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PubMed2006

Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study.

BACKGROUND: Previous studies have associated reduced hemoglobin levels with increased adverse events in heart failure. It is unclear, however, whether this relation is explained by underlying kidney disease, treatment differences, or associated comorbidity. METHODS AND RESULTS: We examined the associations between hemoglobin level, kidney function, and risks of death and hospitalization in persons with chronic heart failure between 1996 and 2002 within a large, integrated, healthcare delivery system in northern California. Longitudinal outpatient hemoglobin and creatinine levels and clinical and treatment characteristics were obtained from health plan records. Glomerular filtration rate (GFR; mL.min(-1).1.73 m(-2)) was estimated from the Modification of Diet in Renal Disease equation. Mortality data were obtained from state death files; heart failure admissions were identified by primary discharge diagnoses. Among 59,772 adults with heart failure, the mean age was 72 years and 46% were women. Compared with that for hemoglobin levels of 13.0 to 13.9 g/dL, the multivariable-adjusted risk of death increased with lower hemoglobin levels: an adjusted hazard ratio (HR) of 1.16 and 95% confidence interval (CI) of 1.11 to 1.21 for hemoglobin levels of 12.0 to 12.9 g/dL; HR, 1.50 and 95% CI, 1.44 to 1.57 for 11.0 to 11.9 g/dL; HR, 1.89 and 95% CI, 1.80 to 1.98 for 10.0 to 10.9; HR, 2.31 and 95% CI, 2.18 to 2.45 for 9.0 to 9.9; and HR, 3.48 and 95% CI, 3.25 to 3.73 for <9.0 g/dL. Hemoglobin levels > or = 17.0 g/dL were associated with an increased risk of death (adjusted HR, 1.42; 95% CI, 1.24 to 1.63). Compared with those with a GFR > or = 60 mL . min(-1).1.73 m(-2), persons with a GFR <45 mL.min(-1).1.73 m(-2) had an increased mortality risk: adjusted HR, 1.39 and 95% CI, 1.34 to 1.44 for 30 to 44; HR, 2.28 and 95% CI, 2.19 to 2.39 for 15 to 29; HR, 3.26 and 95% CI, 3.05 to 3.49 for <15; and HR, 2.44 and 95% CI, 2.28 to 2.61 for those on dialysis. Relations were similar for the risk of hospitalization. The findings did not differ among patients with preserved or reduced systolic function, and hemoglobin level was an independent predictor of outcomes at all levels of kidney function. CONCLUSIONS: Very high (> or = 17 g/dL) or reduced (<13 g/dL) hemoglobin levels and chronic kidney disease independently predict substantially increased risks of death and hospitalization in heart failure, regardless of the level of systolic function. Randomized trials are needed to evaluate whether raising hemoglobin levels can improve outcomes in chronic heart failure.

Adult↗
PubMed2001

Heart failure with a normal ejection fraction: is measurement of diastolic function necessary to make the diagnosis of diastolic heart failure?

BACKGROUND: The diagnosis of diastolic heart failure is generally made in patients who have the signs and symptoms of heart failure and a normal left ventricular (LV) ejection fraction. Whether the diagnosis also requires an objective measurement of parameters that reflect the diastolic properties of the ventricle has not been established. METHODS AND RESULTS: We hypothesized that the vast majority of patients with heart failure and a normal ejection fraction exhibit abnormal LV diastolic function. We tested this hypothesis by prospectively identifying 63 patients with a history of heart failure and an echocardiogram suggesting LV hypertrophy and a normal ejection fraction; we then assessed LV diastolic function during cardiac catheterization. All 63 patients had standard hemodynamic measurements; 47 underwent detailed micromanometer and echocardiographic-Doppler studies. The LV end-diastolic pressure was >16 mm Hg in 58 of the 63 patients; thus, 92% had elevated end-diastolic pressure (average, 24+/-8 mm Hg). The time constant of LV relaxation (average, 51+/-15 ms) was abnormal in 79% of the patients. The E/A ratio was abnormal in 48% of the patients. The E-wave deceleration time (average, 349+/-140 ms) was abnormal in 64% of the patients. One or more of the indexes of diastolic function were abnormal in every patient. CONCLUSIONS: Objective measurement of LV diastolic function serves to confirm rather than establish the diagnosis of diastolic heart failure. The diagnosis of diastolic heart failure can be made without the measurement of parameters that reflect LV diastolic function.

Cardiac Catheterization↗
PubMed1993

Maternal autoantibodies and congenital heart block: no evidence for the existence of a unique heart block-associated anti-Ro/SS-A autoantibody profile.

One of the rare examples of the transfer of autoimmune disease from mother to (unborn) child is the neonatal lupus syndrome. This syndrome comprises the development of fetal heart disease (congenital heart block) or neonatal skin rash and is specifically associated with maternal anti-Ro/SS-A autoantibodies. Previous studies have suggested that especially maternal autoantibody reactivity against the 52 kDa protein of the Ro/SS-A antigen and/or against the La/SS-B antigen is responsible for the development of congenital heart block (CHB). To determine the CHB-associated antibody response in more detail, we analysed the presence of autoantibodies in sera from mothers of children with isolated heart block. All 14 mothers of children with congenital heart block were positive for anti-Ro/SS-A antibodies. Remarkably, their antibody profile, including recognition of different Ro/SS-A proteins and autoantibody levels against these proteins, did not differ from anti-Ro/SS-A positive mothers of healthy children. In contrast, all 8 anti-Ro/SS-A negative mothers had children with acquired heart block. We conclude from our data that maternal anti-Ro/SS-A antibodies are essential for CHB but that fine analysis of this autoantibody response does not predict the occurrence of CHB.

Adult↗
PubMed1992

Relationship between heart rate, left ventricular output, and stroke volume in preterm infants during fluctuations in heart rate.

The relationship between changes in heart rate, left ventricular output, and left ventricular stroke volume was studied in 18 preterm infants, with mean gestational age 29 wk (range 26-33 wk) and mean postnatal age 10 d (range 1-21 d). To yield left ventricular output, the blood flow velocity in the ascending aorta was measured by range-gated Doppler technique and multiplied by the aortic cross-sectional area measured by cross-sectional and M-mode echocardiography. Stroke volume was calculated by dividing left ventricular output by heart rate. The individual mean left ventricular output correlated poorly with heart rate (r2 = 0.17), and, accordingly, there was a closer relationship between stroke volume and left ventricular output. In only four of the 18 infants was a significant correlation between heart rate changes and left ventricular output found. Substantial changes in stroke volume were seen in most infants, and in 13 of the 18 infants the changes exceeded 25%. These variations in stroke volume were closely related to left ventricular output. In 15 of the 18 infants, the maximum heart rate change was associated with a stroke volume change in the opposite direction. The group average of the maximum heart rate increase in each individual, 24 bpm (18%), corresponded to a decrease in stroke volume of 0.15 mL.kg-1 (9%) (p less than 0.05) and an increase in left ventricular output of 22.7 mL.min-1.kg-1 (9%) (p less than 0.05). A reciprocal relationship was seen between afterload and left ventricular output.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗
PubMed2005

Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.

The genetic hierarchies guiding lineage specification and morphogenesis of the mammalian embryonic heart are poorly understood. We now show by gene targeting that murine T-box transcription factor Tbx20 plays a central role in these pathways, and has important activities in both cardiac development and adult function. Loss of Tbx20 results in death of embryos at mid-gestation with grossly abnormal heart morphogenesis. Underlying these disturbances was a severely compromised cardiac transcriptional program, defects in the molecular pre-pattern, reduced expansion of cardiac progenitors and a block to chamber differentiation. Notably, Tbx20-null embryos showed ectopic activation of Tbx2 across the whole heart myogenic field. Tbx2 encodes a transcriptional repressor normally expressed in non-chamber myocardium, and in the atrioventricular canal it has been proposed to inhibit chamber-specific gene expression through competition with positive factor Tbx5. Our data demonstrate a repressive activity for Tbx20 and place it upstream of Tbx2 in the cardiac genetic program. Thus, hierarchical, repressive interactions between Tbx20 and other T-box genes and factors underlie the primary lineage split into chamber and non-chamber myocardium in the forming heart, an early event upon which all subsequent morphogenesis depends. Additional roles for Tbx20 in adult heart integrity and contractile function were revealed by in-vivo cardiac functional analysis of Tbx20 heterozygous mutant mice. These data suggest that mutations in human cardiac transcription factor genes, possibly including TBX20, underlie both congenital heart disease and adult cardiomyopathies.

Animals↗
PubMed2006

Mimicry in recognition of cardiac myosin peptides by heart-intralesional T cell clones from rheumatic heart disease.

Molecular mimicry between Streptococcus pyogenes Ags and human proteins has been considered as a mechanism leading to autoimmune reactions in rheumatic fever and rheumatic heart disease (RHD). Cardiac myosin has been shown as a putative autoantigen recognized by autoantibodies of rheumatic fever patients. We assessed the human heart-intralesional T cell response against human light meromyosin (LMM) and streptococcal M5 peptides and mitral-valve-derived proteins by proliferation assay. Cytokines induced by LMM peptides were also evaluated. The frequency of intralesional T cell clones that recognized LMM peptides was 63.2%. Thirty-four percent of T cell clones presented cross-reactivity with different patterns: 1) myosin and valve-derived proteins; 2) myosin and streptococcal M5 peptides; and 3) myosin, valve-derived proteins and M5 peptides. In addition, several LMM peptides were recognized simultaneously showing a multiple reactivity pattern of heart-infiltrating T cells. Inflammatory cytokines (IFN-gamma and TNF-alpha) were predominantly produced by heart-infiltrating T cells upon stimulation with LMM peptides. The alignment of LMM and streptococcal M5 peptides showed frequent homology among conserved amino acid substitutions. This is the first study showing the cellular response by human heart-infiltrating T cells against cardiac myosin epitopes in RHD patients. The high percentage of reactivity against cardiac myosin strengthens its role as one of the major autoantigens involved in rheumatic heart lesions. T cell reactivity toward myosin epitopes in RHD patients may also trigger the broad recognition of valvular proteins with structural or functional similarities.

Amino Acid Sequence↗
PubMed2004

Job strain in relation to ambulatory blood pressure, heart rate, and heart rate variability among female nurses.

OBJECTIVE: This study examined the effects of exposure to job strain on independent predictors of cardiovascular disease (ambulatory blood pressure, heart rate, and heart rate variability). METHODS: The participants comprised a homogeneous group of 159 healthy female nurses [mean age 35.9 (SD 8.5) years]. The choice of this population minimized variance attributable to gender, socioeconomic status, and work characteristics. Job demands, decision latitude, and social support were measured with the Karasek job content questionnaire, which was administered twice with an average interval of 12.2 months. The nurses' scores for job demands and decision latitude on both occasions were used to define their job-strain category. Ambulatory blood pressure, heart rate, and heart rate variability were assessed on a workday and a day of leisure. RESULTS: No effect on the ambulatory levels of blood pressure, heart rate, or heart rate variability was found for job strain by itself or in interaction with social support. In addition, job strain was not associated with differences in short-term or long-term physiological recovery during sleep after a workday or a day of leisure. High job demand was associated with higher systolic blood pressure at work and with higher diastolic blood pressure at work, but the latter association was found only when decision latitude was concurrently high, rather than low. CONCLUSIONS: High job strain among young female nurses is not associated with an unfavorable ambulatory cardiovascular profile. The robust effect of job strain on male health appears to be less apparent for women.

Adaptation, Psychological↗
PubMed1999

A comparison of esmolol & diltiazem for heart rate control during coronary revascularisation on beating heart.

This prospective study was done to compare the control of heart rate and haemodynamics during coronary artery revascularisation without cardiopulmonary bypass using either esmolol or diltiazem. Sixty adult patients with one or two vessel coronary artery disease, were randomly divided into 2 equal groups. Group A received a 500 micrograms/kg loading dose of esmolol followed by a 100 micrograms/kg/h infusion, for control of heart rate during surgical anastomosis of the coronary vessel. While Group B received 0.15 mg/kg diltiazem as a loading dose followed by a 5 mg/h infusion for heart rate control, during the anastomosis. It was seen that heart rate control was better in Group A, 51.4 (+/- 1.3) beats/min, than in Group B, 69.6 (+/- 3.9) beats/min but the decrease in heart rate was significant in both the groups at peak effect compared to respective predrug values. Group A patients had unchanged systemic resistance and pulmonary artery wedge pressure but mean pulmonary artery pressure and pulmonary vascular resistance were significantly raised. Group B patients had decreased systemic resistance, mean pulmonary artery pressure and pulmonary artery wedge pressure, and reduced right ventricular stroke work index. We concluded that although esmolol provided dramatically slower heart rates, during surgery, the resulting elevations in mean pulmonary artery pressure and pulmonary vascular resistance would require caution if used in patients with underlying right ventricular dysfunction from ischaemia or infarction. Diltiazem by virtue of its effects on systemic vascular resistance, cardiac output, and lowering of mean arterial pressure may be a better choice in hypertensive patients.

Adrenergic beta-Antagonists↗
PubMed2002

Transition of care to adult congenital heart centres: what do patients know about their heart condition?

BACKGROUND: The population of adults with congenital heart disease is growing rapidly, and the transition of care from the pediatric to the adult setting is often not optimal. OBJECTIVES: To assess the level of knowledge that adults with congenital heart disease have of their condition. METHODS: All new patients referred to an adult congenital heart centre were asked to answer questions about their clinical diagnosis, their need and reason for anti-bioprophylaxis, and their risks of pregnancy when applicable. The patient's age at first visit, source of referral and time from last visit in cardiology (defined as the last visit with a cardiologist) were also noted. RESULTS: From November 1999 to July 2000, 104 patients (42 men) were referred to the adult centre by pediatric cardiologists (56), medical cardiologists (26), general practitioners (11), dentists (two) or obstetricians (two), or they were self-referred (seven). The mean age at the time of referral was 28 11 years (range 16 to 72 years, median 24 years). The time from the last visit in cardiology varied widely from one month to 25 years (median three years), with 29 patients (28%) having had no follow-up for more than five years. Among these, 14 patients had no follow-up for more than 10 years, with six patients having been referred for complications related to their cardiac anatomy, such as heart failure (Eisenmenger, Ebstein), syncope (operated and unoperated tetralogy of Fallot) and arrhythmias (atrial septal defect, unoperated Fallot). The clinical diagnosis was completely unknown by 36 patients (34.6%), including patients with repaired Fallot (three patients), Mustard procedure (two), severe aortic stenosis (two), severe pulmonary stenosis (one), Eisenmenger (one), unoperated Fallot (one), ventricular septal defect (six) and bicuspid aortic valve (seven). Seventy-three patients (79%) knew about antibiotic prophylaxis, but 50% did not comprehend why they needed it. Many women (66%) had never discussed the risks of pregnancy with their physician. CONCLUSIONS: A large percentage of adults with congenital heart abnormalities show a poor level of knowledge about their heart condition. These observations suggest the importance of structured transitional programs, the impact of which will need to be validated in prospective studies.

Adolescent↗
PubMed2002

[Heart re-synchronization with biventricular stimulation: new treatment for refractory heart failure].

Despite continuous progress in drug therapy, many patients are still progressing into advanced heart failure, a very poor condition in terms of quality of life and prognosis. Therapeutic resources are quite limited at that end-stage. Heart transplantation may only be proposed to a small minority of patients. New non-pharmacological alternatives like cellular cardiomyo-plasty or left ventricular (LV) implantable assist device are still under evaluation. So simpler and cheaper approaches have imperatively to be developed for treating this highly invalidated and rapidly growing and ageing population. Cardiac resynchronization therapy (CRT) with multisite biventricular pacing has been initiated in France in early 90's. The aim of CRT is to try and correct the electromechanical abnormalities that result from antrioventricular and intraventricular conduction delay (IVCD), a very common observation (30-50%) in patients with chronic heart failure (CHF). IVCD worsens progressively overtime and is responsible for discoordinated interventricular and left-intraventricular contraction-relaxation which in turn enhances the hemodynamic consequences of the baseline LV systolic dysfunction. This new therapeutic concept was first assessed in acute hemodynamic studies with temporary pacing, then in pilot studies with permanent transvenous biventricular pacing. Several controlled studies (MUSTIC, MIRACLE, CONTAKCD...) were conducted afterwards and demonstrated that CRT might improve significantly symptoms, quality of life and exercise tolerance in patients with severe heart failure (NYHA class III -- IV) under optimized drug treatment, low ejection fraction and significant IVCD as indicated by an intrinsic QRS duration QRS> 150 MS. The rehospitalization rate was also significantly reduced with CRT. The clinical benefit was preserved over at least 1 year follow-up. The first validation stem is now completed. There are however several important questions yet to be answered. Which is the impact of CRT on all-cause mortality and sudden cardiac death? Two large-scale studies, CARE-HF in Europe and COMPANION in USA, are ongoing to try and answer this question. Which type of implantable devices has to be developed preferentially: multisite pacemakers or multisite pacemaker-defibrillators? May CRT induce LV reverse remodelling and thus help at preventing heart failure progression? Which cost-effectiveness ratio for heart faulure management? How to better select potential responders?... The whole validation process of CRT should be completed on 2004-2005.

Cardiac Pacing, Artificial↗
PubMed2003

Heart weight and heart weight/body weight ratio in a Jamaican adult autopsy population. A preliminary study.

The heart weight and heart weight/body weight (HW/BW) ratio were assessed in an adult autopsy population and compared with commonly used reference values. Examination of 127 adult post-mortem cases (80 males and 47 females, aged 17 to 91 years) revealed that the mean heart weight and the HW/BW ratios of both genders were significantly greater than the reference values, particularly so in the hypertensive patients. These findings suggest that the Jamaican adult heart is significantly heavier than values used from reference tables. In both genders, heart weight was significantly and positively correlated with body weight and body mass index but not height, for non-hypertensive and hypertensive subjects. The present data are preliminary and not comprehensive enough to establish definitive reference values for the Jamaican population. However, this information needs to be taken into consideration when making pathologic diagnoses using heart weight as a criterion in post-mortem diagnosis.

Adolescent↗
PubMed2003

[Experimental study of myocardial protective effect of cardiac arrest versus beating heart during open heart surgery].

OBJECTIVE: To investigate the myocardial protective effects of beating heart versus heart arrest in goats undergoing open heart surgery with cardiopulmonary bypass (CPB). METHODS: Eighteen healthy and homologous goats were randomly divided into three groups: groupI (n=6), with intermittent cold crystalloid cardioplegia; group II (n=6), with continuous warm blood cardioplegia; group III (n=6), with beating heart. Animals in group II and group III were operated with mild hypothermic CPB. The changes in malondialdehyde (MDA) in the myocardium of the right ventricles and atrial natriuretic peptide (ANP) in venous blood were measured respectively. The myocardial tissues were examined for ultrastructural changes. RESULTS: In group I, contents of MDA and ANP rose significantly during CPB, especially when blood was reperfused routinely. While in group II and group III, the levels were lower than those in group I at the same time points. There was no difference in the values between group II and group III. Ultrastructural changes were distinctly seen in group I, while they were mild in group II and group III. CONCLUSION: Continuous warm blood cardioplegia to keep the heart beating during operation can prevent ischemia-reperfusion injury and protect heart better.

Animals↗
PubMed1992

Collins' solution for cold storage of the heart for transplantation must be reversed with cardioplegic solution before reperfusion. A functional and metabolic study in the rat heart.

The following hypotheses were tested using an isolated perfused working rat heart model: (1) Collins' solution for cold storage of the heart is harmful for the heart during reperfusion; (2) a "reverse" of the intracellular-type Collins' solution with an extracellular-type cardioplegic solution before reperfusion is able to prevent this disadvantage of Collins' solution. The following two major groups (I and II) and five subgroups (-a to -e) in each group were prepared. In group I (reversed group); the hearts were initially stored in Collins' solution but were reversed by a 1-minute flush with cardioplegic solution followed by storage in cardioplegic solution for the last 1 to 180 minutes of the total 3-hour storage, that is, groups I-a (reversed for 1 minute), I-b (10 minutes), I-c (30 minutes), I-d (90 minutes), and I-e (180 minutes). In group II (nonreversed control group); the hearts were stored in Collins' solution throughout 3 hours and were also divided into five subgroups of groups II-a, II-b, II-c, II-d, and II-e in which only a 1-minute flush with Collins' solution was performed at the point corresponding to group I. The coronary flow in any of group II showed a marked decrease during the early reperfusion period. In group I, however, the coronary flow increased significantly in proportion to the duration of the reversing phase. The recovery of the aortic flow and the cardiac output in group I showed a bell-shaped pattern in relation to the duration of the reversing phase, reaching their peak values when reversed for 30 minutes (group I-c). The prolonged reverse (180 minutes) resulted in a deterioration of functional recovery associated with a poorer preservation of high-energy phosphates and a larger enzyme leakage. These results suggest that the beneficial effects of intracellular-type Collins' solution for cold storage of the heart were further improved by reversing Collins' solution with the extracellular-type cardioplegic solution for the last 30 minutes of the 3-hour cold storage because the disadvantageous vasoconstriction due to Collins' solution during reperfusion was successfully prevented by the replacement of intravascular and extravascular Collins' solution with cardioplegic solution before the reperfusion.

Animals↗
PubMed1992

[Heart surgery without previous heart catheterization, in pediatric cardiology].

STUDY OBJECTIVE: To determine the influence of echocardiography in the preoperative diagnosis of heart diseases in children. DESIGN: Retrospective study. SETTING: Hospitalized children admitted in Departments of Pediatric Cardiology and Cardiothoracic Surgery. PATIENTS: Children of both sexes, aged from neonate to 14 years old, with heart disease who underwent cardiac surgery. MATERIAL AND METHODS: From January 1989 to July 1990, 220 consecutive cardiac surgeries were performed in children with heart disease. The initial diagnosis was based on data from clinical examination, electrocardiogram, thorax X-Ray and echocardiogram (M-mode, 2D, conventional and colour Doppler). Patients were separated in three groups according to their ages: newborn infants less than 28 days old; infants less than 12 months old; children more than 1 year old and less than 14 years old. Patients were separated according to the investigations used further for preoperative diagnosis: whether they had or not cardiac catheterization performed prior to surgery. RESULTS: From 220 surgical interventions performed, 124 were "open heart" surgeries (9 neonates, 28 infants and 87 children) and the remaining had "closed heart" operations (14 neonates, 37 infants and 45 children). Preoperative diagnosis was mainly dependent on echocardiography, dispensing catheterization in 90 cardiac interventions. The diagnosis was confirmed at surgery or at autopsy. There were 9 deaths, 3 of which occurred in patients not submitted to cardiac catheterization. CONCLUSIONS: Echocardiography is a reliable method for investigation and establishment of the preoperative diagnosis of heart diseases in children. Its use may further reduce the need for diagnostic catheterization in children, particularly in risk groups.

Adolescent↗
PubMed2005

Timing of the first endomyocardial biopsy in heart transplantation after induction immunosuppressive therapy--experience from Canadian Heart Transplant Centre.

BACKGROUND: The exact time point at which the first endomyocardial biopsy could be safely performed after the heart transplantation has not been systematically studied. In an attempt to determine this time point in our population, the number and severity of acute rejection episodes in the first eight weeks after the heart transplantation were assessed in 91 patients who underwent the procedure at St Paul's Hospital, Vancouver between September 1996 and December 2002. METHODS AND RESULTS: For the purpose of our analysis, acute rejection was defined as the grade > or =2 according the International Society for Heart and Lung Transplantation (ISHLT). Three hundred and sixty two endomyocardial biopsies were performed in 87 patients surviving to the first biopsy from one to eight weeks after the heart transplantation. In 85 patients who received induction immunosuppressive therapy, 13 episodes of acute rejection were identified. In two patients who did not receive the induction therapy, three episodes of acute rejection occurred. Acute rejection grade ISHLT 3 was found in 2 patients who did not receive induction therapy and in three patients who did. ISHLT grade 4 rejection occurred at weeks 5 and 7 in two patients who received induction therapy. Only one patient who received induction therapy had acute rejection within the first three weeks after the heart transplantation. CONCLUSIONS: Our analysis reveals that the frequency of acute rejection within the first eight weeks after the heart transplantation using induction therapy is low in this cohort, suggesting that the first routine endomyocardial biopsy could be delayed until the week four post-transplant.

Adult↗
PubMed2005

Changes of chymase, angiotensin converting enzyme and angiotensin II type 1 receptor expressions in the hamster heart during the development of heart failure.

BACKGROUND: Little is known about the role of dual angiotensin II forming pathways during heart failure. In the present study, the changes of chymase and angiotensin converting enzyme (ACE) expressions in the failing hearts of hamsters were analysed. METHODS: Heart failure was induced by ligation of left anterior descending branch of the coronary artery. Chymase, ACE and angiotensin II type 1 receptor (AT1R) mRNA levels were analysed by reverse transcription polymerase chain reaction (RT-PCR). The activities of chymase and ACE were determined by radioimmunoassay (RIA). Myocardial collagen fibre analysis was performed under optical microscope. RESULTS: Left ventricular systolic pressure (LVSP) and maximum left ventricular developed pressure increase rate (dp/dtmax, mmHg/s) gradually moved lower at 2, 3, 4 and 8 weeks after operation. On the other hand, left ventricular end-diastolic pressure (LVEDP) increased gradually after operation. Compared with the control group (3.55 +/- 0.06, 4.79 +/- 0.70), the heart weight/body weight ratio in operation group had increased significantly at 4 weeks and 8 weeks (4.28 +/- 0.43, 6.17 +/- 0.73) (P < 0.01). Collagen staining showed that the quantity of myocardial collagen fibre increased significantly in the operation group. RT-PCR showed that the chymase mRNA level in the operation group was consistently greater than that in the control group. AT1R mRNA level was also increased significantly at 3 weeks and 4 weeks, both being 1.3 times that of the control group (P < 0.01), whereas ACE mRNA level was not changed. Higher activity of chymase was detected in operation group, being 4, 8, 13 and 19 times that of the control group at 2, 3, 4 and 8 weeks (P < 0.01), respectively. ACE activity was also significantly higher at the same time, being 7, 10, 10 and 3.5 times that of the control (P < 0.01). Angiotensin II (Ang II) level in operation group increased significantly, being 2.5, 2.7, 3.5 and 2 times that of the control group at 2, 3, 4 and 8 weeks, respectively (P < 0.01). CONCLUSIONS: A dual Ang II forming pathway from both ACE and chymase in the hamster hearts plays an important role during the development of heart failure. At the decompensatory stage, the reduction of AngII level may be associated with the decrease of ACE activity.

Angiotensin II↗
PubMed2005

[Association between free thyroxin concentration and degree of heart failure in patients with chronic heart insufficiency].

BACKGROUND: It is evident, that overt thyroid dysfunction (both, hypo- or hyperthyroidism) could be associated with heart failure. The aim of our study was to establish whether also mild changes in free thyroxin (fT4) may influence the degree of heart failure in patients with chronic heart insufficiency. METHODS AND RESULTS: There were included 148 patients (m 121, f 27, mean age 63.8 +/- 1.14) with clinical chronic heart failure were, with fT4 levels within the normal range (9-22 pmol/l) and without thyroid suppression or substitution treatment. Degree of heart failure was quantified by plasma B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP) and big endothelin. Patients with fT4 in the range 11.9-14.6 pmol/l (optimal, 3rd-6th decile) had significantly lower NT-proBNP (718 +/- 70.4 pg/ml), than those with fT4 < or = 11.8 (low-normal, bottom two deciles) (1236 +/- 223.6 pg/ml; p < 0.03) and those with fT4 over 14.6 pmol/l [high-normal, top four deciles] (1192 +/- 114.9 pg/ml; p < 0.0002). These differences remain significant also if adjusted for age, gender and other confounders; adjusted odds ratio was 1.30 (1.05-1.59) for optimal vs. low-normal and 1.27 (1.04-1.55) for optimal vs. high-normal. Similar statistical differences were found also in BNP and high endothelin, but only between optimal and high-normal fT4 strata. CONCLUSIONS: The degree of heart failure could be influenced also by mild changes in fT4 concentration.

Chronic Disease↗
PubMed2006

[Protective effect of protein kinase C on heart function: an experiment with isolated rabbit hearts].

OBJECTIVE: To investigate the protective effect of protein kinase C on heart function. METHODS: The hearts of 40 rabbits were isolated, underwent Langendorff perfusion, and randomly divided into 4 equal groups: Group I (control group, the heart underwent long ischemia or preservation for I hour, was re-warmed and re-infused, and then re-perfused with K-H fluid), Group II (ischemic preconditioning group, perfusion was stopped for 5 minutes before the long ischemia, then the aorta was re-infused), Group III (specific activator of PKC, phorbol myristate acetate was infused inversely via the aorta before the perfusion of K-H fluid), and Group IV (polymyxin B, a specific antagonist of PKC, was infused after the infusion of PKC). Before the preservation and by the end of reperfusion left ventricle end systolic pressure (LVESP), and left ventricle end diastolic pressure (LVDSP) were measured. At the end of experiment specimens of myocardium were collected from each heart to measure the water content, the levels of lactic dehydrogenase and MB isoenzyme of creatine kinase (CK-MB), superoxide dismutase (SOD), and malonyldialdehyde (MDA). TUNEL method was used to measure the number of apoptotic cardiomyocyte. RESULTS: All heart resumed beating. The LVESP of Group II and III were both significantly higher than those of Groups I and IV (all P < 0.05) and the LVESP of Group III was significantly higher than that of Group II too (P < 0.05). The LVEDP of Group II and III were both significantly lower than those of Groups I and IV (all P < 0.05) and the LVEDP of Group III was significantly lower than that of Group II too (P < 0.05). The levels of CK-MB, LDH, and SOD of Group II and III were all significantly higher than those of Groups I and IV (all P < 0.05) and the levels of CK-MB and LDH of Group III was significantly higher than that of Group II too (P < 0.05). The level of MDA of Group II and III were both significantly lower than those of Groups I and IV (all P < 0.05) and the level of MDA of Group III was significantly lower than that of Group II too (P < 0.05). The water contents of Group II and III were both significantly lower than those of Groups I and IV (all P < 0.05). The numbers of TUNEL positive cell and apoptotic cells of Group II and III were all significantly lower than those of Groups I and IV (all P < 0.05). CONCLUSIONS: PKC can be activated by transient ischemia and PMA. PKC protects the heart function effectively.

Animals↗