Reduction In Arterial Pressure Research Articles

Clinical usefulness of endothelial progenitor cells in predicting the efficacy of riociguat in chronic thromboembolic pulmonary hypertension.

Endothelial dysfunction is important in the pathology of pulmonary hypertension, and circulating endothelial progenitor cells (EPCs) have been studied to evaluate endothelial dysfunction. In patients with chronic thromboembolic pulmonary hypertension (CTEPH), riociguat reportedly increases the number of circulating EPCs. However, the relationship between EPC numbers at baseline and changes in clinical parameters after riociguat administration has not been fully elucidated. Here, we evaluated 27 treatment-naïve patients with CTEPH and analyzed the relationships between EPC number at diagnosis and clinical variables (age, hemodynamics, atrial blood gas parameters, brain natriuretic peptide, and exercise tolerance) before and after riociguat initiation. EPCs were defined as CD45dim CD34+ CD133+ cells and measured by flow cytometry. A low number of circulating EPCs at diagnosis was significantly correlated with increased reductions in mean pulmonary arterial pressure (mPAP) (correlation coefficient = 0.535, P = 0.004) and right atrial pressure (correlation coefficient = 0.618, P = 0.001) upon riociguat treatment. We then divided the study population into two groups according to the mPAP change: a weak-response group (a decrease in mPAP of 4 mmHg or less) and a strong-response group (a decrease in mPAP of more than 4 mmHg). The number of EPCs at diagnosis was significantly lower in the strong-response group than in the weak-response group (P = 0.022), but there were no significant differences in other clinical variables or in medication profiles. In conclusion, circulating EPC numbers could be a potential predictor of the therapeutic effect of riociguat in CTEPH patients.

Effect of needling at an acupuncture point zusanli (ST-36) on blood pressure and heart rate variability in patients with hypertension: A randomized placebo-controlled study

BackgroundAcupuncture is a traditional healing system used to prevent and treat hypertension in many countries. Acupuncture point “Zusanli (ST-36)” is used to nourish blood and yin. However, no known studies reported the effect of needling at only ST-36 on cardiovascular parameters. ObjectivesThis study was performed to find the effectiveness of ST-36 on blood pressure (BP) and heart rate variability (HRV) in patients with hypertension. MethodsA total of 100 participants with primary hypertension aged between 30 years and70 years were randomly assigned into either acupuncture group (AG) or control group (CG). AG underwent only one session of bilateral needling at ST-36 acupuncture point for duration of 20 minutes, while the CG underwent only one session of bilateral needling at non-acupuncture point for the same duration. ResultsResults of the study showed a significant reduction in systolic blood pressure, pulse pressure and mean arterial pressure in the AG compared to the CG. In addition, a significant increase in intervals between adjacent QRS complexes (R-R interval), and a significant reduction in heart rate were observed in AG, unlike CG. ConclusionsNeedling at ST-36 acupuncture point may improve cardiovascular function better than needling at non-acupuncture points in patients with hypertension.

Comparison of Fentanyl, Ketamine, and Lidocaine Combined with Propofol Anesthesia in Patients with Crohn Disease Undergoing Colonoscopy.

BACKGROUND Colonoscopy is the predominant invasive procedure for Crohn disease (CD) patients. Opioids and propofol carry risks of respiratory and cardiovascular complications. This study aimed to evaluate whether substituting fentanyl with ketamine or lidocaine could diminish propofol usage and minimize adverse events. MATERIAL AND METHODS In total, 146 patients with CD scheduled for elective colonoscopy were assigned to anesthesia with fentanyl (n=47), ketamine (n=47), or lidocaine (n=55). Propofol was administered to achieve sufficient anesthesia. Measured outcomes in each group included propofol consumption, hypotension and desaturation incidents, adverse event types, consciousness recovery time, abdominal pain intensity, Aldrete scale, and Post Anaesthetic Discharge Scoring System (PADSS). RESULTS Patients administered fentanyl needed significantly more propofol (P=0.017) than those on ketamine, with lidocaine showing no notable difference (P=0.28). Desaturation was significantly less common in the ketamine and lidocaine groups than fentanyl group (P<0.001). The ketamine group experienced milder reductions in mean arterial (P=0.018) and systolic blood pressure (P<0.001). Recovery metrics (Aldrete and PADSS scores) were lower for fentanyl (P<0.001), although satisfaction and pain levels were consistent across all groups (P=0.797). Dizziness occurred less frequently with lidocaine than fentanyl (17.2%, P=0.018) and ketamine (15.1%, P=0.019), while metallic taste incidents were more prevalent in the lidocaine group (13.5%, P=0.04) than fentanyl group. CONCLUSIONS Using ketamine or lidocaine instead of fentanyl in anesthesia for colonoscopy in patients with CD significantly lowers propofol use, reduces desaturation events, maintains blood pressure more effectively, without increasing hypotension risk, and accelerates recovery, without negatively impacting adverse events or patient satisfaction.

Effect of subclavian vein diameter combined with perioperative fluid therapy on preventing post-induction hypotension in patients with ASA status I or II

BackgroundPerioperative hypotension is frequently observed following the initiation of general anesthesia administration, often associated with adverse outcomes. This study assessed the effect of subclavian vein (SCV) diameter combined with perioperative fluid therapy on preventing post-induction hypotension (PIH) in patients with lower ASA status.MethodsThis two-part study included patients aged 18 to 65 years, classified as ASA physical status I or II, and scheduled for elective surgery. The first part (Part I) included 146 adult patients, where maximum SCV diameter (dSCVmax), minimum SCV diameter (dSCVmin), SCV collapsibility index (SCVCI) and SCV variability (SCVvariability) assessed using ultrasound. PIH was determined by reduction in mean arterial pressure (MAP) exceeding 30% from baseline measurement or any instance of MAP < falling below 65 mmHg for ≥ a duration of at least 1 min during the period from induction to 10 min after intubation. Receiver Operating Characteristic (ROC) curve analysis was employed to determine the predictive values of subclavian vein diameter and other relevant parameters. The second part comprised 124 adult patients, where patients with SCV diameter above the optimal cutoff value, as determined in Part I study, received 6 ml/kg of colloid solution within 20 min before induction. The study evaluated the impact of subclavian vein diameter combined with perioperative fluid therapy by comparing the observed incidence of PIH after induction of anesthesia.ResultsThe areas under the curves (with 95% confidence intervals) for SCVCI and SCVvariability were both 0.819 (0.744–0.893). The optimal cutoff values were determined to be 45.4% and 14.7% (with sensitivity of 76.1% and specificity of 86.7%), respectively. Logistic regression analysis, after adjusting for confounding factors, demonstrated that both SCVCI and SCVvariability were significant predictors of PIH. A threshold of 45.4% for SCVCI was chosen as the grouping criterion. The incidence of PIH in patients receiving fluid therapy was significantly lower in the SCVCI ≥ 45.4% group compared to the SCVCI < 45.4% group.ConclusionsBoth SCVCI and SCVvariability are noninvasive parameters capable of predicting PIH, and their combination with perioperative fluid therapy can reduce the incidence of PIH.

The Effect of Mannitol and Hypertonic Sodium Administration on Hemodynamic Parameters Under LiDCO Monitoring in Patients Undergoing Elective Craniotomy

In craniotomy surgery, it is important to maintain hemodynamics and prevent the increase of intracranial pressure. Using semi-invasive methods such as LiDCO monitoring is a good option in this situation. This study aimed to evaluate the effectiveness of mannitol and hypertonic sodium on hemodynamic parameters in patients undergoing elective craniotomy. This randomized clinical trial was done on 40 patients of both genders. Patients whose ages were between 18-65 years, who had American Society of Anesthesiologists (ASA) score I and II, and who underwent craniotomy surgery were eligible for this study. Participants were divided into two groups receiving hypertonic sodium and mannitol. Hemodynamic parameters were evaluated before surgery, 20 minutes, and 60 minutes after surgery in both groups, under Lithium dilution cardiac output (LiDCO) monitoring. The results showed that there was no difference between groups in terms of the average fluid intake, the duration of the operation, the amount of urinary output, and the primary hemodynamic characteristics. Significant differences were recorded in the evaluation of hemodynamic parameters. The results demonstrated a reduction in systolic, diastolic, and mean arterial blood pressure during 20 to 60 minutes after mannitol injection compared to hypertonic sodium injection. Additionally, the effectiveness of both therapies on maintaining cardiac function was similar, but the use of mannitol led to a greater decrease in arterial and peripheral vascular resistance. It can be concluded that mannitol may be more effective than hypertonic sodium during craniotomy procedures in terms of reducing blood pressure monitored with LiDCO.

EFFICACY OF TOLAZOLINE AND VATINOXAN IN REDUCING ADVERSE EFFECTS OF BUTORPHANOL-AZAPERONE-MEDETOMIDINE IMMOBILIZATION IN ROCKY MOUNTAIN ELK (CERVUS CANADENSIS).

A mixture of butorphanol, azaperone, and medetomidine (BAM) is frequently used for immobilization of North American hoofstock. Common adverse effects include respiratory depression, hypoxemia, and bradycardia. In this nonblinded crossover study the efficacy of two a-2 adrenergic antagonists, tolazoline and vatinoxan, were evaluated in alleviating adverse effects of BAM in Rocky Mountain elk (Cervus canadensis). Early administration of these antagonists was hypothesized to cause an increase in heart rate, respiratory rate, partial pressure of oxygen (PaO2) and hemoglobin oxygen saturation (SpO2), as well as reduction in mean arterial blood pressure without affecting sedation levels. Eight captive adult female elk were immobilized on three separate occasions at least 14 d apart with 0.15 mg/kg butorphanol, 0.05 mg/kg azaperone, and 0.06 mg/kg medetomidine. Tolazoline (2 mg/kg IM), vatinoxan (3 mg/mg medetomidine IV) or sterile saline (2 ml IM) were administered 20 min postinduction. The BAM caused hypoxemia, bradycardia, and moderate hypertension, and because of the severe hypoxemia observed, all animals received intratracheal oxygen throughout immobilization. Heart rate, respiratory rate, rectal temperature, SpO2, PaO2, and systolic, diastolic, and mean arterial blood pressure were monitored every 5 min throughout the immobilization. Intramuscular tolazoline caused a brief but significant drop in mean arterial pressure compared with controls and a brief but nonsignificant increase in heart rate. Vatinoxan caused a significant drop in blood pressure and a brief significant increase in heart rate. Changes in respiratory rates and PaO2 were not observed with either antagonist; however, all animals received oxygen, which may have influenced this result. The depth of sedation was unchanged after administration of either drug.

Predictors of cardiovascular and renal complications in patients with resistant arterial hypertension during long-term follow-up

The aim – to evaluate the incidence of cardiovascular and renal complications and its predictors in resistant hypertensive (RH) patients during the long-term follow-up.Materials and methods. The frequency of cardiovascular and renal events was studied in 240 true resistant hypertensive patients. The duration of observation was 5.1±0.1 years. The comparison group consisted of 228 patients with controlled arterial hypertension (CAH) on a triple combination antihypertensive therapy. Cardiovascular endpoints included stroke/transient ischemic attack, myocardial infarction, cardiovascular death, myocardial revascularization, development of atrial fibrillation, hospitalization due to heart failure, and lower limb arterial disease. Kidney outcomes included dialysis or GFR decline by 40 % or greater. All the endpoints formed a composite primary endpoint. New cases of type 2 diabetes mellitus were also estimated.Results and discussion. The patients with resistant hypertension on multi-component antihypertensive therapy and significant reduction in arterial blood pressure (BP) levels (achievement of controlled office BP in 49.6 % of patients, office and ambulatory BP in 34.2 % of patients), maintained a higher risk of cardiovascular and renal events compared to patients with controlled arterial hypertension. It was found that the frequency of occurrence of the composite primary endpoint in resistant hypertensive patients was four times higher than in the group of patients with controlled hypertension – 30.0 % (72/240) versus 7.0 % (16/228) (p=0.001). The frequency of new cases of type 2 diabetes mellitus in patients with RH exceeded compared to CAH patients by 3.7 times (p=0.03).Conclusions. Independent predictors of the risk of cardiovascular and renal complications in patients with RH were the initial indicators of circulating endothelial progenitor cells if their concentration in the blood was ≤ 1818 cells/ml (HR 0.41; 95 % CI (0.21–0.79); p=0.007), the content of citrulline in the blood is more than 68 μmol/l (HR 1.13; 95 % CI (1.07–1.20); p&lt;0.001); value of initial average daily systolic BP &gt; 163 mm Hg (HR 1.10; 95 % CI (1.03–1.18); p=0.008).

Is Tirzepatide the New Game Changer in Type 2 Diabetes?

Background: Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS program. Aims: The goal of this paper was to review the evidence on TZP in terms of glucose control, body weight, and the progression of chronic diabetes-related complications and comorbidities. Results: The mean change in HbA1c ranged from −1.6% to −2.06% over placebo, from −0.29% to −0.92% over each GLP-1RAs, and from −0.7% to −1.09% over basal insulins. In SURPASS-6, TZP was more effective than insulin lispro U100 added to basal insulin in reducing HbA1c levels at the study end (−2.1% vs. −1.1%, respectively). Compared to placebo, TZP induces a significant weight loss: 7.5 (5 mg/week); 11 (10 mg/week); and 12 kg (15 mg/week). Compared to GLP-1RAs, TZP reduces body weight from −1.68 kg to −7.16 kg depending on the dose (5 to 15 mg, respectively). Compared to basal insulin alone rigorously titrated, TZP added onto basal-insulin results in the best strategy for the composite endpoint of improvement of glucose control and weight loss. In SURPASS-6, TZP compared to insulin lispro U100 in add-on to insulin glargine U100 reduced body weight by 9 kg in mean (versus weight gain in basal-bolus users: +3.2 kg). TZP has pleiotropic effects potentially dampening the individual cardiovascular risk, including a reduction in systolic arterial pressure by 4 to 6 mmHg and total cholesterol by 4–6% compared to baseline. A post hoc analysis of SURPASS-4 revealed that TZP, compared to glargine U100, delayed the rate of glomerular filtration decline (−1.4 mL/min vs. −3.6 mL/min, respectively), reduced the rate of urinary albumin excretion (−6.8% vs. +36.9%, respectively), and was associated with a lower occurrence of the composite renal endpoint (HR 0.58 [0.43; 0.80]). Conclusions: Consistent evidence indicates that TZP dramatically changes the clinical course of T2D in different clinical scenarios. The efficacy and safety of TZP on chronic diabetes-related comorbidities and complications seem promising, but ongoing trials will clarify the real benefits.

Impact of rapid sequential combination therapy on distinct haemodynamic measures in newly diagnosed pulmonary arterial hypertension.

In pulmonary arterial hypertension (PAH), upfront combination therapy with ERA and PDE5i is associated with a reduction in morbidity and mortality events and improves standard haemodynamics, but data remain limited. Aims of this study were (i) to capture detailed haemodynamic effects of rapid sequential dual combination therapy in patients with newly diagnosed PAH; (ii) to monitor the impact of treatment initiation on clinical variables and patients' risk status, and (iii) to compare the treatment effect in patients with 'classical PAH' and 'PAH with co-morbidities'. Fifty patients (median age 57 [42-71] years, 66% female) with newly diagnosed PAH (76% idiopathic) were treated with a PD5i/sGC-S or ERA, followed by addition of the respective other drug class within 4weeks. All patients underwent repeat right heart catheterization (RHC) during early follow-up. At early repeat RHC (7±2months), there were substantial reductions in mean pulmonary artery pressure (mPAP: 52.2±13.5 to 39.0±10.6mmHg; -25.3%), and pulmonary vascular resistance (PVR: 12.1±5.7 to 5.8±3.1 WU; -52.1%), and an increase in cardiac index (2.1±0.4 to 2.7±0.7mL/min/m2; +32.2%) (all P<0.05). Haemodynamic improvements correlated with improved clinical parameters including 6-min walking distance (336±315 to 389±120m), NTproBNP levels (1.712±2.024 to 506±550ng/L, both P<0.05) and WHO-FC at 12months, resulting in improved risk status, and were found in patients with few (n=37) or multiple cardiovascular co-morbidities (BMI>30kg/m2, hypertension, diabetes, coronary artery disease [≥3]; n=13), albeit baseline PVR in PAH patients with multiple co-morbidities was lower (9.3±4.4 vs. 13.1±5.9 WU) and PVR reduction less pronounced compared with those with few co-morbidities (-42.7% vs. -54.7%). However, comprehensive haemodynamic assessment considering further variables of prognostic relevance such as stroke volume index and pulmonary artery compliance showed similar improvements among the two groups (SVI: +50.0% vs. +49.2%; PAC: 91.7% vs. 100.0%). Finally, the 4-strata risk assessment approach was better able to capture treatment response as compared with other approaches, particularly in patients with co-morbidities. Rapid sequential combination therapy with PDE5i/sGC-S and ERA substantially ameliorates cardiopulmonary haemodynamics at early follow-up in patients without, and to a lesser extent, with cardiovascular co-morbidities. This occurs in line with improvements of clinical parameters and risk status.

Effect of sitting time on the vasopressor requirement in elderly patients after spinal anesthesia: A randomized controlled study

ABSTRACT Background Neuraxial anesthesia appears to be a highly recommended, well-accepted technique for minimizing perioperative adverse effects in elderly patients. This research was designed to compare the impact of sitting for one, three, and 5 min on ephedrine consumption following spinal anesthesia in the elderly. Methods This randomized, controlled, double-blinded trial was conducted on 66 patients above 65 years undergoing surgeries under spinal anesthesia. Patients were randomly assigned to three equal groups. Patients received spinal anesthesia and then sat before they began to lie down for 1 min in the sitting-1 group, 3 min in the sitting-3 group, and 5 min in the sitting-5 group. Results The most reduction of mean arterial blood pressure (MAP) is in the Sitting-1 group, followed by the Sitting-3 group, and finally, the Sitting-5 group (p < 0.05). The most needed ephedrine was in the sitting-1 group (10 patients), followed by the sitting-3 (6 patients) and then the sitting-5 group (one patient) (p < 0.05). The sensory level was significantly higher in the sitting-1 group, followed by the sitting-3 and then sitting-5 group (p < 0.001). Conclusions Sitting for 5 min after spinal anesthesia in elderly patients decreases the ephedrine requirement and maintains adequate sensory block for surgery.

Comparison of nebulized ropivacaine (0.75%) with nebulized dexmedetomidine on the hemodynamic response on intubation in patients undergoing surgery under general anesthesia: A comparative randomized double-blind placebo-controlled study.

Laryngoscopy and tracheal intubation lead to sympathetic stimulation resulting in hemodynamic fluctuations. We compared local anesthetic ropivacaine 0.75% with alpha agonist dexmedetomidine through ultrasonic nebulization for direct local action of the drug in the airway. In our randomized study, 180 patients were prospectively assigned to three groups of 60 each: group R (0.75%), group D (1 microgram/kg), and group C (control). The primary objective was to determine whether nebulized ropivacaine or nebulized dexmedetomidine can cause a reduction in stress response to laryngoscopy and intubation. The secondary objectives were to compare the hemodynamic parameters at extubation, cough response at extubation, and postoperative sore throat. A total of 165 patients were analyzed. Demographically, all the groups were similar. Group R and group D were found to significantly attenuate the heart rate (HR) at intubation and extubation when compared to group C (P < 0.05). A significant reduction in mean arterial pressure (MAP) was seen (P < 0.05; group D: 90 ± 18.4 mmHg, group C: 99.5 ± 15.9 mmHg, group R: 92.4 ± 16.1 mmHg). There was a significant reduction in cough response in both groups in comparison with group C at 0 minutes (P value; group C vs group D: <.0001; group C vs group R:.01) and 5 minutes (P value; group C vs group D: <.0001; group C vs group R: <.0001). Preinduction topical use of ropivacaine or dexmedetomidine, through the nebulization route, effectively attenuated the pressor responses when compared to placebo.

Existence of Quantum Pharmacology in Sartans: Evidence in Isolated Rabbit Iliac Arteries.

Quantum pharmacology introduces theoretical models to describe the possibility of ultra-high dilutions to produce biological effects, which may help to explain the placebo effect observed in hypertensive clinical trials. To determine this within physiology and to evaluate novel ARBs, we tested the ability of known angiotensin II receptor blockers (ARBs) (candesartan and telmisartan) used to treat hypertension and other cardiovascular diseases, as well as novel ARBs (benzimidazole-N-biphenyl tetrazole (ACC519T), benzimidazole-bis-N,N'-biphenyl tetrazole (ACC519T(2)) and 4-butyl-N,N0-bis[[20-2Htetrazol-5-yl)biphenyl-4-yl]methyl)imidazolium bromide (BV6(K+)2), and nirmatrelvir (the active ingredient in Paxlovid) to modulate vascular contraction in iliac rings from healthy male New Zealand White rabbits in responses to various vasopressors (angiotensin A, angiotensin II and phenylephrine). Additionally, the hemodynamic effect of ACC519T and telmisartan on mean arterial pressure in conscious rabbits was determined, while the ex vivo ability of BV6(K+)2 to activate angiotensin-converting enzyme-2 (ACE2) was also investigated. We show that commercially available and novel ARBs can modulate contraction responses at ultra-high dilutions to different vasopressors. ACC519T produced a dose-dependent reduction in rabbit mean arterial pressure while BV6(K+)2 significantly increased ACE2 metabolism. The ability of ARBs to inhibit contraction responses even at ultra-low concentrations provides evidence of the existence of quantum pharmacology. Furthermore, the ability of ACC519T and BV6(K+)2 to modulate blood pressure and ACE2 activity, respectively, indicates their therapeutic potential against hypertension.

The effect of &lt;i&gt;Dayak&lt;/i&gt; onion brewed water in reducing blood pressure and mean arterial pressure (MAP) in hypertensive patients

Background: The World Health Organization (WHO) estimated that 1.28 billion adults aged 30-79 years worldwide suffered from hypertension. Dayak onion is an herbal plant found in Indonesia, particularly in Kalimantan and traditionally used to treat hypertension. The purpose of this study was to determine the effect of Dayak onion steeping water on the reduction of systolic-diastolic blood pressure and mean arterial pressure (MAP) in hypertensive patients. Methods: This study employed a quasi-experimental research design with a time series approach, utilizing a pre-post-test design with a control group. The sample included two groups (intervention and control), totaling 30 participants. The independent variable was the steeping of Dayak onion bulbs, while the dependent variables were blood pressure values and MAP. The instruments used were Standard Operating Procedures (SPO) Dayak onion herb, SPO blood pressure measurement, SPO calculation of MAP, and a digital sphygmomanometer. Data analysis was performed using paired t-tests. Results: The results of the paired t-test statistical analysis of systolic-diastolic values and MAP in each group revealed significant findings. In the intervention group, a significant result was obtained in the pre-post test difference test, with a p-value of &lt; 0.05 from day 1 to day 3 assessments. This suggests that Dayak onion steeping water had an effect on systolic-diastolic and MAP values in the intervention group. In contrast, the pre-post test in the control group yielded a p-value of &lt; 0.05 for systolic values on days 2 and 3, diastolic values on days 1 and 3, and MAP values on days 1, 2, and 3. This indicates differences in systolic-diastolic and MAP values in the pre-post assessments, although these differences were not evenly distributed across every day. Conclusion: The study found that Dayak onion steeping water had an effect on systolic-diastolic and MAP values in the intervention group. Thus, the use of Dayak onion steeping water, containing allicin, can be considered an approach for controlling hypertension in the realm of complementary and alternative medicine, utilizing natural ingredients for herbal therapy.

Combined Inhibition of Phosphodiesterase-5 and -9 in Experimental Heart Failure

BackgroundIntracellular second messenger cyclic guanosine monophosphate (cGMP) mediates bioactivity of the natriuretic peptides and nitric oxide, and is key to circulatory homeostasis and protection against cardiovascular disease. Inhibition of cGMP-degrading phosphodiesterases (PDEs) PDE5 and PDE9 are emerging as pharmacological targets in heart failure (HF). ObjectivesThe present study investigated dual enhancement of cGMP in experimental HF by combining inhibition of PDE-5 (P5-I) and PDE-9 (P9-I). MethodsEight sheep with pacing-induced HF received on separate days intravenous P5-I (sildenafil), P9-I (PF-04749982), P5-I+P9-I, and vehicle control, in counterbalanced order. ResultsCompared with control, separate P5-I and P9-I significantly increased circulating cGMP concentrations in association with reductions in mean arterial pressure (MAP), left atrial pressure (LAP), and pulmonary arterial pressure (PAP), with effects of P5-I on cGMP, MAP, and PAP greater than those of P9-I. Only P5-I decreased pulmonary vascular resistance. Combination P5-I+P9-I further reduced MAP, LAP, and PAP relative to inhibition of either phosphodiesterase alone. P9-I and, especially, P5-I elevated urinary cGMP levels relative to control. However, whereas inhibition of either enzyme increased urine creatinine excretion and clearance, only P9-I induced a significant diuresis and natriuresis. Combined P5-I+P9-I further elevated urine cGMP with concomitant increases in urine volume, sodium and creatinine excretion, and clearance similar to P9-I alone, despite the greater MAP reductions induced by combination treatment. ConclusionsCombined P5-I+P9-I amalgamated the superior renal effects of P9-I and pulmonary effects of P5-1, while concurrently further reducing cardiac preload and afterload. These findings support combination P5-I+P9-I as a therapeutic strategy in HF.

A comparison of the efficacy and safety between anticoagulation alone and combined with catheter-directed thrombolysis for treatment of pulmonary embolism on outcome: A systematic review and meta-analysis.

Catheter-directed thrombolysis (CDT) is one of the newest treatment options for submassive pulmonary embolism (sPE). This study will compare the efficacy and safety of catheter-directed thrombolysis (CDT) combine with anticoagulation versus anticoagulation alone (AC) in patients with PE. A database search was conducted using PubMed, EMBASE, Cochrane Library, and Clinicaltrials.gov for trials that compared CDT with AC in patients with pulmonary embolism. The primary outcomes was1-year mortality. The secondary outcomes were in-hospital, 30days, 90days mortality, in-hospital major and minor bleeding (Thrombolysis in Myocardial Infarction (TIMI) classification), length of hospital stay (LOS), reduction of pulmonary arterial systolic pressure (PASP) and RV/LV diameter ratio. A total of 16 articles (3 RCTs and 13 non-RCTs) and 10595 patients were included in this study. 2237 patients were in the CDT group and 8358 patients were in the AC group. CDT group was associated with significantly lower in-hospital mortality (2.1% vs 6.2%,OR:0.36, 95%CI:0.26-0.51, p < .00001,I2 = 0%), 30days mortality (3.1% vs 8.6%,OR:0.39,95%CI:0.23-0.66, p = .0005, I2 = 0%), 90days mortality (3.8% vs 7.7%,OR:0.49,95%CI:0.29-0.80,p = .005,I2 = 7%), 1-year mortality (6.1% vs 11%, OR:0.51, 95%CI:0.35-0.76, p = .0008,I2 = 36%) compared to AC group, especially in ultrasound-assisted thrombolysis (USAT) subgroup. There were no differences on major bleeding between two groups (1.8% vs 2.2%, OR:1.10, 95%CI:0.61-1.98, p = .75, I2 = 0%). Minor bleeding was significantly higher in CDT group than AC group (6.2% vs 3.8%, OR:1.93,95%CI:1.27-2.94.66, p = .002, I2 = 1%). CDT group significantly reduced PASP (WMD:11.90,95%CI:6.45-17.35, p < .0001, I2 = 72%) and RV/LV (WMD:0.17,95%CI:0.04-0.30, p = .009, I2 = 69%) rapidly than AC group after treatment. LOS was similar between two groups (WMD:0.02,95%CI: -0.68-0.73, p = .95, I2 = 51%). Results thus confirmed that CDT reduced in-hospital, 30days, 90days and 1-year all-cause mortality in patients with sPE compared to AC, particularly in USAT subgroup. Nonetheless, CDT group was associated with a higher risk of minor bleeding.

TCT-547 Pulmonary Artery Pressure Reduction With Mechanical Thrombectomy for Pulmonary Embolism Predicts Improved Patient Outcomes Within 48 Hours: Results From the FLASH Registry U.S. Cohort

TCT-547 Pulmonary Artery Pressure Reduction With Mechanical Thrombectomy for Pulmonary Embolism Predicts Improved Patient Outcomes Within 48 Hours: Results From the FLASH Registry U.S. Cohort

Cardiovascular and respiratory evaluation in adenosine A2A receptor knockout mice submitted to short-term sustained hypoxia.

Sustained hypoxia (SH) in mice induces changes in the respiratory pattern and increase in the parasympathetic tone to the heart. Among adenosine G-protein-coupled receptors (GPCRs), the A2A receptors are especially important in mediating adenosine actions during hypoxia due to their expression in neurons involved with the generation and modulation of the autonomic and respiratory functions. Herein, we performed an in vivo evaluation of the baseline cardiovascular and respiratory parameters and their changes in response to SH in knockout mice for A2A receptors (A2A KO). SH produced similar and significant reductions in mean arterial pressure and heart rate in both wild-type (WT) and A2A KO mice when compared to their respective normoxic controls. Mice from WT and A2A KO groups submitted to normoxia or SH presented similar cardiovascular responses to peripheral chemoreflex activation (KCN). Under normoxic conditions A2A KO mice presented a respiratory frequency (fR ) significantly higher in relation to the WT group, which was reduced in response to SH. These data show that the lack of adenosine A2A receptors in mice does not affect the cardiovascular parameters and the autonomic responses to chemoreflex activation in control (normoxia) and SH mice. We conclude that the A2A receptors play a major role in the control of respiratory frequency and in the tachypnoeic response to SH in mice. NEW FINDINGS: What is the central question of this study? Are cardiovascular and respiratory parameters and their changes in response to sustained hypoxia (SH) altered in adenosine A2A receptor knockout mice? What is the main finding and its importance? Cardiovascular parameters and their changes in response to SH were not altered in A2A KO mice. The respiratory frequency in A2A KO was higher than in WT mice. In response to SH the respiratory frequency increased in WT, while it was reduced in A2A KO mice. A2A receptors play a major role in the modulation of respiratory frequency and in the tachypnoeic response to SH in mice.

Impaired renal autoregulation and pressure-natriuresis: any role in the development of heart failure in normotensive and angiotensin II-dependent hypertensive rats?

The aim of the present study was to assess the autoregulatory capacity of renal blood flow (RBF) and of the pressure-natriuresis characteristics in the early phase of heart failure (HF) in rats, normotensive and with angiotensin II (ANG II)-dependent hypertension. Ren-2 transgenic rats (TGR) were employed as a model of ANG II-dependent hypertension. HF was induced by creating the aorto-caval fistula (ACF). One week after ACF creation or sham-operation, the animals were prepared for studies evaluating in vivo RBF autoregulatory capacity and the pressure-natriuresis characteristics after stepwise changes in renal arterial pressure (RAP) induced by aortic clamping. In ACF TGR the basal mean arterial pressure, RBF, urine flow (UF), and absolute sodium excretion (UNaV) were all significantly lower tha n in sham-operated TGR. In the latter, reductions in renal arterial pressure (RAP) significantly decreased RBF whereas in ACF TGR they did not change. Stepwise reductions in RAP resulted in marked decreases in UF and UNaV in sham-operated as well as in ACF TGR, however, these decreases were significantly greater in the former. Our data show that compared with sham-operated TGR, ACF TGR displayed well-maintained RBF autoregulatory capacity and improved slope of the pressure-natriuresis relationship. Thus, even though in the very early HF stage renal dysfunction was demonstrable, in the HF model of ANG II-dependent hypertensive rat such dysfunction and the subsequent HF decompensation cannot be simply ascribed to impaired renal autoregulation and pressure-natriuresis relationship.

Dual angiotensin receptor and neprilysin inhibitor reduced portal pressure through peripheral vasodilatation and decreasing systemic arterial pressure in cirrhotic rats.

Portal hypertension develops along with the progression of liver cirrhosis. Natriuretic peptides have been shown to reduce portal pressure but concomitantly activate the renin-angiotensin-aldosterone system (RAAS). Angiotensin receptor-neprilysin inhibitors (ARNIs) upregulate natriuretic peptides and avoid the adverse effects of RAAS activation. ARNIs have been shown to reduce portal pressure in rats with pre-hepatic portal hypertension, which involves relatively little liver injury. This study aimed to evaluate the relevant effects of an ARNI in rats with both liver cirrhosis and portal hypertension. Male Sprague-Dawley rats received common bile duct ligation to induce liver cirrhosis and portal hypertension. Sham-operated rats served as surgical controls. All rats were randomly allocated into three groups to receive distilled water (vehicle), LCZ696 (an ARNI), or valsartan for 4 weeks. Portal hypertension and relevant derangements were assessed after treatment. Portal hypertension and hyperdynamic circulation developed in the cirrhotic rats. In the rats with cirrhosis and portal hypertension, both LCZ696 and valsartan reduced portal hypertension, mean arterial pressure, and systemic vascular resistance. The decrease in portal pressure was highly associated with the reduction in arterial pressure and systemic vascular resistance. Blood flow in hepatic, splanchnic, and portosystemic collateral systems was not altered. LCZ696 did not significantly influence liver injury or plasma cytokine levels. Liver fibrosis and splanchnic angiogenesis were not affected. ARNI treatment exerted portal pressure lowering effects via peripheral vasodilatation and decreasing systemic arterial pressure in the rats with liver cirrhosis and portal hypertension. Caution should be taken when using ARNIs in liver cirrhosis.

Acute and adaptive cardiovascular and metabolic effects of passive heat therapy or high-intensity interval training in patients with severe lower-limb osteoarthritis.

Exercise is painful and difficult to perform for patients with severe lower-limb osteoarthritis; consequently, reduced physical activity contributes to increased cardiometabolic disease risk. The aim of this study was to characterize the acute and adaptive cardiovascular and metabolic effects of two low or no impact therapies in patients with severe lower-limb osteoarthritis: passive heat therapy (Heat) and high-intensity interval training (HIIT) utilizing primarily the unaffected limbs, compared to a control intervention of home-based exercise (Home). Participants completed up to 12 weeks of either Heat (20-30 min immersed in 40°C water followed by ~15-min light resistance exercise), HIIT (6-8 × 60-s intervals on a cross-trainer or arm ergometer at ~90-100% peak O2 ) or Home (~15-min light resistance exercise); all 3 sessions/week. Reductions in systolic (12 & 10 mm Hg), diastolic (7 & 4 mm Hg), and mean arterial (8 & 6 mm Hg) blood pressure (BP) were observed following one bout of Heat or HIIT exposure, lasting for the duration of the 20-min monitoring period. Across the interventions (i.e., 12 weeks), resting systolic BP and diastolic BP decreased with Heat (-9 & -4 mm Hg; p < 0.001) and HIIT (-7 & -3 mm Hg; p ≤ 0.011), but not Home (0 & 0 mm Hg; p ≥ 0.785). The systolic and diastolic BP responses to an acute exposure of Heat or HIIT in the first intervention session were moderately correlated with adaptive responses across the intervention (r ≥ 0.54, p ≤ 0.005). Neither intervention improved indices of glycemic control (p = 0.310). In summary, both Heat and HIIT induced potent immediate and adaptive hypotensive effects, and the acute response was moderately predictive of the long-term response.