Lactate concentration gradient from right atrium to pulmonary artery

INTRODUCTION: We compared simultaneous measurements of blood lactate concentration ([Lac]) in the right atrium (RA) and in the pulmonary artery (PA). Our aim was to determine if the mixing of right atrial with coronary venous blood, having substantially lower [Lac], results in detectable decreases in [Lac] from the RA to the PA. METHODS: A prospective, sequential, observational study was conducted in a medical-surgical intensive care unit. We enrolled 45 critically ill adult individuals of either sex requiring pulmonary artery catheters (PACs) to guide fluid therapy. Immediately following the insertion of the PAC, one paired set of blood samples per patient was drawn in random order from the PAC's proximal and distal ports for measurement of hemoglobin concentration, O(2 )saturation (SO(2)) and [Lac]. We defined Δ[Lac] as ([Lac](ra )- [Lac](pa)), ΔSO(2 )as (S(ra)O(2 )- S(pa)O(2)) and the change in O(2 )consumption (ΔVO(2)) as the difference in systemic VO(2 )calculated using Fick's equation with either S(ra)O(2 )or S(pa)O(2 )in place of mixed venous SO(2). Data were compared by paired Student's t-test, Spearman's correlation analysis and by the method of Bland and Altman. RESULTS: We found S(ra)O(2 )> S(pa)O(2 )(74.2 ± 9.1 versus 69.0 ± 10.4%; p < 0.001) and [Lac](ra )> [Lac](pa )(3.9 ± 3.0 versus 3.7 ± 3.0 mmol.l(-1); p < 0.001). Δ[Lac] correlated with ΔVO(2 )(r(2 )= 0.34; p < 0.001). CONCLUSION: We found decreases in [Lac] from the RA to PA in this sample of critically ill individuals. We conclude that parallel decreases in SO(2 )and [Lac] from the RA to PA support the hypothesis that these gradients are produced by mixing RA with coronary venous blood of lower SO(2 )and [Lac]. The present study is a preliminary observation of this phenomenon and further work is needed to define the physiological and clinical significance of Δ[Lac]

Nucleotide sequence encoding the carboxyl-terminal half of apolipoprotein B from spontaneously hypercholesterolemic pigs.

Previous studies from this laboratory characterized the hypercholesterolemia of pigs with a mutant allele of apolipoprotein B (apoB), designated Lpb5. This apoB allele is associated with low density lipoprotein (LDL) particles deficient in binding to the LDL receptor. To identify potential causative mutations in Lpb5 DNA, 10.6 kb of genomic DNA, encoding the carboxyl-terminal 58% of apoB were sequenced from the Lpb5 allele and from an allele encoding phenotypically normal apoB. Comparison of the two DNA sequences revealed 33 polymorphisms, 13 of which resulted in amino acid polymorphisms. To determine whether any of the amino acids at the polymorphic positions in Lpb5-encoded apoB were unique to that isoform, those positions were sequenced in four other pig apoB alleles encoding phenotypically normal apoB. None of the amino acids were by themselves uniquely encoded by the Lpb5 allele. However, a unique haplotype consisting of Asp3164 in conjunction with Ala3447 distinguished the Lpb5-encoded apoB from all other allelic isoforms sequenced in this region. To gain insight into changes in the tertiary structure of the mutant apoB, 13C-NMR analysis of LDL reductively methylated with [13C]-formaldehyde was performed. LDL has lysine residues that titrate at pH 10.5 and others that titrate at pH 8.9. The latter residues are thought to include those involved in the interaction of LDL with the LDL receptor. LDL from Lpb5 pigs possessed a smaller proportion of lysine residues titrating at pH 8.9 than did LDL from non-Lpb5 pigs, suggesting that the Lpb5-encoded apoB is altered in a manner affecting the microenvironment of particular lysine residues

Cardio-renal syndromes: report from the consensus conference of the Acute Dialysis Quality Initiative

A consensus conference on cardio-renal syndromes (CRS) was held in Venice Italy, in September 2008 under the auspices of the Acute Dialysis Quality Initiative (ADQI). The following topics were matter of discussion after a systematic literature review and the appraisal of the best available evidence: definition/classification system; epidemiology; diagnostic criteria and biomarkers; prevention/protection strategies; management and therapy. The umbrella term CRS was used to identify a disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. Different syndromes were identified and classified into five subtypes. Acute CRS (type 1): acute worsening of heart function (AHF–ACS) leading to kidney injury and/or dysfunction. Chronic cardio-renal syndrome (type 2): chronic abnormalities in heart function (CHF-CHD) leading to kidney injury and/or dysfunction. Acute reno-cardiac syndrome (type 3): acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. Chronic reno-cardiac syndrome (type 4): chronic kidney disease leading to heart injury, disease, and/or dysfunction. Secondary CRS (type 5): systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. Consensus statements concerning epidemiology, diagnosis, prevention, and management strategies are discussed in the paper for each of the syndromes

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Multi-messenger Observations of a Binary Neutron Star Merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ∼ 1.7 {{s}} with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of {40}-8+8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 {M}ȯ . An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ∼ 40 {{Mpc}}) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ∼ 9 and ∼ 16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta.</p