Investigating the variability in pressure–volume relationships during hemorrhage and aortic occlusion

IntroductionThe pressure–volume (P-V) relationships of the left ventricle are the classical benchmark for studying cardiac mechanics and pumping function. Perturbations in the P-V relationship (or P-V loop) can be informative and guide the management of heart failure, hypovolemia, and aortic occlusion. Traditionally, P-V loop analyses have been limited to a single-beat P-V loop or an average of consecutive P-V loops (e.g., 10 cardiac cycles). While there are several algorithms to obtain single-beat estimations of the end-systolic and end-diastolic pressure–volume relations (i.e., ESPVR and EDPVR, respectively), there remains a need to better evaluate the variations in P-V relationships longitudinally over time. This is particularly important when studying acute and transient hemodynamic and cardiac events, such as active hemorrhage or aortic occlusion. In this study, we aim to investigate the variability in P-V relationships during hemorrhagic shock and aortic occlusion, by leveraging on a previously published porcine hemorrhage model.MethodsBriefly, swine were instrumented with a P-V catheter in the left ventricle of the heart and underwent a 25% total blood volume hemorrhage over 30 min, followed by either Zone 1 complete aortic occlusion (i.e., REBOA), Zone 1 endovascular variable aortic control (EVAC), or no occlusion as a control, for 45 min. Preload-independent metrics of cardiac performance were obtained at predetermined time points by performing inferior vena cava occlusion during a ventilatory pause. Continuous P-V loop data and other hemodynamic flow and pressure measurements were collected in real-time using a multi-channel data acquisition system.ResultsWe developed a custom algorithm to quantify the time-dependent variance in both load-dependent and independent cardiac parameters from each P-V loop. As expected, all pigs displayed a significant decrease in the end-systolic pressures and volumes (i.e., ESP, ESV) after hemorrhage. The variability in response to hemorrhage was consistent across all three groups. However, upon introduction of REBOA, we observed significantly high levels of variability in both load-dependent and independent cardiac metrics such as ESP, ESV, and the slope of ESPVR (Ees). For instance, pigs receiving REBOA experienced a 342% increase in ESP from hemorrhage, while pigs receiving EVAC experienced only a 188% increase. The level of variability within the EVAC group was consistently less than that of the REBOA group, which suggests that the EVAC group may be more supportive of maintaining healthier cardiac performance than complete occlusion with REBOA.DiscussionIn conclusion, we successfully developed a novel algorithm to reliably quantify the single-beat and longitudinal P-V relations during hemorrhage and aortic occlusion. As expected, hemorrhage resulted in smaller P-V loops, reflective of decreased preload and afterload conditions; however, the cardiac output and heart rate were preserved. The use of REBOA and EVAC for 44 min resulted in the restoration of baseline afterload and preload conditions, but often REBOA exceeded baseline pressure conditions to an alarming level. The level of variability in response to REBOA was significant and could be potentially associated to cardiac injury. By quantifying each P-V loop, we were able to capture the variability in all P-V loops, including those that were irregular in shape and believe that this can help us identify critical time points associated with declining cardiac performance during hemorrhage and REBOA use

Aquaporin 5 Polymorphisms and Rate of Lung Function Decline in Chronic Obstructive Pulmonary Disease

RATIONALE: Aquaporin-5 (AQP5) can cause mucus overproduction and lower lung function. Genetic variants in the AQP5 gene might be associated with rate of lung function decline in chronic obstructive pulmonary disease (COPD). METHODS: Five single nucleotide polymorphisms (SNPs) in AQP5 were genotyped in 429 European American individuals with COPD randomly selected from the NHLBI Lung Health Study. Mean annual decline in FEV(1) % predicted, assessed over five years, was calculated as a linear regression slope, adjusting for potential covariates and stratified by smoking status. Constructs containing the wildtype allele and risk allele of the coding SNP N228K were generated using site-directed mutagenesis, and transfected into HBE-16 (human bronchial epithelial cell line). AQP5 abundance and localization were assessed by immunoblots and confocal immunofluorescence under control, shear stress and cigarette smoke extract (CSE 10%) exposed conditions to test for differential expression or localization. RESULTS: Among continuous smokers, three of the five SNPs tested showed significant associations (0.02>P>0.004) with rate of lung function decline; no associations were observed among the group of intermittent or former smokers. Haplotype tests revealed multiple association signals (0.012>P>0.0008) consistent with the single-SNP results. In HBE16 cells, shear stress and CSE led to a decrease in AQP5 abundance in the wild-type, but not in the N228K AQP5 plasmid. CONCLUSIONS: Polymorphisms in AQP5 were associated with rate of lung function decline in continuous smokers with COPD. A missense mutation modulates AQP-5 expression in response to cigarette smoke extract and shear stress. These results suggest that AQP5 may be an important candidate gene for COPD

Evaluation of patient characteristics, management and outcomes for COVID-19 at district hospitals in the Western Cape, South Africa : descriptive observational study

CITATION: Mash, R. J. et al. 2021. Evaluation of patient characteristics, management and outcomes for COVID-19 at district hospitals in the Western Cape, South Africa : descriptive observational study. BMJ Open, 11:e047016, doi:10.1136/bmjopen-2020-047016.The original publication is available at https://bmjopen.bmj.comENGLISH ABSTRACT: Objectives To describe the characteristics, clinical management and outcomes of patients with COVID-19 at district hospitals. Design A descriptive observational cross-sectional study. Setting District hospitals (4 in metro and 4 in rural health services) in the Western Cape, South Africa. District hospitals were small (<150 beds) and led by family physicians. Participants All patients who presented to the hospitals’ emergency centre and who tested positive for COVID-19 between March and June 2020. Primary and secondary outcome measures Source of referral, presenting symptoms, demographics, comorbidities, clinical assessment and management, laboratory turnaround time, clinical outcomes, factors related to mortality, length of stay and location. Results 1376 patients (73.9% metro, 26.1% rural). Mean age 46.3 years (SD 16.3), 58.5% females. The majority were self-referred (71%) and had comorbidities (67%): hypertension (41%), type 2 diabetes (25%), HIV (14%) and overweight/obesity (19%). Assessment of COVID-19 was mild (49%), moderate (18%) and severe (24%). Test turnaround time (median 3.0 days (IQR 2.0–5.0 days)) was longer than length of stay (median 2.0 day (IQR 2.0–3.0)). The most common treatment was oxygen (41%) and only 0.8% were intubated and ventilated. Overall mortality was 11%. Most were discharged home (60%) and only 9% transferred to higher levels of care. Increasing age (OR 1.06 (95% CI 1.04 to 1.07)), male (OR 2.02 (95% CI 1.37 to 2.98)), overweight/obesity (OR 1.58 (95% CI 1.02 to 2.46)), type 2 diabetes (OR 1.84 (95% CI 1.24 to 2.73)), HIV (OR 3.41 (95% CI 2.06 to 5.65)), chronic kidney disease (OR 5.16 (95% CI 2.82 to 9.43)) were significantly linked with mortality (p<0.05). Pulmonary diseases (tuberculosis (TB), asthma, chronic obstructive pulmonary disease, post-TB structural lung disease) were not associated with increased mortality. Conclusion District hospitals supported primary care and shielded tertiary hospitals. Patients had high levels of comorbidities and similar clinical pictures to that reported elsewhere. Most patients were treated as people under investigation. Mortality was comparable to similar settings and risk factors identified.https://bmjopen.bmj.com/content/bmjopen/11/1/e047016.full.pdfPublisher's versio

Association of <i>AQP5</i> polymorphisms with lung function decline in continuous smokers and intermittent or former smokers.

<p>Association of <i>AQP5</i> polymorphisms with lung function decline in continuous smokers and intermittent or former smokers.</p

Eight hours of 10% CSE leads to a decrease in wild-type AQP5 but no change in N228K AQP5 (n = 3; * p<0.05 with ANOVA one-way).

<p>Eight hours of 10% CSE leads to a decrease in wild-type AQP5 but no change in N228K AQP5 (n = 3; * p<0.05 with ANOVA one-way).</p

Location, minor allele frequency, and type of selected <i>AQP5</i> SNPs.

<p>Location, minor allele frequency, and type of selected <i>AQP5</i> SNPs.</p

Linkage Disequilibrium for 5 SNPs in the <i>AQP5</i> Gene in European American participants with COPD.

<p>Pairwise LD in subjects is represented as red squares for strong LD, blue squares for non-significant LD, and white squares for little or no LD. LD blocks are identified as noted.</p

Haplotype Analysis.

<p>Using the sliding window approach of 2–4 SNPs/window beginning with the first (5′) marker, and working across the gene, one marker at a time, the results of significant (defined as <i>P</i><0.05) haplotype signals in continuous smokers are shown.</p