial composition on weight loss in African Americans

Objective: We do not know how racial composition of a group influences behavior change for African Americans (AAs) in group‐based weight loss programs. We tested the hypothesis that AA who participate in all AA weight loss intervention groups will lose more weight than AA who participate in mixed race groups. Methods and Procedures: This observational study was ancillary to Phase 1 of the Weight Loss Maintenance Study, a multi‐center trial of strategies to maintain weight loss after a 20‐week behavior modification program. Three of four centers recruited several all‐AA intervention groups. Remaining groups were combinations of AA and non‐AA participants. All participants received the same weight loss intervention. Change in weight was the primary outcome, comparing participants of all‐AA groups with AA participants of mixed race groups conducted by the same AA interventionists. Secondary outcomes included measures of intervention adherence and behavior change. Results: Participants of all‐AA groups (n = 271) were comparable to other AA participants (n = 106). The mean proportion of AA in mixed race groups was 56%. All‐AA group participants had similar weight loss as those in mixed groups (?4.2 vs. ?4.2 kg, P = 0.97). There were no differences between the groups in mean number of sessions attended or changes in dietary intake. Discussion: Significant weight loss was observed in both groups, with no effect of group composition on adherence or weight loss outcomes. Special logistics to accommodate all‐AA groups may not be necessary. Despite varying instructional environments, AA appeared to respond positively to intervention messages with significant changes in dietary intake, physical activity (PA), and weight.     

Salinity effects on greenhouse gas emissions from wetland soils are contingent upon hydrologic setting: a microcosm experiment

Coastal forested wetlands provide important ecosystem services such as carbon sequestration, nutrient retention, and flood protection, but they are also important sources of greenhouse gas emissions. Human appropriation of surface water and extensive ditching and draining of coastal plain landscapes are interacting with rising sea levels to increase the frequency and magnitude of saltwater incursion into formerly freshwater coastal wetlands. Both hydrologic change and saltwater incursion are expected to alter carbon and nutrient cycling in coastal forested wetlands. We performed a full factorial experiment in which we exposed intact soil cores from a coastal forested wetland to experimental marine salt treatments and two hydrologic treatments. We measured the resulting treatment effects on the emissions of carbon dioxide (CO₂), methane (CH₄), and nitrous oxide (N₂O) over 112 days. Salinity effects were compared across four treatments to isolate the effects of increases in ionic strength from the impact of adding a terminal electron acceptor (SO₄^2?). We compared control treatments (DI addition), to artificial saltwater (ASW, target salinity of 5 parts per thousand) and to two treatments that added sulfate alone (SO₄^2?, at the concentration found in 5 ppt saltwater) and saltwater with the sulfate removed (ASW-SO₄^2?, with the 5 ppt target salinity maintained by adding additional NaCl). We found that all salt treatments suppressed CO₂ production, in both drought and flooded treatments. Contrary to our expectations, CH₄ fluxes from our flooded cores increased between 300 and 1200% relative to controls in the ASW and ASW-SO₄^2? treatments respectively. In the drought treatments, we saw virtually no CH₄ release from any core, while artificial seawater with sulfate increased N₂O fluxes by 160% above DI control. In contrast, salt and sulfate decreased N₂O fluxes by 72% in our flooded treatments. Our results indicate that salinization of forested wetlands of the coastal plain may have important climate feedbacks resulting from enhanced greenhouse gas emissions and that the magnitude and direction of these emissions are contingent upon wetland hydrology.     

NMB: a human neuroblastoma cell line with specific opiate binding sites

The human neuroblastoma cell line designated NMB (Brodeur et al., 1977, Cancer 40: 2256) has been shown to have specific opiate binding sites. These sites are highly stereospecific. Two characteristic delta specific peptides, D-Ala2-D-Leu5 enkephalin and D-Thr2-D-Thr6 enkephalin, have high affinity for the binding sites. Morphine binds specifically but with a much lower affinity. Dextrorphan and the mu specific peptide morphiceptin (Tyr-Pro-Phe-Pro-CO-NH2) do not bind to the site. The binding sites are heat and trypsin sensitive. Sodium ions specifically lower agonist binding to the sites. Approximately 14,000 binding sites per cell are found. The binding characteristics of these sites are very similar to those of the delta sites characterized on mouse neuroblastoma cell lines.     

The dynamics of local kinetic parameters of glutamate dehydrogenase in rat liver

Kinetic parameters of glutamate dehydrogenase (GDH, EC 1.4.1.2) for glutamate were determined in periportal and pericentral zones of adult male and female rat liver lobules under normal fed conditions and after starvation for 24 h. GDH activity was measured as formazan production over time against a range of glutamate concentrations in serial cryostat sections using image analysis. Captured gray value images were transformed to absorbance images and local initial velocities (V_ini) were calculated. A hyperbolic function was used to describe the relationship between substrate concentration and local V_ini. Under fed conditions, V_max values were similar in male and female rats (8±2 and 16±2 μmol min⁻¹ cm⁻³ liver tissue in periportal and pericentral zones, respectively). Starvation increased V_max, especially in pericentral zones of females (to 27±1 μmol min⁻¹ cm⁻³ liver tissue). Under fed conditions, the affinity of GDH for glutamate was similar in male and female rats (2.5±0.5 mM and 3.5±0.8 mM in periportal and pericentral zones, respectively). Starvation had no effect on K_m values in male rats, but in female rats affinity for glutamate decreased significantly in both zones (K_m values of 4.0±0.1 mM and 8.6±0.8 mM, respectively). These local changes in the kinetic parameters of GDH indicate that conversion of glutamate to α-oxoglutarate cannot be predicted on the basis of GDH concentrations or zero-order activity in the different zones of liver lobules alone.