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Biomedical subjects

F C Visser

Publications and source records attributed to F C Visser.

At least 19 recordsLinked to original sources
PubMed2006

N(epsilon)-(carboxymethyl)lysine depositions in intramyocardial blood vessels in human and rat acute myocardial infarction: a predictor or reflection of infarction?

OBJECTIVE: Advanced glycation end products (AGEs), such as N(epsilon)-(carboxymethyl)lysine (CML), are implicated in vascular disease. We previously reported increased CML accumulation in small intramyocardial blood vessels in diabetes patients. Diabetes patients have an increased risk for acute myocardial infarction (AMI). Here, we examined a putative relationship between CML and AMI. METHODS AND RESULTS: Heart tissue was stained for CML, myeloperoxidase, and E-selectin in AMI patients (n=26), myocarditis patients (n=17), and control patients (n=15). In AMI patients, CML depositions were 3-fold increased compared with controls in the small intramyocardial blood vessels and predominantly colocalized with activated endothelium (E-selectin-positive) both in infarction and noninfarction areas. A trend of increased CML positivity of the intima of epicardial coronary arteries did not reach significance in AMI patients. In the rat heart AMI model, CML depositions were undetectable after 24 hours of reperfusion, but became clearly visible after 5 days of reperfusion. In line with an inflammatory contribution, human myocarditis was also accompanied by accumulation of CML on the endothelium of intramyocardial blood vessels. CONCLUSIONS: CML, present predominantly on activated endothelium in small intramyocardial blood vessels in patients with AMI, might reflect an increased risk for AMI rather than being a result of AMI.

Aged↗
PubMed2006

Alterations in contractile protein composition and function in human atrial dilatation and atrial fibrillation.

The cellular mechanisms responsible for contractile dysfunction associated with atrial fibrillation (AF) are still poorly understood. Atrial fibrillation is often preceded by atrial dilatation. This study aimed to explain contractile alterations associated with AF and their relation to atrial dilatation, by studying the relationships between atrial dimensions, contractile protein composition, force production and Ca(2+)-sensitivity. Force development was determined in mechanically isolated single skinned cardiomyocytes from right atrial appendages from patients with sinus rhythm without (SR;n=9), or with atrial dilation (SR+AD;n=11) or atrial fibrillation (AF;n=16). Echocardiography showed that, compared to the SR group, mean right atrial dimensions were increased by 18% and 35% in the SR+AD and AF group, respectively (P<0.05). Protein composition was determined by 1- and 2-dimensional gel electrophoresis. Compared to the SR group, the AF group exhibited: a reduction in the kinetics of force redevelopment (K(tr)) in isolated atrial cardiomyocytes, enhanced protein expression of the slow myosin heavy chain isoform (beta-MHC), an increase in troponin T (TnT) phosphorylation and a marked increase (70%) of the cytoskeletal protein desmin. Significant correlations were observed between the right atrial major axis (RA(major)) and beta-MHC expression as well as the desmin/actin ratio. Our findings indicate that dilatation may influence cardiomyocyte stability through altered desmin expression, but that it does not predispose to the alterations in contractile function observed in AF.

Aged↗
PubMed2006

Comparison of the haemodynamics of different pacing sites in patients undergoing resynchronisation treatment: need for individualisation of lead localisation.

BACKGROUND: Biventricular pacing is a new therapy for the treatment of heart failure. However, a substantial number of patients do not respond to this therapy. HYPOTHESIS: Individually determined maximal pacing sites will improve the haemodynamic response and increase the number of responders. METHODS: In 48 patients with heart failure, the acute haemodynamic effects of nine different pacing configurations were studied, using two right and left ventricular pacing sites and their combinations. Cardiac index was measured using Doppler echocardiography. For further analysis, the combination with the highest cardiac index improvement was compared with baseline. Moreover, the number of responders was calculated using a cut-off value of 10% increase in cardiac index. RESULTS: The mean (SD) increase in cardiac index ranged between 3.8% (6.0%) and 11.1% (8.6%). The pacing site with maximal cardiac index was highly variable between patients, and here the cardiac index increased to 14.8% (7.6%; (p<0.001). The number of responders varied between 15% and 64%, increasing to 75% at the site with maximal increase in cardiac index. In a subset of patients, the haemodynamic improvement after pacemaker implantation correlated well with the acute haemodynamics. CONCLUSION: Individualisation of pacing configuration for biventricular pacing leads to further haemodynamic improvement in patients with heart failure and reduces the number of patients not responding to this therapy.

Adult↗
PubMed2006

Patient work in end-stage heart failure: a prospective longitudinal multiple case study.

OBJECTIVE: The most recent WHO definition of palliative care regards living as actively as possible as an important aim. We explored, over a 1-year period, the work this involves for patients with end-stage heart failure. DESIGN: Prospective longitudinal multiple case study using qualitative interview techniques. PARTICIPANTS: Thirty-one respondents from two hospitals who fulfilled one or more of the following criteria: NYHA III or IV, ejection fraction <25%, at least one hospitalization for heart failure. MAIN OUTCOMES: Types and content of patient work involved in living with end-stage heart failure. RESULTS: For patients with advanced heart failure, work consisted mainly of four types of tasks, as identified by Glaser and Strauss: 'managing illness', 'everyday work to keep life going', 'biographical work' and 'arrangement work'. CONCLUSIONS: Systematic attention to patient work, for example using these four categories, could improve the quality of care from the patient's perspective.

Aged↗
PubMed2005

Myosin heavy chain composition and the economy of contraction in healthy and diseased human myocardium.

Changes in myosin heavy chain (MHC) isoform expression and protein composition occur during cardiac disease and it has been suggested that even a minor shift in MHC composition may exert a considerable effect on myocardial energetics and performance. Here an overview is provided of the cellular basis of the energy utilisation in cardiac tissue and novel data are presented concerning the economy of myocardial contraction in diseased atrial and ventricular human myocardium. ATP utilisation and force development were measured at various Ca(2+) concentrations during isometric contraction in chemically skinned atrial trabeculae from patients in sinus rhythm (SR) or with chronic atrial fibrillation (AF) and in ventricular muscle strips from non-failing donor or end-stage failing hearts. Contractile protein composition was analysed by one-dimensional gel electrophoresis. Atrial fibrillation was accompanied by a significant shift from the fast alpha-MHC isoform to the slow beta-MHC isoform, whereas both donor and failing ventricular tissue contained almost exclusively the beta-MHC isoform. Simultaneous measurements of force and ATP utilisation indicated that economy of contraction is preserved in atrial fibrillation and in end-stage human heart failure.

Adenosine Triphosphate↗
PubMed2005

Depression of force production and ATPase activity in different types of human skeletal muscle fibers from patients with chronic heart failure.

Isometric force production and ATPase activity were determined simultaneously in single human skeletal muscle fibers (n = 97) from five healthy volunteers and nine patients with chronic heart failure (CHF) at 20 degrees C. The fibers were permeabilized by means of Triton X-100 (1% vol/vol). ATPase activity was determined by enzymatic coupling of ATP resynthesis to the oxidation of NADH. Calcium-activated actomyosin (AM) ATPase activity was obtained by subtracting the activity measured in relaxing (pCa = 9) solutions from that obtained in maximally activating (pCa = 4.4) solutions. Fiber type was determined on the basis of myosin heavy chain isoform composition by polyacrylamide SDS gel electrophoresis. AM ATPase activity per liter cell volume (+/-SE) in the control and patient group, respectively, amounted to 134 +/- 24 and 77 +/- 9 microM/s in type I fibers (n = 11 and 16), 248 +/- 17 and 188 +/- 13 microM/s in type IIA fibers (n = 14 and 32), 291 +/- 29 and 126 +/- 21 microM/s in type IIA/X fibers (n = 3 and 5), and 325 +/- 32 and 205 +/- 21 microM/s in type IIX fibers (n = 7 and 9). The maximal isometric force per cross-sectional area amounted to 64 +/- 7 and 43 +/- 5 kN/m(2) in type I fibers, 86 +/- 11 and 58 +/- 4 kN/m(2) in type IIA fibers, 85 +/- 6 and 42 +/- 9 kN/m(2) in type IIA/X fibers, and 90 +/- 5 and 59 +/- 5 kN/m(2) in type IIX fibers in the control and patient group, respectively. These results indicate that, in CHF patients, significant reductions occur in isometric force and AM ATPase activity but that tension cost for each fiber type remains the same. This suggests that, in skeletal muscle from CHF patients, a decline in density of contractile proteins takes place and/or a reduction in the rate of cross-bridge attachment of approximately 30%, which exacerbates skeletal muscle weakness due to muscle atrophy.

Adenosine Triphosphatases↗
PubMed2005

Myocardial contraction is 5-fold more economical in ventricular than in atrial human tissue.

OBJECTIVE: Cardiac energetics and performance depend on the expression level of the fast (alpha-) and slow (beta-) myosin heavy chain (MHC) isoform. In ventricular tissue, the beta-MHC isoform predominates, whereas in atrial tissue a variable mixture of alpha- and beta-MHC is found. In several cardiac diseases, the slow isoform is upregulated; however, the functional implications of this transition in human myocardium are largely unknown. The aim of this study was to determine the relation between contractile properties and MHC isoform composition in healthy human myocardium using the diversity in atrial tissue. METHODS: Isometric force production and ATP consumption were measured in chemically skinned atrial trabeculae and ventricular muscle strips, and rate of force redevelopment was studied using single cardiomyocytes. MHC isoform composition was determined by one-dimensional SDS-gel electrophoresis. RESULTS: Force development in ventricular tissue was about 5-fold more economical, but nine times slower, than in atrial tissue. Significant linear correlations were found between MHC isoform composition, ATP consumption and rate of force redevelopment. CONCLUSION: These results clearly indicate that even a minor shift in MHC isoform expression has considerable impact on cardiac performance in human tissue.

Adenosine Triphosphate↗
PubMed2002

Calcium sensitivity of force in human ventricular cardiomyocytes from donor and failing hearts.

In failing human myocardium changes occur, in particular, in isoform composition and phosphorylation level of the troponin T (TnT) and troponin I (TnI) subunits of the actin filament and the myosin light chains (MLC-1 and -2), but it is unclear to what extent they influence cardiac performance. This overview concentrates on the relation between contractile function, contractile protein composition and phosphorylation levels in small biopsies from control (donor) hearts, from biopsies obtained during open heart surgery (NYHA Class I-IV) and from end-stage failing (explanted, NYHA class IV) hearts. Furthermore, attention is paid to the effect of the catalytic subunit of protein kinase A on isometric force development in single Triton-skinned human cardiomyocytes isolated from donor and end-stage failing left ventricular myocardium at different resting sarcomere lengths. A reduction in sarcomere length from 2.2 to 1.8 microm caused reductions in maximum isometric force by approximately 35% both in donor and in failing cardiomyocytes. The midpoints of the calcium sensitivity curves (pCa50) of donor and end-stage failing hearts differed markedly at all sarcomere lengths (mean delta pCa50 = 0.22). Our findings indicate that 1) TnI phosphorylation contributes to the differences in calcium sensitivity between donor and end-stage failing hearts, 2) human ventricular myocardium is heterogeneous with respect of the phosphorylation of TnT, MLC-2 and the isoform distribution of MLC-1 and MLC-2, and 3) the Frank-Starling mechanism is preserved in end-stage failing myocardium.

Calcium↗
PubMed2001

Time course of functional recovery of stunned and hibernating segments after surgical revascularization.

BACKGROUND: Recovery of function is possible in patients with ischemic cardiomyopathy when left ventricular dysfunction is caused by stunning or hibernation. It is plausible that recovery of function after revascularization may take a longer time in hibernating myocardium compared with stunned myocardium. Accordingly, the time courses of functional recovery in hibernating and stunned myocardium were compared. METHODS AND RESULTS: Patients (n=26) with ischemic cardiomyopathy undergoing surgical revascularization were studied; regional perfusion (resting (201)Tl single-photon emission CT), glucose utilization ((18)F-2-deoxyglucose single-photon emission CT), and contractile function (2D echocardiography) were assessed before revascularization. Dysfunctional segments with normal perfusion/glucose utilization were considered to be stunned, and dysfunctional segments with reduced perfusion/preserved glucose utilization were considered to be hibernating. Contractile function was reevaluated 3 months (early) and 14 months (late) after revascularization. Of the 266 dysfunctional segments, 57 (22%) were stunned, 62 (23%) were hibernating, and 147 (55%) were scar tissue. In stunned myocardium, contractile function improved significantly at 3 months, without further improvement at 14 months; 61% of the stunned segments improved at 3 months, and 9% improved at 14 months. In hibernating myocardium, contractile function improved at 3 months, with a further improvement at 14 months; 31% of the hibernating segments improved at 3 months, and 61% showed (additional) recovery at 14 months. CONCLUSIONS: Stunned myocardium is likely to demonstrate early recovery of function, whereas hibernating myocardium may take a longer time to (fully) recover in function after revascularization.

Cardiomyopathies↗
PubMed2001

Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts.

BACKGROUND: During ischemia, the intracellular calcium and inorganic phosphate (P(i)) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the myocardial response to Ca(2+), P(i), and pH. METHODS AND RESULTS: Isometric force was studied in mechanically isolated Triton-skinned single myocytes from left ventricular myocardium. Force declined with added P(i) to 0.33+/-0.02 of the control force (pH 7.1, 0 mmol/L P(i)) at 30 mmol/L P(i) and increased with pH from 0.64+/-0.03 at pH 6.2 to 1.27+/-0.02 at pH 7.4. Force dependency on P(i) and pH did not differ between donor and failing hearts. Incubation of myocytes in a P(i)-containing activating solution caused a potentiation of force, which was larger at submaximal than at maximal [Ca(2+)]. Ca(2+) sensitivity of force was similar in donor hearts and hearts with moderate cardiac disease, but in end-stage failing myocardium it was significantly increased. The degree of myosin light chain 2 phosphorylation was significantly decreased in end-stage failing compared with donor myocardium, resulting in an inverse correlation between Ca(2+) responsiveness of force and myosin light chain 2 phosphorylation. CONCLUSIONS: Our results indicate that contractile protein alterations in human end-stage heart failure alter Ca(2+) responsiveness of force but do not affect the force-generating capacity of the cross-bridges or its P(i) and pH dependence. In end-stage failing myocardium, the reduction in force by changes in pH and [P(i)] at submaximal [Ca(2+)] may even be less than in donor hearts because of the increased Ca(2+) responsiveness.

Adult↗
PubMed2001

Carbon-11 acetate as a tracer of myocardial oxygen consumption.

Estimation of myocardial oxygen consumption (MVO2) and myocardial blood flow (MBF) is important for the understanding of various (patho)physiological mechanisms and diseases. Clearance rates of carbon-11 labelled acetate, determined with positron emission tomography, allow estimation of MVO2 on a segmental level and non-invasively. In addition, MBF can be determined from uptake rates. In this review, the background to estimation of MVO2 and MBF is discussed, as well as the currently available literature that has used 11C-acetate to estimate MVO2 and MBF.

Acetates↗
PubMed2001

Relationship between preoperative viability and postoperative improvement in LVEF and heart failure symptoms.

UNLABELLED: The presence of myocardial viability is predictive of improvement in regional left ventricular (LV) function after revascularization. Studies on predicting improvement in global LV function are scarce, and the amount of viable myocardium needed for improvement in LV ejection fraction (LVEF) after revascularization is unknown. Moreover, whether the presence of viability is associated with relief of heart failure symptoms after revascularization is uncertain. Hence, the aims were to define the extent of viable myocardium needed for improvement in LVEF and to determine whether preoperative viability testing can predict improvement in heart failure symptoms. METHODS: Patients (n = 47) with ischemic cardiomyopathy (mean LVEF +/- SD, 30% +/- 6%) undergoing surgical revascularization were studied with 18F-FDG SPECT to assess viability. Regional and global function were measured before and 3-6 mo after revascularization. Heart failure symptoms were graded according to the New York Heart Association (NYHA) criteria, before and 3-6 mo after revascularization. RESULTS: The number of viable segments per patient was directly related to the improvement in LVEF after revascularization (r = 0.79, P < 0.01). Receiver operating characteristic curve analysis revealed that the cutoff level of four viable segments (representing 31% of the left ventricle) yielded the highest sensitivity and specificity (86% and 92%, respectively) for predicting improvement in LVEF. Furthermore, the presence of four or more viable segments predicted improvement in heart failure symptoms after revascularization, with positive and negative predictive values of 76% and 71%, respectively. CONCLUSION: The presence of substantial viability (four or more viable segments, 31% of the left ventricle) on FDG SPECT is predictive of improvement in LVEF and heart failure symptoms postoperatively.

Cardiomyopathy, Dilated↗
PubMed2001

Imaging of cardiac metabolism using radiolabelled glucose, fatty acids and acetate.

The heart metabolizes a wide variety of substrates such as free fatty acids, glucose, lactate, pyruvate, ketone bodies and amino acids, but under normal conditions, free fatty acids and glucose are the major sources of energy. In contrast, in ischaemia with less than normal delivery of oxygen, oxidative metabolism of free fatty acids is decreased and exogenous glucose becomes the preferred substrate and the production of energy mainly depends on anaerobic glycolysis. These metabolic changes under various pathophysiological conditions of the myocardium stress the importance of metabolism for the function of the heart and allow metabolic imaging of important cardiovascular diseases. For the detection of cardiac energy metabolism, three different tracers have been developed and validated; namely radiolabelled glucose, fatty acids and acetate. [18F]-fluorodeoxyglucose (FDG) is a glucose analogue and the initial uptake of [18F]-fluorodeoxyglucose is almost identical to that of glucose. After uptake, [18F]-fluorodeoxyglucose undergoes phosphorylation but, unlike glucose-6-phosphate, FDG-6-PO4 does not undergo further metabolism and remains trapped in the myocardium. This trapping of FDG allows imaging of FDG by positron-emission-tomography and single photon emission computed tomography (SPECT) cameras. Use of FDG for assessing acute and chronic ischaemic syndromes has been studied, but it is mainly used in clinical practice to assess dysfunction of viable myocardium, which has the ability to improve in function. FDG data have been shown to adequately predict regional and global function improvement after revascularization of patients with chronic left ventricular dysfunction and coronary artery disease (CAD). They can also be a powerful predictor of prognosis in these patients. Fatty-acid metabolism can be studied after labelling with 1-123. Beta-methyl iodine phenylpentadecanoic acid is a structurally modified fatty acid, which is used to trace uptake of fatty acids in the myocardium. Similarly to the case with FDG distinct uptake patterns have been observed in patients with CAD, and preliminary data concerning detection of myocardial viability assessment of prognosis are available. Interesting data suggest that fatty-acid imaging is the most sensitive technique for assessing metabolic changes in patients with hypertrophic cardiomyopathy. [11C]-Acetate immediately enters the tricarboxylic-acid (TCA) cycle and metabolism of [11C]-acetate is dependent solely on the TCA-cycle activity. Because the TCA-cycle activity is directly coupled to myocardial oxygen consumption, clearance rates of [11C]-acetate are used to assess regional myocardial consumption of oxygen. [11C]-acetate imaging has been validated for normal subjects and patients with CAD and appears to be as effective as use of FDG for assessing viability. The unique feature of this technique is to measure the regional consumption of oxygen non-invasively. Thus myocardial metabolic imaging is a promising approach for achieving direct insight into the processes underlying functional abnormalities of the myocardium.

Acetates↗
PubMed2001

Image-derived input functions for determination of MRGlu in cardiac (18)F-FDG PET scans.

UNLABELLED: Image-derived input functions (IDIF) are frequently used in cardiac (18)F-FDG PET studies for determination of the myocardial metabolic rate of glucose (MRGlu). The purpose of this study was to assess which vascular structure is most suited for defining the IDIF, using online arterial blood sampling (AS) as the gold standard. METHODS: In 18 patients with ischemic heart disease, 370 MBq FDG were injected during a hyperinsulinemic euglycemic clamp. Studies were performed with a Siemens/CTI HR+ PET scanner using a dynamic scanning protocol. A fully automated blood-sampling device was used for continuous AS. IDIF were obtained using regions of interest (ROIs) of 3 different sizes defined on the left ventricle (LV), left atrium (LA), ascending aorta (AA), and descending aorta (DA). MRGlu was calculated with all input functions. Ratios between MRGlu obtained with IDIF and AS were calculated for each patient. RESULTS: Time-activity curves from smaller ROIs suffered more from statistical noise with only a modest reduction of spillover effects, which led to more variation in calculated MRGlu. Mean ratios of MRGlu obtained with IDIF and AS were close to 1 when AA and DA (0.97 +/- 0.07 and 1.00 +/- 0.11, respectively) were used to define the input function. However, when LA and LV were used, mean ratios were 0.81 +/- 0.06 and 0.79 +/- 0.08, respectively, reflecting a significant underestimation of MRGlu. The use of AA for defining the input function resulted in the best agreement with AS and the smallest interobserver variation. CONCLUSION: The ascending aorta is the structure of choice for defining IDIF and a large ROI (diameter, approximately 15 mm) should be used to minimize the effects of statistical noise.

Adult↗
PubMed2000

Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial.

BACKGROUND: A high plasma homocysteine concentration is associated with increased risk of atherothrombotic disease. We investigated the effects of homocysteine-lowering treatment (folic acid plus vitamin B6) on markers of subclinical atherosclerosis among healthy siblings of patients with premature atherothrombotic disease. METHODS: We did a randomised, placebo-controlled trial among 158 healthy siblings of 167 patients with premature atherothrombotic disease. 80 were assigned placebo and 78 were assigned 5 mg folic acid and 250 mg vitamin B6 daily for 2 years. The primary endpoint was the development or progression of subclinical atherosclerosis as estimated from exercise electrocardiography, the ankle-brachial pressure index, and carotid and femoral ultrasonography. FINDINGS: Ten participants in the treatment group, and 14 in the placebo group dropped out. Vitamin treatment, compared with placebo, was associated with a decrease in fasting homocysteine concentration (from 14.7 to 7.4 micromol/L vs from 14.7 to 12.0 micromol/L), and in postmethionine homocysteine concentration (from 64.9 to 34.9 micromol/L vs from 64.8 to 50.3 micromol/L). It was also associated with a decreased rate of abnormal exercise electrocardiography tests (odds ratio 0.40 [0.17-0.93]; p=0.035). There was no apparent effect of vitamin treatment on ankle-brachial pressure indices (0.87 [0.56-1.33]), or on carotid and peripheral-arterial outcome variables (1.02 [0.26-4.05] and 0.86 [0.47-1.59], respectively). INTERPRETATION: Homocysteine-lowering treatment with folic acid plus vitamin B6 in healthy siblings of patients with premature atherothrombotic disease is associated with a decreased occurrence of abnormal exercise electrocardiography tests, which is consistent with a decreased risk of atherosclerotic coronary events.

Blood Pressure↗