Effects of calcium in continuous cardioplegia on myocardial protection

The effects of calcium (Ca) on a hyperkalemic cardioplegic solution for continuous cardioplegia were examined in an isolated perfused working rat heart model. The coronary arteries were perfused with a modified Krebs-Henseleit bicarbonate buffer (K-H) solution, containing various concentrations of Ca(0.1, 0.6, 1.2, and 2.5 mmol/l) and a high concentration of potassium (20 mmol/l), for 180 min, after which cardiac arrest was induced at 37°C for 180 min. Cardiac function and creatine kinase (CK) were measured. In the control group, K-H solution was infused in place of the cardioplegic solution, and cardiac arrest was not induced. No significant differences were observed between the groups infused with the K-H solution containing Ca concentrations of 0.6, 1.2, and 2.5 mmol/l in the percent recovery of aortic flow (82.1±2.9%, 80.6±2.0%, and 71.5±3.7% (mean±SEM) respectively) or in the recovery of other indices of cardiac function, or in CK leakage. There were also no significant differences in the recovery of cardiac function and CK leakage between these groups and the control group. In the Ca 0.1 mmol/l group, however, the characteristic Ca paradox was observed. These findings suggest that if the Ca concentration in a cardioplegic solution is higher than 0.6 mmol/l during continuous cardioplegia, excellent cardioprotective effects will be achieved.     

Power and peak blood lactate at 5050 m with 10 and 30 s ‘all out’ cycling

Anecdotal observations suggest that the reduction in peak lactate accumulation in blood ([La]_{b peak}) after exhausting exercise, in chronic hypoxia vs. normoxia, may be related to the duration of the exercise protocol, being less pronounced after short supramaximal exercise than after incremental exercise (IE) lasting several minutes. To test this hypothesis, six healthy male Caucasians (age 36.8 ± 7.3, x¯ ± SD) underwent three exercise protocols on a cycle ergometer, at sea level (SL) and after 21 ± 10 days at 5050 m altitude (ALT): (1) 10 s, (2) 30 s ‘all out’ exercise and (3) IE leading to exhaustion in ～20–25 min. ‘Average’ power output (p¯) was calculated for 10 or 30 s ‘all out’; maximal power output (P_max) was determined for IE. Lactate concentration in arterialized capillary blood ([La]_b) was measured at rest and at different times during recovery; the highest [La]_b during recovery was taken as [La]_{b peak}. No significant differences in p¯ were observed between SL and ALT, for either 10 or 30 s ‘all out’ exercise; P_max during IE was significantly lower at ALT than at SL. [La]_{b peak} after 10 s ‘all out’ was unaffected by chronic hypoxia (7.0 ± 0.9 at ALT vs. 6.3 ± 1.8 mmol L^–1 at SL). After 30 s ‘all out’ the [La]_{b peak} decrease, at ALT (10.6 ± 0.6 mmol L^–1) vs. SL (12.9 ± 1.4 mmol L^–1), was only ～50% of that observed for IE (6.7 ± 1.6 mmol L^–1 vs. 11.3 ± 2.8 mmol L^–1). Muscle power output and blood lactate accumulation during short supramaximal exercise are substantially unaffected by chronic hypoxia.     

Energy deficiency,calcium overload or oxidative stress: Possible causes of irreversible ischemic myocardial injury

Summary After prolonged ischemia or hypoxia myocardial injury is not reversed but exacerbated by a resupply of the tissue with oxygen and substrates. The mechanism by which reversible ischemic or hypoxic myocardial injury becomes irreversible is not yet understood. It has been debated whether reperfusion injury merely uncovers pre-existing irreversible injury, or is indeed caused by the reperfusion/reoxygenation process. In recent years, three theories have been discussed that relate the onset of irreversibility either to: a critical energy loss; a critical accumulation of cellular calcium; or to the deleterious effects of free radical formation. In certain experimental models for each of these theories favourable results have been obtained. Current research suggests that absolute reversibility thresholds in energy depletion or calcium accumulation in the ischemic or hypoxic cell do not exist. A key role of free radical injury for reperfusion injury must also be questioned. There is, however, evidence that in tissue reversibility of ischemic cardiomyocyte injury is limited by conditions that make calcium-induced hypercontracture upon reoxygenation unavoidable. This occurs when, by hypercontracture, mutual mechanical disruption of the cells destroys the tissue. From isolated cardiomyocytes that are able to metabolically survive hypercontracture it has been observed that these metabolic conditions do not represent the last biological possibility to reverse injury.     

Changes in cyclic nucleotides during the calcium paradox in the isolated rat heart

Reperfusion of hearts with a Ca²⁺-containing medium after a perfusion period in Ca²⁺-free medium results in irreversible cell damage (calcium paradox). In this investigation we have studied coronary flow and cyclic AMP and cyclic GMP levels after several periods of Ca²⁺-free perfusion in isolated rat hearts. We also investigated the effects of papaverine (Pap), noradrenaline (NA), acetylcholine (ACh) and absence of inorganic phosphate during Ca²⁺-free perfusion on coronary flow (CF) and cyclic nucleotide levels. Inability of the heart to recover contractile activity with development of contracture during the reperfusion period was accepted as indicative of the calcium paradox. Ca²⁺-free perfusion alone and NA and absence of inorganic phosphate during the Ca²⁺-free perfusion period increased CF, whereas Pap and ACh decreased it. However, only Ca²⁺-free perfusion and NA elevated cyclic AMP. On the other hand, Pap and ACh increased cyclic GMP (with a transient rise of cyclic AMP in Pap infusion), and absence of inorganic phosphate decreased both cyclic AMP and cyclic GMP. Pap, ACh and absence of phosphate prevented the calcium paradox. Our study suggests that increased cyclic AMP during the Ca²⁺-free perfusion may contribute, with the other factors, to the occurrence of the calcium paradox.     

Does there exist an obesity paradox in COVID-19? Insights of the international HOPE-COVID-19-registry

BackgroundObesity has been described as a protective factor in cardiovascular and other diseases being expressed as ‘obesity paradox’. However, the impact of obesity on clinical outcomes including mortality in COVID-19 has been poorly systematically investigated until now. We aimed to compare clinical outcomes among COVID-19 patients divided into three groups according to the body mass index (BMI).MethodsWe retrospectively collected data up to May 31^st, 2020. 3635 patients were divided into three groups of BMI (<25 kg/m²; n = 1110, 25?30 kg/m²; n = 1464, and >30 kg/m²; n = 1061). Demographic, in-hospital complications, and predictors for mortality, respiratory insufficiency, and sepsis were analyzed.ResultsThe rate of respiratory insufficiency was more recorded in BMI 25?30 kg/m² as compared to BMI < 25 kg/m² (22.8% vs. 41.8%; p < 0.001), and in BMI > 30 kg/m² than BMI < 25 kg/m², respectively (22.8% vs. 35.4%; p < 0.001). Sepsis was more observed in BMI 25?30 kg/m² and BMI > 30 kg/m² as compared to BMI < 25 kg/m², respectively (25.1% vs. 42.5%; p = 0.02) and (25.1% vs. 32.5%; p = 0.006). The mortality rate was higher in BMI 25?30 kg/m² and BMI > 30 kg/m² as compared to BMI < 25 kg/m², respectively (27.2% vs. 39.2%; p = 0.31) (27.2% vs. 33.5%; p = 0.004). In the Cox multivariate analysis for mortality, BMI < 25 kg/m² and BMI > 30 kg/m² did not impact the mortality rate (HR 1.15, 95% CI: 0.889?1.508; p = 0.27) (HR 1.15, 95% CI: 0.893?1.479; p = 0.27). In multivariate logistic regression analyses for respiratory insufficiency and sepsis, BMI < 25 kg/m² is determined as an independent predictor for reduction of respiratory insufficiency (OR 0.73, 95% CI: 0.538?1.004; p = 0.05).ConclusionsHOPE COVID-19-Registry revealed no evidence of obesity paradox in patients with COVID-19. However, Obesity was associated with a higher rate of respiratory insufficiency and sepsis but was not determined as an independent predictor for a high mortality.     

The Association between Nutritional Status and In-Hospital Mortality among Patients with Heart Failure—A Result of the Retrospective Nutritional Status Heart Study 2 (NSHS2)

Background: A nutritional status is related to the prognosis and length of hospitalisation of patients with heart failure (HF). This study aims to assess the effect of nutritional status on in-hospital mortality in patients with heart failure. Methods: We conducted a retrospective study and analysis of medical records of 1056 patients admitted to the cardiology department of the University Clinical Hospital in Wroclaw (Poland). Results: A total of 1056 individuals were included in the analysis. A total of 5.5% of patients died during an in-hospital stay. It was found that in the sample group, 25% of patients who died had a BMI (body mass index) within the normal range, 6% were underweight, 47% were overweight, and 22% were obese. Our results show that non-survivors have a significantly higher nutrition risk screening (NRS) ≥3 (21% vs. 3%; p < 0.001); NYHA (New York Heart Association) grade 4 (70% vs. 24%; p < 0.001). The risk of death was lower in obese patients (HR = 0.51; p = 0.028) and those with LDL (low-density lipoprotein) levels from 116 to <190 mg/dL (HR = 0.10; p = 0.009, compared to those with LDL <55 mg/dL). The risk of death was higher in those with NRS (nutritional risk score) score ≥3 (HR = 2.31; p = 0.014), HFmrEF fraction (HR = 4.69; p < 0.001), and LDL levels > 190 mg/dL (HR = 3.20; p = 0.038). Conclusion: The malnutrition status correlates with an increased risk of death during hospitalisation. Higher TC (total cholesterol) level were related to a lower risk of death, which may indicate the “lipid paradox”. Higher BMI results were related to a lower risk of death, which may indicate the “obesity paradox”.     

腺苷脱氨酶抑制剂对氧反常大鼠心脏的保护作用

本文观察到腺苷脱氨酶抑制剂EHNA对离体灌流大鼠心脏氧反常性损伤有明显的作用,此外还发现在缺氧期(无氧灌流30分钟)EHNA也表现出明显的保护作用,心脏收缩幅度的降低和静息张力的升高均显著低于对照组。表明在缺氧期也可能有自由基的产生。     

Birth Outcomes of Immigrant Women in the United States,France, and Belgium

Objectives: To compare maternal characteristics and birth outcomes of Mexico-born and native-born mothers in the United States and those of North African mothers living in France and Belgium to French and Belgian nationals. Methods: We examined information from single live birth certificates for 285,371 Mexico-born and 3,131,632 U.S.-born mothers (including 2,537,264 U.S.-born White mothers) in the United States, 4,623 North African and 103,345 Belgian mothers in Belgium, and a French national random sample consisting of 632 North African and 11,185 French mothers. The outcomes were mean birthweight, low birthweight, and preterm births. Differences between native/nationals and foreign-born mothers in each country were assessed in bivariate and multivariate analyses controlling for maternal risk factors. Results: The adjusted odds for low birthweight were lower for immigrants than native/nationals by 32% in the United States, by 32% in Belgium, and by 30% in France. The adjusted odds for preterm births were lower for immigrants compared with native/nationals by 11% in the United States and by 23% in Belgium. In France, the odds for preterm births were comparable for immigrants and naturalized mothers. Infants of immigrant mothers also had higher mean birthweights in all three countries. Conclusion: Despite their disadvantaged status, Mexico-born and North African-born women residing in the United States, France, and Belgium show good birth outcomes. These cannot be explained solely by traditional risk factors. Protective factors and selective migration may offer further clues.     

Diabetes,inflammation, and the adiponectin paradox: Therapeutic targets in SARS-CoV-2

Aging and pre-existing conditions in older patients increase severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) severity and its complications, although the causes remain unclear. Apart from acute pulmonary syndrome, Coronavirus 2019 (COVID-19) can increasingly induce chronic conditions. Importantly, SARS-CoV-2 triggers de novo type 2 diabetes mellitus (T2DM) linked to age-associated cardiovascular disease (CVD), cancers, and neurodegeneration. Mechanistically, SARS-CoV-2 induces inflammation, possibly through damage-associated molecular pattern (DAMP) signaling and ‘cytokine storm,’ causing insulin resistance and the adiponectin (APN) paradox, a phenomenon linking metabolic dysfunction to chronic disease. Accordingly, preventing the APN paradox by suppressing APN-related inflammatory signaling might prove beneficial. A better understanding could uncover novel therapies for SARS-CoV-2 and its chronic disorders.