Differential effects of atrial and brain natriuretic peptides on human pulmonary artery: An in vitro study.

BACKGROUND: The prevalence of cardiovascular diseases, especially heart failure, continues to rise worldwide. In heart failure, increasing levels of circulating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are associated with a worsening of heart failure and a poor prognosis. AIM: To test whether a high concentration of BNP would inhibit relaxation to ANP. METHODS: Pulmonary arteries were dissected from disease-free areas of lung resection, as well as pulmonary artery rings of internal diameter 2.5-3.5 mm and 2 mm long, were prepared. Pulmonary artery rings were mounted in a multiwire myograph, and a basal tension of 1.61gf was applied. After equilibration for 60 min, rings were pre-constricted with 11.21 µmol/L PGF2α (EC80), and concentration response curves were constructed to vasodilators by cumulative addition to the myograph chambers. RESULTS: Although both ANP and BNP were found to vasodilate the pulmonary vessels, ANP is more potent than BNP. pEC50 of ANP and BNP were 8.96 ± 0.21 and 7.54 ± 0.18, respectively, and the maximum efficacy (Emax) for ANP and BNP was -2.03 gf and -0.24 gf, respectively. After addition of BNP, the Emax of ANP reduced from -0.96gf to -0.675gf (P = 0.28). CONCLUSION: BNP could be acting as a partial agonist in small human pulmonary arteries, and inhibits relaxation to ANP. Elevated levels of circulating BNP could be responsible for the worsening of decompensated heart failure. This finding could also explain the disappointing results seen in clinical trials of ANP and BNP analogues for the treatment of heart failure.

Changing clinical profiles and in-hospital outcomes of octogenarians undergoing cardiac surgery over 18 years: a single-centre experience†.

OBJECTIVES: With an ageing population, increasing numbers of octogenarians are undergoing high-risk cardiac surgery. We examine the changing characteristics and in-hospital outcomes for octogenarians over an 18-year period. METHODS: Clinical data from our prospective database for all octogenarians who had cardiac surgery from March 1999 through May 2016 were reviewed. We examined trends, risk profiles and in-hospital outcomes over 3 eras, namely early (1999-2004), middle (2005-2010) and late (2011-2016). A multivariable analysis was performed to identify independent predictors for adverse outcomes. RESULTS: There were 1022 patients aged 80-94 years in our study cohort. The octogenarian population increased progressively from early to late eras (4.5%, n = 255 vs 7.1%, n = 321 vs 9.3%, n = 446), as the average logistic EuroSCORE predicted mortality (9% vs 9.7% vs 10.1%, P < 0.01). On the contrary, observed mortality declined substantially (9.4% vs 7.8% vs 4.7%, P = 0.04) over this period. While cardiac morbidity and respiratory comorbidities were more prevalent in the late era, chronic renal failure was more frequent in the early era. Over time, more procedures were performed electively (P = 0.05). Common operations across all eras were coronary artery bypass grafting (CABG), aortic valve replacement and CABG + aortic valve replacement. Emergency operation [odds ratio (OR) 4.96, 95% confidence interval (CI) 1.51-16.35; P < 0.01], poor ejection fraction (OR 3.38, 95% CI 1.80-6.32; P < 0.01) and bypass time (OR 1.01, 95% CI 1.00-1.02; P < 0.01) were predictors of in-hospital mortality. The late era of surgery (OR 0.41, 95% CI 0.23-0.73; P < 0.01) was associated with reduced mortality risk. CONCLUSIONS: The operative outcome in this growing surgical population is steadily improving despite the increasing prevalence of comorbidities, and surgery should be performed electively as much as possible.

Mini-extracorporeal circulation technology, conventional bypass and prime displacement in isolated coronary and aortic valve surgery: a propensity-matched in-hospital and survival analysis.

OBJECTIVES: Conventional cardiopulmonary bypass is the most commonly used means of artificial circulation in cardiac surgery. However, it suffers from the effects of haemodilution and activation of inflammatory/coagulation cascades. Prime displacement (PD) can offset haemodilution and mini-extracorporeal technology (MIECT) can offset both. So far, no study has compared all of these modalities together; hence, we compared the outcomes of these 3 modalities at our institution. METHODS: This was a retrospective analysis of our cardiac surgical database. A total of 9626 patients underwent conventional bypass (CB), 3125 patients underwent a modification of CB, called PD, and 904 underwent MIECT. A 1:1 propensity-matching algorithm was employed using IBM SPSS 24 to match (i) 813 MIECT patients with 813 CB patients and (ii) 717 MIECT patients with 717 PD patients. The patients included coronary artery bypass grafting and valve surgery. RESULTS: MIECT had significantly (P < 0.05) longer bypass and cross-clamp times compared to CB and PD. MIECT had significantly higher rates of postoperative atrial fibrillation associated with it compared to CB. The mean red cell blood transfusion was significantly lower in the MIECT group compared to the CB group as was the mean platelet transfusion and fresh frozen plasma transfusion. The overall 5-year survival was higher in the MIECT group compared to the CB group (log-rank, P = 0.018). Between the MIECT and the PD groups, we found the incidence of renal failure and gastrointestinal complications to be significantly higher in the PD group compared to the MIECT group. CONCLUSIONS: MIECT has short-term advantages over CB and PD. However, due to the retrospective limitations of the study, including calendar time bias, a multicentre randomized controlled trial comparing all 3 modalities will be beneficial for the larger cardiac community.

Characterization of optimal resting tension in human pulmonary arteries.

AIM: To determine the optimum resting tension (ORT) for in vitro human pulmonary artery (PA) ring preparations. METHODS: Pulmonary arteries were dissected from disease free sections of the resected lung in the operating theatre and tissue samples were directly sent to the laboratory in Krebs-Henseleit solution (Krebs). The pulmonary arteries were then cut into 2 mm long rings. PA rings were mounted in 25 mL organ baths or 8 mL myograph chambers containing Krebs compound (37 °C, bubbled with 21% O2: 5% CO2) to measure changes in isometric tension. The resting tension was set at 1-gram force (gf) with vessels being left static to equilibrate for duration of one hour. Baseline contractile reactions to 40 mmol/L KCl were obtained from a resting tension of 1 gf. Contractile reactions to 40 mmol/L KCl were then obtained from stepwise increases in resting tension (1.2, 1.4, 1.6, 1.8 and 2.0 gf). RESULTS: Twenty PA rings of internal diameter between 2-4 mm were prepared from 4 patients. In human PA rings incrementing the tension during rest stance by 0.6 gf, up to 1.6 gf significantly augmented the 40 mmol/L KCl stimulated tension. Further enhancement of active tension by 0.4 gf, up to 2.0 gf mitigate the 40 mmol/L KCl stimulated reaction. Both Myograph and the organ bath demonstrated identical conclusions, supporting that the radial optimal resting tension for human PA ring was 1.61 g. CONCLUSION: The radial optimal resting tension in our experiment is 1.61 gf (15.78 mN) for human PA rings.

Short- and long-term outcomes of pneumonectomy in a tertiary center.

BACKGROUND: Surgery is the most important therapeutic modality for lung cancer. Surgical outcomes are normally reported as 30-day or 90-day mortality or 5-year survival; 10-year survival is rarely mentioned in national data or international studies. METHODS: Three hundred and six patients (79% male) underwent pneumonectomy, mainly for lung cancer, from January 1998 to February 2013. Their short- and long-term outcomes up to September 2014 were analyzed retrospectively. The mean age was 64 years (range 22-82 years) and 24% were aged ≥70 years. Thoracoscore was used to calculate the risk of hospital mortality. RESULTS: Operative mortality was 4.5% whereas predicted mortality was 8%. The operative mortality for cancer patients was 3.3%; the national mortality for lung cancer is 6.5%. Only 2 patients died in hospital after a pneumonectomy in the last 5 years. Half of the patients who died in hospital were ≥70 years old; 29% (4 patients) died after urgent operations for nonmalignant disease. Overall 5- and 10-year survival was 32% and 20%. Median and mean survival was 26 and 57 months, respectively. Long-term survival was better in females aged <70 years, in left pneumonectomy patients, and in those with squamous cell lung cancer. CONCLUSION: Our mortality for pneumonectomy was 50% less than the national mortality rate and significantly lower than that predicted by the Thoracoscore for lung cancer. This confirms that pneumonectomy is still an effective modality for the treatment of lung cancer, with low operative mortality and good long-term survival, especially in younger patients.

WITHDRAWN: Is there life after the Mesothelioma and Radical Surgery trial? Does extrapleural pneumonectomy still have a role in the management of pleural mesothelioma? A 13-year, single-center experience.

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Could Thoracoscore predict postoperative mortality in patients undergoing pneumonectomy?

OBJECTIVES: Thoracoscore is incorporated in the new British Thoracic Society and National Institute of Health and clinical Excellence guidelines to evaluate the operative mortality risk of patients undergoing thoracic surgery. This study examines the accuracy of Thoracoscore in predicting postoperative mortality in patients undergoing pneumonectomy. METHODS: All patients who underwent pneumonectomy from January 1998 to March 2008 were included. Thoracoscore was calculated based on the following variables: age, sex, American Society of Anaesthesiologists' class, performance status classification, dyspnoea score, priority of surgery, procedure class, Diagnosis group and comorbidities score. RESULTS: Two hundred and forty-three patients with a mean age of 63 ± 9 years were included and 81% were male. The predicted postoperative mortality based on Thoracoscore was 8 ± 2.6% (95% confidence interval (CI) 4.56-11.43), while actual in-hospital mortality was 4.5% (11/243) (95% CI 1.87-7.12). 54% (6/11) of in-hospital mortality was of those who were >70 years old and 73% (8/11) of patients who died in hospital were male. Nine of 11 (82%) patients had pneumonectomy for malignancy. Thoracoscore was divided into four risk groups: low (0-3), moderate (3.1-5), high (5.1-8) and very high (>8). It underestimated mortality in low-risk group while overestimated in high-risk groups. The 30-day, 1-year, 2-year and 3-year observed mortalities were 5.3, 29, 43 and 55%, respectively. CONCLUSIONS: Although advanced age, the male sex and malignancy proved to be strong predictors of in-hospital mortality in our study, Thoracoscore failed to predict accurate risk of in-hospital mortality in pneumonectomy patients in this study. Further studies are required to validate the Thoracoscore in different subgroups of thoracic surgery.

Antegrade rapid prime displacement in elective coronary artery surgery is associated with lower perioperative blood transfusions and a shorter hospital stay.

OBJECTIVES: Haemodilution during cardiopulmonary bypass is associated with increased perioperative blood transfusions and is thought to reduce intraoperative oxygen delivery to the brain. We sought to evaluate our method of rapid antegrade prime displacement in the context of the perioperative blood transfusion rate, intraoperative cerebral saturations and postoperative hospital stay. METHODS: Retrospective analysis of 160 propensity-matched patients undergoing elective coronary artery bypass grafting was performed comparing different perfusion strategies on perioperative blood transfusion and length of postoperative stay. Eighty patients who had rapid antegrade prime displacement and vacuum-assisted venous drainage (RAD-VAD) were compared with 80 patients who had conventional cardiopulmonary bypass with gravity drainage (CB). RAD-VAD involved displacing all or most of the prime in the circuit with the patient's own blood prior to the initiation of cardiopulmonary bypass within a 15-20 s window. Within each group, 10 patients had intraoperative cerebral saturation measurements. RESULTS: There were no differences in the baseline characteristics between the groups. Both groups had a significant fall (P < 0.05) in haematocrit during cardiopulmonary bypass from preoperative values, however, the fall in haematocrit was significantly less in the RAD-VAD group (P < 0.05). There was significantly (P < 0.05) less intraoperative and postoperative homologous blood transfusions in the RAD-VAD group (47.892 ml ± 8.14 and 76.58 ml ± 21.58) compared with the CB group (229.06 ml ± 105.03 and 199.91 ml ± 47.13). There was a significant fall in cerebral saturations within both groups (P < 0.05) but it was not significant between the groups. The postoperative stay was significantly (P < 0.05) shorter in the RAD-VAD group compared with the conventional group (7.74 days ± 0.51 vs 10.13 days ± 0.95). CONCLUSIONS: RAD-VAD is associated with a significantly lower blood transfusion rate perioperatively and shorter hospital stays compared with CB.

Hyperoxic vasoconstriction of human pulmonary arteries: a novel insight into acute ventricular septal defects.

Objectives. Acute rises in pulmonary artery pressures following postinfarction ventricular septal defects present a challenge. We hypothesised that the abnormally high oxygen content exposure to the pulmonary arteries may be a factor. We investigated the contractile responses of human pulmonary arteries to changes in oxygen tension. Methods. Isometric tension was measured in large and medium sized pulmonary artery rings obtained from lung resections for patients with bronchial carcinoma (n = 30). Fresh rings were mounted in organ baths bubbled under basal conditions with hyperoxic or normoxic gas mixes and the gas tensions varied during the experiment. We studied whether voltage-gated calcium channels and nitric oxide signalling had any role in responses to oxygen changes. Results. Hypoxia caused a net mean relaxation of 18.1% ± 15.5 (P < 0.005) from hyperoxia. Subsequent hyperoxia caused a contraction of 19.2% ± 13.5 (P < 0.005). Arteries maintained in normoxia responded to hyperoxia with a mean constriction of 14.8% ± 3.9 (P < 0.005). Nifedipine inhibited the vasoconstrictive response (P < 0.05) whilst L-NAME had no effect on any hypoxic vasodilatory response. Conclusions. We demonstrate that hyperoxia leads to vasoconstriction in human pulmonary arteries. The mechanism appears to be dependent on voltage-gated calcium channels. Hyperoxic vasoconstriction may contribute to acute rises in pulmonary artery pressures.

Erythrocyte-containing versus crystalloid cardioplegia in the rat: effects on myocardial capillaries.

BACKGROUND: The purpose of this study was to investigate the effects of crystalloid and erythrocyte-containing cardioplegia on capillary morphology of the isolated erythrocyte-perfused rat heart. METHODS: Hearts from adult Sprague-Dawley rats were perfused throughout with resuspended sheep erythrocytes and subjected to the following protocols (n = 6, all groups): (1) 15 minutes nonworking and 30 minutes working heart mode (control; group 1); (2) as for group 1, with 30 minutes erythrocyte-containing (BL) or crystalloid (CR) cardioplegic arrest without reperfusion (groups 2BL and 2CR); (3) as for group 2, with 30 minutes nonworking reperfusion (groups 3BL and 3CR); and (4) as for group 3, with 30 minutes working heart mode (groups 4BL and 4CR). After each protocol troponin I from coronary effluent was measured. Corrosion casts were then made of the coronary microvasculature. Cast density was calculated as cast volume per left ventricular dry weight. Casts also underwent scanning electron microscopy. Analysis was by analysis of variance. Values are mean +/- standard deviation. RESULTS: Prearrest working heart coronary flow averaged 15.1 +/- 4.7 mL/min without any differences among groups. Coronary flow in group 4 working hearts was the same before and after either cardioplegia. Cardiac outputs were similarly consistent in all groups. Cast density in group 1 (control) was 9.60 +/- 1.17 x 10(-2) mm3/mg. It was unaltered by erythrocyte-containing cardioplegia, but after crystalloid cardioplegia (group 2CR), it was 6.52 +/- 0.93 x 10(-2) mm3/mg (p = 0.0001 versus group 1 and p = 0.0007 versus group 2BL). With 30 minutes of nonworking reperfusion (group 3CR, there was slight improvement in cast density at 7.60 +/- 0.90 x 10(-2) mm3/mg (p = 0.0072 versus group 1; p = 0.0242 versus group 3BL). No further improvement was seen in group 4CR. Electron micrographs showed circumferential angularities or narrowings in crystalloid-perfused, arrested hearts, consistent with ischemic damage. Troponin I rose significantly after reperfusion in all groups, but it was higher in crystalloid-perfused, arrested hearts: 0.054 +/- 0.013 microg/L versus 0.024 +/- 0.017 microg/L (p = 0.0273). CONCLUSIONS: Erythrocyte-containing cardioplegia maintained capillary density and morphology. Crystalloid cardioplegia produced capillary loss, visible abnormalities, and higher troponin I release. These hearts may be more vulnerable to myocardial damage during reperfusion than hearts perfused with erythrocyte-containing cardioplegic solution.

Lipolysis generates platelet dysfunction after in vivo heparin administration.

Heparin, when administered to patients undergoing operations using cardiopulmonary bypass, induces plasma changes that gradually impair platelet macroaggregation, but heparinization of whole blood in vitro does not have this effect. The plasma changes induced by heparin in vivo continue to progress in whole blood ex vivo. Heparin releases several endothelial proteins, including lipoprotein lipase, hepatic lipase, platelet factor-4 and superoxide dismutase. These enzymes, which remain active in plasma ex vivo, may impair platelet macroaggregation after in vivo heparinization and during cardiopulmonary bypass. In the present study, proteins were added in vitro to hirudin (200 units.ml(-1))-anticoagulated blood from healthy volunteers, and the platelet macroaggregatory responses to ex vivo stimulation with collagen (0.6 microg.ml(-1)) were assessed by whole-blood impedance aggregometry. Over a 4 h period, human lipoprotein lipase and human hepatic lipase reduced the platelet macroaggregatory response from 17.0+/-2.3 to 1.5+/-1.3 and 1.2+/-0.6 Omega respectively (means+/-S.D.) (both P <0.01; n =6). Other lipoprotein lipases also impaired platelet macroaggregation, but platelet factor-4 and superoxide dismutase did not. Platelet macroaggregation showed an inverse linear correlation with plasma concentrations of non-esterified fatty acids ( r (2)=0.69; two-sided P <0.0001; n =8), suggesting that heparin-induced lipolysis inhibits platelet macroaggregation. Lipoprotein degradation products may cause this inhibition by interfering with eicosanoids and other lipid mediators of metabolism.