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Results for “Hypertrophy”

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At least 199 records · Page 11Linked to original sources

PubMed1994

Effect of duration of depolarisation on contraction of normal and hypertrophied feline ventricular myocytes.

OBJECTIVE: The aim was to test the hypothesis that the prolongation of action potential duration in hypertrophied feline myocytes causes the contractions to be of long duration. METHODS: Left ventricular hypertrophy was induced by slow progressive pressure overload after banding the ascending aorta of young cats. Single myocytes were enzymatically dissociated for whole cell patch clamp studies. Cell shortenings were induced by stimulated action potentials (in current clamp mode) and by step depolarisations using voltage clamp to control the duration of depolarisation. RESULTS: Action potential duration measured at 50% repolarisation (0.5 Hz) was significantly longer in hypertrophied myocytes, at 688(SEM 43) ms, n = 25, v 396(17) ms, n = 22, in control myocytes (p < 0.01). The associated contractions in hypertrophied myocytes had significantly longer durations measured at 50% relengthening [hypertrophied myocytes 609(54) ms, control myocytes 406(13) ms]. The absolute magnitude of shortening normalised to percent diastolic cell length was also significantly reduced in hypertrophied myocytes [7.8(0.8)% diastolic cell length] compared to control myocytes [12.2(0.6)% diastolic cell length] and the duration of contraction time to 50% relengthening was prolonged [406(13) ms v 609(54) ms]. When the duration of depolarisation was controlled with voltage clamp techniques, steady state contractions at +10 mV increased in magnitude in both control and hypertrophied myocytes as the duration of depolarization was lengthened. At all durations tested (100-1000 ms), contractions were significantly longer in duration in hypertrophied myocytes. Changing the duration of depolarisation had no significant effect on the duration of contraction in control myocytes. In hypertrophied myocytes, however, prolongation of depolarisation (500-1000 ms) significantly prolonged the contraction. Steady state contractions initiated from -70 mV (sodium current activated) were larger in both control and hypertrophied myocytes than contractions elicited from -40 mV (sodium current inactivated), and the effect of depolarisation duration on contractile duration was the same. CONCLUSIONS: Changes in sarcolemmal properties which produce a lengthening of the action potential duration in hypertrophy are not primarily responsible for the prolongation of contractile duration. However, there is a portion of contraction which becomes sensitive to the duration of depolarisation in hypertrophied myocytes.

Action Potentials↗

PubMed1997

Coronary vasodilator reserve in primary and secondary left ventricular hypertrophy. A study with positron emission tomography.

OBJECTIVES: Coronary vasodilator reserve is reduced in hypertrophic cardiomyopathy and secondary left ventricular hypertrophy despite angiographically normal coronaries. The aim of the present study was to assess whether quantitative differences exist between these conditions. METHODS: Using positron emission tomography with H2(15)O, myocardial blood flow was measured at baseline and following intravenous dipyridamole (0.56 mg.kg-1) in 12 hypertrophic cardiomyopathy patients (age 34 (11) years, mean (SD), all male), 16 secondary left ventricular hypertrophy patients (age 58 (20) years, P < 0.01 vs hypertrophic cardiomyopathy; 10 female) and 40 normal controls (age 54 (20), 13 female). In view of the known decline of post-dipyridamole myocardial blood flow with age, myocardial blood flow was compared between the patient groups and appropriately matched subsets of the total control group. RESULTS: Baseline myocardial blood flow in the hypertrophic cardiomyopathy patients was 0.82 (0.23) ml.min-1.g-1 vs 0.94 (0.14) ml.min-1.g-1 in its matched control group, P = ns. For the secondary left ventricular hypertrophy patient group, baseline myocardial blood flow was 1.17 (0.40) ml.min-1.g-1 vs 1.06 (0.28) ml.min-1.g-1 for the secondary left ventricular hypertrophy matched control group, P = ns. Following dipyridamole, myocardial blood flow was 1.64 (0.44) ml.min-1.g.-1 in hypertrophic cardiomyopathy patients vs 3.50 (0.95) ml.min-1.g-1 for the hypertrophic cardiomyopathy matched control group, P = 0.0001. For the left ventricular hypertrophy patients, post-dipyridamole myocardial blood flow was 2.27 (0.60) ml.min-1.g-1 vs 2.94 (1.29) ml.min-1.g-1 for the left ventricular hypertrophy controls, P = 0.06. Coronary vasodilator reserve (dipyridamole-myocardial blood flow/baseline-myocardial blood flow) was 2.05 (0.61) for hypertrophic cardiomyopathy patients vs 3.81 (0.98) for the hypertrophic cardiomyopathy controls (P = 0.0001, patients vs controls) and 2.06 (0.62) for left ventricular hypertrophy patients vs 2.90 (1.38) for the left ventricular hypertrophy controls, P < 0.03 patients vs controls. After correction of baseline myocardial blood flow for baseline heart rate x systolic pressure product, coronary vasodilator reserve for the hypertrophic cardiomyopathy patients was 2.06 (1.06) vs 4.34 (1.54) for the hypertrophic cardiomyopathy controls. P = 0.0002 and in the secondary left ventricular hypertrophy patients, the values were 2.13 (0.64) vs 2.89 (1.42) in the secondary left ventricular hypertrophy controls, P < 0.05. CONCLUSION: In both hypertrophic cardiomyopathy and secondary left ventricular hypertrophy, the computed coronary vasodilator reserve is impaired, even after correction for baseline cardiac work. However, the extent of the reduction is greater in the hypertrophic cardiomyopathy patients. In the blunting of vasodilator reserve of secondary left ventricular hypertrophy, the patients' greater hyperaemic response is partly offset by the higher baseline myocardial blood flow.

Adult↗

PubMed1999

Myocardial diastolic impairment caused by left ventricular hypertrophy involves basal septum more than other walls: analysis by pulsed Doppler tissue imaging.

OBJECTIVE: To assess regional diastolic function in patients with hypertension with or without left ventricular hypertrophy using Doppler tissue imaging, a new tool that analyzes myocardial wall motion 'on-line'. METHODS: Ten normotensive subjects, 20 hypertensive patients without hypertrophy and 20 with hypertrophy (left ventricular mass index >50 g/m2.7), all men, underwent Doppler echocardiography and Doppler tissue imaging, which was performed in apical view by placing pulsed sample volume at the level of the basal and middle septum, basal and middle lateral wall, and infero-posterior wall. Peak velocities and time-velocity integrals of myocardial early (Em) and late (Am) waves and their ratios, regional deceleration time and regional relaxation time were measured in each segment. RESULTS: Transmitral peak E/A ratio was 1.37 in normotensive subjects, 1.01 in hypertensive patients without hypertrophy and 0.77 in those with hypertrophy (P < 0.00001). The myocardial diastolic indexes derived by Doppler tissue imaging worsened at all levels in hypertensive patients without hypertrophy compared with normotensive subjects. In hypertensive patients with hypertrophy, the majority of myocardial diastolic indexes were further impaired at the basal septal level, but only marginal differences were found in other regions, compared with indexes in hypertensive patients without hypertrophy. The main diastolic indexes were found, using separate intra-group analyses, to be more compromised at the basal septum than at other levels only in hypertrophic hypertensive patients. The prevalence of regions having peak Em/Am ratios < 1 increased significantly from normotensive subjects to hypertensive patients without hypertrophy, but not significantly from these to the hypertrophic group. Among pooled hypertensive patients, after adjusting for heart rate and diastolic blood pressure using multivariate models, the septal wall thickness was shown to be an independent determinant of the diastolic indexes of the basal and middle septum. CONCLUSIONS: In hypertensive patients without hypertrophy, diastolic dysfunction is uniform along the ventricular walls, whereas in those with hypertrophy it is more evident at the basal septal level than in other walls. Overall among hypertensive patients, the diastolic properties of the interventricular septum worsen as the thickness of the septal wall increases, in the presence and in the absence of hypertrophy.

Case-Control Studies↗

PubMed2002

Microalbuminuria in hypertensive patients with electrocardiographic left ventricular hypertrophy: the LIFE study.

OBJECTIVES: Left ventricular hypertrophy and albuminuria have both been shown to predict increased cardiovascular morbidity and mortality. However, the relationship between these markers of cardiac and renal glomerular damage has not been evaluated in a large hypertensive population with target organ damage. The present study was undertaken to determine whether albuminuria is associated with persistent electrocardiographic (ECG) left ventricular hypertrophy, independent of established risk factors for cardiac hypertrophy, in a large hypertensive population with left ventricular hypertrophy who were free of overt renal failure. METHODS: Patients with stage II-III hypertension were enrolled in the study if they had left ventricular hypertrophy on a screening ECG by Cornell voltage-duration product and/or Sokolow-Lyon voltage criteria, and clinic blood pressures between 160 and 200/95-115 mmHg and plasma creatinine < 160 mmol/l. A second ECG and morning spot urine were obtained after 14 days of placebo treatment. Renal glomerular permeability was evaluated by urine albumin/creatinine (UACR, mg/mmol). Microalbuminuria was present if UACR > 3.5 mg/mmol and macroalbuminuria if UACR > 35 mg/mmol. RESULTS: The mean age of the 8029 patients was 66 years, 54% were women. Microalbuminuria was found in 23% and macroalbuminuria in 4% of patients. Microalbuminuria was more prevalent in patients of African American (35%), Hispanic (37%) and Asian (36%) ethnicity, heavy smokers (32%), diabetics (36%) and in patients with ECG left ventricular hypertrophy by both ECG-criteria (29%). Urine albumin/creatinine was positively related to Sokolow-Lyon voltage criteria and Cornell voltage-duration product criteria. In multiple regression analysis, higher UACR was independently associated with older age, diabetes, higher blood pressure, serum creatinine, smoking and left ventricular hypertrophy. Patients smoking > 20 cigarettes/day had a 1.6-fold higher prevalence of microalbuminuria and a 3.7-fold higher prevalence of macroalbuminuria than never-smokers. ECG left ventricular hypertrophy by Cornell voltage-duration product or Sokolow-Lyon criteria was associated with a 1.6-fold increased prevalence of microalbuminuria and a 2.6-fold increase risk of macroalbuminuria compared to no left ventricular hypertrophy on the second ECG. CONCLUSIONS: In patients with moderately severe hypertension, left ventricular hypertrophy on two consecutive ECGs is associated with increased prevalences of micro- and macroalbuminuria compared to patients without persistent ECG left ventricular hypertrophy. High albumin excretion was related to left ventricular hypertrophy independent of age, blood pressure, diabetes, race, serum creatinine or smoking, suggesting parallel cardiac damage and albuminuria.

Aged↗

PubMed1990

Isoform distribution and tissue contents of contractile and cytoskeletal proteins in hypertrophied smooth muscle from rat portal vein.

Growth of the smooth muscle in the rat portal vein was initiated by an increased transmural pressure. After 7 days, the cross-sectional area of the vessel wall and the maximal active force of the longitudinal muscle layer had increased twofold. Electron microscopy showed that the cell cross-sectional area was increased, suggesting cellular hypertrophy. Increased amounts of intermediate (10 nm) filaments were observed in the hypertrophied cells. The hypertrophied vessels had decreased DNA content per unit wet weight compared with the control vessels (hypertrophied, 1.5 +/- 0.1; control, 1.9 +/- 0.1 micrograms/mg; p less than 0.01). Protein composition was studied with electrophoretic methods. Compared with control preparations the hypertrophied veins had similar myosin and actin contents per unit wet weight (myosin: hypertrophied, 4.4 +/- 0.8; control, 5.9 +/- 0.9; actin: hypertrophied 12.2 +/- 0.6; control, 11.8 +/- 1.0 mg/g). Two different forms of the myosin heavy chain were detected with 5% sodium dodecyl sulfate-polyacrylamide gels. The proportion of the lower molecular weight heavy chain relative to total heavy chain content was about 30% and similar in both preparations. The relation filamin/myosin was increased in the hypertrophied vessels. Pyrophosphate gel electrophoresis revealed two protein bands, with an increase in the slower migrating band in the hypertrophied vessels possibly reflecting an increase in filamin content in the extracts. In the control portal vein alpha-actin is the dominating isoform constituting about 55% of total actin. In hypertrophied vessels, alpha-actin decreased (by 15%) and gamma-actin increased (by 20%). The portal vein contained desmin and vimentin in a ratio of about 6:1. The hypertrophied vessels showed a marked increase in the amount of these proteins (desmin/actin: hypertrophied, 0.32; control, 0.14). In conclusion, during pressure-induced growth of the portal vein, contractile protein contents increase in proportion to the increase in weight. A change in isoforms of actin occurs but no evidence for a change in myosin isoforms was found. The structural proteins increase relative to tissue weight, possibly associated with the increased number of intermediate filaments demonstrated with electron microscopy.

Actins↗

PubMed1995

Expression of smooth muscle myosin isoforms in urinary bladder smooth muscle during hypertrophy and regression.

BACKGROUND: Partial ligation of the urinary out-flow tract of rabbit bladder induces hypertrophy of the smooth muscle layer in the bladder wall, and it is reversible by the removal of the ligature. The expression of smooth muscle myosin heavy chain isoforms SM1 and SM2 after hypertrophy and the regression of hypertrophy (reversal) was investigated at the translational and transcriptional levels using this experimental model. DESIGN: The contractile activity of smooth muscle strips derived from normal, hypertrophied, and reversal bladders was measured using electrical stimulation. Expression of SM1 and SM2 in normal, hypertrophied, and reversal muscle tissue was characterized using SDS-PAGE, reverse transcriptase-PCR (RT-PCR), and RNase protection assay. RESULTS: Smooth muscle strips from hypertrophied urinary bladder revealed a decrease in both force and rate of force generation in response to field stimulation. These alterations in contractility were reversed by removal of the obstruction. The altered function in bladder hypertrophy was also associated with changes in translation and transcription of the smooth muscle heavy chain isoforms SM1 and SM2. Upon regression of the hypertrophy by removal of the obstruction, the relative ratio of myosin heavy chain SM2:SM1 returned to nearly normal values. Analyses by RT-PCR showed a decrease in the mRNA transcript for SM2 in hypertrophied bladder muscle; and, on reversal of the hypertrophy, the SM2 mRNA level returned to that of normal bladder. These data suggest that the obstruction-induced hypertrophy activates a down-regulating mechanism for the expression of myosin SM2 heavy chain. CONCLUSIONS: Obstruction-induced alteration in the contractile characteristics of the urinary bladder smooth muscle is associated with changes in the expression of smooth muscle myosin heavy chains at both the protein and mRNA levels. The contractile function and the myosin heavy chain expression return to normal after regression of the smooth muscle hypertrophy on removal of the obstruction.

Amino Acid Sequence↗

PubMed2001

Antioxidant changes in the hypertrophied heart due to energy metabolic disorder.

Oxidative stress has been implicated in the pathogenesis of both heart hypertrophy and heart failure. Hypertrophied heart, in response to pressure overload, is associated with an increase in antioxidant capacity and a decrease in oxidative stress. However, in the hypertrophied heart due to energy metabolic disorder, antioxidant capacity has not been investigated. Antioxidant changes in juvenile visceral steatosis (JVS) mice, a model of heart hypertrophy due to disorder of fatty-acid oxidation, were examined at 4 weeks (developing hypertrophy stage) and 8 weeks of age (established hypertrophy stage). Superoxide dismutase activity in the JVS mice was higher than that in control mice at 4 weeks of age and was not different from that in the control mice at 8 weeks of age. Glutathione peroxidase activity in the JVS mice at 8 weeks of age was lower than that in the control mice. Catalase activity showed no significant differences between the control and the JVS mice. Lipid peroxidation in the JVS mice was significantly reduced at 4 weeks of age and increased toward control levels at 8 weeks of age. The levels of vitamin E in the heart were increased in the JVS mice at 8 weeks of age. To determine whether antioxidants affect the pathogenesis of hypertrophy in this model, long-term treatments of vitamin E and 2-mercaptopropionyl glycine were performed. Vitamin E treatment partially reduced the heart hypertrophy in these mice. The present study shows that heart hypertrophy in the JVS mice is accompanied with increased antioxidant capacity as indicated in other animal models of heart hypertrophy. The precise mechanism of heart hypertrophy in JVS mice is still unknown, but oxidative stress may play a role in the pathogenesis of heart hypertrophy.

Animals↗

PubMed2002

Energy metabolism in the hypertrophied heart.

In response to a prolonged pressure- or volume-overload, alterations occur in myocardial fatty acid, glucose, and glycogen metabolism. Oxidation of long chain fatty acids has been found to be reduced in hypertrophied hearts compared to non-hypertrophied hearts. However, this observation depends upon the degree of cardiac hypertrophy, the severity of carnitine deficiency, the concentration of fatty acid in blood or perfusate, and the myocardial workload. Glycolysis of exogenous glucose is accelerated in hypertrophied hearts. Despite the acceleration of glycolysis, glucose oxidation is not correspondingly increased leading to lower coupling between glycolysis and glucose oxidation and greater H(+) production than in non-hypertrophied hearts. Although glycogen metabolism does not differ in the absence of ischemia, synthesis and degradation of glycogen are accelerated in severely ischemic hypertrophied hearts. These alterations in carbohydrate metabolism may contribute to the increased susceptibility of hypertrophied hearts to injury during ischemia and reperfusion by causing disturbances in ion homeostasis that reduce contractile function and efficiency to a greater extent than normal. As in non-hypertrophied hearts, pharmacologic enhancement of coupling between glycolysis and glucose oxidation (e.g., by directly stimulating glucose oxidation) improves recovery of function of hypertrophied hearts after ischemia. This observation provides strong support for the concept that modulation of energy metabolism in the hypertrophied heart is a useful approach to improve function of the hypertrophied heart during ischemia and reperfusion. Future investigations are necessary to determine if alternative approaches, such as glucose-insulin-potassium infusion and inhibitors of fatty acid oxidation (e.g., ranolazine, trimetazidine), also produce beneficial effects in ischemic and reperfused hypertrophied hearts.

Cardiomegaly↗

PubMed1985

The distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: comparison to athletes and hypertensives.

Cross-sectional echocardiography was performed in 134 patients with hypertrophic cardiomyopathy and 75 with secondary left ventricular hypertrophy (57 hypertensives and 18 athletes) to determine the diagnostic sensitivity and specificity and predictive value of the pattern of left ventricular hypertrophy. Myocardial wall thickness was assessed in the anterior and posterior septum, free wall and posterior wall in both the upper and lower left ventricle. All patients had at least one region exceeding 2 SD from normal (greater than 1.4 cm). Asymmetrical septal hypertrophy) septum to posterior wall ratio greater than or equal to 1.5:1 in the upper or lower left ventricle) was found in 75 patients with hypertrophic cardiomyopathy (56%), 11 hypertensives (18%) and 4 (22%) athletes. This pattern was more common in patients with primary compared to secondary left ventricular hypertrophy (P less than 0.01). Distal ventricular hypertrophy was only seen in patients with hypertrophic cardiomyopathy (10%). Symmetrical left ventricular hypertrophy was demonstrated in 45 patients with hypertrophic cardiomyopathy (34%), 50 hypertensives (82%) and 14 athletes (78%). This pattern was significantly more common in patients with secondary left ventricular hypertrophy (P less than 0.01). Amongst those with symmetrical hypertrophy, patients with hypertrophic cardiomyopathy had more severe hypertrophy while the athletes had larger left ventricular cavity size. Asymmetrical septal hypertrophy was the most sensitive (56%) and distal ventricular (100%) the most specific pattern for the diagnosis of hypertrophic cardiomyopathy with a predictive value of 83 and 100% respectively. Symmetrical left ventricular hypertrophy was 81% sensitive and 66% specific with a predictive value of 58% for the diagnosis of secondary hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1985

The effect of cardiac hypertrophy on the coronary collateral circulation.

We have previously shown that dogs with renal hypertension and left ventricular hypertrophy have larger infarcts (per risk area size) than do control animals. A potential explanation for this is that collateral resistance is higher in these dogs. Paradoxically, previous postmortem studies in human hearts with left ventricular hypertrophy have suggested that coronary collaterals are actually increased in this condition. To test the hypothesis that left ventricular hypertrophy is associated with alterations in coronary collateral resistance, studies were performed in dogs with renal hypertension and left ventricular hypertrophy and in patients with aortic valvular disease at the time of cardiac surgery. With an isolated, adenosine-vasodilated, blood-perfused cardiac preparation, collateral and normal zone pressure-flow relationships were established by means of radioactive microspheres in nine dogs with renal hypertension and left ventricular hypertrophy and in 17 controls. Collateral resistance calculated from these pressure-flow relationships were similar in both groups (4.0 +/- 0.7 in dogs with renal hypertension and left ventricular hypertrophy and 3.9 +/- 0.4 mm Hg/ml/min/100 g in controls). In addition, normal zone resistance was not different between groups (transmural resistances 0.17 +/- 0.01 in controls and 0.18 +/- 0.02 in dogs with renal hypertension and left ventricular hypertrophy. In five patients with aortic valve disease, left ventricular hypertrophy, and normal coronary arteries and in six patients without left ventricular hypertrophy who had normal left anterior descending coronary arteries, a 7 MHz suction-mounted echo transducer was used to monitor systolic wall thickening during transient occlusions of the left anterior descending artery at the time of cardiac surgery. Because noncollateralized myocardium ceases to contract promptly after coronary occlusion, this approach provides an indirect index of collateral perfusion. Twenty seconds after the onset of coronary occlusion, systolic thickening had markedly decreased in both groups (15 +/- 10% of control values in nonhypertrophied hearts and 10 +/- 10% in hearts with left ventricular hypertrophy; p = NS between groups). Thus the severity of contraction abnormality induced during transient coronary occlusion in these two groups of patients was similar, suggesting that the degree of severity of ischemia was comparable between the two groups. We conclude that collateral resistance is not altered by hypertension and left ventricular hypertrophy and that left ventricular hypertrophy in patients is not associated with functional evidence of an enhanced collateral circulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

[Coronary reserve of the hypertensive heart: relationship to left ventricular hypertrophy].

We investigated the relationship between electrocardiographic left ventricular hypertrophy with ST-changes, and coronary circulation and myocardial metabolism in 25 patients with essential hypertension (systolic blood pressure greater than or equal to 160 mmHg, diastolic blood pressure greater than or equal to 95 mmHg). No patients had abnormal coronary arteriograms. They were categorized in two groups: non-hypertrophy group; cases with no hypertrophy on echocardiograms (interventricular septum and posterior wall thickness less than or equal to 11 mm), and hypertrophy group; cases with hypertrophy (wall thickness greater than or equal to 12 mm). Supine bicycle ergometry (50 watts, 50 rpm, 15 min) was performed during coronary sinus catheterization and electrocardiography. For cardiac hemodynamics, the coronary circulation and myocardial metabolism were observed at rest and during exercise. There was no significant difference in unit coronary blood flow (coronary blood flow per 100 gm) before exercise between the two groups. Unit coronary blood flow was significantly greater in the non-hypertrophy group after exercise. However, total coronary blood flow (coronary blood flow per 100 gm x left ventricular mass) showed no significant difference between the two groups. Coronary vascular resistance per 100 gm was higher in the hypertrophy group during exercise, though there was no significant difference at rest. Myocardial oxygen extraction O2 (A-C) was not different between the two groups at rest and during exercise, but unit myocardial oxygen consumption (MVO2) during exercise was higher in the non-hypertrophy group than in the hypertrophy group. The lactate extraction ratio tended to decrease in the hypertrophy group during exercise, and tended to increase in the non-hypertrophy group. Myocardial potassium flux tended to increase in the hypertrophy group during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1982

[Is secondary myocardial hypertrophy a physiological or pathological adaptive mechanism?].

Physiological hypertrophy is present when the increase in myocardial mass resulting from chronic mechanical loading is associated with normal or enhanced myocardial function and myosin ATPase activity. Morphological alterations occurring during the formation of hypertrophy are fully reversible in physiological hypertrophy. In pathological hypertrophy myocardial function and myosin ATPase activity are depressed and morphological changes do not or only incompletely regress following the elimination of the stimulus of hypertrophy. In the experimental animal myocardial hypertrophy resulting from exercise conditioning or slight to moderate ventricular pressure overload fulfills the criteria of physiological hypertrophy. More severe sudden pressure overload is accompanied by depression of contractile function. These pressure overload models have however, little analogy to the more progressive development of pressure loading in humans. In young dogs and in cats with a gradually increasing pressure load, in vivo ventricular ejection fraction remained within normal limits 37 to 60 weeks after banding of the ventricular outflow vessel. In vitro myocardial function evaluated in the hypertrophied papillary muscle was, however, at least in part depressed, notably when hydroxyproline concentration was augmented. Following debanding in rats with aortic constriction hydroxyproline content did not regress suggesting that fibrosis once established is not reversible. In man myocardial hypertrophy from exercise conditioning is associated with normal ventricular function except in older athletes, who may show a subtle reduction in ventricular shortening. Patients with chronic pressure overload from aortic stenosis or volume overload from aortic insufficiency in whom the angiographic muscle mass is severely increased (greater than or equal to 180 g/m2) elicit a depressed left ventricular contractile function. Preserved left ventricular ejection performance in aortic valve disease is however not associated with normal myocardial structure because interstitial fibrosis evaluated from endomyocardial biopsies or biopsies obtained at surgery was found to be increased. Patients with depressed left ventricular contractility were characterized by having an abnormally high muscle fibre diameter. Normal function after surgery was not accompanied by normalization of myocardial structure: Interstitial fibrosis increased, fibrous content remained the same and cellular hypertrophy regressed incompletely regardless whether angiographic muscle mass had regressed to normal or remained still increased after surgery. In summary, the bulk of available functional and morphological data suggests that the occurrence of true physiological hypertrophy is probably limited to exercise conditioning and eventually to mild chronic mechanical overload. The more severe secondary hypertrophy such as in patients with aortic valve disease who undergo valve replacement, is not a physiological adaptation, but must be considered as a pathological process.

Adenosine Triphosphatases↗

PubMed1981

[Vectorcardiographic criteria of ventricular hypertrophy in a population of athletes].

Competitive sports and the physical training involved give rise to cardiac hypertrophy. The vectocardiographic criteria of hypertrophy (Frank's system) were examined in a population of 1800 athletes of varying disciplines. Hypertrophy, essentially ventricular, was common (78% of cases); it was mainly left (46%) but right sided (18%) and bilateral ventricular hypertrophy (I4%) were also observed. Isolated left ventricular hypertrophy was most common in disciplines with high energy requirements (cycling, rowing athletics). Right ventricular hypertrophy was observed in nearly all activities. The most commonly positive criteria were those related to increased amplitude of the electrical signals, especially during depolarisation. The degree of hypertrophy was modest as shown by the absence of certain very specific criteria (clockwise rotation of QRS in the horizontal plane in right ventricular hypertrophy) and by the average numerical values which remained lower than those recorded in patients with pathological hypertrophy. The electrical recordings were suggestive of several different anatomical and haemodynamic forms of hypertrophy. The degree of hypertrophy was variable and depended most of all on the degree of physical training. Some electrical syndromes appeared to vary in time. The incidence of some electrical changes varied when the population was studied after a 10 year interval: for example, the incidence of atypical repolarisation fell from II,4% to 5%. These results suggest that the development of cardiac hypertrophy in competing athletes may have more than one mechanism.

Cardiomegaly↗

PubMed1999

Effect of angiotensin II receptor antagonism on vascular hypertrophy and aortic impedance in abdominal aortic-banded rat.

Vascular hypertrophy is considered to be an adaptive response to increased arterial wall stress in hypertension. Although there are several reports concerning the effect of angiotensin II inhibition on the development of vascular hypertrophy, little information is available as to its effect on vascular hypertrophy in parallel with the evaluation of arterial wall characteristics. The goal of this study was to evaluate the effect of angiotensin II type 1 receptor antagonist TCV-116 on pressure overload-induced vascular hypertrophy in parallel with the assessment of aortic impedance. Low dose (LD; 0.3 mg/kg/day) or high dose (HD; 3.0 mg/kg/day) of TCV-116 was administered to abdominal aortic-banded rats over 4 weeks; then hemodynamics and morphology were evaluated. In both the LD and HD groups, blood pressures were decreased to a similar extent compared with those of the vehicle-treated group (P < .05). Left ventricular (LV) weight and LV weight/body weight ratio was inhibited in both TCV-116-treated groups (P < .05), whereas the media cross-sectional area of the aorta was inhibited only in the HD group (P < .05). After the treatment of TCV-116 (LD, HD), total systemic resistance was decreased compared with the vehicle-treated group (P < .05), but there was no significant difference between the TCV-116-treated groups. In contrast, the first harmonic of the impedance modulus revealed the decrease only in the HD group (P < .05). TCV-116 attenuated the development of pressure overload LV hypertrophy and vascular hypertrophy as well; however, the dose of TCV-116 required for the inhibition of vascular hypertrophy was significantly higher than that for LV hypertrophy. Vascular hypertrophy may be less pressure dependent than cardiac hypertrophy. On chronic addition of high dose of TCV-116, arterial wave reflection was decreased in association with the attenuation of vascular hypertrophy.

Angiotensin Receptor Antagonists↗

PubMed2004

Promoting angiogenesis protects severely hypertrophied hearts from ischemic injury.

BACKGROUND: Myocardial hypertrophy is associated with progressive contractile dysfunction, increased vulnerability to ischemia-reperfusion injury, and is, therefore, a risk factor in cardiac surgery. During the progression of hypertrophy, a mismatch develops between the number of capillaries and cardiomyocytes per unit area, suggesting an increase in diffusion distance and the potential for limited supply of oxygen and nutrients. We hypothesized that promoting angiogenesis in hypertrophied hearts increases microvascular density, thereby improves tissue perfusion and substrate availability, maintains myocardial function, and improves postischemic recovery. METHODS: Left ventricular hypertrophy was created in 10-day-old rabbits by aortic banding and progression was monitored by echocardiography. At 4 weeks (compensated hypertrophy), 2 microg of vascular endothelial growth factor (VEGF) or placebo was administered intrapericardially. After 2 weeks, microvascular density, coronary flow (CF), and glucose uptake (GU) were measured. Tolerance to ischemia was determined by cardiac function measurements before and after ischemia-reperfusion using an isolated heart preparation. RESULTS: Microvascular density increased significantly following VEGF treatment (1.43 +/- 0.08/nuclei/field vs 1.04 +/- 0.06/nuclei/field untreated hypertrophy). Concomitantly, there was an increase in CF (7 +/- 0.5 vs 5 +/- 0.4 mL/min/g) and GU (1.24 +/- 0.2 vs 0.69 +/- 0.2 micromoles/g/30 minutes; p <or= 0.05). In vivo contractile function (-0.08 +/- 0.48 vs -1.39 +/- 0.35 untreated hypertrophy; p <or= 0.05) and postischemic myocardial recovery (% recovery: 93 +/- 2.0 vs 73 +/- 6.8 untreated hypertrophy; p <or= 0.05) were significantly improved in VEGF-treated hearts compared to untreated hypertrophied hearts. CONCLUSIONS: Treatment of hypertrophied hearts with VEGF resulted in an increase of microvascular density, improved tissue perfusion, and glucose delivery. Promoting angiogenesis proved useful in preserving myocardial function in late hypertrophy and improving postischemic recovery of contractile function.

Angiogenesis Inducing Agents↗

PubMed2002

Pyruvate dehydrogenase and the regulation of glucose oxidation in hypertrophied rat hearts.

OBJECTIVE: Coupling of glucose oxidation to glycolysis is lower in hypertrophied than in non-hypertrophied hearts, contributing to the compromised mechanical performance of hypertrophied hearts. Here, we describe studies to test the hypothesis that low coupling of glucose oxidation to glycolysis in hypertrophied hearts is due to reduced activity and/or expression of the pyruvate dehydrogenase complex (PDC). METHODS: We examined the effects of dichloroacetate (DCA), an inhibitor of PDC kinase, and of alterations in exogenous palmitate supply on coupling of glucose oxidation to glycolysis in isolated working hypertrophied and control hearts from aortic-constricted and sham-operated male Sprague-Dawley rats. It was anticipated that the addition of DCA or the absence of palmitate would promote PDC activation and consequently normalize coupling between glycolysis and glucose oxidation in hypertrophied hearts if our hypothesis was correct. RESULTS: Addition of DCA or removal of palmitate improved coupling of glucose oxidation to glycolysis in control and hypertrophied hearts. However, coupling remained substantially lower in hypertrophied hearts. PDC activity in extracts of hypertrophied hearts was similar to or higher than in extracts of control hearts under all perfusion conditions. No differences were observed between hypertrophied and control hearts with respect to expression of PDC, PDC kinase, or PDC phosphatase. CONCLUSIONS: Low coupling of glucose oxidation to glycolysis in hypertrophied hearts is not due to a reduction in PDC activity or subunit expression indicating that other mechanism(s) are responsible.

Animals↗

PubMed1997

Regional differences in electrical and mechanical properties of myocytes from guinea-pig hearts with mild left ventricular hypertrophy.

OBJECTIVE: To investigate electrical and mechanical properties of single myocytes isolated from different regions of the left ventricle in control and hypertrophied hearts. METHODS: Mild cardiac hypertrophy was induced in guinea-pigs by aortic constriction. Myocytes were isolated from basal sub-endocardial, basal mid-myocardial and apical sub-epicardial layers of the left ventricle. Action potentials were stimulated at 1 Hz. Membrane currents were measured using the switch-clamp technique. Cell shortening was measured using a photodiode array. RESULTS: In control hearts mean action potential duration (APD) was longer in sub-endocardial myocytes than in sub-epicardial myocytes. In hypertrophy APD was prolonged in sub-epicardial and mid-myocardial myocytes and unchanged in sub-endocardial myocytes (APD90 ms, control: sub-endocardial 273 +/- 12, mid-myocardial 254 +/- 14, sub-epicardial 229 +/- 9; hypertrophy: sub-endocardial 259 +/- 13, mid-myocardial 291 +/- 9, sub-epicardial 268 +/- 11, P < 0.005, ANOVA). There was no significant regional difference in APD in hypertrophied hearts. In control hearts L-type calcium current (ICa) was similar in all regions. In hypertrophy ICa was increased in sub-epicardial and mid-myocardial myocytes and reduced in sub-endocardial myocytes. Calcium-activated tail currents were not regionally different in control or hypertrophied hearts, but were increased in hypertrophy. CONCLUSIONS: Changes in electrical and mechanical properties associated with hypertrophy are not homogeneous throughout the left ventricle. The difference in APD between sub-endocardial and sub-epicardial myocytes seen in control hearts is lost in hypertrophy. These results may favour the propagation of re-entry arrhythmias in hypertrophied hearts.

Action Potentials↗

PubMed2000

Down regulation of myocardial beta1-adrenoceptor signal transduction system in pacing-induced failure in dogs with aortic stenosis-induced left ventricular hypertrophy.

We recently demonstrated that rapid ventricular pacing caused cardiac failure (Failure) in dogs with aortic stenosis-induced left ventricular hypertrophy (Hypertrophy) and isoproterenol caused no significant increases in function, O2 consumption and intracellular cyclic AMP level in the failing hypertrophied hearts. We tested the hypothesis that alterations in the beta1-adrenoceptor-signal transduction pathway would correlate with the reduced functional and metabolic responses to beta-adrenergic stimulation during the transition from the compensated hypertrophy to failure. Pressure overload-induced left ventricular hypertrophy was created using aortic valve plication in 10 dogs over a 6-month period. Five months after aortic valve plication, congestive heart failure was induced in 5 dogs by rapid ventricular pacing at 240 bpm for 4 weeks. The density of myocardial beta1-adrenoceptors (fmoles/mg membrane protein; fmoles/g wet tissue) was significantly reduced in the Failure dogs (176+/-19; 755+/-136) when compared to those of the Control (344+/-51; 1,551+/-203) and the Hypertrophy (298+/-33; 1,721+/-162) dogs. The receptor affinities were not significantly different among all groups. There was a small but significant decrease in the percentage of beta1-adrenoceptors of the failing hypertrophied hearts (62+/-3%) when compared to that of the hypertrophied hearts (77+/-5%). The basal myocardial adenylyl cyclase activity (pmoles/mg protein/min) was significantly lower in the Failure dogs (45+/-4) than in the Control (116+/-14) and Hypertrophy (86+/-6) dogs. The forskolin (0.1 mM)-stimulated adenylyl cyclase activity was also significantly lower in the Failure dogs (158+/-17) than in the Control dogs (296+/-35) and slightly lower than in the Hypertrophy dogs (215+/-10). There were no significant differences in low Km cyclic AMP-phosphodiesterase activities among all groups. We conclude that down regulation of beta1-adrenoceptors and reduced adenylyl cyclase activities contribute to the decreases in myocardial functions and beta-adrenergic responses in the failing hypertrophied hearts induced by rapid ventricular pacing.

3',5'-Cyclic-AMP Phosphodiesterases↗