The purpose of this study was to investigate the effects of volatile anesthetic agents isoflurane and sevoflurane, at clinically relevant concentrations, on the fluidity of lipid membranes and permeability of the blood-brain barrier (BBB). We analyzed the in vitro effects of isoflurane or ketamine using erythrocyte ghosts (sodium fluorescein permeability) monolayers of brain microvascular endothelial cells ([ 13 C]sucrose and fluorescein permeability), or liposomes (fluorescence anisotropy). Additionally, we determined the effects of 30-min exposure of mice to isoflurane on the brain tight junction proteins.Finally, we investigated in vivo brain uptake of [ 13 C]mannitol and [ 13 C]sucrose after IV administration in mice under anesthesia with isoflurane, sevoflurane, or ketamine/xylazine in addition to the awake condition. Isoflurane at 1-and 5-mM concentrations increased fluorescein efflux from the erythrocyte ghosts in a concentration-dependent manner. Similarly, in endothelial cell monolayers exposed to 3% (v/v) isoflurane, permeability coefficients rose by about 25% for fluorescein and 40% for [ 13 C]sucrose, while transendothelial resistance and cell viability remained unaffected. Whereas isoflurane caused a significant decrease in liposomes anisotropy values, ketamine/xylazine did not show any effects. Brain uptake clearance (apparent K in ) of the passive permeability markers in vivo in mice approximately doubled under isoflurane or sevoflurane anesthesia, compared to either ketamine/xylazine anesthesia or the awake condition. In vivo exposure of mice to isoflurane did not change any of the brain tight junction proteins. Our data support membrane permeabilization rather than loosening of intercellular tight junctions as an underlying mechanism for increased permeability of the endothelial cell monolayers and the BBB in vivo. Significance Statement:The BBB controls the entry of endogenous substances and xenobiotics from the circulation into the central nervous system. Volatile anesthetic agents like isoflurane alter the lipid structure of cell membranes, transiently facilitating the brain uptake of otherwise poorly permeable, hydrophilic small molecules. Clinical implications may arise when potentially neurotoxic drugs gain enhanced access to the CNS under inhalational anesthetics.
Objective: To highlight association of coronary artery disease on angiograms and high altitude-related ECG abnormalities that is thought to be ischemic in origin. Place and Duration of Study: This was a cross sectional study done in Armed Force Institute of Cardiology/National Institute of Heart Disease from Oct 2016 to Oct 2021. Methodology: This was a cross sectional study done in AFIC/NIHD from Oct 2016–Oct 2021 (5years). A total of 103 patients at a range of 9000 to 22000 feet in altitude, with new ECG changes were selected via consecutive sampling. Data was analyzed by SPSS version-23. Descriptive statistics were run to present categorical data in frequencies and percentages. Chi-square and Fisher Exact Test was applied to find the association between study variables at 95% CI and 5% margin of error (α= 5%). Results: The data was collected from a total of 103 respondents, mean age (years) of the respondents was 30.57±6.27, and mean duration of stay (days) at high altitude was 64.8±68.3 (Table-I). ECG changes that were recorded were: T-wave inversion in anterior leads (V1, V2, V3) were reported in n=33(32%), T- wave inversion in Inferior leads (II, III, aVF) in 21(20.3%), T-wave inversion in lateral leads (V3-V6) 10(9.7%). Normal Ejection fraction was observed in 97% of the study participants while only 3% had mild left ventricular systolic impairment. Angiographic findings were found to be normal in n=92 (89.30%), minor coronary artery disease (CAD) in n=9 (8.70%), muscle bridge in LAD in n=2 (1.90%). Our results also showed that amongst other final diagnosis, of note were vasovagal syncope (n=5; 4.8%), pulmonary embolism (n=5; 4.8%) and pulmonary arterial hypertension (n=3; 2.9%). Conclusion: Our work leads us to the conclusion that ECG abnormalities at high altitude do not indicate coronary artery disease since they do not reflect a delay in electrical conduction or ischemia. These patients should be treated separately based on their high altitude disease symptoms (HAI).
Objective: To determine the prevalence of Echocardiographically-recognizable Mitral Annular Disjunction in patients of Myxomatous Mitral Valve Disease/Mitral Leaflet Prolapse. Study design: Analytical Cross sectional . Place & Duration of study: Armed Forces Institute of Cardiology/National Institute of Heart Disease (AFIC/NIHD),Rawalpindi Pakistan from Jul 2021 to Sep 2021. Methodology: A total (n=45) diagnosed patients of Myxomatous Mitral Valve disease, were included through non-probability consecutive sampling. Mitral Annular Disjunction (MAD) was assessed by 2D TTE imaging as the distance between the point of insertion of the posterior leaflet into the left atrial wall (upper boundary of the disjunction) and the link between the left atrium and the left ventricle myocardium (lower border of the disjunction)at end-systole in parasternal long axis view. A distance equal to or greater than 2mm was used as a threshold for diagnosing the presence of MAD. The data analysis was done with the help of computer software programme SPSS version 24. Results: Total number of patients were 45 patients with males being 32 (71.11%) while females being 13 (28.88%), with a mean age of 30.24 + 5.21 years. MAD was present in 26 (57.8%) of the patients with mean length of 2.88mm + 2.77 mm. Patients with MAD had more chest pain, palpitations and dyspnoea than those without MAD. Mitral regurgitation was more severe in patients with MAD than without. The MAD severity correlated with the presence of Non Sustained Ventricular Tachycardia. Conclusion: MAD is not an uncommon finding in patients having myxomatous mitral valve disease/mitral valve prolapse........
Objective: To assess the maternal and fetal outcome in pregnant patients with preexisting cardiac conditions and to determine the prevalence of different cardiac diseases among pregnant patients. Study Design: This was across sectional study. Place and Duration of Study: Tertiary Cardiac Care Center in Rawalpindi Pakistan, from Dec 2021 to Apr 2022. Methodology: This was across sectional study done in a tertiary cardiac care center in Rawalpindi. A total of (n=100) pregnant patients with pre-existing cardiac diseases were included in the study from Dec 2021 to Apr 2022 over a period of 5 months. Prospective data including patients' demographics and their outcomes was collected using preformed proformas. Data was analyzed by SPSS version-23. Prevalence of maternal death, fetal death, maternal complications and neonatal complications were the primary outcomes of study. Descriptive statistics were run to present categorical data in frequencies and percentages. Chi-square and Fisher Exact Test was applied to find the association between study variables at 95% CI and 5% margin of error (α=5%). Results: A total of (n=100) patients were included in our study which was conducted from Dec 2021 to Apr 2022. Maternal mortality was observed in 6% (n=6) of patients. Maternal outcomes of pulmonary edema were seen in 24% (n=24) of patients and post-partum hemorrhage was seen in 14% (n=14) patients. Three parameters of perinatal outcome were studied i.e., low birth weight, preterm delivery and death. 39% (n=39) neonates were found to have low birth weight, 22% (n=22) were preterm and perinatal mortality was 21% (n=21). The primary results of our study showed 6% (n=6) maternal mortality and 21% (n=21) perinatal mortality. Conclusion: Overall maternal mortality was 6% while perinatal mortality was 21%. There existed a statistically significant (p<0.05) association of age and neonatal outcome with maternal complications. With proper counseling, some of the avoidable maternal and perinatal deaths can be prevented.
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