Pre-Treatment With Glucagon-Like Peptide-1 Protects Against Ischemic Left Ventricular Dysfunction and Stunning Without a Detected Difference in Myocardial Substrate Utilization

AbstractObjectivesThis study sought to determine whether pre-treatment with intravenous glucagon-like peptide-1 (GLP-1)(7-36) amide could alter myocardial glucose use and protect the heart against ischemic left ventricular (LV) dysfunction during percutaneous coronary intervention.BackgroundGLP-1 has been shown to have favorable cardioprotective effects, but its mechanisms of action remain unclear.MethodsTwenty patients with preserved LV function and single-vessel left anterior descending coronary artery disease undergoing elective percutaneous coronary intervention were studied. A conductance catheter was placed into the LV, and pressure-volume loops were recorded at baseline, during 1-min low-pressure balloon occlusion (BO), and at 30-min recovery. Patients were randomized to receive an infusion of either GLP-1(7-36) amide at 1.2 pmol/kg/min or saline immediately after baseline measurements. Simultaneous coronary artery and coronary sinus blood sampling was performed at baseline and after BO to assess transmyocardial glucose concentration gradients.ResultsBO caused both ischemic LV dysfunction and stunning in the control group but not in the GLP-1 group. Compared with control subjects, the GLP-1 group had a smaller reduction in LV performance during BO (delta dP/dTmax, –4.3 vs. –19.0%, p = 0.02; delta stroke volume, –7.8 vs. –26.4%, p = 0.05), and improved LV performance at 30-min recovery. There was no difference in transmyocardial glucose concentration gradients between the 2 groups.ConclusionsPre-treatment with GLP-1(7-36) amide protects the heart against ischemic LV dysfunction and improves the recovery of function during reperfusion. This occurs without a detected change in myocardial glucose extraction and may indicate a mechanism of action independent of an effect on cardiac substrate use. (Effect of Glucgon-Like-Peptide-1 [GLP-1] on Left Ventricular Function During Percutaneous Coronary Intervention [PCI]; ISRCTN77442023

Glucagon-like peptide-1 derived cardioprotection does not utilize a KATP-channel dependent pathway: mechanistic insights from human supply and demand ischemia studies.

BACKGROUND: Glucagon-like peptide-1 (7-36) amide (GLP-1) protects against stunning and cumulative left ventricular dysfunction in humans. The mechanism remains uncertain but GLP-1 may act by opening mitochondrial K-ATP channels in a similar fashion to ischemic conditioning. We investigated whether blockade of K-ATP channels with glibenclamide abrogated the protective effect of GLP-1 in humans. METHODS: Thirty-two non-diabetic patients awaiting stenting of the left anterior descending artery (LAD) were allocated into 4 groups (control, glibenclamide, GLP-1, and GLP-1 + glibenclamide). Glibenclamide was given orally prior to the procedure. A left ventricular conductance catheter recorded pressure-volume loops during a 1-min low-pressure balloon occlusion (BO1) of the LAD. GLP-1 or saline was then infused for 30-min followed by a further 1-min balloon occlusion (BO2). In a non-invasive study, 10 non-diabetic patients were randomized to receive two dobutamine stress echocardiograms (DSE) during GLP-1 infusion with or without oral glibenclamide pretreatment. RESULTS: GLP-1 prevented stunning even with glibenclamide pretreatment; the Δ % dP/dtmax 30-min post-BO1 normalized to baseline after GLP-1: 0.3 ± 6.8 % (p = 0.02) and GLP-1 + glibenclamide: -0.8 ± 9.0 % (p = 0.04) compared to control: -11.5 ± 10.0 %. GLP-1 also reduced cumulative stunning after BO2: -12.8 ± 10.5 % (p = 0.02) as did GLP-1 + glibenclamide: -14.9 ± 9.2 % (p = 0.02) compared to control: -25.7 ± 9.6 %. Glibenclamide alone was no different to control. Glibenclamide pretreatment did not affect global or regional systolic function after GLP-1 at peak DSE stress (EF 74.6 ± 6.4 vs. 74.0 ± 8.0, p = 0.76) or recovery (EF 61.9 ± 5.7 vs. 61.4 ± 5.6, p = 0.74). CONCLUSIONS: Glibenclamide pretreatment does not abrogate the protective effect of GLP-1 in human models of non-lethal myocardial ischemia. Trial registration Clinicaltrials.gov Unique Identifier: NCT02128022

Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies

BACKGROUND: We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. METHODS AND RESULTS: Ten subjects with single-vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low-pressure BO for 1 minute or a cumulative duration of RP for up to 1 minute. Ischemia-induced diastolic dysfunction was seen 1 minute after RP (end-diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1, P<0.001) and BO (end-diastolic pressure [mm Hg]: 8.1±4.0 versus 8.7±4.0, P=0.03). Impairment of systolic and diastolic function after BO remained at 15-minutes recovery (ejection fraction [%]: 55.7±9.0 versus 47.8±6.3, P<0.01; end-diastolic pressure [mm Hg]: 8.1±4.0 versus 9.2±3.9, P<0.01). Persistent diastolic dysfunction was also evident in the RP group at 15-minutes recovery (end-diastolic pressure [mm Hg]: 8.1±4.1 versus 9.9±4.4, P=0.03) and there was also sustained impairment of load-independent indices of systolic function at 15 minutes after RP (end-systolic elastance and ventriculo-arterial coupling [mm Hg/mL]: 1.25±0.31 versus 0.85±0.43, P<0.01). CONCLUSIONS: RP and right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve

Acne and smoking: is there a relationship?

BACKGROUND: There are contradictory reports on the relationship between acne vulgaris and cigarette smoking. The objective of this study was to examine the relation between acne and cigarette smoking in a case-control study. METHODS: A questionnaire on smoking habits was offered to 350 patients with acne vulgaris and 350 patients suffering from skin diseases other than acne, aged 15 – 40 years, attending in a skin clinic in Tehran, Iran. The patients completed the questionnaires anonymously in the waiting room. RESULTS: Two hundred and ninety-three patients with acne (response rate 83.7 %) and 301 patients with other skin diseases (response rate 86.0 %) completed the questionnaires. Twelve acne patients (4.1 %) and 27 control patients (9.0 %) were current smokers (odds ratio = 0.43, 95% confidence limits 0.22 – 0.87, p < 0.05). But after adjustment for sex, this difference was not significant (odds ratio: 0.61, 95% CI: 0.30–1.26, p > 0.05, Mantel-Haenszel test). CONCLUSION: An association between acne and cigarette smoking was not found in this study

Uncertainty estimation for operational ocean forecast products-a multi-model ensemble for the North Sea and the Baltic Sea

Multi-model ensembles for sea surface temperature (SST), sea surface salinity (SSS), sea surface currents (SSC), and water transports have been developed for the North Sea and the Baltic Sea using outputs from several operational ocean forecasting models provided by different institutes. The individual models differ in model code, resolution, boundary conditions, atmospheric forcing, and data assimilation. The ensembles are produced on a daily basis. Daily statistics are calculated for each parameter giving information about the spread of the forecasts with standard deviation, ensemble mean and median, and coefficient of variation. High forecast uncertainty, i.e., for SSS and SSC, was found in the Skagerrak, Kattegat (Transition Area between North Sea and Baltic Sea), and the Norwegian Channel. Based on the data collected, longer-term statistical analyses have been done, such as a comparison with satellite data for SST and evaluation of the deviation between forecasts in temporal and spatial scale. Regions of high forecast uncertainty for SSS and SSC have been detected in the Transition Area and the Norwegian Channel where a large spread between the models might evolve due to differences in simulating the frontal structures and their movements. A distinct seasonal pattern could be distinguished for SST with high uncertainty between the forecasts during summer. Forecasts with relatively high deviation from the multi-model ensemble (MME) products or the other individual forecasts were detected for each region and each parameter. The comparison with satellite data showed that the error of the MME products is lowest compared to those of the ensemble members

Selective reporting: a half signalling load algorithm for distributed sensing

Spectrum sensing is a powerful tool of the cognitive cycle to help circumvent the apparent spectrum scarcity faced by wireless transmission systems. To overcome the challenging issues faced by the localized sensing, multiple cognitive radios can cooperate to explore the multiuser diversity and generate a more reliable decision on the presence of a signal in the frequencies of interest. In such a cooperative sensing scenario, a common reporting channel is needed for the transmission of the information of each element. As the number of elements that participate in the sensing operation increases, so does the bandwidth demanded for the reporting channel, quickly becoming the limiting factor in this scenario. To tackle the issue of reducing the sensing report overhead, this paper introduces a new cooperative sensing scheme that introduces silence periods in the reporting and, relying on information theory principles, explores the information present in these periods to reduce by 50% the sensing reporting overhead while maintaining the same performance of standard reporting schemes. Numerical and experimental results confirm the theoretical analysis and show the predicted reduction in reporting overhead and performance preservation

Ventriculo-arterial coupling detects occult RV dysfunction in chronic thromboembolic pulmonary vascular disease.

Chronic thromboembolic disease (CTED) is suboptimally defined by a mean pulmonary artery pressure (mPAP)  0.68 and Ees/Ea < 0.68 subgroups demonstrated constant RV stroke work but lower stroke volume (87.7 ± 22.1 vs. 60.1 ± 16.3 mL respectively, P = 0.006) and higher end-systolic pressure (36.7 ± 11.6 vs. 68.1 ± 16.7 mmHg respectively, P < 0.001). Lower Ees/Ea in CTED also correlated with reduced exercise ventilatory efficiency. Low Ees/Ea aligns with features of RV maladaptation in CTED both at rest and on exercise. Characterization of Ees/Ea in CTED may allow for better identification of occult RV dysfunction

The Baltic Sea Tracer Release Experiment. Part I: Mixing rates

In this study, results from the Baltic Sea Tracer Release Experiment (BATRE) are described, in which deep water mixing rates and mixing processes in the central Baltic Sea were investigated. In September 2007, an inert tracer gas (CF3SF5) was injected at approximately 200 m depth in the Gotland Basin, and the subsequent spreading of the tracer was observed during six surveys until February 2009. These data describe the diapycnal and lateral mixing during a stagnation period without any significant deep water renewal due to inflow events. As one of the main results, vertical mixing rates were found to dramatically increase after the tracer had reached the lateral boundaries of the basin, suggesting boundary mixing as the key process for basin-scale vertical mixing. Basin-scale vertical diffusivities were of the order of 10−5 m2 s−1 (about 1 order of magnitude larger than interior diffusivities) with evidence for a seasonal and vertical variability. In contrast to tracer experiments in the open ocean, the basin geometry (hypsography) was found to have a crucial impact on the vertical tracer spreading. The e-folding time scale for deep water renewal due to mixing was slightly less than 2 years, the time scale for the lateral homogenization of the tracer patch was of the order of a few months. Key Points: Mixing rates in the Gotland Basin are dominated by boundary mixing processes; The time scale for Gotland Basin deep water renewal is approximately 2 years; Mixing rates determined from the tracer CF3SF