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PubMed1986

Histopathological study on the effects of aging in myocardium of hypertrophied hearts.

To clarify the effects of aging in myocardium of hypertrophied hearts, 555 autopsied hearts were studied histopathologically. Degrees of myocyte hypertrophy, disarrangement and fibrosis and lipofuscin deposits were estimated light-microscopically in tissue specimens taken from the anterior wall of the left ventricle. Myocyte hypertrophy was assigned to one of four classes from 0 to 3+ according to size. Other findings were estimated using the conventional three classes. All cases were divided according to heart weight, into the following groups: severe hypertrophy (Group I; more than 450 g for males and 400 g for females), mild hypertrophy (Group II; 450 greater than HW greater than 350 g for males and 400 greater than HW greater than 300 g for females) and no hypertrophy (Group III: less than 350 g for males and 300 g for females). Lipofuscin deposits increased with aging, but in Group I the increase was delayed in comparison to that in other groups. As a rule, myocyte size in the outer layer was equal to or smaller than that in the inner layer (outer-layer-selective atrophy). This was particularly true in pressure-overloaded hypertrophy and less so in volume-overloaded hypertrophy. Myocyte disarrangement was observed in the inner and median layers in the oldest group. Peri-vascular fibrosis became thick with aging, and perimysial fibrosis increased with age. The fibrotic process was accelerated in hypertrophied myocardium. As to the mode of hypertrophy, aging appears to result in a kind of myocardial asymmetry of layer-selective atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2006

[The acute electrophysiological effects of amiodarone on normal and hypertrophied rat myocytes].

OBJECTIVE: The aim of the present study was to investigate the acute action of amiodarone (AM) on the inward currents I(Na), I(Ca-L) and outward currents I(k), I(k1), I(to) in hypertrophied and normal rat ventricular myocytes. METHODS: The pressure overload hypertrophy rat model was established by partial ligation of ascending aorta for 4 weeks. Ventricular myocytes were exposed to 0.01, 0.1, 1, 10 and 50 micromol/L AM and whole cell patch clamp technique was used to study the acute effects of AM on the inward currents I(Na), I(Ca-L) and outward currents I(k), I(k1), I(to). RESULTS: (1) Compared with the normal ventricular myocytes, the current density of I(k), I(ks), I(to) and I(k1) were all decreased in hypertrophied myocytes, but I(Na) and I(Ca-L) remained unchanged. (2) I(Ca-L) was blocked by 59.0% +/- 4.4% in normal myocytes but only blocked by 16.7% +/- 8.0% in hypertrophied myocytes after 50 micromol/L AM application; IC(50) of I(Na) were 9.2 micromol/L and 5.9 micromol/L in normal and in hypertrophied myocytes, respectively; I(to) was blocked by 55.9% +/- 5.5% in normal myocytes and 23.0% +/- 2.8% in hypertrophied myocytes after 50 micromol/L AM application. I(k1) was not affected by AM in both normal and hypertrophied myocytes; I(ks) was blocked by 21.6% +/- 5.6% in normal myocytes and 42.7% +/- 9.2% in hypertrophied myocytes after 10 micromol/L AM application. CONCLUSION: Our results show that the sensitivity of hypertrophied myocytes to AM on I(Na), I(ks) were higher than that of normal myocytes, while the sensitivity on I(Ca-L), I(k1), I(to) were lower than that of normal myocytes favoring the use of AM on hypertrophied myocardium for antiarrhythmic therapy.

Amiodarone↗

PubMed1985

[The role of hypertension in apical hypertrophy].

Recent advances in echocardiography have revealed that hypertension causes several types of cardiac hypertrophy. We classified hypertensive patients by type of cardiac hypertrophy, and evaluated left ventricular function and the severity of hypertension. The subjects consisted of 257 hypertensive patients, 13 patients with cardiac hypertrophy, and 95 normotensive controls. The hypertensives were classified in four groups: no hypertrophy, concentric hypertrophy, asymmetrical septal hypertrophy (ASH), and asymmetrical apical hypertrophy (AAH). The normotensive patients with cardiac hypertrophy included nine with ASH and four with AAH. Cardiac functions in these patients were determined by echocardiography, RI-angiocardiography and cardiac catheterization. The results were as follows: Among 257 hypertensive patients, the incidence of concentric hypertrophy, ASH, and AAH was 53%, 10%, and 4%, respectively. In patients with AAH and hypertension, the hypertensive blood pressure levels and hypertensive organ involvements were mild. The blood pressures of most of these patients fell to the normal range after admission. The cardiac index and left ventricular systolic function (FS, mVCF, and ejection fraction) were significantly higher in AAH with hypertension than in the other hypertensive groups or in the normotensive controls. The hypertensive patients showed lower E-F slopes and higher A/E ratios than the normotensive controls, as well as the normotensive patients with ASH or AAH. Cardiac function did not differ appreciably between normotensive AAH and hypertensive AAH. Left ventricular dimension and left ventricular end-diastolic volume index were larger in AAH with hypertension. The total peripheral resistance of the hypertensive AAH was significantly lower than that of the hypertensives with concentric hypertrophy (p less than 0.01), though it was higher than that of the normotensive AAH (p less than 0.01). It was, therefore, concluded that mild hypertension observed in patients with AAH may be the result of regulatory mechanisms in the hyperkinetic states.

Adolescent↗

PubMed1984

Myocardial characteristics of pressure overload hypertrophy. A structural and functional study.

The effects of pressure overload hypertrophy were studied in the left ventricular myocardium of young adult cats. Hypertrophy was induced by a 90% constriction of the ascending aorta, and animals were studied 4, 7, 30, 120, and 248 days after constriction. Cardiac hypertrophy, as determined by heart weight, was evident at each experimental time period. Ultrastructural data indicate that during the early stages of hypertrophy (4 and 7 days) there is an enhancement of the myofibrillar volume relative to the mitochondrial volume. After 30 days the normal balance between the myofibrillar and mitochondrial volumes has been reestablished. The later stages of hypertrophy (120 and 248 days) are characterized by a reduced mitochondrial volume relative to the myofibrillar volume. This late stage of hypertrophy (248 days) is also characterized by reduced surface densities of the T-tubular and diadic junctional systems. Analysis of the microvasculature indicated that capillary density decreased with increasing time of hypertrophy. The effects of chronic hypertrophy on myocardial blood flow were also measured. In hypertrophied hearts, coronary reserve, measured as the percentage increase in blood flow from control to near maximal flow during adenosine infusion, was reduced. Left ventricular minimal coronary resistance (per gram) was elevated during hypertrophy. These results indicate that the alterations in flow reserve are largely due to the reduced capillary density. This, combined with the inability of the myocardium at the cellular level to maintain normal structural parameters, may play an important role in the transition of a compensated heart to a failing heart.

Animals↗

PubMed1981

Response of hypertrophied myocardium to ischemia: correlation with biochemical and physiological parameters.

The increased susceptibility of hypertrophied hearts to ischemic injury during cardiac operations has long been recognized. Although the imbalances in oxygen supply and demand which may occur with hypertrophy during hypotension, ventricular fibrillation, or reperfusion have been extensively studied, the biochemical response of hypertrophied myocardium to ischemia has not been fully elucidated. In the present investigation, rat hearts in which hypertrophy was induced by chronic pressure overload were used to examine the relationship of the physiological parameter, ischemic contracture, to high-energy phosphate content and mitochondrial function during global ischemia. Hypertrophied hearts developed ischemic contracture after significantly shorter duration of ischemia than did normal hearts (5.8 +/- 0.3 minutes versus 10.1 +/- 0.7 minutes). High-energy phosphate content was lower in hypertrophied hearts at control and at ischemic contracture initiation and completion than in normal hearts, whereas mitochondrial function was consistently greater in the hypertrophy group. This investigation demonstrates that the hypertrophied myocardium, independent of flow-related events, is more vulnerable to ischemic injury than normal myocardium and suggests that the increased susceptibility may result from lower high-energy phosphate stores present at the onset of ischemia. The results emphasize the need for rapid cardiac arrest with the induction of ischemia in hypertrophied myocardium and suggest the potential for increasing myocardial high-energy phosphate content in the hypertrophied ventricle by interventions such as arrested perfusion with substrate containing oxygenated cardioplegic solutions prior to the onset of planned ischemia.

Animals↗

PubMed1995

Prevalence and determinants of cardiac and vascular hypertrophy in hypertension.

Hypertrophy of the capacitance arteries has recently been documented in hypertensive patients by noninvasive ultrasound techniques. To better define the prevalence and determinants of vascular hypertrophy and its potential association with ventricular hypertrophy in hypertension, we compared carotid and cardiac ultrasound findings in 172 normotensive and 172 unmedicated hypertensive subjects matched for age and sex. Despite similar body size, hypertension was associated with increased left ventricular wall thicknesses, mass, and mass index (89 versus 80 g/m2, P < .0001 for all comparisons) and increased carotid wall thickness (0.82 versus 0.77 mm) and cross-section area (17.1 versus 15.3 mm2, P < .005 for both comparisons). Among the 172 normotensive subjects, left ventricular hypertrophy was noted in 9 (5.2%) and arterial hypertrophy was found in 9 (5.2%), whereas ventricular hypertrophy was found in 21 (12.2%) and arterial hypertrophy in 19 (11%) hypertensive subjects. Arterial hypertrophy was found in 9% of hypertensive subjects with normal ventricular mass and in 24% with left ventricular hypertrophy (P < .05). Among hypertensive subjects carotid wall thickness and cross-sectional area were most strongly related to age and systolic pressure (P < .0001 for all comparisons), with little contribution form body size. Carotid relative wall thickness was only related to increasing age (P < .01). In contrast, left ventricular wall thickness and mass were strongly related to body size and systolic pressure (P < .0001 for comparisons) but not to age (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

A novel serum protein of molecular weight 182 kDa: a molecular marker for an early detection of increased left ventricular mass in patients with cardiac hypertrophy.

BACKGROUND: Earlier studies in our laboratory have shown the presence of a cardiac-hypertrophy-specific high-molecular-weight protein of 182 kDa in the sera of laboratory rats which were subjected to aortic stenosis. On the basis of a number of criteria, these studies have pointed out that this protein may be a molecular signal of hypertrophic growth in the aorta-constricted animals. Further, a similar high-molecular-weight protein has been observed in the sera of normal humans and patients with cardiac anomalies. We have tried to correlate the levels of 182 kDa serum protein with various parameters such as age, severity of hypertrophy and left ventricular muscle (LVM) mass in patients with cardiac hypertrophy. METHODS: Two hundred and ten patients with left and right ventricular hypertrophy evidenced by clinical history, physical examination, electrocardiogram and echocardiogram were selected for the study. Sandwich enzyme-linked immunosorbent assay (ELISA) technique was used to quantify the 182 kDa serum protein in the sera of patients by using anti-rat 182 kDa protein antibodies. RESULTS: The 182 kDa protein levels in the serum correlated with the age and stage of the LVM mass of hypertrophied heart in patients. It was noted that this protein was significantly elevated in early and moderate stages of cardiac hypertrophy and decreased when the hypertrophy became severe in patients only up to 40 years of age, whereas no significant difference exists in 182 kDa protein levels between normal individuals and patients with cardiac hypertrophy aged over 40 years. CONCLUSION: The level of this protein could be an early molecular marker identifying the stages of increase in LVM mass in patients with cardiac hypertrophy, below 40 years of age. The induction of 182 kDa protein levels in human serum may be an age-dependent phenomenon.

Adolescent↗

PubMed2000

Normal detrusor is more sensitive than hypertrophied detrusor to in vitro ischemia followed by re-oxygenation.

Partial outlet obstruction results in marked metabolic as well as contractile alterations. Specifically, the ratio of anaerobic to oxidative metabolism is significantly greater in hypertrophied than normal bladder smooth muscle, lactate dehydrogenase (LDH) and lactic acid production are increased, and the contractile apparatus is altered to allow for metabolically more efficient tension generation. In addition, contractile responses of hypertrophied bladder are apparently more resistant than those of normal bladder to hypoxia. In the current experiment, we studied the effects of in vitro ischemia (hypoxia + substrate deprivation) followed by an in vitro model of reperfusion (re-oxygenation + substrate replacement) on contractile responses of normal and hypertrophied urinary bladder strips. We used repetitive field stimulation (FS) during the hypoxic period as a model for hyperreflexia. The purpose of the current study was to compare the responses of normal and hypertrophied bladder smooth muscle to repetitive stimulation in the presence of in vitro ischemia followed by re-oxygenation and substrate replacement. Thirty-two rats were separated into four groups of eight each. The rats in groups 1 and 3 were subjected to partial outlet obstruction. Two weeks later, all rats were anesthetized; their bladders were isolated and cut into four strips. Each strip was mounted in an isolated bath, and after 1-hour incubation in Tyrode's solution containing glucose (in the presence of O(2)), contractile responses to FS, carbachol, and KCl were determined. After this first set of stimulations, the strips were incubated without glucose and in the presence of N(2) for 30 minutes and 1 hour (groups 1 and 2); and for 2 and 4 hours (groups 3 and 4). For groups 1 and 2, the tissues were stimulated at 5-minute intervals with FS at 32 Hz, 1-millisecond duration, 3-second trains (in vitro model of hyperreflexia). For groups 3 and 4, no stimulations were performed during the ischemic period. At the end of the ischemic period, all strips were washed and incubated for 1 hour in the presence of O(2) and with glucose. At the end of this incubation, all strips received a second set of stimulations. a) Partial outlet obstruction resulted in a significant increase in bladder weight. b) Responses to in vitro ischemia: After in vitro ischemia, contractile responses of both normal and hypertrophied tissues to FS were reduced to a significantly greater degree than were responses to carbachol and KCl. The rate of development of contractile dysfunction was significantly greater in normal bladder tissue strips than in hypertrophied bladder strips. c) Responses to repetitive stimulation: The rate of development of contractile dysfunction was significantly greater in all strips subjected to repetitive stimulation than in those not repetitively stimulated; in addition, normal bladder strips were more sensitive than hypertrophied strips to hypoxia and substrate deprivation-induced contractile dysfunction. The rate of contractile failure induced by in vitro ischemia followed by re-oxygenation and substrate replacement was significantly greater for normal bladder strips than for hypertrophied bladder strips. These results indicate that, after partial outlet obstruction, the hypertrophied tissue is more resistant than normal tissue to hypoxia and substrate deprivation.

Animals↗

PubMed1993

Sarcomere shortening velocity in pressure overload hypertrophied rabbit right ventricular myocardium at physiological sarcomere lengths.

Earlier we noted the importance of internal loads for sarcomere shortening in heart muscle. Internal loading may change with hypertrophy and influence sarcomere shortening velocity. Therefore, we force clamped trabeculae from normal rabbit right ventricles and those hypertrophied due to pulmonary artery constriction. Diffraction of a laser (lambda = 632.8 nm) by a trabecula was used to measure sarcomere length (SL) in isotonic twitches. Resting SL was set at 2.36 +/- 0.17 microns in the normal (n = 5) and 2.23 +/- 0.08 microns in the hypertrophied (n = 5) (+/- S.E.M.) muscles. The relationship of total stress with log10 sarcomere shortening velocity was linear. In the normals, log(SL/s) = 0.39-1.32 (P(total)/P(isom)), and in hypertrophy, log(SL/s) = -0.16-0.57 (P(total)/P(isom)). SL/s is sarcomere shortening velocity in microns/s divided by SL at the onset of constant force. P(total) is isotonic plus resting stress and P(isom) is peak total isometric stress. The hypertrophy (P(total)/P(isom))-(SL/s) relationship is depressed below normal at low loads (P < 0.001). Estimated unloaded SL/s in the normals was 2.47 and 0.69 in hypertrophy. Paired stimulation had no effect on normal SL/s. In hypertrophy, paired stimulation increased SL/s at low loads to normal levels. Thus, depressed sarcomere shortening velocity at low loads in hypertrophy at physiological sarcomere lengths disappeared when myoplasmic [Ca2+] increased. The results suggested that internal loading was greater than normal during shortening of hypertrophied myocardium. Increased myoplasmic [Ca2+] increased the number of crossbridges and reduced the load per crossbridge. This was a likely mechanism for the increase of sarcomere shortening velocity to normal levels.

Animals↗

PubMed2000

Endogenous and exogenous coronary vasodilatation are attenuated in cardiac hypertrophy: a morphological defect?

Reactive hyperaemia (RH) following brief ischaemia is reduced in hypertrophied hearts, and this may contribute to reduced coronary flow reserve. We studied vasodilatation during RH and in response to exogenous stimuli in control and hypertrophied hearts and explored the mechanisms underlying RH. Vascular reactivity was assessed in isolated hypertrophied hearts (55+/-3 days after aortic banding or sham operation) by constructing dose-response curves to acetylcholine (ACh), sodium nitroprusside (SNP) and adenosine. Reactive hyperaemic vasodilatation was assessed after global ischaemia (5-120 s) in the presence/absence of L -NAME, 8-phenyltheophylline (8-PT) and glibenclamide. Purine release and NO overflow in the coronary perfusate were analysed. Aortic constriction increased heart/body weight ratio (47%), myocyte size (19%) and arteriolar wall thickness (51%), all P<0.01. Coronary reserve was reduced in hypertrophy (105+/-8%v 182+/-12%, P<0.01). Dose response curves for ACh, SNP and adenosine were reduced in hypertrophy (69%, 86% and 68%, all P<0.01) v shams; however ED(50)values were unchanged. The peak flow and duration of RH were also attenuated (50%, P<0.001) in hypertrophy. While purine washout during RH was related to the duration of preceding ischaemia, nitrate washout was not. RH experiments in the presence of L -NAME, 8-PT and glibenclamide indicated that RH is mediated by combined actions of K(ATP)channels>adenosine>NO in both groups. RH is mediated by similar mechanisms in control and hypertrophied hearts. All vasodilatation was similarly attenuated in hypertrophy, independent of endothelial activation. We hypothesize that increased arteriolar wall thickness may limit vasodilator responses to all stimuli in hypertrophy.

Animals↗

PubMed2005

Vascular endothelial growth factor delays onset of failure in pressure-overload hypertrophy through matrix metalloproteinase activation and angiogenesis.

OBJECTIVE: Pressure-overload hypertrophy is associated with decreased capillary density in myocardium resulting in impaired substrate delivery. Treatment of hypertrophied hearts with vascular endothelial growth factor (VEGF) induces angiogenesis. Since angiogenesis is associated with extracellular matrix degradation, we sought to determine whether VEGF induced angiogenesis in hypertrophy required matrix metalloproteinases (MMP) activation. METHODS: Newborn rabbits underwent aortic banding. Progression of hypertrophy (mass-to-volume (M/V) ratio) and mid-wall contractility index was monitored by echocardiography. At 4 and 6 weeks, VEGF (2 microg/kg), vehicle or VEGF combined with GM6001 (5 mg/kg), a MMP inhibitor, was administered intrapericardially. CD-31 (indicator of angiogenesis), MMP-2, MT1-MMP and TIMPs (endogenous MMP inhibitors) expression were measured by immunoblotting. MMP-2 activity was determined by gelatin zymography. RESULTS: Untreated hypertrophied hearts progressed to ventricular dilatation at 7 wks (M/V ratio: 0.75 +/- 0.07), but compensatory hypertrophy was maintained with VEGF (0.91 +/- 0.07; p < 0.05). LV contractility declined in untreated hearts from -0.41 +/- 0.9 (5 wks) to -0.73 +/- 0.5 (7 wks; p < 0.05) but remained normal with VEGF (+1.61 +/- 0.6 vs. +0.47 +/- 0.2). MMP-2 expression and activity were significantly elevated in VEGF treated hypertrophied hearts (p < 0.05) and were blocked by concomitant administration of GM6001. VEGF induced neovascularization was inhibited by addition of GM6001. MT1-MMP showed a trend to higher levels in VEGF treated hearts. TIMPs were unchanged in all three groups. CONCLUSIONS: Exogenous VEGF and resultant MMP-2 activation leads to increased capillary formation in severe hypertrophy, preventing progression to ventricular dilation and dysfunction. VEGF and the associated MMP-2 activation play an important and potentially therapeutic role in vascular remodeling of hypertrophied hearts.

Angiogenesis Inducing Agents↗

PubMed1996

Intracellular pH and intrinsic H+ buffering capacity in normal and hypertrophied right ventricle of ferret heart.

OBJECTIVE: To answer the questions: (a) What is the effect of hypertrophy on the intracellular pH (pHi) and buffering power of cardiac muscle, and (b) How does hypertrophy affect the ability of cardiac muscle to recover from intracellular acidosis induced by hypoxia. METHODS: In nominally HCO3(-)-free, HEPES-buffered Tyrode solution (35 degrees C), pHi and the intrinsic buffering power (beta i, measured in the presence of amiloride) was investigated using pH-sensitive microelectrodes. RESULTS: beta i was similar in both preparations (25 mM/pH unit at pHi 7.04). beta i was inversely related to pHi but the relationship was not significantly modified by hypertrophy. In the absence of amiloride, the time constant of pHi recovery (tau r) on removal of NH+4, was similar in normal (4.0 +/- 0.2 min, n = 5) and in hypertrophied muscles (4.3 +/- 0.3 min, n = 4; n.s.). In both preparations, net acid extrusion (JH) was similarly increased at lower values of pHi. Lowering temperature from 35 degrees to 22 degrees caused an alkalinization (0.15 pH units) of pHi. At 22 degrees C the mean values of pHi, beta i, tau r and JH were similar in normal and in hypertrophied muscles. At both temperatures and in both groups of preparations, recovery of pHi following hypoxia is approximately exponential. The time constant of recovery of pHi following hypoxia (tau rh) at 22 degrees C was not significantly different in hypertrophied muscles (7.2 +/- 0.9 min, n = 8) compared to controls (10.6 +/- 1.8 min, n = 13). However, at 35 degrees C, there was a significant difference in the mean values of tau rh which was smaller for hypertrophied muscles (3.9 +/- 0.3 min, n = 7) than for normal (7.1 +/- 1.1 min, n = 4, P < 0.005). For pHi 6.8-7.0, net acid extrusion in hypertrophied preparations was increased by a factor of 4 compared to normal. CONCLUSIONS: The intracellular buffering capacity and the pHi regulating capacity via Na+/H+ exchange are not significantly modified by right ventricular hypertrophy in ferret heart. The faster pHi recovery from hypoxia-induced acidification can be interpreted in terms of the role of lactate efflux in pHi control. The possible role of energy compartmentalization, its influence on the Na+ gradient and thus on pHi control after hypoxia, is discussed.

Amiloride↗

PubMed1994

Captopril cardioplegia on myocardial protection in the hypertrophied rat hearts.

Hearts with pressure-overload hypertrophy show an increased intracardiac activation of the renin-angiotensin system (RAS) which may contribute to myocardial ischemia and reperfusion injury. This study investigates whether the hypertrophied myocardium is more vulnerable to ischemia and reperfusion injury and whether the specific inhibition of the cardiac RAS by captopril would modify ischemia and reperfusion injury in the hypertrophied myocardium. By using the isolated working rat heart model, hypertrophied hearts, induced by abdominal aortic banding for 6 weeks, were subjected to 120 min of hypothermic ischemic arrest followed by 30 min of reperfusion. The postischemic cardiac function recovery was measured in both the untreated (n = 10) and the captopril-treated (n = 11) groups and was compared with that of the sham-operated non-hypertrophied control hearts (n = 10). Captopril (23.0 microM) was given to one group with the hypertrophied hearts from the beginning of ischemia to the end of reperfusion. In comparison with the normal control hearts, the cardiac function recovery after 30 min reperfusion was poorer in the hypertrophied hearts, which was associated with a lower recovery of coronary flow (CF), a higher myocardial lactate content and a retarded peak myocardial creatinkinase (CK) release. Captopril significantly improved the cardiac function recovery, which was associated with an increased CF recovery and a lower myocardial lactate content, and a rapid peak CK release. In conclusion, this study shows that the hypertrophied myocardium leads to an increased susceptibility to ischemia and reperfusion injury. Captopril, most likely by its inhibition of the cardiac RAS, is effective in preventing the ischemia and reperfusion injury in the hypertrophied heart.

Animals↗

PubMed1995

Empiric determination of the transition from concentric hypertrophy to congestive heart failure in essential hypertension.

OBJECTIVES: Our aim was to determine whether there is a final transition from left ventricular hypertrophy to congestive heart failure in the late stage of essential hypertension. BACKGROUND: A theoretic model using the concept of systolic transmural nonuniform wall thickening was applied to develop a concentric two-shell geometry allowing evaluation of the mechanics of circumferential midwall fibers. METHODS: We evaluated pressure-volume data from 46 normal control subjects (control group) and 70 patients with hypertension: 33 without hypertrophy (hypertension only group), 14 with hypertrophy (hypertrophy group) and 23 with heart failure in addition to hypertrophy (heart failure group). RESULTS: End-diastolic volume index was higher in the heart failure group than in the control group (p < 0.01). Although left ventricular wall thickness and mass index were increased in both the hypertrophy and the heart failure group, concentricity indexes as assessed by ratios of left ventricular wall thickness to dimension and mass index to end-diastolic volume index were maximal in the former. Although endocardial and standard midwall fractional shortening did not differ among the control, hypertension only and heart failure groups, that of the modified midwall by concentric two-shell geometry was decreased in the hypertrophy and the heart failure groups (p < 0.05). The Hotelling T2 test and Mahalanobis distance clearly discriminated the latter two groups with end-systolic stress and modified midwall fractional shortening relation. CONCLUSIONS: A fitting segmented regression model predicted a progression to hypertrophy and identified a transition from hypertrophy to heart failure by a combination of modified midwall fractional shortening and concentricity indexes.

Adult↗

PubMed1995

Effects of hypertrophy and heart failure on [Na+]i in pressure-overloaded guinea pig heart.

Intracellular free sodium levels ([Na+]i) were assessed with 23Na nuclear magnetic resonance (NMR) spectroscopy in isolated, Langendorff-perfused normal, compensated hypertrophied, and hypertrophied failing guinea pig hearts under several conditions. Baseline [Na+]i measured with a shift reagent was significantly greater than normal in the compensated hypertrophied hearts (12.8 +/- 1.2 mmol/L v 6.4 +/- 0.7 mmol/L, means +/- SEM, P < .01), but not in the hypertrophied failing hearts (8.7 +/- 1.9 mmol/L, P = N.S.). Moreover, the highest levels of [Na+]i were seen just 3 to 4 weeks after aortic constriction. [Na+]i was inversely related to both time after aortic constriction (R = -0.71, P < .03) and to the degree of left ventricular hypertrophy (R = -0.79, P < .01), suggesting that the hypertrophied failing heart is capable of maintaining relatively normal [Na+]i. In addition, triple quantum filtered NMR measurements were made to assess changes in [Na+]i subsequent to altered perfusion or loading conditions. In hypertrophied failing hearts, but not normal hearts, low coronary perfusion pressure (60 cm H2O) was associated with relatively higher [Na+]i (ANOVA, P < .05), suggesting greater sensitivity of hypertrophied failing hearts to hypoperfusion. On the other hand, when all hearts were perfused at 90 cm H2O and intraventricular balloon volume was increased from 100 microL to 300 microL, [Na+]i increased significantly only in the normal guinea pig hearts (12.3 +/- 1.8%, P < .01). These findings suggest complex changes in the expression or modulation of proteins involved in Na+ regulation. Interpretation regarding the physiological significance of these changes depends on the specific mechanism(s) proposed. Previous work in this and other models of hypertrophy suggest that changes in the number or activity of both Na(+)-K(+)-ATPase and Na(+)-Ca2+ exchange proteins are involved.

Analysis of Variance↗

PubMed2004

The effects of overexpression of the Na+/Ca2+ exchanger on calcium regulation in hypertrophied mouse cardiac myocytes.

In cardiac hypertrophy and failure it has been shown that the amount of Na/Ca exchanger protein can increase. Several studies have investigated this modification in overt heart failure. However, the role of Na/Ca exchanger overexpression during the development of hypertrophy is unknown. To address this question we investigated Ca2+ regulation in an early stage of cardiac hypertrophy before signs of heart failure occurred and evaluated the role of Na/Ca exchanger overexpression. Cardiac hypertrophy was induced by a constant infusion of angiotensin II (Ang, 1 microg/min/kg) via an osmotic pump for 14 days. Thereafter, ventricular myocytes from either wild type (NON) or transgenic mice overexpressing the Na/Ca exchanger (TR) were isolated. Myocytes were loaded with indo-1 AM or fluo-4 AM to monitor cytoplasmic [Ca2+] with all experiments performed at 37 degrees C. In myocytes exposed to Ang there was an increase in cell capacitance of more than 20% indicating cellular hypertrophy. Ca2+ transients were prolonged in hypertrophied NON myocytes but not in TR myocytes. Action potentials had a less negative plateau in TR myocytes. Sarcoplasmic reticulum (SR) Ca2+ content, measured using rapid caffeine application, was greater in TR myocytes but unaffected by hypertrophy. Ca2+ spark frequency was significantly greater in TR. Na/Ca exchanger overexpression prevented the prolongation of the Ca2+ transient observed in hypertrophy and maintained a similar SR Ca2+ leak suggesting a compensatory role in Ca2+ regulation in hypertrophied cardiac myocytes from transgenic mice. We suggest this compensatory effect is mediated by increased SR Ca2+ content and faster Ca2+ removal via the Na/Ca exchanger.

Action Potentials↗

PubMed2005

Positive correlations between serum calcineurin activity and left ventricular hypertrophy.

BACKGROUND: Among various intracellular signaling cascades associated with cardiac hypertrophy, the involvement of calcineurin (CaN; Ca2+-calmodulin dependent protein phosphatase) is gaining credence because of its enhanced activity in ventricular myocardium and the ability of CaN inhibitors to prevent pressure-overload hypertrophy. Since our recent findings attribute clinical significance to serum CaN, the present investigation was conducted to evaluate its significance in cardiac hypertrophy. METHODS: The study group comprised of patients diagnosed for hypertensive hypertrophy, hypertrophic cardiomyopathy, chronic coronary artery disease with compensatory left ventricular hypertrophy, dilated cardiomyopathy and acute myocardial infarction. Serum contents of CaN and calmodulin were determined and activities of CaN as well as of acid and alkaline phosphatases were assayed and correlated with 2D echocardiography findings. The results were compared with those obtained from age-matched healthy volunteers. RESULTS: Serum CaN activity, but not of acid or alkaline phosphatases, was significantly enhanced by 2-fold in hypertensive hypertrophy, 3-fold in hypertrophic cardiomyopathy and 3.75-fold in chronic coronary artery disease associated with left ventricular hypertrophy, unaccompanied by changes in serum contents of calmodulin and CaN. No such increases were observed in acute myocardial infarction and dilated cardiomyopathy. CONCLUSIONS: Positive correlations observed between serum CaN activity and enhanced left ventricular mass in cardiac hypertrophy suggest that assaying serum CaN activity may be useful in the diagnosis and management of left ventricular hypertrophy.

Adult↗

PubMed1996

Prognostic value of left ventricular mass and geometry in systemic hypertension with left ventricular hypertrophy.

To determine the independent prognostic significance of left ventricular (LV) mass and geometry (concentric vs eccentric pattern) in hypertensive subjects with LV hypertrophy at echocardiography, 274 subjects were followed for up to 8.7 years (mean 3.2). All patients had systemic hypertension and LV mass > or = 125 g/body surface area (BSA) and underwent ambulatory blood pressure (BP) monitoring and echocardiography before treatment. Eccentric and concentric hypertrophy were defined by the ratio between LV posterior wall thickness and LV radius at telediastole <0.45 and > or = 0.45, respectively. Age, sex ratio, body mass index, office BP and serum glucose, cholesterol, and triglycerides did not differ between the groups with eccentric (n=145) and concentric (n=129) hypertrophy. Average 24-hour daytime, and nighttime systolic ambulatory BPs were higher in concentric than in eccentric hypertrophy (all p <0.01). LV mass was slightly greater in concentric than in eccentric hypertrophy (157 vs 149 g/BSA, p <0.05). Endocardial and midwall shortening fraction were lower in concentric than in eccentric hypertrophy (96.5% vs 106.0% of predicted and 71.4% vs 89.7% of predicted, respectively; both p <0.01). The rate of major cardiovascular morbid events was 2.20 and 3.34 per 100 patient-years in eccentric and concentric hypertrophy, respectively (log rank test, p=NS). Age >60 and LV mass above median (145 g/BSA) were significant adverse prognostic predictors, while LV geometry (eccentric vs concentric hypertrophy) and ambulatory BP were not. The event rates per 100 patient-years were 1.38 and 3.98, respectively, in the patients with LV mass below and above median (age-adjusted relative risk 2.70; 95% confidence interval [CI] 1.03 to 6.63; p=0.015). In hypertensive subjects with established LV hypertrophy, LV mass, but not its geometric pattern, provides important prognostic information independent of conventional risk markers including office and ambulatory BP.

Blood Pressure↗