Pulse of Asia 2021

The proceedings contain 67 papers. The topics discussed include: cardiovascular system and COVID-19;long term sequale on COVID-19;fighting vascular disease: thoughts about 2022 Taiwan hypertension guidelines;quantification of hemodynamic parameters using 4D flow MRI;nanomedicine for the treatment of atherosclerosis;direct thrombus imaging;clinical outcome in patients with deep vein thrombosis;cardiovascular benefits of SGLT-2 inhibitor;central blood pressure and pressure wave reflection in cardiovascular abnormalities: do not put them in shade;association between excess pressure and cognitive function among elderly population;visceral adipose tissue, coronary artery calcification and heart failure: a moderated mediation analysis;and the cardio-ankle vascular index was associated with CHADS2 score in patients with atrial fibrillation: a coupling registry study.

DEVELOPING VACCINES TO COMBAT HUMAN DISEASES: A HISTORY

This article traces the development of vaccines from the early attempts to combat a fatal disease caused by variola (smallpox) virus in antiquity, through to the highly technical advances which have led to the efficacious vaccines targeting COVID-19. As vaccine preparation has advanced, so has the understanding of the immune response to immunisation and the realisation that the use of adjuvants is essential to boosting the immune response. Furthermore, coupling polysaccharides to proteins is important in achieving vaccine efficacy in young children and older adults. Successful vaccination programmes have led to marked reductions in mortality associated with the diseases targeted by those vaccines – and to the unintended consequence of cultural amnesia regarding those diseases. The anti-vaccination movement has gained traction by riding on this cultural amnesia to capitalise on spurious associations, infrequent public-health disasters around inadvertent administration of faulty vaccine preparations and rare adverse events to build a case against vaccination. This tension between the advances in vaccine production and the criticism cast at the pro-vaccination agenda should be viewed as an agent for growth in the development of safe and effective vaccines, and in the planning to combat future pandemics.

SASA 2022 Virtual Conference Abstracts

The proceedings contain 23 papers. The topics discussed include: petroleum jelly as an alternative coupling medium in focus assessed transthoracic echocardiography;perspectives on desflurane;use of high-flow nasal oxygenation outside COVID-19: a rural hospital experience;fitness for purpose of South African anesthesiologists;the effect of caregiver's recorded voice on emergence delirium in children undergoing dental surgery;perioperative outcomes of mitral valve surgery at Charlotte Maxeke Johannesburg Academic Hospital;comparison of a novel low-cost hyperangulated optic intubation stylet with the Bonfils fiberscope: a simulated difficult airway manikin study;the awareness of local anaesthetic systemic toxicity amongst registrars from surgical disciplines in a tertiary hospital, South Africa;and SARS-CoV-2 infection prevalence in healthcare workers, administrative and support staff: the first wave experience at three academic hospitals in the Tshwane District of Gauteng.

Targeting brain-resident viruses across the blood-brain barrier in vitro using peptideporphyrin conjugates

The recent SARS-CoV-2 pandemic brought awareness to the permanent dangers of viral infections and outbreaks. Beyond its inherent infections, several viruses such as Dengue (DENV), Zika (ZIKV), HIV and even SARS-CoV-2 have the potential to infect the brain, causing more aggressive and irreversible injuries. These brain infections are particularly hard to treat not only because the number of efficient antiviral drugs against these viruses is scarce, but also due to the restrictive permeability of the blood- brain barrier (BBB) that hinders brain drug-intake. To overcome these issues, we designed peptide-drug conjugates formed by covalent attachment of a BBB peptide shuttle and a broad-spectrum antiviral porphyrin drug. We synthesized eighteen novel peptide-porphyrins conjugates (PPCs) and tested their activity in vitro, both in BBB-translocation and antiviral capacity against DENV, ZIKV, HIV and SARS-CoV-2. Cytotoxicity towards pharmacologic relevant cell lines was also studied. After careful fine-tuning of the on-resin synthetic chemistry, DIC/Oxyma coupling has emerged as preferred method, bearing a 99% conjugation yield. Ten PPCs inactivate at least two different viruses in vitro, a selection criterion for further evaluation, with IC50s ranging between 0.5 to 33 lM. Although all ten PPCs efficiently translocate the cellular BBB model in vitro, a set of seven stand out as the most druggable since they are not cytotoxic towards all cell lines tested. Overall, peptide-porphyrin conjugation shows to be an innovative and promising strategy to treat viral brain infections.

Eicosapentaenoic acid increases endothelial function and Heme oxygenase-1 in pulmonary inflammation

INTRODUCTION: Endothelial cell (EC) dysfunction results in reduced nitric oxide (NO) bioavailability leading to inflammation and increased susceptibility to infectious agents. Heme oxygenase-1 (HO-1) produces potent antioxidant and anti-inflammatory products including carbon monoxide. SARS-CoV-2 and influenza affect ECs in multiple vascular beds, including pulmonary tissue. The omega-3 fatty acid eicosapentaenoic acid (EPA) and its metabolites preserve EC function in a manner that may contribute to reduced incident cardiovascular events (REDUCE-IT). Currently, EPA is being tested in patients with or at risk for COVID-19. This study tested the effects of EPA on NO and peroxynitrite (ONOO-) release under conditions of inflammation using lipopolysaccharide (LPS) and the cytokine IL-6. We also measured expression of HO-1 after cell challenge with IL-6. METHODS: Human lung microvascular endothelial cells (HMVEC-L) were pretreated with vehicle or EPA (40 μM) in 2% FBS for 2 h, then challenged with either IL-6 (12 ng/ml) or LPS (200 ng/ml) for 24 h. Cells (including untreated controls) were stimulated with calcium ionophore to measure maximum production of NO and peroxynitrite (ONOO-) using tandem porphyrinic nanosensors. Proteomic analysis was performed using LC/MS to assess relative expression levels. Only significant (p< 0.05) changes in protein expression between treatment groups >1-fold were analyzed. RESULTS: HMVEC-L challenged with LPS and IL-6 showed a pronounced loss of NO release by 22% (p< 0.01) and 18% (p< 0.01), respectively, concomitant with an increase in ONOO- by 28% (p< 0.01) and 26% (p< 0.01), respectively. As a result, the [NO]/[ONOO-] ratio, a marker of eNOS coupling efficiency, decreased by 39% (p< 0.001) and 35% (p< 0.001) with LPS and IL-6, respectively. However, EPA increased this ratio by 39% (p< 0.01) in both LPS and IL-6 treated cells. EPA also caused a 5.7-fold (p = 4.4 × 10-38) increase in expression of HO-1 with IL-6. CONCLUSIONS: These findings indicate that EPA improves NO bioavailability and reduces nitroxidative stress in pulmonary ECs during inflammation with LPS or IL-6. These studies indicate a protective effect of EPA on pulmonary ECs that may reduce inflammatory activation during sepsis, influenza, or advanced COVID-19 that may mediate many aspects of multiorgan system failure.

Hemodynamic assessment of inhalational epoprostenol for post-operative right ventricular dysfunction in cardiac surgery patients

Introduction: Right ventricular (RV) dysfunction after cardiac surgery presents a significant challenge. Epoprostenol (EPO) is a pulmonary vasodilator that can be administered via inhalation and is often used in patients with post-operative RV dysfunction. However, the effects of EPO on RV performance have not been well studied. Furthermore, EPO is generally contraindicated in WHO Group 2 pulmonary hypertension. The purpose of this study is to describe the hemodynamic consequences of weaning inhaled epoprostenol (iEPO) in post-operative RV dysfunction and potentially identify any predictive markers for successful weaning. Methods: This is a single-center case series of patients receiving iEPO after cardiac surgery identified by convenience sampling. Inclusion criteria included post-cardiac surgery patients, >18 years, and receiving iEPO for RV dysfunction. Exclusion criteria included pregnancy, open chest, SARS-COV-2 pneumonia, left ventricular assist device use, extracorporeal membrane oxygenation use, heart transplantation, or receiving iEPO for refractory hypoxia. A paired two sample t-test compared the hemodynamic parameters collected pre and post iEPO weaning. Results: EPO weaning was associated with a decrease in mean pulmonary artery pulsatility index (PAPi) (pre-wean 1.81 vs post-wean 1.57, p=0.04) and increase in pulmonary artery systolic pressure (PASP) (46.5mmHg vs 55.1mmHg, p=0.01). Cardiac index and right atrial pressure were not significantly different (p=0.35 and p=0.26 respectively). Case 5 had EPO weaning failure and had the lowest baseline PAPi in the cohort. Conclusion: iEPO weaning is associated with dynamic changes in PASP and PAPI in post-operative cardiac surgery patients. This finding supports the conceptual role of iEPO in improving post-operative RV-PA coupling and RV performance. Baseline PAPi may be a predictive marker to guide the weaning process. However, larger cohorts are needed to confirm these findings.

P.0892 The effect of urethane on respiratory coupling between prefrontal cortex and hippocampus

Background: COVID-19 is the latest example of neurological abnormalities originating from pathology of the olfactory epithelium [1]. According to current understanding [2,3], SARS-CoV-2 does not directly infect olfactory sensory neurons;their deficit is mediated instead by the altered microenvironment maintained by cells in the olfactory epithelium expressing ACE2 receptors. However, smell is not the only signal originated in the olfactory bulb (OB) and affecting higher brain function. Respiratory modulation of forebrain activity, long considered hard to reliably separate from breathing artifacts, has been firmly established in recent years using a variety of advanced techniques [4]. Respiratory related oscillation (RRO) is derived from rhythmic nasal airflow in the OB and is conveyed to higher order brain networks, including the prefrontal cortex (PFC) and hippocampus (HC), where it may potentially contribute to communication between these structures by synchronizing their activities at the respiratory rate. RRO was shown to change with sleep-wake states, it is strongest in quiet waking, somewhat less in active waking, characterized with theta activity in the HC, and absent in sleep [5]. The goal of this study was to test RRO synchronization between PFC and HC under urethane anesthesia where theta and non-theta states spontaneously alternate. The major strength of this preparation is that behavioral confounds of waking (e.g. locomotion, cognition) on one hand and fragmentation of sleep patterns (e.g. short REM sleep, never lasting longer than a few minutes in rodents) on the other are effectively eliminated. Methods: Local field potentials were recorded in OB, PRF and HC along with diaphragmal (dia) EMG on six rats under urethane anesthesia. Multiple segments were selected from stable episodes of theta and non-theta states and analyzed using procedures identical to those in a prior study on freely moving rats [5]. To quantify neuronal synchronization between different structures we used pairwise coherences, calculated between four signal pairs, representing the potential transfer of the RRO signal to higher-order structures through the OB (i.e. dia with OB and OB with PFC and HC) and between these higher order structures (i.e. PFC with HC). Differences between coherences in different states were tested using Student's t-test after Fisher r to z transformation to obtain z-scored values with normal distribution. Correlation between pair-wise coherences were statistically tested using Excel's T-DIST procedure. Results: First, we found significant correlation between coherences connecting OB activity to respiration on one hand and to PFC and HC activities on the other, in both theta and non-theta states. Second, in theta states, PFC-HC coherences significantly correlated with OB-HC (R2=0.72, p=0.02) but not with OB-PFC (R2=0.30, p=0.16), even though RRO was stronger in PFC than in HC. In non-theta states, PFC-HC synchrony correlated with coherences connecting OB to either PFC or HC. Conclusions: Thus, similar to freely behaving rats [5], PFC-HC synchrony at RRO was primarily dependent on the response of HC to the common rhythmic drive, but only in theta state. The differences however suggest a cautious approach when interpreting the results of RRO under urethane anesthesia in mechanistic studies of RRO. No conflict of interest