Hemodynamic effects of contrast media during coronary angiography: a comparison of three nonionic agents to Hypaque-76

Coronary angiography with standard ionic contrast media is associated with marked alterations in cardiac hemodynamics because of the depressant effects of the contrast media on cardiac contractility. Nonionic contrast media have been reported to produce less hemodynamic alteration than standard ionic contrast media. However, there is no information on how one nonionic media compares to another. Thus we compared the hemodynamic effects of three nonionic contrast media, Iopamidol (IOP), Iohexol (IOH), and Ioversol (IOV) to each other as well as to the standard ionic contrast media Hypaque-76 (H76). In 20 closed-chest anesthetized dogs, we recorded the maximal change in left ventricular systolic pressure (LVSP), mean aortic pressure, left ventricular diastolic pressure (LVDP), and left ventricular dp/dt during 10-cc left main coronary artery injections of H76, IOP, IOH, and IOV. The mean aortic pressure and LVSP decreased 36 +/- 17 mm Hg and 46 +/- 21 mm Hg with H76 but only 5 +/- 5 mm Hg and 6 +/- 5 mm Hg with IOP, 5 +/- 4 mm Hg and 6 +/- 6 mm Hg with IOH, and 5 +/- 4 mm Hg and 7 +/- 6 mm Hg with IOV (P less than 0.001). The LVDP increased 6 +/- 5.0 mm Hg with H76 but only 0.2 +/- 0.5 mm Hg with IOP, 0.2 +/- 0.3 mm Hg with IOH, and 0.5 +/- 1.0 mm Hg with IOV (P less than 0.001). The LV dp/dt decreased 545 +/- 261 mm Hg/sec with H76 but increased 886 +/- 477 mm Hg/sec with IOP, 910 +/- 96 mm Hg/sec with IOH, and 473 +/- 335 mm Hg/sec with IOV (P less than 0.001). Whereas each nonionic agent produced significantly less hemodynamic abnormalities than H76, there was no significant difference between any of the nonionic agents on any hemodynamic parameter. Thus, as compared to H76, these nonionic contrast media produced only trivial alterations in hemodynamics and LV dp/dt. These agents may be preferable in patients with LV dysfunction.     

Oncogenic mutation in the Kit receptor tyrosine kinase alters substrate specificity and induces degradation of the protein tyrosine phosphatase SHP-1

Activating mutations in the Kit receptor tyrosine kinase have been identified in both rodent and human mast cell leukemia. One activating Kit mutation substitutes a valine for aspartic acid at codon 816 (D816V) and is frequently observed in human mastocytosis. Mutation at the equivalent position in the murine c-kit gene, involving a substitution of tyrosine for aspartic acid (D814Y), has been described in the mouse mastocytoma cell line P815. We have investigated the mechanism of oncogenic activation by this mutation. Expression of this mutant Kit receptor tyrosine kinase in a mast cell line led to the selective tyrosine phosphorylation of a 130-kDa protein and the degradation, through the ubiquitin-dependent proteolytic pathway, of a 65-kDa phosphoprotein. The 65-kDa protein was identified as the src homology domain 2 (SH2)-containing protein tyrosine phosphatase SHP-1, a negative regulator of signaling by Kit and other hematopoietic receptors, and the protein product of the murine motheaten locus. This mutation also altered the sites of receptor autophosphorylation and peptide substrate selectivity. Thus, this mutation activates the oncogenic potential of Kit by a novel mechanism involving an alteration in Kit substrate recognition and the degradation of SHP-1, an attenuator of the Kit signaling pathway.     

Attenuation of lysophosphatidylcholine-induced suppression of ANP release from hypertrophied atria

Lysophosphatidylcholine (LPC) is an endogenous phospholipid released from the cell membrane during ischemia, and it has potent cardiac effects, including inhibition of atrial natriuretic peptide (ANP) release. The aim of this study was to investigate the effects of LPC on hemodynamics and ANP release in hypertrophied atria and to define its mechanism. Isolated, perfused, beating, hypertrophied atria from monocrotaline-treated rats were used. LPC (30 micromol/L), a mixture of stearoyl-LPC, palmitoyl-LPC, and oleoyl-LPC, caused suppression of ANP release, which was markedly attenuated in hypertrophied atria compared with nonhypertrophied atria. Suppression of ANP release by stearoyl-LPC, palmitoyl-LPC, or oleoyl-LPC was also attenuated in hypertrophied atria. The potency appeared to be dependent on the species of fatty acid residue of LPC. Changes in ANP release by LPC, palmitoyl-LPC, and oleoyl-LPC were positively correlated with the degree of cardiac hypertrophy, but that by stearoyl-LPC was not. Changes in ANP release by LPC also were negatively correlated with changes in pulse pressure. Stearoyl-LPC caused an increase in intracellular Ca2+ in single, atrial myocytes in a concentration-dependent manner, which was markedly attenuated in hypertrophied atrial myocytes. These results suggest that attenuation of LPC-induced suppression of ANP release from hypertrophied atria might partly be related to changes in pulse pressure in terms of cardiac hypertrophy and/or disturbance of intracellular Ca2+ regulation.     

The mechanism and significance of ventricularization of intracoronary pressure during coronary angiography

Ventricularization of pressure during coronary angiography has been said to identify the presence of left main coronary artery disease, but the hemodynamic features and the mechanism of this process have not been studied. Twenty consecutive patients with ventricularization were identified prospectively in our laboratory. Four patients had a discrete ostial left main stenosis and 16 patients had stenosis of the entire length of the left main coronary artery. The degree of pressure drop upon cannulation of the diseased left main coronary artery was highly variable; the systolic pressure decreased by 9 to 94 mm Hg, and the diastolic pressure decreased by 6 to 60 mm Hg. The morphology of the ventricularized pressure was distinct. It had a presystolic deflection resembling an a wave. The upstroke of this waveform was slower and the downstroke was steeper than that of the aortic pressure. An identical waveform was observed in dogs after partial occlusion of the left main coronary artery with a balloon-tipped catheter. The waveform of the so-called ventricularized pressure is derived from the aortic pressure, which is altered by its transmission across the left main coronary stenosis. The appearance of ventricularization is an important clue to the presence of left main coronary artery disease.     

Endoscopic management for pancreatic injuries due to blunt abdominal trauma decreases failure of nonoperative management and incidence of pancreatic-related complications

Introduction

The actual benefit of endoscopic techniques in the non-operative management (NOM) of pancreatic injury is still unclear, with its role and effectiveness in the NOM of pancreatic injury remains defined and doubted. The purpose of this study was to evaluate the feasibility and long-term results of endoscopic techniques in the NOM of blunt pancreatic injury, and to determine whether NOM can be performed safely for selective patients with pancreatic injury.

Patients and methods

The records and follow-up data of all patients with blunt pancreatic injuries over 16-year period from October 1, 1996, to September 30, 2012 at our department were retrospectively reviewed. Failure of NOM (FNOM) occurred if laparotomy was required after attempted NOM.

Results

132 patients (32% of all patients with blunt pancreatic injury) underwent NOM, including 58 who underwent endoscopic management (EM) and 74 who were observed without EM (NO-EM). FNOM of overall NOM was 20%, including 30% of NO-EM and 9% of EM. There was no significant difference in FNOM for NO-EM versus EM for grade I, however, a significant decrease in FNOM was noted with the addition of EM for grade II and III. EM was a statistically significant independent risk factor. Regular follow-up of 1 year showed that, for patients from grade I to III, 53 patients (42%) from operative management (OM) and 34 patients (46%) of the NO-EM developed various pancreatic-related complications, while only 15 patients (26%) of the EM developed such complications, and the difference was significant.

Conclusion

Application of strictly defined selection criteria for NOM and EM in patients with blunt pancreatic injury resulted in one of the lowest FNOM rates (9%) and pancreatic-related complications incidence (25%). Selective application of EM for hemodynamically stable patients with blunt pancreatic injury will extend the indications for, and improve success of NOM.     

Exposure to ambient black carbon derived from a unique inventory and high-resolution model

Black carbon (BC) is increasingly recognized as a significant air pollutant with harmful effects on human health, either in its own right or as a carrier of other chemicals. The adverse impact is of particular concern in those developing regions with high emissions and a growing population density. The results of recent studies indicate that BC emissions could be underestimated by a factor of 2–3 and this is particularly true for the hot-spot Asian region. Here we present a unique inventory at 10-km resolution based on a recently published global fuel consumption data product and updated emission factor measurements. The unique inventory is coupled to an Asia-nested (∼50 km) atmospheric model and used to calculate the global population exposure to BC with fully quantified uncertainty. Evaluating the modeled surface BC concentrations against observations reveals great improvement. The bias is reduced from −88% to −35% in Asia when the unique inventory and higher-resolution model replace a previous inventory combined with a coarse-resolution model. The bias can be further reduced to −12% by downscaling to 10 km using emission as a proxy. Our estimated global population-weighted BC exposure concentration constrained by observations is 2.14 μg⋅m⁻³; 130% higher than that obtained using less detailed inventories and low-resolution models.Black carbon (BC), or soot, emitted from incomplete combustion of carbonaceous fuels is an air pollutant which also plays an important role in climate change (1). BC is an indicator of air particulate pollution and BC in ambient air has an impact on human health (2). In a recent study in China, it was found that the effects of BC on morbidity appear to be more robust than the effects of fine particles in general (3, 4).However, global atmospheric aerosol models often underestimate the concentration of BC at the surface, particularly over Asia, by a factor that typically ranges from 2 to 10 (5–7). In one study, the observed BC surface concentration for China could only be reproduced by doubling the emissions prescribed to a transport model (8). It is often argued that the underestimation is due to a low bias in BC emission inventories, suggesting a need to revisit these previous inventories (9).In a bottom-up approach, BC emission is estimated based on the amount of fuel consumed and an emission factor (EF_BC, defined as the amount of BC emitted per unit mass of fuel consumed) for each of various combustion sources. For previous inventories, the lack of EF_BC measurements in developing countries led to high uncertainty in estimating the total emissions (10). In addition, the use of fuel data at the national level is likely to distort the geographical distribution of emissions within large countries such as China and India (11). Recently, a 0.1° × 0.1° fuel database with 64 types of combustion has been developed based on local or national fuel consumption statistics. This database improves the resolution of the spatial distribution of emissions for large countries (12). To fill the data gap in developing countries, a set of EF_BC values has been compiled for various residential solid fuel combustion devices and vehicles (13–20). In addition to the problems with the emission inventories, the coarse resolution of existing global aerosol models also hinders our ability to capture detailed spatial variation, leading to poor agreement between model prediction and observations (7).In this study we develop and evaluate a unique global BC emission inventory using a zoomed aerosol model, and estimate the global population’s exposure to BC with a focus on Asia. The influence of model resolution and the use of an updated emission inventory on the calculated BC concentration are evaluated against field observations.     

LDL cholesterol as a novel risk factor for contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention

Background: Low density lipoprotein cholesterol (LDL-C) is associated with endothelial dysfunction, inflammation and increased vasoconstriction, which are involved in the development of contrast-induced acute kidney injury (CI-AKI). However, whether LDL-C is an independent risk factor of CI-AKI in patients undergoing percutaneous coronary intervention (PCI) is unknown. Methods: We prospectively enrolled 3236 consecutive patients undergoing PCI between January 2010 and September 2012. Multivariate logistic regression analysis was used to determine whether LDL-C is an independent risk factor of CI-AKI. CI-AKI was defined as an absolute increase in serum creatinine of ≥0.5 mg/dL or ≥25% over the baseline value within 48–72 h after contrast exposure. Results: CI-AKI was observed in 338 patients (10.4%). Patients with CI-AKI had a significantly higher rate of in hospital mortality (4.4% vs. 0.5%, p < 0.001), and significantly higher rates of other in hospital complications compared with those without CI-AKI. The LDL-C quartiles were as follows: Q1 (<2.04 mmol/L), Q2 (2.04–2.61 mmol/L), Q3 (2.61–3.21 mmol/L) and Q4 (>3.21 mmol/L). Patients with high baseline LDL-C levels were more likely to develop CI-AKI and composite end points including all-cause mortality, renal replacement therapy, non-fatal myocardial infarction, acute heart failure, target vessel revascularization or cerebrovascular accident during the observation period of hospitalization (8.9%, 9.9%, 10.5%, 12.6%, p = 0.001, and 5.0%, 5.2%, 6.1%, 8.1%, respectively; p = 0.007). Univariate logistic analysis showed that LDL-C levels (increment 1 mmol/L) were significantly associated with CI-AKI (odds ratio = 1.25, 95% confidence interval (CI), 1.11–1.39, p < 0.001). Furthermore, LDL-C remained a significant risk factor of CI-AKI (odds ratio = 1.23, 95% CI, 1.04–1.45, p = 0.014), even after adjusting for potential confounding risk factors. Conclusions: Measurement of plasma LDL-C concentrations in patients undergoing PCI may be helpful to identify those who are at risk of CI-AKI and poor in hospital outcomes.     

Protective properties of a fusion pneumococcal surface protein A (PspA) vaccine against pneumococcal challenge by five different PspA clades in mice

An increase in the appearance of nonvaccine serotypes in both children and adults with invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccine represents a limitation of this vaccine. In this study, we generated three recombinant pneumococcal surface protein A (PspA) proteins comprising PspA families 1 and 2, and we examined the reactivity of antisera raised in mice immunized with a PspA fusion protein in combination with CpG oligonucleotides plus aluminum hydroxide gel. The protective effects of immunization with PspA fusion proteins against pneumococcal challenge by strains with five different PspA clades were also examined in mice. Flow cytometry demonstrated that PspA3+2-induced antiserum showed the greatest binding of PspA-specific IgG to all five challenge strains with different clades. PspA2+4- or PspA2+5-induced antiserum showed the lowest binding of PspA-specific IgG to clade 3. Immunization with PspA3+2 afforded significant protection against pneumococcal challenge by five strains with different clades in mice, but immunization with PspA2+4 or PspA2+5 failed to protect mice from pneumococcal challenge by strains with clades 1 and 3. The binding of PspA-specific IgG in antisera raised by three PspA fusion proteins was examined in 68 clinical isolates from adult patients with IPD. Immunization of mice with PspA3+2-induced antiserum with a high binding capacity for clinical isolates expressing clades 1–4, but not clade 5. Our results suggest that the PspA3+2 vaccine has an advantage over the PspA2+4 or PspA2+5 vaccine in terms of a broad range of cross-reactivity with clinical isolates and cross-protection against pneumococcal challenge in mice.