Nanostructured Lipid Carriers Deliver Resveratrol, Restoring Attenuated Dilation in Small Coronary Arteries, via the AMPK Pathway

Nanostructured lipid carriers (NLCs) are an emerging drug delivery platform for improved drug stability and the bioavailability of antihypertensive drugs and vasoprotective nutraceutical compounds, such as resveratrol (RV). The objective of this study was to ascertain NLCs’ potential to deliver RV and restore attenuated dilator function, using an ex vivo model of acute hypertension. Trimyristin–triolein NLCs were synthesized and loaded with RV. The uptake of RV-NLCs by human coronary artery endothelial cells (HCAECs) maintained their viability and reduced both mitochondrial and cytosolic superoxide levels. Acute pressure elevation in isolated coronary arteries significantly attenuated endothelial-dependent dilator responses, which were reversed following incubation in RV-NLCs, superoxide dismutase or apocynin (p < 0.0001). RV-NLCs demonstrated a five-fold increase in potency in comparison to RV solution. At elevated pressure, in the presence of RV-NLCs, incubation with Nω-nitro-l-arginine (L-NNA) or indomethacin resulted in a significant reduction in the restored dilator component (p < 0.0001), whereas apamin and TRAM-34 had no overall effect. Incubation with the adenosine monophosphate-activated protein kinase (AMPK) inhibitor dorsomorphin significantly attenuated dilator responses (p < 0.001), whereas the SIRT-1 inhibitor EX-527 had no effect. RV-NLCs improved the impaired endothelial-dependent dilation of small coronary arteries, following acute pressure elevation, via NO and downstream COX elements, mediated by AMPK. We suggest that RV-NLCs are an effective delivery modality for improved potency and sustained drug release into the vasculature. Our findings have important implications for the future design and implementation of antihypertensive treatment strategies.

Comparative Study of Clevidipine to Nicardipine for Perioperative Hypertension in Patients Undergoing Cardiac Surgery

Objective The primary objective of this study was to compare the efficacy of clevidipine to nicardipine in the treatment of perioperative acute hypertension in patients undergoing cardiac surgery. Methods This was a single-center retrospective study which included patients who received either clevidipine or nicardipine. Patients were followed for the duration of study drug infusion or for a maximum of 48 hours. Outcomes assessed included the percent of time spent within patient specific goal blood pressure, incidence of hypertensive events per patient, safety outcomes, and cost of medication treatment. Results There were 201 cardiac surgeries performed between August 2018–January 2019 and July 2019–February 2020. Sixty-seven patients met our inclusion criteria of receiving either clevidipine (n = 29) or nicardipine (n = 38). The median percent of time spent within goal blood pressure range for clevidipine was 55.2% compared to 36.4% for nicardipine treatment ( P = .036). The median number of hypertensive episodes per patient was 3 for clevidipine and 2 for nicardipine ( P = .211). There were no identified differences in safety outcomes such as hypotension, vasopressor use, serum creatinine elevation, tachycardia, and atrial fibrillation. The median cost of treatment required for the observed 48-hour period with clevidipine was $128.58 compared to $55.74 for nicardipine ( P < .001). Conclusion Our findings suggest that patients undergoing cardiac surgery on clevidipine had better perioperative blood pressure control compared to nicardipine, with a negligible increase in cost, and no observed difference in safety.

Pengaruh Ramipril Terhadap Gambaran Histopatologis Otak Tikus Wistar yang Mengalami Edema Otak

Background. Brain edema is excessive accumulation of fluid in the intracranial or extracellular space of the brain. It can be caused by head trauma, brain tumors, hypoxia, metabolic disorders, or acute hypertension. Acute myocardial infraction is damage to the myocard that occurs due to lack oxygen. When acute myocardial infarction occurs, there will be disruption of blood flow in the form of stasis which allows emboli and decreased Cardiac Output which will cause a decrease in Cerebral Blood Flow. There will be a state of ischemia and hypoxia so that the hemostatic mechanism is disturbed which will trigger brain edema. Objective. This research was conducted to see the effect of giving ramipril to histopathological of the brain of wistar rat with brain edema. Methods. This research is an experimental study. We used 32 animals which were divided into 4 groups (K-, K +, P1, and P2). P1 was given 3 mg/kgBW ramipril for 7 consecutive days. P2 was given 4 mg/kgBW ramipril for 7 consecutive days. On days 8 and 9, P1, P2, and K+ induced isoproterenol 85 mg/kgBW for 2 consecutive days to induce brain edema through the mechanism of acute myocardial infarction. Data analysis was performed using One Way Anova test and Post Hoc Bonferroni test. Results. The mean area of ​​brain edema in the K-, K +, P1, and P2 groups respectively were 20.76%, 34.69%, 22.70%, and 21.90%. Conclusion. There was a significant effect of giving ramipril to histopathological of the brain of wistar rat with brain edema

Transient Global Amnesia (TGA): Influence of Acute Hypertension in Patients Not Adapted to Chronic Hypertension

Objective: Transient global amnesia (TGA) is defined by an acute memory disturbance of unclear etiology for a period of &lt;24 h. Several studies showed differences in vascular risk factors between TGA compared to transient ischemic attack (TIA) or healthy controls with varying results. This retrospective and cross-sectional study compares the cardiovascular risk profile of TGA patients with that of acute stroke patients.Methods: Cardiovascular risk profile and MR imaging of 277 TGA patients was retrospectively analyzed and compared to 216 acute ischemic stroke patients (26% TIA).Results: TGA patients were significantly younger and predominantly female compared to stroke patients. A total of 90.6% of TGA patients underwent MRI, and 53% of those showed hippocampal diffusion-weighted imaging (DWI) lesions. Scores for cerebral microangiopathy were lower in TGA patients compared to stroke patients. After statistical correction for age, TGA patients had higher systolic and diastolic blood pressure, higher cholesterol levels, lower HbA1c, as well as blood glucose levels, and lower CHA2DS2-VASc scores. Stroke patients initially displayed higher CRP levels than TIA and TGA patients. TGA patients without DWI lesions were older and showed higher CHA2DS2-VASc scores compared to TGA patients with DWI lesions.Conclusion: This study revealed significant differences between TGA and stroke patients in regard to the cardiovascular risk profile. Our main findings show a strong association between acute hypertensive peaks and TGA in patients not adapted to chronic hypertension, indicating a vascular cause of the disease.

The burden of perioperative hypertension/hypotension: a systematic review

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Ferrer Background Hypertension/hypotension in the perioperative setting may result in a high economic burden for healthcare systems and patients affected in terms of clinical outcomes. Although previous systematic reviews have shown IV antihypertensive treatments to be highly effective, there is currently a clear gap in the literature regarding a review on the implications of acute hypotensive/hypertensive episodes. Purpose Our goal is to review the outcomes of acute hypertensive/hypotensive episodes from articles published in the past 10 years that assessed the short- and long-term impact of acute hypertensive/hypotensive episodes in the perioperative setting. Methods We conducted a systematic peer-review based upon PROSPERO and Cochrane Handbook protocols. The following study characteristics were collected: study type, author, year, population, sample size, definition of acute hypertension, hypotension or other measures, and outcomes (probabilities, odds ratio, hazard ratio, and relative risk) and the p-values. Quality of the studies was graded with the Scottish Intercollegiate Guidelines Network. Results A total of 4,197 articles were identified and 47 articles satisfied criteria for data extraction. We present evidence on outcomes associated with acute hypertension/hypotension distinguishing cardiac from non-cardiac surgeries. For the perioperative setting, the number of articles varies by outcome: 17 mortality, 11 renal outcomes, 3 stroke, 6 delirium, and 21 others. Hypotension was reported to be associated with mortality (OR 1.02-20.826) as well as changes from blood pressure patient’s baseline (OR 1.02-1.36); hypotension had also a role in the development of acute kidney injury (OR 1.03-14.11). Postsurgical delirium was found in relation with lability (OR 1.018-1.038) and intra- and postsurgical hypotension (OR 1.05-1.22), and hypertension (OR 1.44-2.34). However, no statistically significant result was found for the relation between hypotension and stroke, and no study investigating hypertension influence over stroke was found. There was a wide range of additional diverse outcomes related to hypo-, hypertension and blood pressure liability, for example myocardial damage related to a 50% decrease in systolic blood pressure (SBP) (OR 4.4), increased odds 9.6 for new onset of atrial fibrillation associated with intraoperative SBP below 80 mmHg for 15 min or more; myocardial injury, length of stay in hospital, hematoma, or anastomotic leakage were also found to be related to hypertension. Conclusions The perioperative management of blood pressure influences short- and long-term effects of surgical procedures. These findings support the burden of blood pressure fluctuations in this setting. It sounds pertinent to further investigate the role of newer antihypertensive agents with favourable pharmacodynamic and pharmacokinetic properties to guarantee the fine-tuning of blood pressure and an individualised therapy for patients.