Mechanisms involved in the hemodynamic alterations in congestive heart failure as a basis for a rational pharmacological treatment

Marı́n, Jesús; Marı́n, Esperanza; Gutiérrez-Iñiguez, M.Angeles; Avendaño, Cristina; Rodríguez-Martínez, María

doi:10.1016/s0163-7258(00)00076-0

Cited by 10 publications

(6 citation statements)

References 166 publications

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“…Furthermore, as pharmacologic treatment plays an important role in the treatment of heart failure patients, biochemical monitoring of radiation patients may facilitate the initiation of medication (e.g. ␤ -blockers or ACE inhibitors) to prevent heart failure and/or attenuate its progression [28] .…”

Section: Discussionmentioning

confidence: 99%

Effects of Radiation Therapy on Myocardial Cell Integrity and Pump Function: Which Role for Cardiac Biomarkers?

Nellessen¹,

Zingel²,

Hecker

et al. 2010

Chemotherapy

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Background: Radiation therapy to the mediastinum and breast can be associated with cardiac complications. Cardiac damage may manifest early during radiation therapy or occur late, years after radiation therapy has been finished. Hypothesis: Myocardial damage is associated with the release of both troponin I (TnI) and brain natriuretic peptide (BNP). The current study sought to determine whether radiation treatment to the mediastinum and breast leads to the release of cardiac biomarkers. Methods: The study comprised 23 patients: 18 with lung cancer and 5 with breast cancer. Radiation therapy was performed for up to 6 weeks. Total radiation dose was >45 Gy in each patient with a dose of 1.8 Gy per fraction. Blood samples to determine TnI and BNP were taken before and once a week during radiation therapy. Echocardiography was done before and after radiation had been finished. Results: Two patients died during the study. Both TnI and BNP levels increased significantly during the study (log₁₀ scale); however, absolute and mean values remained on a relatively low level (mean preradiation and postradiation TnI: 0.007 ± 0.008, 0.014 ± 0.01 ng/ml; mean preradiation and postradiation BNP: 123 ± 147, 159 ± 184 pg/ml). Conclusion: Radiation therapy leads to cardiac cell damage and changes in the left ventricular loading conditions as suggested by a significant increase of the cardiac biomarkers TnI and BNP. Determination of serum levels seems to be superior to echocardiography in detecting radiation-induced cardiac damage. Serial measurements of cardiac biomarkers may facilitate the management of patients undergoing radiation therapy and may help to define subgroups at high risk of developing heart failure.

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Section: Discussionmentioning

confidence: 99%

Effects of Radiation Therapy on Myocardial Cell Integrity and Pump Function: Which Role for Cardiac Biomarkers?

Nellessen¹,

Zingel²,

Hecker

et al. 2010

Chemotherapy

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“…11 These observations may be clinically relevant, because the initial stage of heart disease is typically characterized by I to downregulation 2,10 and neurohumoral activation, 30 both of which may elevate Ca 2ϩ influx and intracellular Ca 2ϩ , thereby helping to maintain adequate cardiac output from the diseased heart. Our results suggest that normalization of Ca 2ϩ cycling via I Ca,L blockade or decoupling of the beneficial inotropic effects of Ca 2ϩ from its detrimental hypertrophic effects via inhibition of Ca 2ϩ -dependent signaling pathways may present a useful therapeutic strategy for heart disease treatment.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Calcineurin and Sarcolemmal Ca ²⁺ Influx Protects Cardiac Morphology and Ventricular Function in K _v 4.2N Transgenic Mice

et al. 2002

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Background-Cardiac-targeted expression of truncated K v 4.2 subunit (K v 4.2N) reduces transient outward current (I to ) density, prolongs action potentials (APs), and enhances contractility in 3-to 4-week-old transgenic mice. By 13 to 15 weeks of age, these mice develop severely impaired cardiac function and signs of heart failure. In this study, we examined whether augmented contractility in K v 4.2N mice results from elevations in intracellular calcium ([Ca 2ϩ ] i ) secondary to AP prolongation and investigated the putative roles of calcineurin activation in heart disease development of K v 4.2N mice. Methods and Results-At 3 to 4 weeks of age, L-type Ca 2ϩ influx and peak [Ca 2ϩ ] i were significantly elevated in K v 4.2N myocytes compared with control because of AP prolongation. Cardiac calcineurin activity was also significantly elevated in K v 4.2N mice by 5 weeks of age relative to controls and increased progressively as heart disease developed. This was associated with activation of protein kinase C (PKC)-␣ and PKC-but not PKC-⑀, as well as increases in ␤-myosin heavy chain (␤-MHC) and reductions in sarcoplasmic/endoplasmic reticulum Ca 2ϩ -ATPase (SERCA)-2a expression. Treatment with either cyclosporin A or verapamil prevented increases in heart weight to body weight ratios, interstitial fibrosis, impaired contractility, PKC activation, and changes in the expression patterns of ␤-MHC and SERCA2a.Conclusions-Our results demonstrate that AP prolongation caused by I to reduction results in enhanced Ca 2ϩ cycling and hypercontractility in mice and suggests that elevations in [Ca 2ϩ ] i via I Ca,L and activation of calcineurin play a central role in disease development after I to reduction using the K v 4

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“…Following the trigger event, a variety of compensatory neurohumoral processes are activated, resulting in a normal cardiac output in the presence of elevated filling pressures, thus keeping the patient asymptomatic. [1][2][3] However, over time the patient will undergo transition from asymptomatic to symptomatic HF due to cardiac decompensation on the basis of left ventricular (LV) remodeling with subsequent myocardial damage. Up to now, the role of biochemical markers indicating severe progression of the disease has yet to be defined.…”

Section: Introductionmentioning

confidence: 99%

Serial analysis of troponin I levels in patients with ischemic and nonischemic dilated cardiomyopathy

Nellessen

Goder

Schobre

et al. 2006

Clinical Cardiology

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SummaryBackground: Ongoing myocardial cell damage forms the basis for progression of chronic heart failure. Evidence is accumulating that progressive loss of cardiac myocytes is associated with the release of cardiac troponin I (cTnI).Hypothesis: This study sought to determine whether levels of cTnI are of prognostic value for risk stratification of patients with chronic heart failure.Methods: Release of cTnI was measured by conventional enzyme immunoassay following serum ultrafiltration in 58 consecutive patients hospitalized for chronic heart failure and 31 healthy volunteers serving as control group. Determination of serum levels was performed every 2 weeks over a time interval of 3 months. According to the results of coronary angiography, patients were divided into Group D showing normal coronary arteries (n = 33, ejection fraction 27 ± 6.1%) and Group I showing severe coronary heart disease (n = 25, ejection fraction 28.8 ± 7.8%). Survival of patients was evaluated after a mean time interval of 3 years.Results: The mean cTnI serum level over all measurements was 0.66 ± 1.8 ng/ml in patients versus 0.11 ± 0.48 ng/ml in volunteers. At all six points of analysis, the mean cTnI serum level was significantly different (p < 0.001) between patients and volunteers. There was no significant difference between patients with and without coronary heart disease following hospital discharge, however, troponin release was significantly different between survivors and nonsurvivors (n = 27) (0.56 ng/ml vs. 0.84 ng/ml; p < 0.05).

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Mechanisms involved in the hemodynamic alterations in congestive heart failure as a basis for a rational pharmacological treatment

Cited by 10 publications

References 166 publications

Effects of Radiation Therapy on Myocardial Cell Integrity and Pump Function: Which Role for Cardiac Biomarkers?

Effects of Radiation Therapy on Myocardial Cell Integrity and Pump Function: Which Role for Cardiac Biomarkers?

Inhibition of Calcineurin and Sarcolemmal Ca ²⁺ Influx Protects Cardiac Morphology and Ventricular Function in K _v 4.2N Transgenic Mice

Serial analysis of troponin I levels in patients with ischemic and nonischemic dilated cardiomyopathy

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Mechanisms involved in the hemodynamic alterations in congestive heart failure as a basis for a rational pharmacological treatment

Cited by 10 publications

References 166 publications

Effects of Radiation Therapy on Myocardial Cell Integrity and Pump Function: Which Role for Cardiac Biomarkers?

Effects of Radiation Therapy on Myocardial Cell Integrity and Pump Function: Which Role for Cardiac Biomarkers?

Inhibition of Calcineurin and Sarcolemmal Ca 2+ Influx Protects Cardiac Morphology and Ventricular Function in K v 4.2N Transgenic Mice

Serial analysis of troponin I levels in patients with ischemic and nonischemic dilated cardiomyopathy

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Inhibition of Calcineurin and Sarcolemmal Ca ²⁺ Influx Protects Cardiac Morphology and Ventricular Function in K _v 4.2N Transgenic Mice