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British Journal of Pharmacology Jan 19991. Etomoxir (2[6(4-chlorophenoxy)hexyl]oxirane-2-carboxylate), an irreversible carnitine palmitoyl-transferase 1 inhibitor, reduces the expression of the myocardial...
1. Etomoxir (2[6(4-chlorophenoxy)hexyl]oxirane-2-carboxylate), an irreversible carnitine palmitoyl-transferase 1 inhibitor, reduces the expression of the myocardial foetal gene programme and the functional deterioration during heart adaption to a pressure-overload. Etomoxir may, however, also improve the depressed myocardial function of hypertrophied ventricles after a prolonged pressure overload. 2. To test this hypothesis, we administered racemic etomoxir (15 mg kg(-1) day(-1) for 6 weeks) to rats with ascending aortic constriction beginning 6 weeks after imposing the pressure overload. 3. The right ventricular/body weight ratio increased (P<0.05) by 20% in etomoxir treated rats (n = 10) versus untreated rats with ascending aortic constriction (n = 10). Left ventricular weight was increased (P<0.05) by 8%. Etomoxir blunted the increase in left ventricular chamber volume. Etomoxir raised the proportion of V1 isomyosin (35+/-4% versus 24+/-2%; P<0.05) and decreased the percentage of V3 isomyosin (36+/-4% versus 48+/-3%; P<0.05). 4. Maximum isovolumically developed pressure was higher in etomoxir treated rats than in untreated pressure overloaded rats (371+/-22 versus 315+/-23 mmHg; P<0.05). Maximum rates of ventricular pressure development (14,800+/-1310 versus 12,340+/-1030mmHg s(-1); P<0.05) and decline (6440+/-750 versus 5040+/-710 mmHg s(-1); P<0.05) were increased as well. Transformation of pressure values to ventricular wall stress data revealed an improved myocardial function which could partially account for the enhanced function of the whole left ventricle. 5. The co-ordinated action of etomoxir on ventricular mass, geometry and myocardial phenotype enhanced thus the pressure generating capacity of hypertrophied pressure-overloaded left ventricles and delayed the deleterious dilative remodelling.
Topics: Animals; Blood Pressure; Body Weight; Carnitine O-Palmitoyltransferase; Enzyme Inhibitors; Epoxy Compounds; Heart Rate; Heart Ventricles; Hypertrophy, Left Ventricular; Isoenzymes; Male; Myosins; Organ Size; Rats; Rats, Wistar; Ventricular Function, Left
PubMed: 10077244
DOI: 10.1038/sj.bjp.0702312 -
Hypertension (Dallas, Tex. : 1979) Mar 2002Left ventricular hypertrophy is associated with significant excess mortality and morbidity. The study and treatment of this condition, in particular the prognostic... (Review)
Review
Left ventricular hypertrophy is associated with significant excess mortality and morbidity. The study and treatment of this condition, in particular the prognostic implications of changes in left ventricular mass, require an accurate, safe, and reproducible method of measurement. Cardiovascular magnetic resonance is a suitable tool for this purpose, and this review assesses the technique in comparison with others and examines the clinical and research implications of the improved reproducibility.
Topics: Echocardiography; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Reproducibility of Results; Tomography, X-Ray Computed
PubMed: 11897757
DOI: 10.1161/hy0302.104674 -
Cardiovascular Research Aug 2012Cardiac hypertrophy is accompanied by reprogramming of gene expression, where the altered expression of ion channels decreases electrical stability and increases the...
AIMS
Cardiac hypertrophy is accompanied by reprogramming of gene expression, where the altered expression of ion channels decreases electrical stability and increases the risk of life-threatening arrhythmias. However, the underlying mechanisms are not fully understood. Here, we analysed the role of the depolarizing current I(f) which has been hypothesized to contribute to arrhythmogenesis in the hypertrophied ventricle.
METHODS AND RESULTS
We used transverse aortic constriction in mice to induce ventricular hypertrophy. This resulted in an increased number of I(f) positive ventricular myocytes as well as a strongly enhanced and accelerated I(f) when compared with controls. Of the four HCN (hyperpolarization-activated cyclic nucleotide-gated channels) isoforms mediating I(f), HCN2 and HCN4 were the predominantly expressed subunits in healthy as well as hypertrophied hearts. Unexpectedly, only the HCN1 transcript was significantly upregulated in response to hypertrophy. However, the combined deletion of HCN2 and HCN4 disrupted ventricular I(f) completely. The lack of I(f) in hypertrophic double-knockouts resulted in a strong attenuation of pro-arrhythmogenic parameters characteristically observed in hypertrophic hearts. In particular, prolongation of the action potential was significantly decreased and lengthening of the QT interval was reduced.
CONCLUSIONS
We suggest that the strongly increased HCN channel activity in hypertrophied myocytes prolongs the repolarization of the ventricular action potential and thereby may increase the arrhythmogenic potential. Our results provide for the first time a direct link between an upregulation of ventricular I(f) and a diminished repolarization reserve in cardiac hypertrophy.
Topics: Action Potentials; Animals; Aorta; Arrhythmias, Cardiac; Cyclic Nucleotide-Gated Cation Channels; Disease Models, Animal; Electrocardiography; Gene Expression Regulation; Heart Ventricles; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Hypertrophy, Left Ventricular; Ion Channels; Ligation; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocytes, Cardiac; Potassium Channels; RNA, Messenger; Time Factors; Ventricular Remodeling
PubMed: 22652004
DOI: 10.1093/cvr/cvs184 -
The Journal of Experimental Biology May 1998We examined the morphometric and biochemical effects of ventricular hypertrophy in male rainbow trout (Oncorhynchus mykiss) during sexual maturation. Our investigation...
We examined the morphometric and biochemical effects of ventricular hypertrophy in male rainbow trout (Oncorhynchus mykiss) during sexual maturation. Our investigation focused on characterizing the growth of ventricular layers, on cardiomyocyte dimensions (length, cross-sectional area and cell volume) and on the activities of enzymes involved in intermediary metabolism. Relative ventricle mass (100 x ventricle mass/body mass) increased by as much as 2.4-fold during sexual maturation [as defined by an increasing gonadosomatic index (100 x gonad mass/body mass)], and this resulted in an increased proportion of epicardium relative to endocardium. Ventricular enlargement was associated with increased length (+31 %) and transverse cross-sectional area (+83 %) of cardiomyocytes, which resulted in an expansion of up to 2.2-fold in mean myocyte volume (from 1233 to 2751 micron3). These results indicate that sexual maturation induces ventricular enlargement through myocyte hypertrophy. Cell length and cross-sectional area were similar in both myocardial layers, and myocytes were elliptical rather than circular in transverse cross section. Ventricular hypertrophy did not alter transverse cell shape, perhaps reflecting the maintenance of short diffusion distances for small molecules as cells hypertrophy. Myocyte hypertrophy could not account entirely for the sevenfold range of ventricle masses from different-sized fish, indicating that myocyte hyperplasia contributes substantially to ventricular growth as trout grow. Measurements of the maximal activities of metabolic enzymes demonstrated that ventricular hypertrophy was associated with (1) higher epicardial but not endocardial activities of citrate synthase (by 23 %) and beta-hydroxyacyl-CoA dehydrogenase (by 20 %); (2) lower activities of hexokinase (by 50 %) in both layers, and (3) no change in lactate dehydrogenase or pyruvate kinase activities, which were also similar between layers. These results suggest that the energetic needs of the hypertrophied trout ventricle may be met through increased reliance on fatty acid oxidation, particularly by the endocardium, but decreased reliance on glucose as a metabolic fuel in both layers.
Topics: Animals; Body Weight; Cardiomegaly; Heart Ventricles; Hyperplasia; Male; Myocardium; Oncorhynchus mykiss; Organ Size; Sexual Maturation
PubMed: 9556537
DOI: 10.1242/jeb.201.10.1541 -
Acta Cardiologica Jun 2023
Topics: Humans; Heart Ventricles; Hypertrophy, Left Ventricular
PubMed: 36398787
DOI: 10.1080/00015385.2022.2146875 -
American Heart Journal Aug 1949
Topics: Cardiomegaly; Electrocardiography; Heart Ventricles; Humans; Hypertrophy, Right Ventricular
PubMed: 18133359
DOI: 10.1016/0002-8703(49)91335-6 -
American Heart Journal Feb 1949
Topics: Cardiomegaly; Electrocardiography; Heart Ventricles; Humans; Hypertrophy, Left Ventricular
PubMed: 18107386
DOI: 10.1016/0002-8703(49)90562-1 -
Computers in Biology and Medicine May 2023In our paper, we simulated cardiac hypertrophy with the use of shell elements in parametric and echocardiography-based left ventricle (LV) models. The hypertrophy has an...
In our paper, we simulated cardiac hypertrophy with the use of shell elements in parametric and echocardiography-based left ventricle (LV) models. The hypertrophy has an impact on the change in the wall thickness, displacement field and the overall functioning of the heart. We computed both eccentric and concentric hypertrophy effects and tracked changes in the ventricle shape and wall thickness. Thickening of the wall was developed under the influence of concentric hypertrophy, while the eccentric hypertrophy produces wall thinning. To model passive stresses we used the recently developed material modal based on the Holzapfel experiments. Also, our specific shell composite finite element models for heart mechanics are much smaller and simpler to use with respect to conventional 3D models. Furthermore, the presented modeling approach of the echocardiography-based LV can serve as the basis for practical applications since it relies on the true patient-specific geometry and experimental constitutive relationships. Our model gives an insight into hypertrophy development in realistic heart geometries, and it has the potential to test medical hypotheses regarding hypertrophy evolution in a healthy and heart with a disease, under the influence of different conditions and parameters.
Topics: Humans; Heart Ventricles; Hypertrophy, Left Ventricular; Echocardiography; Cardiomegaly; Heart; Hypertension
PubMed: 36933415
DOI: 10.1016/j.compbiomed.2023.106742 -
Terapevticheskii Arkhiv 2000
Review
Topics: Animals; Catecholamines; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Myocardium; Renin-Angiotensin System
PubMed: 10717936
DOI: No ID Found -
Current Hypertension Reports May 2014Hypertension is a powerful risk factor for cardiovascular mortality and morbidity, including heart failure with both preserved and reduced ejection fraction.... (Review)
Review
Hypertension is a powerful risk factor for cardiovascular mortality and morbidity, including heart failure with both preserved and reduced ejection fraction. Hypertensive heart disease (HHD) defines the complex and diverse perturbations of cardiac structure and function occurring secondary to hypertension. Left ventricular hypertrophy (LVH) is one of the most recognized features of HHD and is an established risk factor for adverse cardiovascular (CV) outcomes in hypertension. Beyond LVH, LV geometry provides additional information regarding the cardiac response to hypertension. Imaging studies from larger cohorts of hypertensive patients reveal wide variability in the prevalence of LVH and LV geometric patterns, with the prevalence of concentric LVH similar to that of eccentric LVH. Hypertension is also associated with concomitant impairments in LV diastolic and systolic function. It remains uncertain why patients develop different patterns of LVH, although demographics and clinical comorbidities appear to influence that response.
Topics: Animals; Echocardiography; Heart Failure; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Ventricular Remodeling
PubMed: 24639061
DOI: 10.1007/s11906-014-0428-x