Pharmacological therapy can increase capillary density in post-infarction remodeled rat hearts

Kerckhoven, Roeland Van

doi:10.1016/j.cardiores.2003.09.026

Cited by 36 publications

(27 citation statements)

References 47 publications

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“…In another recent study of rats with myocardial infarction, 3 weeks treatment with agents that normalised post-infarction tachycardia (aspirin, methylprednisolone) led to increases in capillary-to-fibre ratio in the remaining viable left ventricle despite myocyte hypertrophy [38], and in the same model, even modest heart rate reductions of 2--18% induced over 3 months by a sinoatrial node modulator ivabradine almost doubled CD in viable tissue compared to untreated infarcted hearts [39].…”

Section: Figurementioning

confidence: 96%

Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia

2005

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Angiogenesis and improved left ventricular function as a consequence of long-term bradycardia were first demonstrated in normal hearts, either electrically paced (rabbits, pigs) or treated with a selective sinus blocking drug alinidine (rats). Here we review the evidence that chronic heart rate reduction can have similar effects in the heart with compromised vascular supply, due to either hypertensive or haemodynamic overload hypertrophy (rats, rabbits) or ischaemic damage (rats, rabbits, pigs). Bradycardia induced over several weeks increased capillarity in all hypertrophied hearts, and in border and remote left ventricular myocardium of infarcted hearts. In some, but not all cases, coronary blood flow was improved by heart rate reduction, suggesting enlargement of the resistance vasculature in some circumstances. Cardiac or left ventricular function indices, which were depressed by hypertrophy or ischaemic damage, were preserved or even enhanced by chronic heart rate reduction. The expansion of the capillary bed in the vascularly compromised heart induced by bradycardia may be stimulated by mechanical stretch of the endothelium and/or VEGF activated by chamber dilation and myocyte stretch. The increased number of capillaries and more homogeneous distribution of capillary perfusion would support the better pump function, even in the absence of higher coronary flow. The beneficial impact of chronic heart rate reduction on myocardial angiogenesis and function in cardiac hypertrophy and infarction may be major factor in the success of beta-blockers in treatment of human heart failure.

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Section: Figurementioning

confidence: 96%

Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia

2005

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“…This model has been described previously [23]. Briefly, rats were anesthetized with 2.5% isoflurane and placed on a heating pad (37°C).…”

Section: Myocardial Infarction Modelmentioning

confidence: 99%

“…Deparaffinised 5-μm thick sections were stained with a Gomori's silver staining. Using image analysis (Zeiss KS 400, Germany), concentric myocyte hypertrophy in the viable LV wall, remote from the infarcted area, was measured as the cross-sectional area of transversally cut myocytes showing a nucleus [23]. Myocyte density was calculated as the average number of myocytes per tissue area (mm 2 ).…”

Section: Infarct Size and Myocyte Hypertrophymentioning

confidence: 99%

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Low‐dose erythropoietin improves cardiac function in experimental heart failure without increasing haematocrit

Lipšic

Westenbrink

Meer

et al. 2008

European J of Heart Fail

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Background: Erythropoietin (EPO) may improve cardiac function and induce neovascularisation in experimental models of chronic heart failure (CHF). However, the increased haematocrit associated with EPO treatment might exert concomitant deleterious effects. Aim: To investigate the haematocrit independent effects of EPO on cardiac function. Methods and results: Rats underwent permanent coronary artery ligation to induce myocardial infarction (MI) or sham surgery. Three weeks after MI, rats were randomly allocated to treatment with vehicle (MI) or the long-acting EPO analogue darbepoetin alfa administered in a high (40 μg/kg/3 weeks, MI-EPO-high) or a low-dose (0.4 μg/kg/3 weeks, MI-EPO-low). After 9 weeks, haemodynamic parameters, myocardial histology and Myosin Heavy Chain (MHC) isoforms were determined. High-dose EPO resulted in a significant increase in haematocrit (p b 0.01) while low-dose EPO had no effect on haematocrit levels. EPO significantly improved cardiac function in both EPO groups, reflected by increased left ventricular (LV)-developed pressure and improved contractility (dP/dt max ) and relaxation (dP/dt min ) indices of the LV at 9-weeks (all p b 0.05 compared to MI). The improved cardiac function was associated with increased capillary growth (38% in MI-EPO-high (p b 0.01) and 27% in MI-EPO-low (p b 0.05)) and an attenuated switch to slow β-MHC isoforms in both EPO groups. Conclusions: EPO improves cardiac function and induces neovascularisation at a dose that does not increase haematocrit, thereby circumventing the possible deleterious effects of increased erythropoiesis.

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“…Sections were weighed separately and fixed in 3.6% formalin. De-paraffinised 5-mm thick transverse cardiac sections at midventricular level were stained with Gomori silver staining for analysis of myocyte size, and with Griffonia simplicifolia lectin staining (Sigma Chemical Co.) of endothelial cells for analysis of capillary density [13,14]. Image analysis (Image-Pro Plus 4.5) was used to measure capillary density and myocyte size.…”

Section: Right Ventricular Remodellingmentioning

confidence: 99%

Effects of erythropoietin on advanced pulmonary vascular remodelling

Albada

Sarvaas²,

Koster³

et al. 2007

Eur Respir J

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Erythropoietin (EPO) mobilises endothelial progenitor cells and promotes neovascularisation in heart failure. The present authors studied the effects of EPO on pulmonary vascular and cardiac remodelling in a model for flow-associated pulmonary arterial hypertension (PAH).PAH was induced in adult male Wistar rats by the injection of monocrotaline combined with an abdominal aortocaval shunt 1 week later (PAH or experimental group). Immediately afterwards, rats were randomised into those who received treatment with EPO (PAH+EPO group) and controls. Pulmonary and systemic haemodynamics, and right ventricular and pulmonary vascular remodelling were evaluated 3 weeks later.Vascular occlusion of the intra-acinar pulmonary vessels (13.4¡0.7 versus 16.7¡1.3% in PAH+EPO and PAH, respectively) and medial wall thickness of the pre-acinar arteries (wall-tolumen ratio 0.13¡0.01 versus 0.17¡0.01 in PAH+EPO and PAH, respectively) decreased after treatment with EPO. Moreover, right ventricular capillary density was increased by therapy (2,322¡61 versus 2,100¡63 capillaries?mm -2 in PAH+EPO and PAH, respectively). Increased mean pulmonary arterial pressure and decreased right ventricular contractility in the model were not altered by EPO treatment. In this rat model of flow-associated pulmonary arterial hypertension, erythropoietin treatment beneficially affected pulmonary vascular and cardiac remodelling. These histopathological effects were not accompanied by significantly improved haemodynamics.

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Pharmacological therapy can increase capillary density in post-infarction remodeled rat hearts

Cited by 36 publications

References 47 publications

Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia

Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia

Low‐dose erythropoietin improves cardiac function in experimental heart failure without increasing haematocrit

Effects of erythropoietin on advanced pulmonary vascular remodelling

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