Prediction of early mortality in acute pancreatitis using arterial base excess: an international multicenter cohort study.

The effects of heat exposure on dynamic cerebral autoregulation (dCA), the capacity of the cerebrovasculature to buffer rapid changes in arterial pressure, and its directional sensitivity, defined as the asymmetric cerebrovascular response to increases versus decreases in mean arterial pressure (MAP), remain incompletely understood. This uncertainty is largely attributable to concomitant heat-induced reductions in arterial carbon dioxide. We hypothesized that moderate isocapnic hyperthermia would impair dCA, particularly at higher frequencies of MAP oscillations, while preserving directional sensitivity across thermal conditions. Twenty healthy young participants (9 females, age: 24 ± 5 yrs) completed oscillatory lower body negative pressure trials at 0.05 and 0.10 Hz under normothermic and hyperthermic (core temperature +1.0°C) conditions. End-tidal carbon dioxide partial pressure (PETCO2) was clamped at baseline using a computer-controlled gas delivery system. Middle cerebral artery mean blood velocity (MCAvmean), MAP, PETCO2, heart rate, and core temperature were continuously recorded. dCA was assessed using transfer function analysis (TFA), and directional sensitivity was quantified using time-adjusted absolute (∆MCAvmeanT/∆MAPT) and relative (RelMCAvmeanT/RelMAPT) metrics. Moderate isocapnic hyperthermia increased TFA coherence at both frequencies and selectively impaired dCA at 0.10 Hz, as evidenced by increased TFA gain and normalized gain. Directional sensitivity was present at 0.05 Hz, indicated by higher ∆MCAvmeanT/∆MAPT and RelMCAvmeanT/RelMAPT during MAP decreases compared with increases, but was absent at 0.10 Hz. These findings demonstrate that isocapnic hyperthermia impairs dCA at higher frequency while preserving directional sensitivity at lower frequency, suggesting that distinct physiological mechanisms govern these components of cerebrovascular regulation beyond the influence of carbon dioxide.

Severe hypertension without associated hypertensive target organ injury is termed hypertensive urgency. Treatment guidelines for the initial 4-6 hours uniformly warn against extreme (e.g. >80 mmHg) reduction in SBP and reduction more than 25% below baseline mean arterial pressure (MAP), the approximate lower limit of cerebral autoregulation. We hypothesized that rapid-acting antihypertensive regimens commonly employed for hypertensive urgency can reduce SBP and MAP in excess of these limits, potentially compromising cerebral blood flow. Retrospective cohort study in 1553 patients with hypertensive urgency to assess 5-hour SBP and MAP responses to the most commonly administered single-drug regimens ( n = 453), combined single-drug and multiple-drug regimens ( n = 1051), and no drug ( n = 199). Co-primary endpoints: number (%) SBP reduction greater than 80 mmHg and number (%) MAP reduction more than 25%. rapid-acting oral clonidine ( n = 214), intravenous hydralazine ( n = 93), and intravenous labetalol ( n = 40), produced 5-hour SBP reduction of more than 80 mmHg in 38/214 (18%), 17/93 (18%), and 8/40 (20%) patients, respectively, and MAP reduction of more than 25% in 98/214 (46%), 41/93 (44%), and 15/40 (38%) patients, respectively. Conversely, oral extended-release nifedipine ( n = 84) and oral lisinopril ( n = 22) produced SBP reduction of more than 80 mmHg in 1/84 (1%) and 1/22 (5%) patients. MAP reductions of more than 25% were also fewer: 18/84 (21%) and 2/22 (9%) patients.Combined single-drug/multidrug combinations ( n = 1051) and no drug ( n = 199) demonstrated similar excessive SBP and MAP reductions. Our results demonstrate frequent extreme SBP and MAP reductions exceeding safety and autoregulatory limits with rapid-acting antihypertensives and the crucial need to develop and test novel clinical algorithms for the well tolerated and effective management of hypertensive urgency.

Orthostatic hypotension is thought to be associated with coronary heart disease, falls, and syncope due to low blood pressure (BP) upon standing. The ARIC (Atherosclerosis Risk in Communities) study measured supine and standing BP among adult participants aged 45 to 64 years once at baseline and followed them for over 35 years. We evaluated higher and lower supine and standing systolic BP, diastolic BP, mean arterial pressure, pulse pressure, absolute and relative orthostatic changes in BP after standing, and mean BP across positions. Associations with adjudicated coronary heart disease and mortality events, as well as hospitalizations and medical claims-based falls and syncope, were assessed via adjusted Cox models in strata of antihypertensive treatment. Among 11 386 participants (mean age, 54 years [SD, 5.7 years]; 56% female; 25% Black adults), drops in systolic BP upon standing (absolute or relative) were associated with coronary heart disease, syncope, and mortality. Higher supine systolic BP and mean arterial pressure were associated with syncope among untreated participants. Increases in systolic BP ≥20 mm Hg upon standing were associated with falls (hazard ratio, 1.52 [95% CI, 1.14-2.02]) and syncope (hazard ratio, 1.40 [95% CI, 1.03-1.92]), particularly among untreated participants. Lower standing systolic BP was associated with a higher risk of syncope among treated participants (hazard ratio, 1.55 [95% CI, 1.14-2.12]). Regardless of treatment status, a higher pulse pressure was associated with coronary heart disease and mortality, but this was not observed for falls or syncope. Higher BP, rather than lower standing BP alone, may be an important risk factor for both cardiovascular and hypotension-related events, especially among untreated adults.

The objective of this study was to evaluate effects of measurement environment and owner presence on oscillometric blood pressure (BP) values in 14 clinically healthy dogs. Without removing the cuff, noninvasive BP measurements were taken in 3 consecutive in-clinic situations: Situations 1) a quiet waiting room with only the owner present, 2) an examination room with the owner and veterinary personnel present, and 3) an examination room without the owner present. Only measurements with bell-shaped oscillograms were considered valid. Systolic, diastolic, and mean BP; pulse pressure; pulse rate; percentage of valid measurements; and success rate were compared among situations. Systolic and mean BP were significantly higher in the absence of the owner, whereas no significant differences were observed among other parameters. The overall success rate of obtaining 5 consecutive valid measurements was low (26.2%). We concluded that owner absence was associated with higher in-clinic BP values and may influence BP assessment in dogs. Results supported measuring BP with the owner present under standardized conditions in clinical practice.

Geriatric patients with isolated systolic hypertension (ISH) and wide pulse pressure (PP) were treated using enhanced external counter pulsation (EECP) combined with amlodipine versus amlodipine alone. The efficacy of both treatment modalities was assessed based on hemodynamic parameters. Retrospectively included 132 elderly patients with ISH and wide PP in our hospital (Mar 2022-Jun 2024). After exclusion, 120 cases were analyzed and divided into the amlodipine group and the combined group. Primary indicators include endothelin-1 (ET-1), nitric oxide (NO), systolic blood pressure (SBP), PP, systemic vascular resistance (SVR), coronary flow reserve (CFR), flow-mediated vasodilatation (FMD); secondary measures include mean arterial pressure (MAP), wall shear stress (WSS) and adverse reaction incidence. After 4 courses of treatment, patients in the combined group had significantly lower rates of ET-1, SBP, PP, MAP, SVR and the incidence of adverse reactions (all P<0.05); NO, FMD, WSS and CFR were higher (all P<0.05) than in the amlodipine group. EECP plus amlodipine has advantages over amlodipine monotherapy in treating elderly patients with ISH and wide PP, which provides a scientific basis for optimizing clinical treatment.

To evaluate the cost-effectiveness of the Fetal Medicine Foundation (FMF) strategy, compared with the National Institute for Health and Care Excellence (NICE) strategy, for first-trimester screening for preterm preeclampsia (PE) in the United Kingdom (UK). Cost-effectiveness analysis. UK National Health Service and personal social services perspective. A total of 10 000 simulated patients with singleton pregnancies at 11-13 weeks' gestation, across a lifetime time horizon. A decision-tree model was developed to perform a cost-effectiveness analysis. In the base-case analysis, NICE-recommended screening was compared with FMF screening, using maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and placental growth factor (PlGF). The model assumed that patients identified as high-risk for PE were prescribed 150 mg aspirin daily until 36 weeks' gestation. Scenario analyses varied PE incidence, aspirin adherence and biomarker combinations of FMF strategy components. Incremental cost-effectiveness ratios (ICERs) were calculated using incremental costs and quality-adjusted life years (QALYs). Dominant ICERs demonstrated lower costs and higher QALYs. Compared with NICE-recommended screening, the FMF strategy demonstrated a cost-saving of £3191 and QALY gain of 0.92 per 10 000 patients (dominant ICER), with a cost-saving of £199 per preterm PE case avoided. In scenario analyses, the FMF strategy was cost-effective across 3%, 5% and 7% PE incidence, and 75% and 100% aspirin adherence. The base-case FMF strategy (maternal factors + MAP + UtA-PI + PlGF) was the most clinically effective option. The FMF strategy was more cost-effective versus the NICE strategy for first-trimester preterm PE screening in the UK.

Postoperative hypotension in patients recovering from noncardiac surgery: a prospective, blinded observational study.

Adolescent blood pressure guidelines rely on expert consensus because evidence on cardiovascular outcomes is limited. This study aimed to examine the link between adolescent blood pressure indices and early cardiovascular events. We conducted a cohort study among 902 741 adolescents aged 16 to 19 years who were evaluated for mandatory service from 1979 to 2019, excluding those with preexisting cardiometabolic conditions. Individuals were followed until 50 or death or insurance loss or December 31, 2021, whichever occurred first. Exposures included baseline blood pressure and American Academy of Pediatrics categories: normal (<120/<80 mm Hg), elevated (120/<80-129/<80 mm Hg), stage 1 (130/80-139/89 mm Hg), stage 2 (≥140/90 mm Hg), and hypertension (clinical diagnosis). The primary outcome was incident cardiovascular events (ischemic heart disease or cerebrovascular disease). Hazard ratios were estimated using Cox models adjusted for demographic, socioeconomic, and clinical confounders. During over 18 million person-years of follow-up, 6305 cardiovascular disease events were recorded, yielding an incidence rate of 0.35 per 1000 person-years. Increased diastolic, systolic, and mean arterial blood pressure were significantly associated with increased risk. Compared with the Normal group, adjusted hazard ratios for cardiovascular disease were 1.14 (95% CI, 1.08-1.22) for stage 1, 1.31 (1.20-1.44) for stage 2, and 2.42 (1.87-3.12) for hypertension. Risk in the stage 1 category was particularly sensitive to diastolic blood pressure. Higher blood pressure indices during adolescence were strongly associated with an elevated risk of early cardiovascular disease, highlighting the potential need to refine current guidelines to better reflect cardiovascular risk.

Swept-Source Optical Coherence Tomography Angiography Vascular Metrics as Biomarkers for Renal Function in Patients with Diabetes Mellitus.

To compare clinical outcomes of terlipressin as continuous versus bolus infusion for the management of acute variceal hemorrhage. Terlipressin is commonly used in the management of acute variceal bleeding, but evidence on the optimal method of administration-continuous infusion versus intermittent bolus-is limited. Patients presented with acute variceal bleeding were randomized into 2 arms: the intervention arm and the control arm received continuous and bolus infusion of terlipressin, respectively. Clinical endpoints included in-hospital mortality, 6-week mortality, the length of hospital stay, rebleeding and transfusion rates, and adverse events. Hemodynamic outcomes included were stability of heart rate, systolic, diastolic, and mean arterial blood pressures. A total of 128 patients were analysed. In-hospital mortality was none in both arms ( P =0.490). Mean length of stay for the intervention arm was 60.56±30.87 hours and the control arm was 57.80±33.35 hours ( P =0.569). Rebleeding was reported in 2 patients in each arm ( P =0.569). Packed cell transfusion rates were, 2.47±1.59 versus 2.17±0.98 units in intervention and control arm, respectively ( P =0.256). The 6-week mortality was 7 in the intervention and 12 in the control arms ( P =0.220). Bolus administration led to a greater reduction in heart rate at 4, 8, and post-20 hours ( P <0.05). Systolic blood pressure improved at 16 and 24 hours in the intervention arm ( P =0.02). There was no difference in length of hospital stay, packed cell volume, rebleeding, and mortality between both modes of terlipressin administration. Somewhat better improvement in systolic blood pressure was observed in patients who received a continuous infusion of terlipressin without any impact on clinical outcomes.

Elevated muscle sympathetic nerve activity (MSNA) at high altitude is associated with blunted transduction of sympathetic signals to blood pressure in lowlanders and indigenous Andean highlanders. However, it is unclear whether this is due to reduced adrenergic communication or other factors (e.g., augmented dilatory signaling). Therefore, we quantified the contribution of α-adrenoreceptor activity to 1) resting systemic sympathetic transduction and 2) pressor responses to sympathoexcitation in acclimatizing lowlanders (9 M and 4 F) and Andean highlanders (15 M) at 4,300 m. MSNA (microneurography) and mean arterial pressure (MAP; finger photoplethysmography) were measured at rest, during maximal voluntary apnea, and with an α1-adrenergic agonist (phenylephrine) before and following partial α-adrenergic blockade (phentolamine). Sympathetic transduction was quantified as the slope of the relationship between MAP and total MSNA associated with sequences of sympathetic bursts. Transduction was attenuated in both lowlanders (0.0041 ± 0.0037 to 0.0017 ± 0.0017 mmHg·%-1, P = 0.026) and highlanders (0.0033 ± 0.0024 to 0.0008 ± 0.0007 mmHg·%-1, P = 0.005) under α-adrenergic blockade (main effect P < 0.001) and was not different between groups (main effect P = 0.276). However, pressor responses to apnea (lowlanders, +25 ± 5 mmHg and highlanders, +22 ± 7 mmHg) were unchanged following phentolamine (lowlanders, +25 ± 8 mmHg and highlanders, +20 ± 8 mmHg; main effect P = 0.174) despite unchanged MSNA responses between conditions (main effect P = 0.162). Highlanders exhibited reduced MSNA responses compared with lowlanders regardless of condition (main effect P = 0.014). Partial α-adrenergic blockade reduced sympathetic transduction similarly in both groups. Yet, apnea responsiveness was maintained, achieved through lesser sympathoexcitation in highlanders. This suggests that resting blood pressure control is modulated primarily through α-adrenergic receptors in both populations, but pressor responses to stress may result from alternative mechanisms.NEW & NOTEWORTHY This study provides insight into the mechanisms involved in the sympathetic control of blood pressure at rest and in response to autonomic stress in different populations at high altitude. We demonstrate that resting blood pressure regulation is mediated primarily through α-adrenergic mechanisms in both lowlanders and Indigenous Andean highlanders at high altitude. However, pressor responses to apneic stress appear to be regulated by an alternative mechanism, particularly in highlanders who require less sympathetic activation.

Predictive accuracy of a perioperative hemodynamic indices-based prediction model for moderate-to-severe acute kidney injury after orthotopic heart transplantation.

The antihypertensive and cardiovascular effects of lawsone methyl ether in high salt-induced hypertensive rats are mediated through multiple pathways.

Voluntary apnea markedly attenuates exercise-induced increases in active muscle blood flow, a response known as the diving reflex, which is thought to preserve oxygen within the body. However, the underlying mechanisms of this response remain unknown. Since voluntary apnea elevates arterial CO2 partial pressure, which can induce vasoconstriction in active muscles during exercise, we hypothesized that arterial CO2 partial pressure modulates diving reflex-related regulation of active muscle blood flow. Fourteen young adults (1 female) performed maximal-duration breath-holding during a dynamic two-legged knee extension exercise that elicits a heart rate of 100 beats·min-1. The apnea was preceded by 3-min voluntary hyperventilation, which reduced end-tidal CO2 partial pressure to ∼20 mmHg (i.e., hypocapnic hyperventilation). As a control trial, hyperventilation was performed while keeping the end-tidal CO2 partial pressure at normocapnic level by CO2 inhalation (normocapnic hyperventilation). Hypocapnic hyperventilation increased apnea duration compared with normocapnic hyperventilation (52 ± 16 vs. 31 ± 13 s, P < 0.001). At matched time points between conditions, leg blood flow was higher in the hypocapnic than in the normocapnic hyperventilation condition (2236 ± 583 vs. 1643 ± 576 mL·min-1, P = 0.002). Hypocapnic hyperventilation also attenuated apnea-induced bradycardia, as well as increases in mean arterial pressure and middle cerebral artery mean blood velocity, compared with normocapnic hyperventilation at the iso-time point (all P < 0.001). We show that, based on end-tidal CO2 measurements, arterial CO2 partial pressure appears to modulate diving reflex-related active muscle hypoperfusion, as well as bradycardia, pressor response, and cerebral hyperemia in exercising adults.NEW & NOTEWORTHY We show that arterial CO2 partial pressure is a major factor that largely influences apnea-induced vasoconstriction in exercising muscles as well as bradycardia, pressor responses, and cerebral hyperemia during exercise. Thus, the diving reflex, which is traditionally regarded as an oxygen-conservation response, may also serve to regulate CO2 homeostasis.

Whether central systolic blood pressure (cSBP) compared with brachial systolic blood pressure (bSBP) improves risk stratification remains debated. This study investigated whether cSBP is more closely associated with total and cardiovascular mortality than bSBP when recorded by 24-hour ambulatory BP monitoring with an arm cuff-based oscillometric monitor. Consecutive patients referred for ambulatory BP monitoring and enrolled in the Shanghai Ruijin Ambulatory BP Monitoring Registry (2017-2023) were analyzed. bSBP and cSBP were recorded over 24 hours. cSBP was calibrated on brachial systolic and diastolic BP (cSBPc1) or on mean arterial pressure and brachial diastolic BP (cSBPc2). Total and cardiovascular mortality up to December 31, 2024, was assessed by record linkage with International Classification of Diseases, Tenth Revision, coded death certificates. Linear and nonlinear Cox proportional hazard regression was applied with age as the underlying time-scale and adjusted for established cardiovascular risk factors. Over 4.0 years of follow-up, 505 of 36 594 participants (52.8% women; median age, 53.4 years) died, 174 from cardiovascular disease. With multivariable adjustment applied, the nonlinear compared with linear Cox models provided a better model fit for both end points (P<0.001), irrespective of the period of the day and the calibration method of cSBP. Adding any 24-hour SBP to the base model increased the C statistics for total and cardiovascular mortality (0.003≤P≤0.06). Adding cSBPc1 or cSBPc2 to the base model extended by bSBP also increased the C statistics, but not by a statistically significant amount (0.054≤P≤0.22). cSBP compared with bSBP did not improve the associations with mortality. Measurement of the ambulatory bSBP is adequate for BP-based risk stratification.

Current guidelines recommend albumin infusion as a first-line treatment for acute kidney injury (AKI) in patients with cirrhosis. However, recent large-scale randomized trials have questioned its universal benefit. We aimed to identify distinct pathophysiological subphenotypes of cirrhotic AKI using machine learning and to evaluate the heterogeneous treatment effects of albumin infusion across these groups. A retrospective cohort study was conducted using the MIMIC-IV (v3.1) database, including 3209 critically ill patients with cirrhosis and AKI. Unsupervised K-means clustering was applied to eight clinical variables (creatinine, bilirubin, INR, sodium, lactate, platelets, mean arterial pressure [MAP], and baseline albumin) to derive phenotypes. The causal effect of albumin infusion within 48h of ICU admission on 28-day mortality was assessed using inverse probability of treatment weighting (IPTW)-adjusted Cox proportional hazards models. Three distinct phenotypes were identified: Phenotype A (severe hepatic failure type, N = 405), Phenotype B (hemodynamically stable type, N = 1390), and Phenotype C (typical decompensated type, N = 1414). In the overall population, after adjustment for an expanded set of confounders, albumin infusion was associated with a modest increase in mortality (adjusted HR, 1.211; 95%CI 1.046-1.401). However, significant treatment heterogeneity was observed. In Phenotype B, characterized by the highest MAP (75.8mmHg) and lowest bilirubin (1.15mg/dL), albumin infusion was associated with an approximately 1.7-fold increase in the risk of 28-day mortality (adjusted HR, 1.744; 95%CI 1.312-2.320; p < 0.001). Conversely, Phenotype A, representing patients with extreme hyperbilirubinemia, exhibited a potential but non-significant protective trend (HR, 0.895; 95%CI 0.643-1.245). Albumin infusion in cirrhotic AKI exhibits a divergent treatment response dictated by baseline pathophysiological phenotypes. For patients with relatively stable hemodynamics and low inflammatory burden (Phenotype B), aggressive albumin therapy may be harmful, potentially due to fluid overload and cardiorenal congestion. These findings advocate for a phenotype-driven, precision medicine approach rather than a "one-size-fits-all" strategy for volume expansion in cirrhosis.

Intra-operative hypotension is common during caesarean section and may result in adverse maternal effects, such as nausea and vomiting. While oscillometric blood pressure and continuous non-invasive arterial pressure monitoring enable reactive treatment, the hypotension prediction index offers a machine learning-based approach that may allow proactive haemodynamic intervention. This study investigated whether hypotension prediction index-guided management could reduce the incidence of intra-operative hypotension compared with oscillometric and continuous non-invasive arterial pressure monitoring. Patients scheduled for elective caesarean section under spinal anaesthesia were allocated randomly to one of three haemodynamic monitoring strategies: oscillometric blood pressure; continuous non-invasive arterial pressure; or hypotension prediction index-guided monitoring. Hypotension and hypertension were defined as mean arterial pressure < 65 mmHg and ≥ 100 mmHg, respectively. Hypotension was treated using intermittent intravenous boluses of noradrenaline. The primary outcome was the time-weighted average of hypotension. Secondary outcomes included time-weighted average hypertension and maternal adverse effects, including bradycardia, nausea and vomiting. Data from 171 patients were analysed. Median time-weighted average hypotension was significantly higher in patients allocated to the oscillometric and continuous non-invasive arterial pressure groups compared with the hypotension prediction index group (0.89 mmHg and 0.30 mmHg vs. 0.08 mmHg, respectively, p < 0.001). Patients allocated to the oscillometric group had a higher incidence of maternal nausea and vomiting compared with those allocated to the continuous non-invasive arterial pressure and hypotension prediction index groups (nausea: 43/59 vs. 29/55 and 30/57, respectively, p = 0.038; and vomiting: 13/59 vs. 6/55 and 3/57, respectively, p = 0.023). Hypotension prediction index-guided management during caesarean section significantly reduced intra-operative hypotension without increasing the risk of hypertension. This approach provides a proactive strategy for haemodynamic optimisation in obstetric anaesthesia.

Is a Slow Decline in Mean Arterial Pressure and SpO2 During Agonal Time in Donation After Circulatory Death Donors Associated with Increased Risk of Early Allograft Dysfunction?

Dobutamine exerts its pharmacological effects by stimulating α1-, β1-, and β2-adrenergic receptors. Activation of these receptors increase both the force of cardiac contraction (inotropy) and heart rate (chronotropy). Despite its well-established cardiac effects, the influence of dobutamine on vascular tone remains poorly understood and its impact on venous return and the underlying determinants of this process has not been thoroughly investigated. In eight healthy pigs, we measured cardiac output (CO) by pulmonary thermodilution, right atrial pressure (RAP) and arterial pressure. We measured mean circulatory filling pressure (PMSF), by transiently inflating a balloon in the right atrium and thus temporarily stopping blood flow and allowing venous pressure to plateau. After obtaining baseline measurements, dobutamine was administered at 10 and 20 µg/kg/min. Two fluids bolus were given at baseline and with a dobutamine infusion at 20 µg/kg/min to produce cardiac function curves. Repeated measures ANOVA were performed for comparisons. Dobutamine increased CO from 3.4 ± 0.3 to 4.3 ± 0.4 (p = 0.0145) and 4.5 ± 0.5 L/min/m2 (p = 0.0163) at 10 and 20µg/kg/min, with an upward shift of the cardiac function curve, indicating improved inotropy. Stroke volume and RAP did not change, but heart rate increases linearly with the dosage of dobutamine (p = 0.0009). Mean arterial pressure did not change but systemic vascular resistance decreased (p < 0,0001). PMSF also increased with dobutamine from 8.7 ± 0.7 to 9.8 ± 0.8 and 10.4 ± 0.8mmHg at 20µg/kg/min (p = 0.0455), and the pressure difference for venous return (PMSF-RAP) increased from 5.6 ± 0.6 to 7.3 ± 0.6 at 10µg/kg/min and 7.0 ± 0.5mmHg at 20µg/kg/min (p = 0.0292). There was no change in venous compliance or resistance to venous return, thus indicating a reduction in venous capacitance. No time-effect of dobutamine was detected over a 2-h period. Dobutamine increased cardiac output by increasing cardiac function by increase heart rate but also by improving venous return by increasing PMSF by decreasing venous capacitance and lowering arterial vascular resistance, underscoring the importance of its α1 and β2-adrenergic activity.