Heart rate turbulence after ventricular and atrial premature beats in subjects without structural heart disease

INTRODUCTION: Studies assessing heart rate (HR) behavior after premature beats have focused on HR responses to ventricular premature beats (VBPs), but there is less information of HR behavior after atrial premature beats (APBs). METHODS AND RESULTS: HR turbulence after VPBs and APBs was first measured in response to ambient APBs and VPBs occurring during 24-hour ambulatory ECG recordings in 29 subjects without structural heart disease, and in response to programmed atrial (AE) and ventricular extrastimuli (VE) in 6 subjects undergoing electrophysiologic (EP) examination. Turbulence onset (TO) was more negative (-2.3 +/- 3.2% vs -0.9 +/- 2.8%, P < 0.01) and turbulence slope (TS) was steeper (11 +/- 11 vs 5.1 +/- 4.1 msec/R-R interval, P < 0.05) after VPBs than APBs. Compared to VPBs, the acceleration of HR after APBs was delayed by one beat, and APBs were associated with a short R-R interval preceding the APB, resulting in a blunted TO. Studies of patients undergoing an EP test confirmed the one-beat delay of HR acceleration and the blunted TO after programmed AE compared to VE (P < 0.05). TO and TS after VPBs were related to baroreflex sensitivity. TO also was related to 24-hour standard deviation of N-N intervals (SDNN). However, the TO or TS following APBs was not related to either SDNN or baroreflex sensitivity. CONCLUSION: HR behavior is different in response to APBs and VBPs among subjects without structural heart disease. Different definitions and calculation formulas should be used in the analysis of HR turbulence after APBs and VPBs.     

Solar geoengineering may not prevent strong warming from direct effects of CO2 on stratocumulus cloud cover

Discussions of countering global warming with solar geoengineering assume that warming owing to rising greenhouse-gas concentrations can be compensated by artificially reducing the amount of sunlight Earth absorbs. However, solar geoengineering may not be fail-safe to prevent global warming because CO₂ can directly affect cloud cover: It reduces cloud cover by modulating the longwave radiative cooling within the atmosphere. This effect is not mitigated by solar geoengineering. Here, we use idealized high-resolution simulations of clouds to show that, even under a sustained solar geoengineering scenario with initially only modest warming, subtropical stratocumulus clouds gradually thin and may eventually break up into scattered cumulus clouds, at concentrations exceeding 1,700 parts per million (ppm). Because stratocumulus clouds cover large swaths of subtropical oceans and cool Earth by reflecting incident sunlight, their loss would trigger strong (about 5 K) global warming. Thus, the results highlight that, at least in this extreme and idealized scenario, solar geoengineering may not suffice to counter greenhouse-gas-driven global warming.

Solar geoengineering is predicated on the notion that the global effects of perturbations to the climate system principally depend on the net radiative-energy balance at the top of the atmosphere (TOA). Elevated greenhouse gas (GHG) concentrations make the atmosphere more opaque to thermal longwave radiation. Hence, immediately after a rise of GHG concentrations, the longwave radiative energy fluxes emanating from TOA weaken. The climate system responds by warming globally, until TOA balance between outgoing longwave and absorbed solar radiative energy fluxes is restored. Solar geoengineering attempts to short-circuit this process by artificially reducing the amount of solar radiation absorbed in the climate system, thus obviating the global-warming response of the climate system. Simulations with multiple climate models have shown that global warming owing to rising GHG concentrations indeed can be fully or partially compensated by reducing the amount of solar radiation that is being absorbed. This can be achieved, for example, by injecting scattering aerosols into the stratosphere (1–5). There usually are some regional disparities in the degree of compensation (6–8). Additionally, global-mean evaporation and precipitation weaken, even when greenhouse warming is compensated for by solar geoengineering. This occurs because the reduced solar radiative energy available to evaporate surface water is not completely compensated for by a weakened longwave radiative cooling of the surface, even when the TOA compensation of radiative fluxes is complete (9, 10). Of course, nonradiative effects of elevated GHG concentrations, such as ocean acidification and ecosystem effects, remain uncompensated for by solar geoengineering (3, 11, 12). Other risks of solar geoengineering include moral hazards and governance issues, particularly related to what is known as the termination shock—the rapid realization of warming avoided up to that point if solar geoengineering were started and, at a later time, after more GHGs have accumulated, suddenly stopped (12–15).But there is another set of risks of solar geoengineering that has not received the attention it deserves. It arises through direct effects of GHGs on clouds. It is well known that elevated GHG concentrations directly reduce or thin cloud cover because they modify the longwave radiative cooling within the atmosphere, even without any surface-temperature changes, but possibly amplified by them (16–20). Stratocumulus cloud decks over subtropical oceans, especially, are vulnerable to changes in longwave cooling: They are sustained by longwave cooling at their cloud tops, which drives turbulent air motions from the cloud tops downward and, thereby, couples stratocumulus decks to their moisture supply at the surface (21, 22) (Fig. 1). This longwave cooling weakens as GHGs, such as CO₂ and water vapor, accumulate in the atmosphere, in much the same way that the capacity of Earth’s surface to cool itself radiatively is lower in humid nights than in dry. Weakening cloud-top radiative cooling, in turn, thins the clouds and reduces the amount of incident sunlight they reflect back to space (23–26). Because stratocumulus decks cover large swaths of tropical oceans, their albedo effect cools Earth globally. Subtropical marine stratocumulus clouds currently lower Earth’s surface temperature by about 8 K in the global mean compared with what it would be if they were replaced by scattered cumulus clouds (27). Hence, elevated GHG concentrations may trigger substantial global warming by reducing the cooling effect stratocumulus clouds provide, even when all or much of the effect of GHGs at TOA is compensated by solar geoengineering.Open in a separate windowFig. 1.Radiative energy fluxes at marine stratocumulus decks. Stratocumulus decks cool the surface by reflecting solar radiation. They are sustained by longwave radiative cooling of their cloud tops, which drives air motions downward and convectively connects the clouds to their moisture supply at the sea surface. When the concentration of GHGs, such as CO₂ and water vapor, increases, the longwave cooling of the cloud tops weakens, leading to cloud thinning and possibly, at high enough GHG concentrations, to breakup. Because these processes act through longwave radiation, they can lead to strong surface warming even under solar geoengineering scenarios.We recently showed that stratocumulus decks may become unstable and break up at CO₂ concentrations above around 1,200 parts per million (ppm). This would trigger global warming of up to about 8 K, in addition to the warming that arose from the elevated CO₂ concentrations before the clouds broke up (27). Surface warming that led to enhanced evaporation and weakened cloud-top longwave cooling both played important roles in the stratocumulus instability. We obtained these results in a large-eddy simulation (LES) setup that inverts the standard approach in climate modeling: Instead of simulating the large-scale dynamics of the atmosphere explicitly in a general circulation model (GCM) while representing the important smaller-scale dynamics of clouds semiempirically, as is common, we simulated the dynamics of clouds explicitly and represented large-scale dynamics semiempirically. This approach complements GCM studies by focusing computational effort not on large-scale dynamics, as in GCMs, but on clouds—one of the principal uncertainties in the global climate response to elevated GHG concentrations. Here, we used the same simulation setup to investigate how stratocumulus decks respond to elevated GHG concentrations in an idealized solar geoengineering scenario.     

An autoradiographic study of [(18)F]FDG uptake to islets of Langerhans in NOD mouse

To evaluate the potential of in vivo imaging of accumulation of lymphocytes to islets of Langerhans (insulitis), we compared 2-[¹⁸F]fluoro-2-deoxy-d-glucose ([¹⁸F]FDG) uptake in the pancreas and pancreatic islets of healthy BALB/c mice, phenotypically healthy NOD mice with insulitis and diabetic NOD mice. [¹⁸F]FDG was injected i.v. to 14 female BALB/c mice (age 13 ± 3 weeks, plasma glucose 8 ± 2 mmol/l) and 21 age-matched female NOD mice (plasma glucose 8 ± 4 mmol/l, p = 0.06). The mice were killed 90-min post injection and distribution of radioactivity was analysed using digital autoradiography. There was no correlation of plasma glucose concentration with the [¹⁸F]FDG uptake values. Uptake of radioactivity in NOD mice to the islets affected by insulitis was up to 2.3 times higher (p = 0.001) than that to unaffected islets in the same pancreas. Uptake to NOD islets with insulitis was also clearly enhanced (1.0–2.3 times higher) compared to the islets in the BALB/c mice.

In conclusion, NOD mouse islets with insulitis accumulate [¹⁸F]FDG markedly more than islets without insulitis or BALB/c islets. However, the relatively small difference in the [¹⁸F]FDG intensity between healthy and diseased islets, combined with the limited resolution ability of the positron emission tomography (PET), probably prevent the use of [¹⁸F]FDG in PET studies aiming at in vivo documentation of onset and progression of insulitis and prediabetes in mouse and man.     

Right atrial overdrive pacing does not prevent atrial fibrillation after coronary artery bypass surgery.

AIMS: The purpose of this prospective randomized study was to investigate the efficacy of atrial overdrive pacing (AOP) and bradycardia prevention pacing (BPP) in the prophylaxis of atrial fibrillation (AF) after coronary artery bypass surgery (CABG). METHODS: One hundred and twenty-four on-pump CABG patients were randomized into three groups: AOP, BPP, and NP (no pacing). AOP patients were paced via epicardial wires using an atrial preference pacing algorithm, and BPP patients were paced in the AAI mode with a base rate of 60/min. Patients were paced for 48 h starting on the first postoperative day. The endpoint of the study was the first onset of AF lasting longer than 5 min. RESULTS: Preoperative risk factors and surgical data of patients did not differ between the AOP, BPP and NP groups. Pacing was technically successful in 80.5% of patients in the AOP and in 92.7% in the BPP groups. The incidence of AF in the AOP (26.8%), BPP (19.5%) and NP (28.6%) groups did not differ significantly. In the AOP group, AF in three patients was probably induced by inappropriate pacing due to sensing failure. CONCLUSIONS: Atrial overdrive pacing and bradycardia prevention pacing were not effective in the prevention of AF after CABG.     

Adventures in radiosynthesis of clinical grade [68Ga]Ga-DOTA-Siglec-9

We finally managed to establish a protocol for generating Good Manufacturing Practice (GMP)-grade gallium-68-labelled 1,4,7,0-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugated sialic acid-binding immunoglobulin-like lectin 9 motif containing peptide ([⁶⁸Ga]Ga-DOTA-Siglec-9), the first radiopharmaceutical for positron emission tomography imaging of vascular adhesion protein 1.

[⁶⁸Ga]Ga-DOTA-Siglec-9 is the first vascular adhesion protein-1 targeting radiopharmaceutical for positron emission tomography imaging of inflammation, and here we present its long-awaited clinical grade radiosynthesis.     

Staged method using antibiotic beads and subsequent autografting for large traumatic tibial bone loss: 22 of 23 fractures healed after 5-20 months

Introduction The vascularity of surrounding soft tissues, which is related to muscle cover, is important for the healing of traumatic bone loss. Muscle cover on the distal tibia is limited compared to the diaphyseal and proximal tibia, and delayed healing of fractures in this area is common. We evaluated the healing of traumatic bone loss in the proximal, diaphyseal, and distal tibia.

Patients and methods 23 open tibial fractures with substantial bone loss (mean 52 (34-104) mm) were treated using a staged method with antibiotic-impregnated beads and later autologous bone grafting at second-stage surgery on average 8 weeks after the injury.

Results 22 fractures healed after mean 40 (20-79) weeks. The average healing time in the distal tibia (mean 30 weeks) was 7 weeks shorter (95% CI: 12-26 weeks) than in the proximal tibia (37 weeks), and 16 weeks shorter (95% CI: 3-29 weeks) than in the tibial shaft (47 weeks). The length of the bone and the type of soft tissue cover (free muscle or secondary suture) had no effect on healing time.

Interpretation Our study suggests that the method we used is applicable in all parts of the tibia, although the healing of bone loss is slower in the diaphyseal tibia than in the proximal and distal tibia.     

Does coronary artery bypass surgery affect metoprolol bioavailability

Background

β-blockers are commonly administered in patients with coronary artery bypass surgery (CABG). Despite this therapy, however, the incidence of postoperative atrial fibrillation (AF) is high (9–19%), and it is unknown why the β-blockers do not reduce the incidence of AF more efficiently. In this pharmacokinetics study, in which the patients acted as their own controls, we have evaluated the bioavailability of perioperative metoprolol tablets in CABG surgery patients.

Methods

Twelve male patients, aged 45–64 years, scheduled for CABG surgery were administered an initial 50 mg metoprolol tartrate tablet orally on the morning of the preoperative day and thereafter at 12-h intervals. Regular blood samples were collected up to 12 h after the first administration of the drug on the preoperative day as well on the first and third postoperative days. The plasma concentration for metoprolol was analyzed (limit of quantification = 0.001 mg/L) using liquid chromatography-tandem mass spectrometry.

Results

The bioavailability of the metoprolol was significantly less on the first postoperative day, with AUC_0–12 values ranging from 0.7 to 17.1 (median: 7.2) mg min/L, than on the preoperative day, with AUC_0–12 values of 5.1–26.7 (12.6) mg min/L; however, it returned to the preoperative values on the third postoperative day, with AUC_0–12 values of 3.5–25.2 (15.2) mg min/L. Similar changes were observed in C_max values: preoperative C_max ranged between 0.026 and 0.123 (0.060) mg/L, on the first postoperative day, the C_max ranged between 0.003 and 0.093 (0.025) mg/L, and on the third postoperative day, the C_max ranged between 0.009 and 0.136 (0.061) mg/L. There was no correlation between the pharmacokinetic parameters and patient characteristics, but both the preoperative C_max and C₆₀ correlated significantly with the postoperative C_max (Pearson correlation coefficient: 0.61–0.72). One patient with one of the lowest rates and extent of metoprolol absorption developed AF.

Conclusion

This study indicates that the bioavailability of metoprolol is markedly reduced when administered in tablet form during the early phase after CABG.