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Biomedical subjects

Karl Werdan

Publications and source records attributed to Karl Werdan.

At least 37 records · Page 2Linked to original sources
PubMed2005

Prognostic impact of autonomic information flow in multiple organ dysfunction syndrome patients.

BACKGROUND: Multiple organ dysfunction syndrome (MODS) is the sequential failure of several organ systems after a trigger event, like cardiogenic shock or decompensated heart failure. Mortality is high, up to 70%. Autonomic dysfunction (AD) may substantially contribute to the development of MODS. In cardiology, it has recently been shown that nonlinear parameters could predict mortality. Our study aimed at 1. characterising the complex characteristics of AD of critically ill MODS patients by the nonlinear parameters of autonomic information flow (AIF), 2. comparing AIF with autonomic function of healthy controls, and 3. characterising the accuracy of this parameter in predicting mortality in MODS. METHODS: We enrolled 43 score-defined MODS patients who were consecutively admitted to a twelve-bed medical intensive care unit in a university centre into this prospective outcome study. Additionally, we assigned 50 healthy controls to the study. AIF was assessed as a complexity function of AD using 24-h ECG. Measures of AIF were introduced according to the standard HRV concept. The patients were followed up for 28-day mortality. RESULTS: MODS causes a disorganisation of short term AIF in favour of an enhanced (rigid) long term AIF. Concerning prognosis increased short term AIF was associated with survival. Short term AIF discriminated between MODS survivors and non-survivors at the level of APACHE II score. CONCLUSIONS: This is the first study providing evidence that complex AD of MODS patients is specifically assessed by AIF time scales and that AIF has significant prognostic impact.

Adult↗
PubMed2005

The human FGF2 level is influenced by genetic predisposition.

BACKGROUND: The fibroblast growth factor 2 (FGF2) is involved in various processes possibly leading to the development of complex diseases such as atherosclerosis. In recent studies, its cardioprotective properties, due to its ability to stimulate the proliferation of collateral vessels, could be shown. STUDY DESIGN: In this clinical study, the relation between clinical risk markers, a genomic variant of FGF2, namely the c.223C>T polymorphism, and the in vivo FGF2 expression was evaluated. Therefore, 198 clinically well-characterized probands, all of Caucasian origin, were included. The FGF2 mRNA level was determined in monocytes by competitive RT-PCR, whereas the plasma level of circulating FGF2 protein was analysed by ELISA. By considering the angiographically proven stenotic state of the patient, a significant increase in FGF2 mRNA, but not in protein level, could be shown for patients with significant stenosis. Apart from this, no influence on FGF2 expression was found in the case of all of the clinical and biochemical markers investigated. However, in the case of the c.223C>T polymorphism, a significant increase in the individual FGF2 mRNA and protein level in CC-carriers was shown. In multivariate analysis, this relation was independent of all other risk markers investigated. CONCLUSIONS: Our results suggest that an increase in FGF2 mRNA expression, related to coronary atherosclerosis, may be necessary for the maintenance of the individual FGF2 plasma level. Since the individual FGF2 mRNA and protein level are, to a large extent, triggered off by genetic background, the FGF2 expression cannot be referred to as an independent clinical marker for CAD.

Coronary Artery Disease↗
PubMed2005

Chemo- and ergoreflexes in health, disease and ageing.

The chemo- and ergoreflexes (muscle receptors) are among the major reflex arches, which adapt the respiratory and the cardiovascular system to the needs of the body and contribute to its homeostasis. The present paper reviews the interplay of these reflexes with other major cardiovascular reflex arches; the methods used for their calculation and their normal range data. The clinical implications of chemoreflex sensitivities and ergoreflexes in chronic heart failure (CHF) as well as the application of chemoreflexes in coronary artery disease, sudden cardiac death and multiple organ dysfunction syndrome are discussed.

Aging↗
PubMed2005

Divergent siblings: E2F2 and E2F4 but not E2F1 and E2F3 induce DNA synthesis in cardiomyocytes without activation of apoptosis.

Proliferation of mammalian cardiomyocytes ceases around birth when a transition from hyperplastic to hypertrophic myocardial growth occurs. Previous studies demonstrated that directed expression of the transcription factor E2F1 induces S-phase entry in cardiomyocytes along with stimulation of programmed cell death. Here, we show that directed expression of E2F2 and E2F4 by adenovirus mediated gene transfer in neonatal cardiomyocytes induced S-phase entry but did not result in an onset of apoptosis whereas directed expression of E2F1 and E2F3 strongly evoked programmed cell death concomitant with cell cycle progression. Although both E2F2 and E2F4 induced S-phase entry only directed expression of E2F2 resulted in mitotic cell division of cardiomyocytes. Expression of E2F5 or a control LacZ-Adenovirus had no effects on cell cycle progression. Quantitative real time PCR revealed that E2F1, E2F2, E2F3, and E2F4 alleviate G0 arrest by induction of cyclinA and E cyclins. Furthermore, directed expression of E2F1, E2F3, and E2F5 led to a transcriptional activation of several proapoptotic genes, which were mitigated by E2F2 and E2F4. Our finding that expression of E2F2 induces cell division of cardiomyocytes along with a suppression of proapoptotic genes might open a new access to improve the regenerative capacity of cardiomyocytes.

Adenoviridae↗
PubMed2005

Surgical trauma affects the proinflammatory status after cardiac surgery to a higher degree than cardiopulmonary bypass.

OBJECTIVES: Cytokines contribute to the development of the systemic inflammatory response syndrome or multiple-organ failure frequently observed after cardiopulmonary bypass-supported cardiac surgery. To quantify the contribution of bypass-induced versus trauma-induced inflammatory response after coronary artery bypass grafting, we examined plasma cytokine levels in 120 patients with coronary artery disease who were treated with or without cardiopulmonary bypass-assisted procedures. METHODS: Patients were treated in accordance with one of the following protocols: (1) elective percutaneous coronary intervention without cardiopulmonary bypass (n = 69), (2) cardiopulmonary bypass-supported percutaneous coronary intervention (cardiopulmonary bypass-percutaneous coronary intervention; n = 10), and (3) cardiopulmonary bypass-supported coronary artery bypass grafting (cardiopulmonary bypass-coronary artery bypass grafting; n = 41). Cytokine levels (picograms/milliliter) were measured by enzyme-linked immunosorbent assay from plasma samples obtained at various time points. RESULTS: Interleukin-6 was measured in blood samples from all 3 patient populations. The maximum interleukin-6 level was 13.6 +/- 22.3 pg/mL in the percutaneous coronary intervention group, 170.4 +/- 165.4 pg/mL in the cardiopulmonary bypass-percutaneous coronary intervention group, and 640.3 +/- 285.7 pg/mL in the cardiopulmonary bypass-coronary artery bypass grafting group. Interleukin-6 levels were significantly different, and the 95% confidence intervals did not overlap. In the cardiopulmonary bypass-percutaneous coronary intervention group, bypass duration correlated well with interleukin-6 production ( r = 0.915; P < .001), whereas these parameters did not correlate in patients who underwent cardiopulmonary bypass-coronary artery bypass grafting ( r = 0.307; P = .054). CONCLUSIONS: These findings support the suggestion that surgical trauma and cardiopulmonary bypass contribute to the inflammatory response after cardiac surgery, although trauma may contribute to a higher degree.

Angioplasty, Balloon, Coronary↗
PubMed2005

Apoptosis-modulating interaction of the neuregulin/erbB pathway with anthracyclines in regulating Bcl-xS and Bcl-xL in cardiomyocytes.

During chemotherapy with anthracyclines, attenuated neuregulin signaling by the erbB2 receptor inactivating antibody Trastuzumab enhances the heart failure risk. We compared the effects of attenuated neuregulin/erbB signaling and of daunorubicin on splicing of the Bcl-x gene and on mitochondrial activation of apoptosis in cardiomyocytes. Attenuating erbB signals in cultured neonatal rat cardiomyocytes by the erbB2 antagonist tyrphostin AG825, by the erbB1/4 antagonist AG1478 or by antisense-induced lowering of erbB2 receptors resulted in an augmented Bcl-xS/Bcl-xL ratio, mitochondrial release of cytochrome c, activation of caspase 9 and caspase 3, and nucleosome-sized DNA fragmentation. A similar DNA fragmentation and caspase 3 activation was induced by TNF-alpha, but without Bcl-xS/Bcl-xL increase, cytochrome c release or caspase 9 activation. A BH4-domain containing HIV TAT fusion protein added to cardiomyocytes under attenuated erbB signaling lowered the enhanced Bcl-xS/Bcl-xL ratio, the cytochrome c release, the caspase 3 activation and the DNA fragmentation, while apoptosis was not modified by the fusion protein in TNF-alpha treated cardiomyocytes. Enhancement of Bcl-xS/Bcl-xL by reducing Bcl-xL via siRNA transfection mimicked the mitochondrial apoptotic activation due to erbB signal attenuation. Daunorubicin also caused Bcl-xS/Bcl-xL enhancement and mitochondrial apoptotic activation in cultured cardiomyocytes; this was attenuated by BH4-fusion protein or by neuregulin-1 and augmented by siRNA-mediated Bcl-xL lowering. We conclude that activation of mitochondrial apoptosis due to altered Bcl-x splicing contributes as a common mechanism of anthracyclines and erbB signal attenuation to the enhanced heart failure risk under this combination.

Animals↗
PubMed2005

Autonomic dysfunction predicts mortality in patients with multiple organ dysfunction syndrome of different age groups.

OBJECTIVE: Multiple organ dysfunction syndrome (MODS) is the sequential failure of several organ systems after a trigger event, like sepsis or cardiogenic shock. Mortality rate is high, up to 70%. Autonomic dysfunction may substantially contribute to the development of MODS. Our study aimed to characterize a) the spectrum of autonomic dysfunction of critically ill MODS patients; b) whether autonomic dysfunction is different in patients receiving sedation, mechanical ventilation, or catecholamines; c) the age dependency of autonomic dysfunction in MODS; and d) whether autonomic dysfunction predicts mortality in MODS. DESIGN: Prospective cohort study. SETTING: Twelve-bed medical intensive care unit in a university center. PATIENTS: Ninety consecutively admitted score-defined MODS patients. INTERVENTIONS: Assessment of heart rate variability, baroreflex sensitivity, and chemoreflex sensitivity as markers of autonomic dysfunction. The patients were followed for 28-day mortality. MEASUREMENTS AND MAIN RESULTS: Baroreflex sensitivity, chemoreflex sensitivity, and almost all indexes of heart rate variability were attenuated in comparison to normal range data. There was no association between the assessed heart rate variability variables, baroreflex sensitivity or chemoreflex sensitivity, and the presence of sedation or catecholamine therapy. Except for frequency-domain variables, pNN50 (percentage of differences of successive RR intervals differing >50 msecs) and rMSSD (root mean square of successive difference of N-N intervals), none of the measured variables were related to the presence of mechanical ventilation. Age dependency was detected for baroreflex sensitivity but not for heart rate variability indexes or chemoreflex sensitivity (across ages 24-96 yrs). lnVLF predicted 28-day mortality best in the entire cohort of patients and in a subgroup of patients with cardiogenic-triggered MODS. CONCLUSIONS: Autonomic function of MODS patients is blunted, and this attenuation has prognostic implications. The extensive influence of MODS on autonomic function overwhelms and masks the well-known age dependency of autonomic function seen in healthy persons.

Adult↗
PubMed2005

Optimal maximum tracking rate of dual-chamber pacemakers required by children and young adults for a maximal cardiorespiratory performance.

INTRODUCTION: Children and young adults require a higher maximum tracking rate (MTR) for physical activity. The objective of the present study was to observe whether higher MTR of 170 or 190 beats per minute (bpm) have a positive impact on the maximal cardiorespiratory capacity of children and young adults in comparison with a lower MTR of 140 bpm. METHODS: Fifteen patients with atrioventricular block and normal sinus-node chronotropic function (age 7-24 years) with DDD- (14) or VDD-pacemakers (PM) (1) were enrolled. First, the MTR was adjusted to 140 bpm for 6 weeks and elevated in a second step to 170 or 190 bpm. At the end of each period two cardiopulmonary exercise tests, a 24-hour ECG and a PM test were performed. RESULTS: All patients increased their maximal heart rate (139.0 +/- 1.0 vs 177.0 +/- 10.0 bpm, P < 0.001), peak cardiorespiratory capacity (2.4 +/- 0.6 vs 2.8 +/- 0.7 W/kg, P < 0.001), peak oxygen uptake (28.3 +/- 7.0 vs 35.7 +/- 9.5 mL/kg/min, P < 0.005), and oxygen uptake (23.7 +/- 7.4 vs 29.3 +/- 8.4 mL/kg/min, P < 0.02) at the anaerobic threshold. There were no evident heart rhythm disturbances with elevated MTR. Patients with a Wenckebach behavior of the PM had an attenuated increase of maximal cardiorespiratory performance. CONCLUSION: Children and young adults with DDD-/VDD-PM benefit from an elevated MTR by an increased cardiorespiratory capacity, without having more heart rhythm disturbances. A Wenckebach behavior of the PM should be avoided.

Adolescent↗
PubMed2004

Systemic inflammatory response and progression to severe sepsis in critically ill infected patients.

RATIONALE: The systemic inflammatory response syndrome has low specificity to identify infected patients at risk of worsening to severe sepsis or shock. OBJECTIVE: To examine the incidence of and risk factors for worsening sepsis in infected patients. METHODS: A 1-year inception cohort study in 28 intensive care units of patients (n = 1,531) having a first episode of infection on admission or during the stay. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of progression to severe sepsis or shock was 20% and 24% at Days 10 and 30, respectively. Variables independently associated (hazard ratio [HR]) with worsening sepsis included: temperature higher than 38.2 degrees C (1.6), heart rate greater than 120/minute (1.3), systolic blood pressure higher than 110 mm Hg (1.5), platelets higher than 150 x 109/L (1.5), serum sodium higher than 145 mmol/L (1.5), bilirubin higher than 30 mumol/L (1.3), mechanical ventilation (1.5), and five variables characterizing infection (pneumonia [HR 1.5], peritonitis [1.5], primary bacteremia [1.8], and infection with gram-positive cocci [1.3] or aerobic gram-negative bacilli [1.4]). The 12 weighted variables were included in a score (Risk of Infection to Severe Sepsis and Shock Score, range 0-49), summarized in four classes of "low" (score 0-8) and "moderate" (8.5-16) risk (9% and 17% probability of worsening, respectively), and of "high" (16.5-24) and "very high" (score > 24) risk (31% and 55% probability, respectively). CONCLUSIONS: One of four patients presenting with infection/sepsis worsen to severe sepsis or shock. A score estimating this risk, using objectively defined criteria for systemic inflammatory response syndrome, could be used by physicians to stratify patients for clinical management and to test new interventions.

Adult↗
PubMed2004

[Intensive care medicine 2004].

The following survey is supposed to present the most important new therapeutic approaches und the current standard of treatment in intensive care medicine including pathophysiological and diagnostic aspects of important diseases, particularly sepsis, septic and cardiogenic shock. Furthermore, advances in the following issues are summarized in detail: ventilation, especially acute respiratory distress syndrome (ARDS) and the broad spectrum of non-invasive ventilation, new therapeutic options in the field of cardiopulmonary resuscitation, and the importance of albumin dialysis in acute liver failure.

Adult↗
PubMed2004

Impaired chemoreflex sensitivity in adult patients with multiple organ dysfunction syndrome--the potential role of disease severity.

OBJECTIVE: The cardiac chemoreflex sensitivity is a powerful predictor of autonomic dysfunction in chronic heart failure and after myocardial infarction. The objective of the present study was to characterize cardiac chemoreflex sensitivity in patients with multiple organ dysfunction syndrome (MODS). We also aimed to elucidate the effect of the severity of MODS on the assessment of cardiac chemoreflex sensitivity. DESIGN: Prospective cohort study. SETTING: Twelve-bed medical intensive care unit in a university center. PATIENTS: Forty consecutively admitted patients with MODS during a 7-month period. Patients with MODS were identified by an APACHE II score of 20 or more. Sepsis was defined as a Sepsis Score, according to Elebute and Stoner, of 12 or more. INTERVENTIONS: The cardiac chemoreflex sensitivity was assessed using the regression of heart interval (ms) versus arterial oxygen pressure (mmHg). MEASUREMENTS AND RESULTS: First, we established a new method to assess cardiac chemoreflex sensitivity and applied it to healthy controls and patients. Second, we found that cardiac chemoreflex sensitivity correlated with the severity of MODS as calculated by the APACHE II score ( r(2)=0.34, p=0.001). This relation was best fitted by a model including minimum heart rate and standard bicarbonate in 24 h ( r(2)=0.5, p<0.001) and Glasgow Coma Scale ( r(2)=0.5, p=0.005). Age, however, did not significantly contribute ( r(2)=0.001, p=0.8). CONCLUSIONS: The calculation of cardiac chemoreflex sensitivity enabled us to quantify an important component of the cardiorespiratory interactions in patients with MODS. Severity of illness was a more pronounced determinant of impaired cardiac chemoreflex sensitivity than age. The quantification of the cardiorespiratory interactions by measuring the cardiac chemoreflex sensitivity has potential to identify a subgroup of patients with worse prognosis.

APACHE↗
PubMed2004

[Arteriosclerosis and coronary heart disease--a hundred years later].

Within the last century, cardiovascular medicine has seen incredible progress. In 1904 history and physical examination were the sole diagnostic tools, and only lifestyle changes and a few effective medications could be recommended therapeutically. In 2004, however, nearly every vascular region can be visualized and treated either medically, interventionally or surgically. And treatment is not only based upon expert consensus but often on evidence-based recommendations. In view of the demographic development, cardiovascular medicine in the following decades will be able to provide great benefit to the elderly population as regards quality of life and autonomy -- at the prize, though, of increasing socioeconomic challenges that society will have to face.

Arteriosclerosis↗
PubMed2003

Plasma atrial natriuretic peptide and brain natriuretic peptide are increased in septic shock: impact of interleukin-6 and sepsis-associated left ventricular dysfunction.

OBJECTIVE: Interest has recently focused on the use of neurohormonal markers such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) as indices of left ventricular systolic dysfunction and prognosis in heart failure. Also, peptides belonging to the interleukin-6 (IL-6) family have been shown to induce ANP and BNP secretion. We hypothesized that BNP and ANP spillover in the peripheral circulation reflects left ventricular dysfunction and IL-6 production in septic shock. DESIGN AND SETTING: Retrospective, clinical study in the medical intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: 17 patients with septic shock and 19 control subjects. INTERVENTIONS: Collection of clinical and demographic data in relation to ANP, BNP, IL-6, and soluble TNF receptors (sTNF-R-p55, sTNF-R-p75) in plasma over a period of 4 days. MEASUREMENTS AND RESULTS: In septic shock we found a significant increase in ANP (82.7+/-9.9 vs. 14.9+/-1.2 pg/ml) and BNP (12.4+/-3.6 vs. 5.5+/-0.7 pg/ml). Plasma ANP peaked together with IL-6. Peaks of ANP and IL-6 were significantly correlated (r=0.73; p<0.01). BNP was inversely correlated to cardiac index (r=-0.56; p<0.05). CONCLUSIONS: ANP and BNP increase significantly in patients with septic shock. BNP reflects left ventricular dysfunction. ANP is related to IL-6 production rather than to cardiovascular dysfunction.

Atrial Natriuretic Factor↗
PubMed2003

Role of LDL receptor-related protein (LRP) in coronary atherosclerosis.

The development and progression of coronary atherosclerosis is influenced by a variety of genetic and environmental factors. Among the genetic factors, the cell surface receptor LRP/A2MR (LDL receptor-related protein/alpha2-macroglobulin receptor) was shown to be involved in a variety of biological processes leading to atherosclerotic plaque formation. That is why the individual expression of this receptor may, therefore, be considered as an evident predictor for coronary atherosclerosis. In this clinical ex vivo study the expression was measured by competitive RT-PCR and macroarray analysis in native monocytes. Both methods were first tested in an in vitro model using different human cells and cell lines (fibroblasts: chorion, skin; endothelial cells from umbilical cord vein; monocyte cell line: Mono-Mac-6): after stimulation with an LRP/A2MR ligand, leptin, the anticipated direct effect of this ligand, namely an increase in both receptor mRNA and protein expression, was confirmed. In disease-related ex vivo studies the mRNA and protein-expression of LRP/A2MR was investigated in 36 male patients suffering from myocardial infarction. In comparison to the control group (36 healthy male blood donors), a significant up-regulation of mRNA was detected in the myocardial infarction patient group (control: 122.3 ag/cell versus patients: 223 ag/cell; P<0.001). Investigating the LRP/A2MR protein expression a significant down-regulation of protein expression was determined in the patient group (control: 6 pg/cell versus patients: 1.6 pg/cell; P<0.001). The ratio of LRP/A2MR mRNA and protein expression is obviously an evident marker for coronary atherosclerosis, recommendable for the assessment of the individual coronary risk profile.

Blood Donors↗
PubMed2002

Direct costs of severe sepsis in three German intensive care units based on retrospective electronic patient record analysis of resource use.

OBJECTIVE: To determine the direct costs of severe sepsis patients in German intensive care units (ICUs). DESIGN: Retrospective electronic data analysis. SETTING: Three adult intensive care units (surgical/medical) in three university hospitals in Germany. PATIENTS: 385 patients identified by standard definitions as suffering from severe sepsis. MEASUREMENTS AND RESULTS: A bottom-up approach was used to determine the direct ICU cost on actual resource use (medication, laboratory tests, microbiological analysis, disposables, and clinical procedures) for patients with severe sepsis. To determine the total direct costs, center-specific personnel and basic bed ("hotel") costs were added to total resources consumed. Average hospital mortality of severely septic patients was 42.6%. Mean ICU length of stay (LOS) was 16.6 days. Survivors stayed on average 4 days longer than nonsurvivors. The mean direct ICU costs of care were 23,297+/-18,631 euros per patient and 1,318 euros per day. In comparison, average daily charges being paid for an ICU patient by the health care system in Germany are 851 euros (based on official statistics). Nonsurvivors were more expensive than survivors in total direct costs (25,446 vs. 21,984 euros) and in per day direct cost (1,649 vs. 1,162 euros). Medication makes up the largest part of the direct costs, followed by expenses for personnel. CONCLUSIONS. Patients with severe sepsis have a high ICU mortality rate and long ICU LOS and are substantially expensive to treat. Nonsurviving septic patients are more costly than survivors despite shorter ICU LOS. This is due to higher medication costs indicating increased efforts to keep patients alive.

Adult↗
PubMed2002

The LDL receptor-related protein (LRP1/A2MR) and coronary atherosclerosis--novel genomic variants and functional consequences.

The LDL receptor-related protein/alpha 2-macroglobulin receptor (LRP1/A2MR) is a multifunctional cell-surface glycoprotein that endocytoses several structurally and functionally distinct ligands. In clinical studies different genomic variants of the LRP1/A2MR and its role in the development of degenerative diseases like atherosclerosis or Alzheimer's disease were studied. We screened for novel genomic variants of LRP1/A2MR and investigated the importance of these variants in 214 coronary patients suffering from myocardial infarction as well as in 224 healthy controls. We detected a novel C>G polymorphism at position -25 in the functionally important promoter region of LRP1/A2MR. This polymorphism (c.1-25C>G) leads to the creation of a new GC-box, recognized by the constitutively expressed SP 1 transcription factor. Investigating the LRP1/A2MR gene expression with respect to this polymorphism, carriers of the mutant G-allele were found to have a higher mRNA expression level. A novel polymorphism in exon 22 (c.4012C>T), and two novel polymorphisms in intron 24 (IVS24+123C>A and IVS24+690G>A) associated with a previously described polymorphism in exon 61 (c.10249G>A), were related to the development of myocardial infarction. Two novel rare genetic variants of exon 88 (c.13933C>T) and intron 88 (IVS88+15G>A) were identified in four patients with severe coronary symptoms. However, the LRP1/A2MR gene expression was found to be independent of all identified novel genomic variants as well as other previously described changes (A217V, A775P, D2080N, D2632E, G4379S) except the promoter polymorphism.

Adult↗
PubMed2002

The ageing heart: influence of cellular and tissue ageing on total content and distribution of the variants of elongation factor-2.

The involvement of elongation factor-2 (EEF-2), a key-protein of peptide-chain elongation, in the slowing down of protein synthesis during cardiac ageing was addressed. EEF-2 was measured in rat heart extracts and isolated rat cardiomyocytes (CM) from newborn and adult rats using sodium-dodecylsulphate polyacrylamide gel electrophoresis after specific labeling with [32P]ADP-ribosylation or immunoblot. The age-dependent proportional content of several eucaryotic elongation factor-2 (eEF-2) subtypes in rat CM and rat heart extracts was compared using one-dimensional isoelectric focusing. EEF-2 was considerably reduced in the hearts of adult compared to neonatal rats (P<0.01). EEF-2 was also significantly decreased in isolated CM from adult versus newborn rats and during prolonged cultivation of neonatal CM. Cellular ageing was combined with reduced protein synthesis. During adolescence the eEF-2 variants shifted to acidic subtypes. Young adult and old rats revealed similar amounts and subtype distribution of cardiac eEF-2. Only the more acidic eEF-2 variants appeared to contain phosphorylated eEF-2. We concluded that total cardiac eEF-2 and its subtype pattern might play an important role in developmental and age-related proteomic changes.

Adenosine Diphosphate↗