Prospective Evaluation of a Multibeat Analysis Cardiac Index Estimation in Patients With Cardiogenic Shock.

OBJECTIVES: The decision algorithm for managing patients in cardiogenic shock depends on cardiac index (CI) estimates. Cardiac index estimation via thermodilution (CI-TD) using a pulmonary artery catheter is used commonly for obtaining CI in these patients. Minimally invasive methods of estimating CI, such as multibeat analysis (CI-MBA), may be an alternative in this population. DESIGN: A prospective, observational study. SETTING: Cardiac intensive care unit. PARTICIPANTS: Twenty-two subjects in cardiogenic shock provided 101 paired CI measurements. INTERVENTIONS: Measurements were obtained concomitantly by intermittent CI-TD and CI-MBA (Argos Cardiac Output Monitor; Retia Medical, Valhalla, NY). For each CI-TD, CI-MBA estimates were averaged over 1 minute to provide paired values. Bland-Altman and 4-quadrant analyses were performed by plotting changes between successive CI measurements (ΔCI) from each of the 2 methods. Concordance was calculated as a percentage using ΔCI data points from the 2 methods, outside an exclusion zone of 15%. MEASUREMENTS AND MAIN RESULTS: The correlation coefficient between CI-MBA and CI-TD was 0.78 across patients. Mean CI-TD was 2.19 ± 0.46 L/min/m2 and mean CI-MBA was 2.38 ± 0.59 L/min/m2. The mean difference between CI-MBA and CI-TD (bias ± SD) was 0.20 ± 0.47 L/min/m2, and the limits of agreement were -0.72 to 1.11 L/min/m2. The percentage error was 40.0%. The concordance rate was 94%. A secondary analysis of a subgroup of patients during periods of arrhythmia demonstrated a similar accuracy of performance of CI-MBA. CONCLUSIONS: Cardiac index-MBA is not interchangeable with CI-TD. However, CI-MBA provides reasonable correlation and clinically acceptable trending ability compared with CI-TD. Cardiac output-MBA may be useful in trending changes in CI in patients with cardiogenic shock, especially in those whose pulmonary artery catheterization placement carries a high risk or is unobtainable.

Protein Stabilization and Delivery: A Case Study of Invasion Plasmid Antigen D Adsorbed on Porous Silica.

Approximately half of all vaccines produced annually are wasted because effectivity is dependent on protein structure and heat exposure disrupts the intermolecular interactions needed to maintain the structure. Thus, most vaccines require a temperature-controlled supply chain to minimize waste. A more sustainable technology was developed via the adsorption of invasion plasmid antigen D (IpaD) onto mesoporous silica, improving the thermal stability of this protein-based therapeutic. Seven silicas were characterized to determine the effects of pore diameter, pore volume, and surface area on protein adsorption. The silica-IpaD complex was then heated above the IpaD denaturing temperature and N,N-dimethyldodecylamine N-oxide was used to remove IpaD from the silica. Circular dichroism confirmed that the adsorbed IpaD after the heat treatment maintained a native secondary structure rich in α-helix content. In contrast, the unprotected IpaD after heat treatment lost its secondary structure. Isotherms using Langmuir, Freundlich, and Temkin models demonstrated that the adsorption of IpaD onto silicas is best fit by the Langmuir model. If pores are less than 15 nm, adsorption is negligible. If the pores are between 15 and 25 nm, then monolayer coverage is achieved and IpaD is protected from thermal denaturing. If pores are larger than 25 nm, the adsorption is a multilayer coverage and it is easier to remove the protein from the silica because of a less-developed hydrogen bond network. This case study provides strong evidence that IpaD is thermally stabilized via adsorption on mesoporous silica with the proper range of pore sizes.

Development of Silica-Immobilized Vaccines for Improving Thermo-Tolerance and Shelf-Life.

INTRODUCTION: It is estimated that 50% of vaccines produced annually are wasted because effectivity is dependent on protein structure and heat exposure disrupts the intermolecular interactions that maintain this structure. Since 90% of vaccines require a temperature-controlled supply chain, it is necessary to create a cold chain system to minimize vaccine waste. We have developed a more sustainable technology via the adsorption of Invasion Plasmid Antigen D (IpaD) onto mesoporous silica gels, improving the thermal stability of protein-based therapeutics. METHODS: The solution depletion method using UV-Vis was utilized to study the adsorption of IpaD onto silica gels. The silica-IpaD complex is heated above the denaturing temperature of the protein and then the IpaD is removed using N,N-Dimethyldodecylamine N-oxide (LDAO) and their secondary structure is tested using circular dichroism (CD). RESULTS: Pore diameter, pore volume and surface area were characterized for seven different silica gels. Silica gels designated as 6389, 6378, and 6375 had an adsorption percentage above 95% at pore volumes of 2.2, 2.8 and 3.8 cm3 mg-1, respectively. CD analyses confirmed that the adsorbed IpaD after the heat treatment displayed a similar "W" shape CD signal as the native IpaD, indicating the conservation of α-helices. In contrast, the unprotected IpaD after being exposed to high temperature shows a flat CD signal, demonstrating the loss of secondary structure. CONCLUSION: We have successfully increased the thermo-tolerance for IpaD using mesoporous silica and continue to further optimize mesoporous silica's physiochemical properties to improve adsorption and desorption yields.