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PubMed2002

Midwall myocardial shortening in athletic left ventricular hypertrophy.

BACKGROUND: Patients with pathological left ventricular hypertrophy have depressed midwall systolic shortening in spite of normal indices of left ventricular chamber function and a reduced midwall function has been observed to be an independent predictor of cardiovascular risk. Whether midwall shortening is depressed in physiological hypertrophy is unknown. METHODS: Forty-two subjects, 27 athletes and 15 age- and sex-matched normal control subjects (group 1) were studied. The athletes were divided into those with eccentric hypertrophy (group 2) and those with concentric hypertrophy (group 3). Systolic left ventricular function was assessed at the midwall and endocardium using two-dimensional echocardiography in all subjects. RESULTS: Left ventricular mass index was significantly greater in both athletic groups than in controls (group 1, 101+/-5.8 g/m(2), group 2, 141+/-11.1*, group 3, 155+/-5.8*; *P<0.01 compared with group 1). Left ventricular systolic function assessed at the endocardium was similar among all three groups (ejection fraction: group 1, 66.2+/-2.38, group 2, 66.8+/-1.44, group 3, 63.7+/-1.66%; endocardial fractional shortening: group 1, 37.1+/-1.71, group 2, 37.6+/-1.13, group 3, 35.1+/-1.25%). However, fractional shortening at the midwall was reduced in the concentric hypertrophy athletes compared with the other two groups (midwall fractional shortening: group 1, 21.9+/-1.1, group 2, 21.9+/-0.86, group 3, 18.4+/-0.96*%; P<0.05 compared with groups 1 and 2). CONCLUSION: Subjects with physiological concentric hypertrophy have depressed midwall fractional shortening. This suggests that the observed discrepancy between midwall and endocardial shortening in patients with left ventricular hypertrophy is likely to be a function of the geometry and not necessarily a reflection of pathology within the myocardium.

Adult↗
PubMed1998

Effect of choline ester analogues, noradrenaline and nifedipine on normal and hypertrophied human urinary bladder detrusor muscle.

1. Acetylcholine, bethanechol, carbachol and propionylcholine were all agonists of normal human detrusor smooth muscle. The order of potency was found to be carbachol > acetylcholine > bethanachol > propionylcholine. 2. In hypertrophied detrusor smooth muscle carbachol was more potent than acetylcholine, but hypertrophied detrusor preparations were less sensitive to carbachol than normal detrusor smooth muscle. 3. Noradrenaline had no direct effect on either normal or hypertrophied detrusor muscle, but it had a reversible inhibitory effect on the spontaneous contractile activity of normal detrusor preparations. Hypertrophied detrusor preparations usually lacked such spontaneous activity. 4. In calcium-free saline, agonist-induced responses of both normal and hypertrophied detrusor muscle were dramatically reduced indicating that choline ester activity in the muscles was strongly dependent upon extracellular calcium. 5. Nifedipine at 10(-5) mol l-1 inhibited acetylcholine responses and K(+)-induced contractures of both normal and hypertrophied detrusor muscles. Acetylcholine-induced responses of normal detrusor preparations were much more sensitive to inhibition by nifedipine than were the responses of hypertrophied detrusor muscle. 6. The properties and densities of both the muscarinic cholinoreceptors and calcium channels appear to have been altered by the hypertrophic response secondary to benign prostatic hyperplasia.

Acetylcholine↗
PubMed1999

Volume overload hypertrophy of the newborn heart slows the maturation of enzymes involved in the regulation of fatty acid metabolism.

OBJECTIVES: The purpose of this study was to determine the effect of volume overload hypertrophy in the newborn heart on the cardiac enzymes controlling fatty acid metabolism. BACKGROUND: Shortly after birth, a rise in 5'-adenosine monophosphate-activated protein kinase (AMPK) activity results in the phosphorylation and inhibition of acetyl coenzyme A (CoA) carboxylase (ACC), and a decline in myocardial malonyl CoA levels with increased fatty acid oxidation rates. Whether the early onset of hypertrophy in the newborn heart alters this maturational increase in fatty acid oxidation is unknown. METHODS: Newborn piglets underwent endovascular stenting of the ductus arteriosus on day 1 of life with a 4.5-mm diameter stent, resulting in a left to right shunt, and left ventricular (LV) volume loading. Left ventricular and right ventricular samples from fetal, newborn, three-week control and three-week stented animals were compared. RESULTS: Stenting resulted in echocardiographic evidence of volume overload and myocardial hypertrophy. In control animals, left ventricular ACC activity declined from 274 +/- 30 pmol/mg/min on day 1 to 115 +/- 12 after three weeks (p < 0.05), but did not display this maturation drop in hypertrophied hearts, remaining elevated (270 +/- 50 pmol/mg/min, p < 0.05). At three weeks, malonyl CoA levels remained 2.8-fold higher in hypertrophied hearts than in control hearts. In control hearts, LV AMPK activity increased 178% between day 1 and three weeks, whereas in hypertrophied hearts AMPK activity at three weeks was only 71% of control values, due to a significant decrease in expression of the catalytic subunit of AMPK. CONCLUSIONS: Early onset LV volume overload with hypertrophy results in a delay in the normal maturation of fatty acid oxidation in the newborn heart.

Acetyl-CoA Carboxylase↗
PubMed1999

Different effects of antihypertensive agents on cardiac and vascular hypertrophy in the transgenic rat line TGR(mRen2)27.

The hypertensive transgenic rat model TGR(mRen2)27 has been used to investigate the development of cardiac and vascular hypertrophy in response to two different drug regimes. Cardiac hypertrophy was shown to be related to age and gender with the copy number of mouse renin transgenes having an additive effect. A similar observation was noted for hypertrophy in the vasculature, which was assessed using flow cytometry cell cycle DNA analysis of aortic vascular smooth muscle cells. Chronic treatment from weaning with equihypotensive doses of perindopril (2 mg/kg/day) or hydralazine and hydrochlorothiazide (4 mg/day of each) prevented the development of cardiac hypertrophy. Perindopril treatment also effectively prevented the development of vascular hypertrophy; however, treatment with hydralazine and hydrochlorothiazide was not as effective despite equivalent blood pressure reduction. These studies have demonstrated the presence of marked vascular and cardiac hypertrophy in the hypertensive transgenic TGR(mRen2)27 model of hypertension. Furthermore, these results provide new evidence to support the role of a locally activated renin angiotensin system in the blood vessel wall, which is involved in the pathogenesis of vascular hypertrophy in this transgenic rat model.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Renal hypertrophy in streptozotocin diabetic rats: role of proteolytic lysosomal enzymes.

Renal protein mass increases in diabetic renal hypertrophy. Accretion of protein may be the result of increased protein synthesis and/or decreased protein degradation. The lysosomal proteases, cathepsins B and L, are key enzymes in cellular protein catabolism. To evaluate the role of protein degradation in diabetic renal hypertrophy, the activities of cathepsins B and L were measured in microdissected proximal tubule segments and in kidney cortex homogenates. In rats four and ten days following induction of diabetes by streptozotocin, the kidney weight was increased and the cathepsin activities were reduced in proximal tubule segments. Treatment with insulin prevented both changes. The liver weight in diabetic rats was decreased and the activity of cathepsins B and L was increased, while the activity in kidney cortex was reduced. This excluded that diabetes per se may be accompanied by decreased cathepsin activities independent of organ hypertrophy. Renal hypertrophy as a cause rather than as the consequence of reduced cathepsin activities was excluded by the finding of unchanged cathepsin activities in proximal tubule segments from rats with compensatory renal hypertrophy four days and ten days following unilateral nephrectomy. Decreased activities of cathepsins B and L may reflect decreased intracellular protein degradation. Decreased protein breakdown in proximal tubules may contribute to diabetic renal hypertrophy. In agreement with this interpretation are the results from rats six months following induction of diabetes. Renal hypertrophy is complete at that time. No further accretion of protein occurs and the cathepsin activities in the proximal tubule were not different from controls.

Animals↗
PubMed1996

Biphasic glomerular hypertrophy in rats administered puromycin aminonucleoside.

Recent evidence suggests that glomerular hypertrophy is a key event in the development of focal and segmental glomerulosclerosis and hyalinosis (FSGS) in humans and in many experimental models of FSGS. The initial aim of the present study was to determine if glomerular hypertrophy occurs in a puromycin aminonucleoside (PAN) model of FSGS, previously considered not to involve glomerular hypertrophy. Upon identifying significant glomerular hypertrophy, our second aim was to determine the contribution of glomerular capillary growth to this hypertrophy. Female Sprague-Dawley rats (approximately 200 g) were administered either PAN (2 mg/100 g body wt) subcutaneously, or an equivalent volume of 0.9% saline at weeks 0, 1, 2, 4, 6, 8 and 10. Tissue was analyzed at weeks 7 and 13. Unbiased stereological methods were used to estimate a range of glomerular parameters. Mean glomerular tuft volume in PAN-treated rats was 48% greater than in saline-treated rats at seven weeks, and 63% greater at 13 weeks. Similar results were found for mean renal corpuscle volume. FSGS was absent at seven weeks and minor at 13 weeks. Two-way analysis of variance indicated: significant effects (P < 0.05 at least) of PAN on capillary length per glomerulus, capillary surface area per glomerulus, capillary diameter and length of capillaries per unit volume of glomerulus; and significant effects of time on capillary diameter, capillary length per unit volume of glomerulus and capillary surface area per unit volume of glomerulus. The mean length of capillaries per glomerulus was 45% greater in PAN-treated rats at week 7 and 22% greater in PAN-treated rats at week 13. Taken together, these results indicate a biphasic pattern of glomerular hypertrophy in this model. In the first phase (to 7 weeks), an increase in capillary length contributes to glomerular hypertrophy. In the second phase (7 to 13 weeks), the continued glomerular enlargement appears more likely to be due to an increase in capillary diameter and/or mesangial matrix expansion.

Analysis of Variance↗
PubMed1999

Left ventricular hypertrophy in primary hyperparathyroidism. Effects of successful parathyroidectomy.

OBJECTIVE: The association between primary hyperparathyroidism (PHPT) and increased mortality mainly from cardiovascular disease is still debated. The increased mortality previously reported in PHPT was not confirmed in a recent population based study. A high prevalence of left ventricular (LV) hypertrophy was, however, reported in this disease. Although arterial hypertension is regarded as the principal factor, the pathogenesis of LV hypertrophy in PHPT is complex and not completely defined, moreover the effects of successful parathyroidectomy (PTX) are not fully elucidated. The aims of this study were: to ascertain the prevalence of LV hypertrophy in a series of patients with PHPT in comparison to a control population, to seek for relationship between biochemical markers of disease, blood pressure (BP) levels and LV measurements and to evaluate the effects of successful PTX on LV hypertrophy during short-term follow-up. SUBJECTS AND DESIGN: Forty-three patients affected by active PHPT (16 males and 27 females, mean age 60.2 +/- 12.7 years) and 43 controls age- and sex-matched with the same prevalence of arterial hypertension were studied in a case-control analysis. Each subject underwent a M- and 2D mode echocardiographic evaluation and repeated BP measurement. In 21 PHPT submitted to surgery the echocardiographic measurement was repeated 6 months after successful PTX. MEASUREMENTS: Serum concentrations of parathyroid hormone (PTH), total-(Ca) and ionized calcium (iCa), phosphate, creatinine, total alkaline phosphatase (TALP) were measured in patients with PHPT at diagnosis and six months after PTX in the subgroup operated on; BP values were measured in three different occasion; mono and 2D echocardiographic evaluation was performed in control subjects and patients with PHPT either before and after PTX. RESULTS: LV hypertrophy, measured by LV mass index (LVMI), was present in 28/43 PHPT patients (65.1%) and in 15/43 (34.8%) controls, P < 0.05; among hypertensive subjects, 21/21 (100%) PHPT patients and 13/21 (61.9%) controls P < 0.05 were hypertrophic while among normotensive subjects, these figures were 7/22 (31.8%) for PHPT patients and 2/22 (9%) for controls, P = 0.67. At multiple regression analysis in a model including biochemical parameters and BP values, serum PTH levels were associated with LVMI values as the strongest predicting variable (0.46, P < 0.02). Six months after PTX, LVMI decreased (137.8 +/- 37.3 vs 113.0 +/- 28.5, P < 0.05) without changes in mean BP values and ratio of hypertensive patients. CONCLUSION: The present data confirm the high prevalence of LV hypertrophy in primary hyperparathyroidism also in a group of patients with an asymptomatic clinical presentation. The correlation between PTH values and left ventricular mass index suggests an action of the hormone in the pathogenesis of LV hypertrophy confirmed also by the decrease of left ventricular mass index after the reduction of PTH levels. The reversal of left ventricular mass index after parathyroidectomy could affect mortality in primary hyperparathyroidism. An echocardiographic study could be suggested in the clinical work-up of primary hyperparathyroidism in order to evaluate heart involvement and the response to successful parathyroidectomy.

Aged↗
PubMed2001

Insulin-like growth factor-I induces renal cell hypertrophy via a calcineurin-dependent mechanism.

Insulin-like growth factor-I (IGF-I) may play an important role in the development of renal hypertrophy. In this study we determined the effect of IGF-I on cultured mesangial cells (MCs) and examined activation of key signaling pathways. IGF-I induced hypertrophy as determined by an increase in cell size and an increase in protein to DNA ratio and increased accumulation of extracellular matrix (ECM) proteins. IGF-I also activated both Erk1/Erk2 MAPK and phosphatidylinositol 3-kinase (PI3K) in MCs. Inhibition of either MAPK or PI3K, however, had no effect on IGF-I-induced hypertrophy or ECM production. Next, we examined the effect of IGF-I on activation of the calcium-dependent phosphatase calcineurin. IGF-I treatment stimulated calcineurin activity and increased the protein levels of calcineurin and the calcineurin binding protein, calmodulin. Cyclosporin A, an inhibitor of calcineurin, blocked both IGF-I-mediated hypertrophy and up-regulation of ECM. In addition, calcineurin resulted in sustained Akt activation, indicating possible cross-talk with other signaling pathways. Finally, IGF-I treatment resulted in the calcineurindependent nuclear localization of NFATc1. Therefore, IGF-I induces hypertrophy and increases ECM accumulation in MCs. IGF-I-mediated hypertrophy is associated with activation of Erk1/Erk2 MAPK and PI3K but does not require either of these pathways. Instead, IGF-I mediates hypertrophy via a calcineurin-dependent pathway.

Animals↗
PubMed1998

Pathological versus physiological left ventricular hypertrophy: a review.

Left ventricular hypertrophy is recognized as an independent risk factor for cardiovascular morbid events. The primary mechanisms responsible for stimulating it are unknown. Epidemiological theories suggest that left ventricular hypertrophy is a continuous variable with no threshold, while morphological studies argue that it is the structure, or quality, and function of the myocardium (and therefore non-continuous), not the quantity of the myocardial mass, that poses the cardiovascular risk. Although left ventricular hypertrophy has been classically viewed as an adaptive response of the cardiovascular system to an imposed load, it has been demonstrated that haemodynamic overloading in selected hypertensive patients is not the sole determinant of left ventricular structure and function. Pathological and physiological states of left ventricular hypertrophy have been described primarily using criteria focusing on normal chamber performance and oxygen delivery as well as the reversibility of the hypertrophy once the overload is removed. Both states are also defined by the nature of the imposed load and the resulting myocardial adaptations. This review addresses the pathological and physiological states of left ventricular hypertrophy, the hypertrophy patterns, and the corresponding structural and functional characteristics, together with some of the biochemical factors thought to influence remodelling.

Cardiomyopathy, Hypertrophic↗
PubMed1992

Left ventricular hypertrophy in a canine model of reversible pressure overload.

OBJECTIVE: The goal of therapy for left ventricular pressure overload should include regression of the associated left ventricular hypertrophy, but this process is incompletely understood. The aim of the study was to characterise the extent and time course of the progression and regression of pressure overload left ventricular hypertrophy in a canine hypertrophy model. METHODS: Six puppies were studied longitudinally with haemodynamic and echocardiographic measurements for 10 months. The study animals underwent ascending aortic banding at nine weeks of age which produced an initial gradient of 30 mm Hg. Subsequent growth led to an increase in gradient and the development of left ventricular hypertrophy. Then thoracotomy was again performed to remove the band. One month later, balloon aortoplasty was performed to remove the residual gradient. The animals were then observed for six months. RESULTS: Growth increased the gradient to 105(SEM 10) mm Hg three months after banding. The left ventricular weight to body weight ratio (g.kg-1), an index of hypertrophy, was 7.2(0.5) after three months of pressure overload. Subsequently the band was surgically removed, reducing the gradient to an average of 58(10) mm Hg. Balloon dilatation of the residual aortic stricture reduced the gradient further to 6(5) mm Hg. Over the ensuing six months, echocardiographic determination of left ventricular mass showed the regression in left ventricular hypertrophy. After six months, left ventricular weight to body weight ratio in the previously banded animals was significantly reduced from 7.2(0.5) to 5.3(0.2) (p less than 0.05). CONCLUSIONS: The model produced over 100% left ventricular hypertrophy, most of which regressed following removal of the pressure overload.

Angioplasty, Balloon↗
PubMed1995

Coronary reserve in experimental myocardial hypertrophy.

Three types of dysfunction of the coronary circulation have been described in experimental models of hypertension associated with left ventricular hypertrophy: (1) reduced coronary reserve, (2) a relative decrease in perfusion of subendocardial layers, (3) a shift to the right, i.e. to higher pressures, of the circulation pressure autoregulation range. These abnormalities are also observed in hypertensive patients, although it is significant that they do not appear to be related to the extent of left ventricular hypertrophy. The exact causes of these abnormalities have yet to be elucidated. Left ventricular hypertrophy does not seem to be an essential factor, although in certain experimental models of hypertension, there does appear to be a mismatch between the development of the coronary vasculature and hypertrophy of the myocytes. The stresses in vessels due to the increase in systolic, and especially intraventricular diastolic pressure can be viewed as additional aggravating factors. The essential abnormalities are structural and/or functional alterations in arterial walls. The structural alterations are reflected by a narrowed lumen due to parietal thickening. This may result from growth of muscle fibres (hypertrophy or hyperplasia) or collagen tissue and/or remodelling of tissues with no overall change in mass. Functionally, the reduced ability of the arteries to stretch, resulting from endothelial alterations may also play a role in the abnormalities observed in hypertensive patients. In our studies, we examined the effect of the antihypertensive drug perindopril on the coronary circulation in renovascular hypertensive rat (two kidneys--1 clip). We found that this inhibitor of angiotensin converting enzyme (ACE) led to a regression of left ventricular hypertrophy with a return to normal of the coronary reserve. Other studies using either this model or the spontaneously hypertensive rate has also pointed to a beneficial action of ACE inhibitors and other antihypertensive agents on the coronary circulation with reversal of the structural alterations in arterioles. Coronary disease is the main cause of mortality in hypertensive patients. Ironically, antihypertensive therapy has yet to live up to its promise of reducing significantly either the incidence or severity of coronary disease in such patients. Specific alterations of the coronary circulation may account for the relative failure of antihypertensive drugs, despite their proven efficacy in other systems (e.g., stroke prevention). The coronary circulation is unique in certain important respects. It is tightly regulated, maintaining an almost constant flow rate over a wide range of aortic arterial pressures (40-160 mmHg). Extraction of oxygen by the myocardium is almost maximal under resting conditions, and so the circulatory reserve depends almost entirely on the capacity to increase blood flow. This reserve is quite large since there may be a 4 to 5-fold increase in coronary flow rate in response to effort. Another significant detail is that myocardial contraction may lead to an interruption of coronary flow, especially in the deep subendocardial layers, which thus tend to be perfused solely during diastole. This last factor can be seen as the Achilles heel of the coronary circulation, which may be severely limited by myocardial hypertrophy, especially in patients with hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Left ventricular hypertrophy in aortic valve stenosis: preventive or promotive of systolic dysfunction and heart failure?

AIMS: In aortic stenosis (AS), left ventricular (LV) hypertrophy is considered a compensatory response helping maintain systolic function. Recent research in experimental AS suggests, however, that LV hypertrophy is not necessary to sustain LV contractions but may in fact be maladaptive. The present work aimed to clarify the role of LV hypertrophy in AS-related heart failure (HF) in man. METHODS AND RESULTS: We studied 137 adult patients with isolated AS undergoing pre-operative echocardiography and cardiac catheterization. HF was diagnosed by the European criteria and LV hypertrophy by sex-specific limits of echocardiographic LV mass. The higher the LV mass was, the poorer was the LV ejection fraction (beta=-0.26, P< 0.001, linear regression) and the greater the likelihood of HF independent of the severity of AS (P< 0.001, logistic regression). In the subgroup of critical AS (valve area <0.4 cm(2)/m(2), n=85), patients with absent LV hypertrophy (n=19) had better preserved ejection fraction (mean+/-SE, 64+/-3 vs. 57+/-2%, P=0.045) and less HF (16 vs. 48%, P=0.025) than patients with LV hypertrophy (n=66). CONCLUSION: In isolated AS, increased LV mass predicts the presence of systolic dysfunction and HF independent of the severity of valvular obstruction. LV hypertrophy may be maladaptive rather than beneficial in AS in man.

Adaptation, Physiological↗
PubMed2006

Attenuation of cardiac hypertrophy in carnitine-deficient juvenile visceral steatosis (JVS) mice achieved by lowering dietary lipid.

We examined the development of cardiac hypertrophy in juvenile visceral steatosis (JVS) mice, a model of systemic carnitine deficiency, by varying the amount of lipid in the diet. Cardiac hypertrophy was markedly attenuated by decreasing soy bean oil (SBO) from 5% (w/w) to 1%. Triglyceride contents of the ventricles of JVS mice fed 1% SBO were significantly lower than in JVS mice fed 5% SBO. The addition of medium-chain triglycerides metabolically utilized by JVS mice did not affect the development of cardiac hypertrophy. On the other hand, the mRNA levels of atrial natriuretic peptide and skeletal alpha-actin, which are related to cardiac hypertrophy, were also attenuated by decreasing lipid in the diet. Adenylate energy charge and creatine phosphate in the heart of JVS mice at the early stage of hypertrophy were not significantly different from control mice given the same laboratory chow (4.6% of lipid). Although urinary prostaglandin F(2alpha) levels were found to be increased in JVS mice at 15 days of age when they developed cardiac hypertrophy, administration of aspirin was not efficacious. We, therefore, propose that the proportion of lipid in the diet is important in the development of cardiac hypertrophy in carnitine-deficient JVS mice, and that this is not related to prostaglandin formation.

Animals↗
PubMed1996

Myocardial beta adrenoceptor density in primary and secondary left ventricular hypertrophy.

OBJECTIVES: Myocardial beta-adrenoceptor density has been found to be reduced in hypertrophic cardiomyopathy, even when systolic function is preserved. Our purpose in the current study was to investigate whether beta-adrenoceptor down-regulation was unique to hypertrophic cardiomyopathy, or is also present in secondary myocardial hypertrophy. METHODS: Myocardial beta-adrenoceptor density was measured in 11 patients with hypertrophic cardiomyopathy, eight patients with left ventricular hypertrophy secondary to arterial hypertension or aortic valve disease and 18 normal control subjects, using positron emission tomography with 11C-CGP-12177 as the myocardial beta-adrenoceptor ligand. RESULTS: Reflecting the natural incidence of the conditions, the age of the hypertrophic cardiomyopathy patients was 37 (10) [mean (SD), range 20-51] years and that of the secondary hypertrophy patients 64 (18), [range 26-80] years; P < 0.01. The controls' ages were 50 (13), [range 21-65] years; however, since beta-adrenoceptor density is known to be influenced by age, the controls' data was split into groups matched to the hypertrophic cardiomyopathy and secondary hypertrophy patient sets. For the hypertrophic cardiomyopathy patients, mean left ventricular beta-adrenoceptor was 7.70 (1.86) pmol.g-1 compared to 10.17 (2.44) pmol.g-1 for a matched set of 15 controls; P < 0.01. In secondary left ventricular hypertrophy, beta-adrenoceptor was 6.35 (1.70) pmol.g-1 compared to 9.16 (2.00) pmol.g-1 for a matched set of 10 controls; P < 0.01. Plasma noradrenaline was 5.5 (2.2) nmol.l-1 in hypertrophic cardiomyopathy and 2.5 (1.0) nmol.l-1 for the matched controls; P < 0.01. The results for adrenaline were 2.2 (1.1) vs 0.4 (0.3) nmol.l-1 respectively; P < 0.001. For the secondary hypertrophy patients, the corresponding figures were 2.5 (1.2) vs 2.5 (1.0) nmol.l-1 for noradrenaline for patients and controls respectively (P = ns); and for adrenaline 0.2 (0.1) and 0.3 (0.2) nmol.l-1 respectively, P = ns. On multiple regression analysis, no relationships could be demonstrated amongst plasma catecholamines, beta-adrenoceptor, myocardial blood flow and echocardiographic E/A ratio and fractional shortening. CONCLUSION: Myocardial beta-adrenoceptor density appears to be comparably decreased in both primary and secondary left ventricular hypertrophy in the presence of preserved left ventricular systolic function.

Adult↗
PubMed1998

Pathologic fibrosis and connective tissue matrix in left ventricular hypertrophy due to chronic arterial hypertension in humans.

OBJECTIVE: To investigate pathologic fibrosis and connective tissue matrix in left ventricular hypertrophy due to chronic arterial hypertension in humans. DESIGN AND METHODS: Seventeen human hearts were studied. Group 1 consisted of control hearts (four hearts, weighing 280 +/- 40 g each), from subjects who had had no evidence of heart disease and for whom the diagnoses of death were noncardiac. Groups 2 (five hearts, weighing 440 +/- 50 g each), 3 (five hearts, weighing 560 +/- 50 g each), and 4 (three hearts, weighing 680 +/- 60 g each) consisted of hearts from subjects who had had a history of systemic hypertension. All hearts had no valvular deformities and no evidence of ischemic disease at the postmortem examination. A cell-maceration method was employed to evaluate the myocardial connective matrix after removal of the nonfibrous elements of myocardial tissue, leaving behind a noncollapsed matrix, thus allowing a better three-dimensional view. Myocardial tissue was also processed for conventional light microscopic and morphometric studies. RESULTS: The minor transverse diameter of myocytes from hearts in groups 1-4 hearts were 13.7 +/- 7.8, 23.7 +/- 3.4, 26.6 +/- 3.7, and 32.8 +/- 5.8 microm, respectively. The volume fraction of fibrosis of the controls was 6.5%, whereas the volume fractions in hypertensive hearts increased progressively according to heart weight: 15.4, 22.9, and 31.1% for hearts in groups 2, 3, and 4, respectively. The most striking feature was the diffuse marked increase in amount of pericellular collagen weave fibers (endomysial matrix), parallel to the increase of heart weight. The hypertrophied myocytes were encased in a dense weave of collagen fibrils continuous with those of adjacent myocytes. The muscle fibers in hypertrophied hearts were markedly larger than normal, although this was extremely variable from an area to another. Besides, a diffuse increase in the number of thick collagen fibers constituting broad bands and sheets of collagen surrounding disorganized muscle bundles (perimysial matrix) was observed. Scattered dense scar-like foci, apparently replacing areas of myocyte loss, could be seen, mainly on the periphery of muscle bundles. This latter finding was more commonly observed among hypertrophied hearts from group 3 and, mainly, among hypertrophied hearts of group 4. Importantly, a progressive disarray of the connective tissue skeleton of the myocardium could be seen in parallel to the progressive increase of cardiac hypertrophy. CONCLUSIONS: The progressive accumulation of interstitial collagen fibers in left ventricular hypertrophy, in parallel to an increase in heart weight, can be expected to contribute to a spectrum of ventricular dysfunction involving either the diastolic or systolic phase of the cardiac cycle, or both, that is associated with the greater than normal arrhythmogenic risk for a hypertensive heart. Moreover, the methodology used is useful for studying the spatial organization of the collagen fibrils of the myocardium under normal and pathologic conditions.

Adult↗
PubMed1999

Temporal regulation of extracellular matrix components in transition from compensatory hypertrophy to decompensatory heart failure.

OBJECTIVE: Extracellular matrix, particularly type I fibrillar collagen, provides tensile strength that allows cardiac muscle to perform systolic and diastolic functions. Collagen is induced during the transition from compensatory hypertrophy to heart failure. We hypothesized that cardiac stiffness during decompensatory hypertrophy is partly due to a decreased elastin:collagen ratio. MATERIALS AND METHODS: We prepared left ventricular tissue homogenates from spontaneously hypertensive rats (SHR) aged 30-36 weeks, which had compensatory hypertrophy with no heart failure, and from SHR aged 70-92 weeks, which had decompensatory hypertrophy with heart failure. Age- and sex-matched Wistar-Kyoto (WKY) rats were used as normotensive controls. In both SHR groups, increased levels of collagen were detected by immuno-blot analysis using type I collagen antibody. Elastin and collagen were quantitated by measuring desmosine/isodesmosine and hydroxyproline spectrophometrically, respectively. To determine whether the decrease in elastin content was due to increased elastinolytic activity of matrix metalloproteinase-2, we performed gelatin and elastin zymography on left ventricular tissue homogenates from control rats, SHR with compensatory hypertrophy and SHR with heart failure. RESULTS: The elastin:collagen ratio was 0.242 +/- 0.008 in hearts from WKY rats. In SHR without heart failure, the ratio was decreased to 0.073 +/- 0.003 and in decompensatory hypertrophy with heart failure, the ratio decreased to 0.012 +/- 0.005. Matrix metalloproteinase-2 activity was increased significantly in SHR with heart failure compared with controls (P < 0.001). The level of tissue inhibitor of metalloproteinase-4 was increased in compensatory hypertrophy and markedly reduced in heart failure. Decorin was strongly reduced in decompensatory heart failure compared with control hearts. CONCLUSIONS: Since collagen was induced in SHR with heart failure, decorin and elastin were decreased and the ratios of gelatinase A and elastase to tissue inhibitor of metalloproteinase-4 were increased, we conclude that heart failure is associated with adverse extracellular matrix remodeling.

Animals↗
PubMed2000

Evaluation of brain natriuretic peptide as marker of left ventricular dysfunction and hypertrophy in the population.

OBJECTIVE: To evaluate brain natriuretic peptide (BNP) as marker of left ventricular (LV) dysfunction and hypertrophy in a population-based sample of 610 middle-aged subjects (50-67 years) who were further characterized with respect to hemodynamic and anthropometric parameters and by echocardiography. RESULTS: Left ventricular (LV) systolic function, LV mass-index, age, gender, heart rate, and medication with beta adrenergic receptor blockers were significant and independently correlated with BNP (multivariate analysis, P < 0.05 each). As compared to subjects with normal LV function and mass-index (control), subjects with LV dysfunction (LV fractional shortening < 28%) or hypertrophy (LV mass-index > 110 g/m2 in women and > 134 g/m2 in men) were characterized by increased BNP. The increase in BNP associated with LV hypertrophy (n = 69, +101% versus control, P < 0.0001) was similar in magnitude to that associated with LV dysfunction (n = 39, +98% versus control, P < 0.03). These increases were markedly exceeded in subjects with severe LV dysfunction (n = 11, LV fractional shortening < 22%, BNP +197% versus control, P < 0.01), particularly in the presence of concomitant hypertrophy (n = 7, +227%, P < 0.01). The predictive values of BNP varied considerably with the degree of LV dysfunction and the presence or absence of concomitant LV hypertrophy. With 0.81, the highest area under the receiver operator characteristic curve was obtained for the detection of severe LV dysfunction and concomitant hypertrophy and sensitivity, specificity, positive and negative predictive value for this condition were 71, 86, 7 and 99.5%, respectively, for a cut-off of 34 pg/ml. CONCLUSIONS: The current study provides new insight into regulation and diagnostic value of BNP in middle-aged subjects and demonstrates important independent effects of LV function and mass upon BNP plasma concentrations. Although measurement of BNP cannot be recommended for the detection of marginally impaired LV function in the population, it may be helpful to suggest or exclude severe LV dysfunction with concomitant hypertrophy.

Analysis of Variance↗
PubMed2000

Measuring health state preferences in women with breast hypertrophy.

The purpose of this article is to introduce the measurement of utilities, or patient preferences, to the plastic surgery community. Specifically, the study demonstrated the development and validation of a utility measure for estimating the health-related quality of life in women with breast hypertrophy. Two self-administered instruments were developed, a Wheel and a Table. All subjects completed the utility assessments for their "current health" and again for "breast-related symptoms." The reliability of the instruments was assessed in repeat (test-retest) interviews of 47 women within 10 to 18 days. Utilities obtained with the new instruments were also compared with the performance of other validated utility assessment instruments, including a visual analogue scale, a computer-based instrument (U-Titer), and a preference classification system (EuroQol). Of the 47 women in the test-retest reliability study, 21 had experienced breast hypertrophy (13 had not had reduction surgery and 8 had undergone reduction mammaplasty). Mean utility values for breast-related symptoms among women with breast hypertrophy (n = 13) were: Table, 0.85; Wheel, 0.90; and U-Titer, 0.66. Current health utility scores were significantly lower for women with breast hypertrophy (n = 13), as measured by all instruments except the Wheel. The Table had good reliability and distinguished women with breast hypertrophy from those without. Although the Table provided higher utility values for the same health state compared with the computer-based interview (U-Titer), it is much less costly to implement. The Table is recommended as a reasonable alternative for use in multicenter studies of women with breast hypertrophy. The reported utility value for breast hypertrophy of 0.86 is much lower than predicted. It is comparable with the reported burden of living with other health conditions, such as moderate angina (0.90) and a kidney transplant (0.84).

Adult↗