Pulmonary arterial pressure in fattened Angus steers at moderate altitude influences early postmortem mitochondria functionality and meat color during retail display

Pulmonary hypertension is a noninfectious disease of cattle at altitudes > 1524 m (5,000 ft). Mean pulmonary arterial pressures (PAP) are used as an indicator for pulmonary hypertension in cattle. High PAP cattle (≥ 50 mmHg) entering the feedlot at moderate elevations have lower feed efficiency as compared to low PAP cattle (< 50 mmHg). The impact of pulmonary arterial pressure on mitochondrial function, oxidative phosphorylation (OXPHOS) protein abundance, and meat color was examined using longissimus lumborum (LL) from high (98 ± 13 mmHg; n = 5) and low (41 ± 3 mmHg; n = 6) PAP fattened Angus steers (live weight of 588 ± 38 kg) during early postmortem period (2 h and 48 h) and retail display (day 1 to 9), respectively. High PAP muscle had greater (P = 0.013) OXPHOS-linked respiration and proton leak-associated respiration than low PAP muscles at 2 h postmortem but rapidly declined to be similar (P = 0.145) to low PAP muscle by 48 h postmortem. OXPHOS protein expression was higher (P = 0.045) in low PAP than high PAP muscle. During retail display, redness, chroma, hue, ratio of reflectance at 630 nm and 580 nm, and metmyoglobin reducing activity decreased faster (P < 0.05) in high PAP steaks than low PAP. Lipid oxidation significantly increased (P < 0.05) in high PAP steaks but not (P > 0.05) in low PAP. The results indicated that high PAP caused a lower OXPHOS efficiency and a greater fuel oxidation rates under conditions of low ATP demand in premortem beef LL muscle, this could explain the lower feed efficiency in high PAP feedlot cattle compared to low PAP counterparts. Mitochondrial integral function (membrane integrity or/and protein function) declined faster in high PAP than low PAP muscle at early postmortem. LL steaks from high PAP animals had lower color stability than those from the low PAP animals during simulated retail display, which could be partially attributed to the loss of muscle mitochondrial function at early postmortem by ROS damage in high PAP muscle. Pulmonary arterial hypertension could also decrease type I/type II muscle fiber ratio in skeletal muscle, which needs to be investigated further.

New Insights into Pulmonary Hypertension: A Role for Connexin-Mediated Signalling

Pulmonary hypertension is a serious clinical condition characterised by increased pulmonary arterial pressure. This can lead to right ventricular failure which can be fatal. Connexins are gap junction-forming membrane proteins which serve to exchange small molecules of less than 1 kD between cells. Connexins can also form hemi-channels connecting the intracellular and extracellular environments. Hemi-channels can mediate adenosine triphosphate release and are involved in autocrine and paracrine signalling. Recently, our group and others have identified evidence that connexin-mediated signalling may be involved in the pathogenesis of pulmonary hypertension. In this review, we discuss the evidence that dysregulated connexin-mediated signalling is associated with pulmonary hypertension.

A more gradual positive end-expiratory pressure increase reduces lung damage and improves cardiac function in experimental acute respiratory distress syndrome

Increases in positive end-expiratory pressure (PEEP) or recruitment maneuvers may increase stress in lung parenchyma, extracellular matrix, and lung vessels; however, adaptative responses may occur. We evaluated the effects of PEEP on lung damage and cardiac function when increased abruptly, gradually, or more gradually in experimental mild/moderate acute respiratory distress syndrome (ARDS) induced by Escherichia coli lipopolysaccharide intratracheally. After 24h, Wistar rats (n=48) were randomly assigned to four mechanical ventilation strategies according to PEEP levels: (1) 3 cmH2O for 2-h (control); (2) 3 cmH2O for 1-h followed by an abrupt increase to 9 cmH2O for 1-h (no adaptation time); (3) 3 cmH2O for 30 min followed by a gradual increase to 9 cmH2O over 30 min then kept constant for 1-h (shorter adaptation time); and (4) more gradual increase in PEEP from 3 cmH2O to 9 cmH2O over 1-h and kept constant thereafter (longer adaptation time). At the end of the experiment, oxygenation improved in the shorter and longer adaptation time groups compared to the no-adaptation and control groups. Diffuse alveolar damage and expressions of interleukin-6, club cell protein-16, vascular cell adhesion molecule-1, amphiregulin, decorin, and syndecan were higher in no adaptation time compared to other groups. Pulmonary arterial pressure was lower in longer adaptation time than in no adaptation (p=0.002) and shorter adaptation time (p=0.025) groups. In this model, gradually increasing PEEP limited lung damage and release of biomarkers associated with lung epithelial/endothelial cell and extracellular matrix damage, as well as the PEEP-associated increase in pulmonary arterial pressure.

Pulmonary Hypertension and COVID-19

Coronavirus disease 2019 (COVID-19) is a primary respiratory infectious disease, which can result in pulmonary and cardiovascular complications. From its first appearance in the city of Wuhan (China), the infection spread worldwide, leading to its declaration as a pandemic on March 11, 2020. Clinical research on SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) suggests that the virus may determine changes in the pulmonary hemodynamics through mechanisms of endothelial dysfunction, vascular leak, thrombotic microangiopathy, and venous thromboembolism that are similar to those leading to pulmonary hypertension (PH). Current available studies report echocardiographic signs of PH in approximately 12 to 13% of hospitalized patients with COVID-19. Those with chronic pulmonary obstructive disease, congestive heart failure, pulmonary embolism, and prior PH are at increased risk to develop or worsen PH. Evidence of PH seems to be associated with increased disease severity and poor outcome. Because of the importance of the pulmonary hemodynamics in the pathophysiology of COVID-19, there is growing interest in exploring the potential therapeutical benefits of inhaled vasodilators in patients with COVID-19. Treatment with inhaled nitric oxide and prostacyclin has shown encouraging results through improvement of systemic oxygenation, reduction of systolic pulmonary arterial pressure, and prevention of right ventricular failure; however, data from randomized control trials are still required.

Long-Term Outcomes in Adult Patients With Pulmonary Hypertension After Percutaneous Closure of Atrial Septal Defects

Background: Pulmonary hypertension (PH), recently redefined as mean pulmonary arterial pressure >20 mm Hg (PH 20 ), may be observed in patients with atrial septal defects (ASD). We aimed to determine the effect of preprocedural PH 20 status on outcomes among patients undergoing ASD closure. Methods: Study population was selected from a retrospective registry of adult patients who underwent percutaneous ASD closure from 1998 to 2016 from a single center and had right heart catheterizations during the procedure. The clinical registry was linked to administrative databases to capture short- and long-term outcomes. Results: We included a total of 632 ASD closure patients of whom 359 (56.8%) had PH 20 . The mean follow-up length was 7.6±4.6 years. Patients with PH 20 were older (mean age 56.5 versus 43.1 years, P <0.001) and a higher prevalence of comorbidities including hypertension (54.3% versus 21.6%, P <0.001) and diabetes (18.1% versus 5.9%, P <0.001) than those without PH. In a Cox proportional hazards model after covariate adjustment, patients with PH had a significantly higher risk of developing major adverse cardiac and cerebrovascular events (heart failure, stroke, myocardial infarction, or cardiovascular mortality), with hazards ratio 2.45 (95% CI, 1.4–4.4). When applying the prior, mean pulmonary arterial pressure ≥25 mm Hg (PH 25 ) cutoff, a significantly higher hazard of developing major adverse cardiac and cerebrovascular events was observed in PH versus non-PH patients. Conclusions: ASD patients with PH undergoing closure suffer from more comorbidities and worse long-term major adverse cardiac and cerebrovascular events outcomes, compared with patients without PH. The use of the new PH 20 definition potentially dilutes the effect of this serious condition on outcomes in this population.

Long-Term Follow-Up of Pediatric Patients with Severe Postoperative Pulmonary Hypertension After Correction of Congenital Heart Defects

The surgical repair of congenital heart defects in children with preoperative pulmonary hypertension (PH) is to varying degree associated with the occurrence of postoperative PH. The objective of this study was to follow up children with severe postoperative PH (pulmonary arterial/aortic pressure ratio ≥ 1.0) to evaluate if pulmonary arterial pressure spontaneously normalized or needed PH-targeting therapy and to identify potential high-risk diagnoses for bad outcome. Twenty-five children who developed clinically significant severe PH on at least three occasions postoperatively were included in the follow-up (20–24 years). Data from chart reviews, echocardiographic investigations, and questionnaires were obtained. Three children died within the first year after surgery. Three children were lost to follow-up. The remaining 17 children normalized their pulmonary arterial pressure without the use of PH-targeting drugs at any time during the follow-up. Two children had a remaining mild PH with moderate mitral valve insufficiency. All three children with bad outcome had combined cardiac lesions causing post-capillary pulmonary hypertension. Normalization of the pulmonary arterial pressure occurred in almost all children with severe postoperative PH, without any need of supplemental PH-targeting therapies. All children with bad outcome had diagnoses conformable with post-capillary PH making the use of PH-targeting therapies relatively contraindicated. These data emphasize the need to perform randomized, blinded trials on the use of PH-targeting drugs in children with postoperative PH before accepting it as an indication for routine treatment.