Sympathetic mechanism of regulating heart function in acute transitory coronary insufficiency of different duration

Experiments on 102 outbred white male rats with experimental acute transitory coronary insufficiency (ATCI) were carried out to show a consistent phasic time course of the functioning of the sympathetic cardiac activity regulation mechanism. The sympathetic neuroeffector influence on the myocardium with ATCI depends to a large measure on the intensity of the neurotransmitter biosynthesis and function of cardiomyocyte adrenoreceptors. It is suggested that the time couse of heart contractility and rhythm under ATCI is related to changes in the pre- and post-synaptic component of the sympathetic regulation mechanism of cardiac function. It is also assumed that cardiomyocyte receptors might exert a substantial influence on the possibility and development of arrhythmias. The advantages of pharmacological correction (as compared with the blockade) of sympathetic neuroeffector influences on the myocardium under ATCI are emphasized.     

Sympathetic and parasympathetic regulation of the heart in transitory coronary insufficiency

Experiments were made on 480 rats and 60 rabbits with transitory insufficiency (duration of myocardial ischemia 10.40 and 120 min the length of subsequent reperfusion 40-60 min). It was discovered that there was natural development of the phenomenon of limitation of drawing the heart in direct and reflectory reactions of the circulation system within the increase of duration of local ischemia and the beginning of the subsequent reperfusion. The phenomenon of "limitation", which is realized with the involvement of sympathetic and parasympathetic mechanisms, promotes a decrease of the extent of heart alteration during its local ischemia and increase of reparative process in the heart at the reperfusion period.     

Validation of heart failure quality of life tool and usage to predict all-cause mortality in acute heart failure in Uganda: the Mbarara heart failure registry (MAHFER)

Background

The health-related quality of life (HRQoL) is an important treatment goal that could serve as low-cost prognostication tool in resource poor settings.We sought to validate the Kansas City Cardiomyopathy Questionnaire (KCCQ) and evaluate its use as a predictor of 3?months all-cause mortality among heart failure participants in rural Uganda.

Methods

The Mbarara Heart Failure Registry Cohort study observes heart failure patients during hospital stay and in the community in rural Uganda. Participants completed health failure evaluations and HRQoL questionnaires at enrollment, 1 and 3?months of follow-up. We used Cronbach’s alpha coefficients to define internal consistency, intraclass correlation coefficients as a reliability coefficient, and Cox proportional hazard models to predict the risk of 3?months all-cause mortality.

Results

Among the 195 participants who completed HRQoL questionnaires, the mean age was 52 (standard deviation (SD) 21.4) years, 68% were women and 29% reported history of hypertension. The KCCQ had excellent internal consistency (87% Cronbach alpha) but poor reliability. Independent predictors of all-cause mortality within 3?months included: worse overall KCCQ score (Adjusted Hazard ratio (AHR) 2.9, 95% confidence interval (CI) 1.1, 8.1), highest asset ownership (AHR 3.6, 95% CI 1.2, 10.8), alcoholic drinks per sitting (AHR per 1 drink 1.4, 95% CI 1.0, 1.9), New York Heart Association (NYHA) functional class IV heart failure (AHR 2.6, 95% CI 1.3, 5.4), estimated glomerular filtration rate (eGFR) 30 to 59?ml/min/1.73?m² (AHR 3.4, 95% CI 1.1, 10.8), and eGFR less than 15?ml/min/1.73?m² (AHR 2.7, 95% CI 1.0, 7.1), each 1?pg/mL increase in Brain Natriuretic Peptide (BNP) (AHR, 1.0, 95% CI 1.0, 1.0), and each 1?ng/mL increase in Creatine-Kinase MB isomer (CKMB) (AHR 1.0, 95% CI 1.0, 1.1).

Conclusion

The KCCQ showed excellent internal consistency. Worse overall KCCQ score, highest asset ownership, increasing alcoholic drink per sitting, NYHA class IV, decreased estimated glomerular filtration rate, BNP, and CKMB predicted all-cause mortality at 3?months. The KCCQ could be an additional low-cost tool to aid in the prognostication of acute heart failure patients.

     

Myocardial lesions in experimental acute heart failure

The present study concerns the morphological and biochemical lesional picture of the myocardium in cases of acute heart failure induced by various experimental models: ligature of the coronary artery, direct electric stimulation of the heart by catheterism, lethal hemorrhage, pneumothorax, beta-adrenergic shock. Worthy of note was the similitude of the lesional myocardium pictures characterized electron microscopically by a wide range of lesions, from reversible to focal cytolysis, and biochemically by decrease of mitochondrial enzymes, ATP, Mg2-1 X K+ and increase of Na+ X H2O, Ca2+. Problems linked to the pathogenesis, reversibility of the lesions and efficiency of certain therapeutical means are discussed.     

放化疗对胃肠道的损伤以及微生态制剂防治的研究进展

肿瘤患者放化疗后不良反应较多,尤其是胃肠道反应.放化疗对胃肠道的损伤主要包括:严重损伤肠粘膜,造成肠黏膜免疫功能紊乱,以及肠道菌群失调,引发腹泻或便秘.研究发现,微生态制剂可用于防治放化疗对胃肠道的损伤,减少或避免不良反应的发生.     

Prognostic prediction in acute heart failure patients with extreme BNP values

Background: Some patients have good prognosis despite elevated B-type natriuretic peptide (BNP), while others have ominous outcome with low BNP. We aimed at characterising these groups of patients.

Methods: We analysed patients prospectively included in an acute HF registry. Vital status within 1-year post discharge was ascertained. A receiver–operating characteristic curve was used to define discharge BNP cut-offs for 1-year death prediction. Among survivors, we compared patients with low and not-low BNP (cut-off 400?pg/mL); and among non-survivors those with high vs not-high BNP (cut-off 2000?pg/mL). In the specific subgroups of patients with low and high BNP, mortality predictors were assessed with multivariate Cox-regression analysis.

Results: We studied 584 patients, median age 78 years, 62.5% had HF with reduced ejection fraction; and 199 (34.1%) died during the first year. Non-survivors were very homogeneous irrespective of BNP, survivors were substantially different. In patients discharged with BNP <400?pg/mL, increasing age independently predicted death; when BNP ≥2000?pg/mL death predictors were higher NYHA class, and non-use of evidence-based therapy. BNP was outcome associated in both groups.

Conclusions: Different prognostic predictors may play a role in different BNP levels. We suggest that risk stratification in HF would probably be more accurate if made on top of BNP knowledge.     

应用C-反应蛋白区别急性失代偿性心力衰竭与肺炎

目的研究通过测定入院时C-反应蛋白（CRP）水平和CRP速度来鉴别急性失代偿性心力衰竭（ADHF）与肺炎的功效。方法回顾性研究三级医院两年的ADHF与肺炎患者的病例资料。住院时已经用抗生素治疗的患者除外。CRP作为诊断标志物的有效性通过ROC来评估。结果 72例ADHF和50例肺炎患者被纳入研究。ADHF患者入院时平均CRP水平为（13.5±13.5）mg/L,而肺炎患者为（127±84）mg/L（P〈0.001）。CRP增加大于等于0.56 mg/（L·h）时诊断肺炎。入院时CRP水平和CRP升高作为区别肺炎与ADHF的标记物时的敏感度是0.96,特异性为0.972。结论本研究强调生物标志物的动态特性,证实了急性期反复测量CRP的有效性,它将为临床医生提供有价值的工具来建立正确的诊断及减少不必要的抗生素使用。     

Lycopene,tomatoes, and the prevention of coronary heart disease

Coronary heart disease (CHD) is one of the primary causes of death in the Western world. The emphasis so far has been on the relationship between serum cholesterol levels and the risk of CHD. More recently, oxidative stress induced by reactive oxygen species (ROS) is also considered to play an important part in the etiology of this disease. Oxidation of the circulating low-density lipoprotein (LDL(ox)) is thought to play a key role in the pathogenesis of atherosclerosis and CHD. According to this hypothesis, macrophages inside the arterial wall take up the LDL(ox) and initiate the process of plaque formation. Dietary antioxidants such as vitamin E and beta-carotene have been shown in in vitro studies to prevent the formation of LDL(ox) and their uptake by microphages. In a recent study, healthy human subjects ingesting lycopene, a carotenoid antioxidant, in the form of tomato juice, tomato sauce, and oleoresin soft gel capsules for 1 week had significantly lower levels of LDL(ox) compared with controls. The antioxidant effects of lycopene have also been shown in four other human trials, including one where lycopene consumption reduced the levels of breath pentane. However, in one recent study, dietary supplementation with beta-carotene but not with lycopene was shown to inhibit LDL oxidation. The sources of lycopene used in most of these studies were either tomato products or lycopene extracted from tomatoes containing other carotenoids in various proportions. Therefore, it is not possible to attribute the effects solely to lycopene. Mechanisms other than the antioxidant properties of lycopene have also been shown to reduce the risk of CHD. Lycopene was shown to inhibit the activity of an essential enzyme involved in cholesterol synthesis in an in vitro and a small clinical study suggesting a hypocholesterolemic effect. Other possible mechanisms include enhanced LDL degradation, LDL particle size and composition, plaque rupture, and altered endothelial functions. Recent epidemiological studies have also shown an inverse relationship between tissue and serum levels of lycopene and mortality from CHD, cerebrovascular disease, and myocardial infraction. However, the most impressive population-based evidence comes from a multicenter case-control study where subjects from 10 European countries were evaluated for relationship between antioxidant status and acute myocardial infarctions. After adjusting for a range of dietary variables, only lycopene levels but not beta-carotene were found to be protective. At present, the role of lycopene in the prevention of CHD is strongly suggestive. Although the antioxidant property of lycopene may be one of the principal mechanism for its effect, other mechanisms may also be responsible. Controlled clinical and dietary intervention studies using well-defined subject populations and disease end points must be undertaken in the future to provide definitive evidence for the role of lycopene in the prevention of CHD. Mechanistic studies must also be initiated to understand the mode of lycopene action.     

Reperfusion injury of myocardial biomembranes after acute fatal hemorrhage and their correction with carnosine]

Studies on inbred male rats revealed that ischemia associated with clinical death caused by haemorrhage with subsequent recirculation and reoxygenation during resuscitation led to an increase in enzyme activities in blood serum and perfusate passed through the coronary bed of isolated hearts, presumably due to impaired membrane integrity. Damage to cardiomyocyte membranes was caused by intensification of LPO concomitant with enhanced glycolysis and lactate accumulation in the cardiac muscle. Carnosine (25 mg/kg) injected simultaneously with recirculation and reoxygenation prevented membrane damage and created optimal conditions for the functioning of membrane enzymes.     

Electrophysiological changes in heart failure and their implications for arrhythmogenesis

Heart failure is the final common pathway of various cardiac pathologies and is associated with sudden cardiac death, mostly caused by ventricular arrhythmias. In this paper we briefly review the electrophysiological remodeling and the alterations in intracellular calcium handling, and the resulting arrhythmogenic mechanisms associated with heart failure. Intercellular uncoupling and fibrosis are identified as a major arrhythmogenic factors. Diet and ventricular wall stretch are discussed as modulating factors. Finally, emphasis is placed on the hitherto poorly studied aspects of right ventricular failure. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions.     

Oxygen and effective vasular compliance in acute heart failure.

The effect of hypoxemia on total vascular compliance was studied in anesthetized dogs using a venous bypass technique. Cardiac output was kept constant with an extracorporeal pump and respiration controlled to maintain normocapnia. When nitrogen was added to the respired gas to produce an arterial PO2 approximately 45 mm Hg, total vascular compliance was rapidly and significantly reduced to 0.93 ml (mm Hg)(-1) kg(-1) with incomplete recovery to baseline values of 1.30 plus or minus 0.06 ml (mm Hg)(-1) kg(-1) during subsequent ventilation with 100% oxygen. Acute heart failure was induced by gradual aortic constriction. Ventilation with 100% oxygen failed to prevent a gradual reduction in total vascular compliance to 0.86 ml (mm Hg)(-1) kg(-1) from a baseline value of 1.23 plus or minus 0.06 ml (mm Hg)(-1) kg(-1). Ventilation with 100% oxygen following the reduction in vascular compliance during acute heart failure also failed to significantly alter this parameter. Thus, improvement of arterial oxygen tension in patients with acute heart failure would be beneficial in providing greater oxygen delivery to the tissues without abolishing a compensatory mechanism of reduced vascular compliance which attempts to maintain a cardiac filling gradient of pressure.     

Real-world heart failure management in 10,910 patients with chronic heart failure in the Netherlands

Aims

Data from patient registries give insight into the management of patients with heart failure (HF), but actual data from unselected real-world HF patients are scarce. Therefore, we performed a cross sectional study of current HF care in the period 2013–2016 among more than 10,000 unselected HF patients at HF outpatient clinics in the Netherlands.

Methods

In 34 participating centres, all 10,910 patients with chronic HF treated at cardiology centres were included in the CHECK-HF registry. Of these, most (96%) were managed at a specific HF outpatient clinic. Heart failure was typically diagnosed according to the ESC guidelines 2012, based on signs, symptoms and structural and/or functional cardiac abnormalities. Information on diagnostics, treatment and co-morbidities were recorded, with specific focus on drug therapy and devices. In our cohort, the mean age was 73 years (SD 12) and 60% were male. Frequent co-morbidities reported in the patient records were diabetes mellitus 30%, hypertension 43%, COPD 19%, and renal insufficiency 58%. In 47% of the patients, ischaemia was the origin of HF. In our registry, the prevalence of HF with preserved ejection fraction was 21%.

Conclusion

The CHECK-HF registry will provide insight into the current, real world management of patient with chronic HF, including HF with reduced ejection fraction, preserved ejection fraction and mid-range ejection fraction, that will help define ways to improve quality of care. Drug and device therapy and guideline adherence as well as interactions with age, gender and co-morbidities will receive specific attention.

     

Double product reflects the association of heart rate with MACEs in acute coronary syndrome patients treated with percutaneous coronary intervention

Background

There is little information about the prognostic value of double product (DP) for acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI). The aim of this study was to investigate whether DP reflects the predictive power of heart rate (HR) or systolic blood pressure (SBP) in ACS patients treated with PCI.

Methods

A total of 7590 ACS patients who had undergone PCI, free from cardiac shock, were included. The follow-up duration was two years. The main adverse cardiovascular events (MACEs) included all-cause death, recurrent myocardial infarction and stroke.

Results

In the unadjusted model, significantly higher rates of MACEs were recorded in the high DP group (relative risk 1.41, 95%CI 1.08 to 1.83, p?=?0.012). However, in the full adjusted models, after including HR and SBP, the predictive value of DP was not significant (relative risk 0.86, 95%CI 0.55 to1.33, p?=?0.499). The predictive value of HR for MACEs was statistically significant (relative risk 1.74, 95% CI 1.33–2.28, p?<?0.001). It was worth noting that the history of hypertension was strongly associated with MACEs (relative risk 1.53, 95% CI 1.11–2.11, p?=?0.009).

Conclusion

High DP is associated with MACEs for ACS patients treated with PCI. However, the predictive value of DP weakened when adjusted for HR. Therefore, we have shown that DP may reflect the predictive power of HR for ACS patients treated with PCI.

     

Disorders of the heart contractile function in chronic hemolytic anemia and their prevention

The coronary blood flow and heart contractile function were studied on rats with phenylhydrazine-induced chronic hemolytic anemia. The coronary blood flow in the animals' hearts was increased 2.5-fold, whereas the main parameters of contractile function were reduced but insignificantly. After the coronary blood flow dropped to the control level, the pressure and contraction rate fell by 40% and the relaxation rate diminished 2-fold. Thus, the enhanced coronary blood flow in the hearts of animals with hemolytic anemia appears to be a factor that compensates for the maintenance of myocardial contractility at the subnormal level. Administration of the antioxidant ionol, an inhibitor of lipid peroxidation, coupled with phenylhydrazine did not prevent the development of anemia but made the coronary blood flow descend in the hearts of anemic animal only by 80%. Since the iron-containing products of red cell dissolution activate lipid peroxidation during hemolytic anemia, this might play a role in the occurrence of heart muscle injuries. It is suggested that ionol prevents such injuries to a considerable extent, thereby preventing the development of compensatory enhancement of the coronary blood flow and heart contractile function disturbances during its normalization.     

Congestive heart failure complicating non-ST segment elevation acute coronary syndrome: incidence, predictors, and clinical outcomes

There are limited data regarding the incidence and clinical significance of congestive heart failure (CHF) in patients with non-ST segment elevation acute coronary syndromes (ACS). The objectives of this study were to examine the incidence, predictors, and clinical outcomes in patients with ACS without ST elevation who develop CHF. We studied patients with unstable angina or non-ST segment elevation myocardial infarction (NSTEMI) randomized to hirudin or unfractionated heparin in the Organisation to Assess Strategies for Ischemic Syndromes (OASIS-2) trial. The diagnosis of CHF was based on a combination of clinical and radiographic features. Patients were followed for 6 months. Of 10 141 randomized patients, 501 (4.9%) developed CHF within the first week and 643 (6.3%) during 6 months of followup. Independent predictors for the development of CHF were older age, female sex, diabetes, prior MI, prior CHF, and NSTEMI at presentation. Compared with patients who did not develop CHF, patients who developed CHF were at increased risk of death (odds ratio (OR) 3.4, 95% CI 2.7-4.3), new MI (OR 2.8, 95% CI 2.2-3.6), and the need for intra-aortic balloon pump insertion (OR 5.4, 95% CI 3.5-8.4) at 7 days and 6 months. There was no increase in use of cardiac catheterization (OR 0.8, 95% CI 0.7-1.0) or revascularization (OR 0.9, 95% CI 0.7-1.1) in patients who developed CHF. CHF is a common complication in patients presenting with non-ST segment elevation ACS and is strongly associated with adverse clinical outcomes including new MI and death. Despite this worse prognosis, patients with ACS developing CHF are less likely to be referred for invasive management.