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PubMed1995

The relationship of left ventricular geometry and hypertrophy to left ventricular function in valvular heart disease.

Valvular heart disease imposes a hemodynamic load on the left or right ventricle. This load is compensated by the development of ventricular hypertrophy. The pattern of hypertrophy which develops is characteristic of each type of valvular lesion with concentric hypertrophy compensating the pressure overload of aortic stenosis, eccentric hypertrophy compensating the volume overload of mitral regurgitation and both concentric and eccentric hypertrophy compensating the combined pressure and volume overload of aortic regurgitation. While these patterns are characteristic, there is substantial variation in the geometric distribution of hypertrophy among individuals with the same valvular disease. This variability in turn produces variability in the amount of compensation from patient to patient. The geometric pattern of hypertrophy which develops primarily affects left ventricular function as it relates to the Laplace equation. An increase in the radius to thickness ratio increases wall stress while a decrease in this ratio decreases wall stress. Discussed below are the mechanisms by which the various geometries that develop in valvular heart disease affect loading to become adaptive or maladaptive or both.

Aortic Valve Insufficiency↗
PubMed1998

[Effects of uvulopalatopharyngoplasty on patients with obstructive sleep apnea--the severity of preoperative tonsillar hypertrophy].

Predicting outcome following uvulopalatopharyngoplasty (UPPP) in obstructive sleep apnea is difficult. We hypothesized that UPPP is effective in obstructive sleep apnea patients with severe tonsillar hypertrophy. We examined the relationship between the severity of pre-operative tonsillar hypertrophy and the effect of UPPP in 38 patients with obstructive sleep apnea (oxygen desaturation index (ODI) > or = 20). The patients were classified into three groups according to the Mackenzie Classification of tonsillar hypertrophy. Ten patients were classified as grade 1 (M1) hypertrophy, i.e. tonsils just visible beyond the palatal arch. Five patients had grade 3 (M3) hypertrophy, i.e. tonsils appearing to contact each other at the midline. The remaining 23 patients had grade 2 (M2) hypertrophy, i.e. intermediate enlargement. We measured the apnea index, ODI, DST 90, and DST 85 (%time with SaO2 < or = 90% and < or = 85%, respectively) using a screening device for sleep apnea (Apnomonitor II, CHEST M. I. Co. Tokyo, Japan) before and after UPPP. Following UPPP, the mean ODI decreased significantly in all groups: 59 to 9/hr (p < 0.005) in the M3 group, 53 to 27/hr (p < 0.001) in the M2 group, and 48 to 33/hr (p < 0.05) in the M1 group. Post-UPPP ODI decreased by 83% in M3, 45% in M2, and 28% in M1 patients. Successful UPPP, defined by a post-UPPP ODI of less than 20/hr and a greater than 50% decrease in post-UPPP ODI, occurred in 80% of M3, 43% of M2, and 10% of M1 patients. We conclude that tonsillar hypertrophy can predict a successful response to UPPP in obstructive sleep apnea patients.

Adult↗
PubMed1988

The relationship between hypertrophy and dilatation in the postmortem heart.

Confusion may exist at the time of postmortem examination as to whether the diseased heart is dilated, hypertrophied, or both. Ventricular dilatation and ventricular hypertrophy were therefore evaluated by cardiac partition techniques in 441 subjects at autopsy to determine their relationship. Specific weight and surface area of each ventricle were obtained and patients were divided into categories of disease. Wall thickness measurements, a parameter routinely used in the ordinary autopsy, were found to be unreliable in defining hypertrophy. Ventricular surface area (an index of dilatation) was highly correlated with ventricular weight in most disease categories. Exceptions were cardiomyopathy and aortic stenosis, in which hypertrophy predominated. We conclude from these data that dilatation and hypertrophy occur proportionately in the postmortem heart in most disease categories except in cardiomyopathy and aortic stenosis. These findings clarify the relationship of dilatation and hypertrophy at the time of autopsy in most cases. Therefore, uncertainty as to whether cardiac dilatation or hypertrophy is present or which predominates is usually related to the inability to assess these states critically at the time of autopsy when the ordinary pathological methods are used.

Cardiomegaly↗
PubMed1989

New perspectives on left ventricular hypertrophy: anatomy, physiology, and significance.

The advent of echocardiography has added an important and sensitive tool for assessment of left ventricular hypertrophy (increased left ventricular mass). Recent echocardiographic studies in large population-based samples suggest an epidemic of left ventricular hypertrophy. Preliminary data suggesting important prognostic importance for such left ventricular hypertrophy (independent of standard risk factors) has fueled interest in the development, determinants, and other features of the hypertrophy. Hemodynamic and neurohumoral factors are the most prominent stimuli to adaptive (physiologic) myocardial hypertrophy, which can progress to maladaptive (pathologic) hypertrophy. The overall blood pressure experience, overweight, the cardiovascular response to recurrent psychosocial stress and physical activity level are four important correlates and potential determinants of left ventricular mass in various urban-suburban populations. Determination of the relative contributions and interrelations of these and other factors (such as heredity) to various forms of left ventricular hypertrophy found in various demographic groups warrants intensive investigation.

Cardiomegaly↗
PubMed1999

Reduced myocardial sarcoplasmic reticulum Ca(2+)-ATPase protein expression in compensated primary and secondary human cardiac hypertrophy.

Pathological intracellular calcium handling has been proposed to underlie the alterations of contractile behavior in hypertrophied myocardium. However, the myocardial protein expression of intracellular calcium transport proteins in compensated human left ventricular hypertrophy has not yet been studied. We investigated septal myocardial specimens of patients suffering from hypertrophic obstructive cardiomyopathy (n=14) or from acquired aortic valve stenosis (n=11) undergoing myectomy or aortic valve replacement, respectively. For comparison, we studied non-hypertrophied myocardium of six non-failing hearts which could not be transplanted for technical reasons. The myocardial density of the calcium release channel of the sarcoplasmic reticulum (SR) was determined by(3)H-ryanodine binding. Myocardial contents of SR Ca(2+)-ATPase, phospholamban, calsequestrin and Na(+)/Ca(2+)-exchanger were analysed by Western blot analysis. The myocardial SR calcium release channel density was not significantly different in hypertrophied and non-failing human myocardium. In both hypertrophic obstructive cardiomyopathy and in aortic valve stenosis, SR Ca(2+)-ATPase expression was reduced by about 30% compared to non-failing myocardium (P<0.05), whereas the expression of phospholamban, calsequestrin, and the Na(+)/Ca(2+)-exchanger was unchanged. The decrease of SR Ca(2+)-ATPase expression was still observable when related to its regulatory protein phospholamban or to the myosin content of the homogenates (P<0.05). Furthermore, the SR Ca(2+)-ATPase expression was inversely correlated to the septum thickness assessed by echocardiography, but not to age, cardiac index or outflow tract gradient. In primary as well as in secondary hypertrophied human myocardium, the expression of SR Ca(2+)-ATPase is reduced and inversely related to the degree of the hypertrophy. The diminished SR Ca(2+)-ATPase expression might result in reduced Ca(2+)reuptake into the SR and might contribute to altered contractile behavior in hypertrophied human myocardium.

Adult↗
PubMed2001

Increased sensitivity of mitochondrial respiration to inhibition by nitric oxide in cardiac hypertrophy.

Cardiac hypertrophy is a significant risk factor for the development of congestive heart failure (CHF). Mitochondrial defects are reported in CHF, but no consistent mitochondrial alterations have yet been identified in hypertrophy. In this study selective metabolic inhibitors were used to determine thresholds for respiratory inhibition and to reveal novel mitochondrial defects in hypertrophy. Cardiac hypertrophy was produced in rats by aortic banding. Mitochondria were isolated from left ventricular tissue and the effects of inhibiting respiratory complexes I and IV on mitochondrial oxygen consumption were measured. At 8 weeks post-surgery, 65+/-2% complex IV inhibition was required to inhibit respiration half maximally in control mitochondria. In contrast, only 52+/-6% complex IV inhibition was required to inhibit respiration half maximally in mitochondria from hypertrophied hearts (P=0.046). This effect persisted at 22 weeks post-surgery and was accompanied by a significant upregulation of inducible nitric oxide synthase (iNOS, 3.0+/-0.7-fold, P=0.006). We conclude that respiration is more sensitive to complex IV inhibition in hypertrophy. Nitric oxide is a well documented inhibitor of complex IV, and thus the combination of increased NO(.)from iNOS and an increased sensitivity to inhibition of one of its targets could result in a bioenergetic defect in hypertrophy that may be a harbinger of CHF.

Animals↗
PubMed2001

Src and multiple MAP kinase activation in cardiac hypertrophy and congestive heart failure under chronic pressure-overload: comparison with acute mechanical stretch.

Activation of members of the mitogen-activated protein (MAP) kinase family and their downstream effectors has been proposed to play a key role in the pathogenesis of cell survival, ischaemic preconditioning, cardiac hypertrophy and heart failure. This study investigated the responses of Src kinase and multiple MAP kinases during the transition from compensated pressure-overload hypertrophy to decompensated congestive heart failure. Extracellular signal-regulated protein kinase (ERK) 1/2, p38, and Src were activated by chronic pressure-overload and their activity was sustained for 8 weeks after aortic banding. In contrast, while p90 ribosomal S6 kinase (90RSK) and big MAP kinase 1 (BMK1) were activated in compensated hypertrophy, their activities were significantly decreased in hearts with heart failure. No changes were found in C-Jun NH2 terminal kinase (JNK) activity after aortic banding. These data suggest that differential activation of MAP kinase family members may contribute to the transition from compensated to decompensated hypertrophy. We also examined acute effects of mechanical stretch on the activation of these kinases in normal and hypertrophied hearts. In the isolated coronary-perfused heart, a balloon in the left ventricle was inflated to achieve minimum end-diastolic pressure of 25 mmHg for 10-20 min. In normal guinea pig hearts, stretch activated ERK1/2, p90RSK, p38, Src, and BMK1 but not JNK. However in hypertrophied hearts, further activation of these kinases was not observed by acute mechanical stretch. Mechanical stretch-induced activation of ERK1/2 and p38 kinase in normal hearts was attenuated significantly by a protein kinase C inhibitor, chelerythrine. We demonstrate that ERK1/2, p90RSK, p38, Src, and BMK1 are activated by chronic pressure-overload and by acute mechanical stretch. These data suggest that Src, BMK1 and p90RSK play a role as novel signal transduction pathways leading to cardiac hypertrophy. In addition, the differential inhibition of p90RSK and BMK1 in hearts with congestive heart failure suggests the specific role of these two kinases to maintain cardiac function under chronic pressure-overload.

Alkaloids↗
PubMed1987

Development and regression of right heart ventricular hypertrophy: biochemical and morphological aspects.

Male Wistar rats were exposed, in a hypobaric chamber, to a simulated altitude of 6000 m for up to four weeks. The animals quickly developed pulmonary hypertension with an important media hypertrophy of the pulmonary arteries, followed by severe right heart hypertrophy (cor pulmonale). Right heart hypertrophy is evident in three morphologically and biochemically definable stages. In stage 1 (1st-2nd week) a manifest thickening of heart muscle cells develops due to increased protein synthesis. In stage 2 (2nd-3rd week) one can find, in the regular biochemical composition of heart muscle, an activation of mitochondrial ATPase, a multiplication of mitochondria, a proliferation of interstitial cells and an increase in interstitial volume. In stage 3 (3rd-4th week) the hypertrophied myocardium exhibits signs of biochemical and morphological decompensation. Besides a loss of myofibrils and a reduction in mitochondrial ATPase, DNA and protein concentrations sink to subnormal values. Only myocardium from stage 1 of hypertrophy shows complete reversibility after cessation of hypobaric conditions, but not so in stage 3. Parallel with the developing cor pulmonale, the animals also react with a small hypertrophy of the left heart ventricle. This concomitant growth persists under normobaric conditions, too. These investigations document that growth of myocardium under extreme conditions shows a phasic development. Severe forms of myocardial hypertrophy do not always seem to be reversible.

Adenosine Triphosphatases↗
PubMed1986

Function and energy-rich phosphate content of the hypertrophied ventricle after global ischemia and reperfusion.

Using an isolated rat heart preparation (Langendorff perfusion, perfusion pressure 100 cm H2O) the response of the hypertrophied heart (spontaneous hypertensive rats lv/bw ratio 3.6 +/- 0.5) to global normothermic (30 min) and hypothermic (25 degrees C, 120 min) ischemic and cardioplegic arrest and reperfusion (30 min) was examined and compared with normal hearts (Wistar rats lv/bw ratio 2.0 +/- 0.3). St. Thomas solution and verapamil (2 mg/l Ringer solution) were used as cardioplegic agents. Before ischemia hypertrophied hearts had a significantly higher pressure-rate product, a lower myocardial perfusion/g myocardium and a lower myocardial ATP and adenine nucleotide content. Unmodified ischemia reduced myocardial function in the hypertrophied hearts to a greater degree than in normal hearts in both normo- and hypothermia. St. Thomas solution and verapamil protected significantly the myocardial function in the normal and hypertrophied heart after normothermic ischemia in a similar manner (60-70% of the initial value). In the hypertrophied ventricle ATP decay and adenine nucleotide loss was greater in verapamil than in St. Thomas solution treated hearts. In hypothermic ischemia only St. Thomas solution protected left ventricular function and adenine nucleotide loss in both normal and hypertrophied hearts. Verapamil was ineffective in the normal ventricle and protected left ventricular function but not the ATP and adenine nucleotide decay in the hypertrophied heart.

Animals↗
PubMed1982

Myocardial lysosomes in pressure-overload hypertrophy.

Combined electron microscopic and cytochemical studies were used to investigate the effects of chronic-pressure overload hypertrophy on myocardial lysosomes, mitochondria, and myofibrils in the left ventricle of the cat. Myocardial hypertrophy was induced by an 84% banding constriction of the ascending aorta. After one month of aortic constriction the experimental animals demonstrated a 51% increase in left ventricular mass. No qualitative ultrastructural differences were noted between the myocardial tissues of the hypertrophy and normal group. However, the cytochemical reaction product to acid phosphatase appeared more frequently in the myocardium of the hypertrophy group compared to that of the normal group. By use of quantitative morphometry the percentage of mitochondria, myofibrils and lysosomes per myocardial cell was determined in both hypertrophy and normal groups of animals. Despite significant increases in the left ventricular mass of hypertrophy animals, a normal balance of mitochondria and myofibrils was maintained within the myocardium. Further analysis indicated an enhanced lysosomal population in the hypertrophy group compared to the normal group.

Animals↗
PubMedDate not supplied

Morphometric analysis of collagen network and plasma perfused capillary bed in the myocardium of rats during evolution of cardiac hypertrophy.

In order to investigate the consequences of different types of cardiac hypertrophy on myocardial capillary and fibrosis density in rats we describe here, in the same hearts, the pattern of capillary bed density visualized by fluorescein isothiocyanate dextran (FITC-dextran) and the pattern of fibrosis density as determined by automated image analysis. Pressure overload was induced by clipping one renal artery in rats (one-clip, two-kidney Goldblatt hypertension, RHV). Volume overload was induced by creation of an arteriovenous shunt between the abdominal aorta and the vena cava (aorto-caval fistula model ACF). Animals were sacrified at 1, 3 and 6 months following surgical procedure. Immediately prior to sacrifice, FITC-dextran (MW 150,000) was injected with the animal under ether anesthesia. Five minutes later, cardiac diastolic arrest was induced by the i.v. injection of potassium chloride. The heart was rapidly excised and placed in a formaldehyde solution. The degree of cardiac hypertrophy was calculated after measurement of cardiac weight. Left ventricular wall thickness and cavity area were measured by microscopic methods. Capillary density and geometry were determined by morphometric methods, under ultraviolet light microscopy, using a graphic tablet connected to a microcomputer. The degree of myocardial fibrosis, visualized with Sirius Red, was estimated by the use of automated image analysis using light microscopy. In renovascular hypertension, cardiac hypertrophy was maximum at one month (36%) and persisted through the six months of the study. This increase in cardiac mass was concentric, due to a significant increase in ventricular wall thickness and was associated with a marked increase in fibrosis and a significant decrease in subendocardial capillary density. These effects existed already one month and did not change with time. In the aorto-caval fistula model, cardiac hypertrophy was also maximum at one month (+56%), but this eccentric increase in cardiac mass was associated with no significant change in left ventricular wall thickness, but rather with a significant increase in the surface area of the left ventricular cavity. This volume overload hypertrophy was associated with a decrease in subendocardial capillary density which was negatively correlated with time. In contrast to concentric hypertrophy there was no increase in the fibrosis density compared to the sham-operated groups. Despite the identical degrees of hypertrophy, pressure and volume cardiac overload differed in a significant manner in both left ventricular wall thickness and cavity surface area.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMedDate not supplied

Regional oxygen supply and consumption balance in experimental left ventricular hypertrophy.

The aim of the present study was to determine if the relationship between myocardial O2 supply and O2 consumption was preserved after prolonged pressure overload due to aortic valve stenosis. This was examined in anesthetized open-chest dogs in which the aortic valve was plicated 6 months previously. We measured coronary blood flow with radioactive microspheres and regional small vessel O2 saturation with microspectrophotometry, to obtain O2 supply, and O2 consumption. Regional O2 consumption was calculated as the product of flow and O2 extraction. The left ventricular weight/body weight ratio was 81% greater in the dogs with aortic valve stenosis. There were no hemodynamic differences between the groups except that left ventricular systolic pressure was 38 +/- 22 mm Hg greater than aortic in the hypertrophied group. Coronary blood flow did not differ between the control and hypertrophied groups nor were there subepicardial vs subendocardial differences. When maximal coronary flow was determined with chromonar (10 mg/kg), the flow increase was significantly attenuated in the hypertrophied subendocardium (242.1 +/- 82.3 (hypertrophy) vs 512.4 +/- 204.1 ml.min-1.100 g-1 (control). There were no significant differences in O2 extraction or O2 consumption/g between control and hypertrophied animals. There was a significantly lower O2 supply/consumption ratio in the subendocardium compared to the subepicardium of both groups. However, the O2 supply/consumption ratio was not decreased by hypertrophy. Thus, despite significant hypertrophy, a loss of flow reserve and a high left ventricular pressure, O2 supply/consumption balance is preserved in valvular aortic stenosis at rest.

Animals↗
PubMedDate not supplied

Comparison between isomyosin pattern and contractility of right ventricular myocytes isolated from rats with right cardiac hypertrophy.

The contractile properties of single rat cardiac cells isolated from normal and hypertrophied right ventricles have been investigated. These have been correlated with the isoenzyme composition of the whole ventricle. Right cardiac hypertrophy was induced by injecting rats with monocrotaline, an alkaloid which induces severe pulmonary hypertension. Ca2+ ATPase activity and myosin alpha-chain percentage were decreased in the hypertrophied right ventricle as compared with that of control rats. The contraction amplitude and speed of shortening of the isolated cells were measured using an inverted microscope, video camera, and edge detection device. Cells from the hypertrophied ventricle showed a significantly decreased contraction amplitude and speed of shortening in maximally activating concentrations of isoprenaline. A statistically significant correlation existed between myosin alpha-chain percentage and both contraction amplitude and speed of shortening in maximum isoprenaline. This was true when all cells studied were included, as well as within the hypertrophy group. A similar, although not always statistically significant, correlation was observed when cells were maximally activated with calcium. These results suggest that changes in isomyosin pattern that occur in cardiac hypertrophy produce alterations in contraction amplitude and speed of shortening which can be detected in single cells isolated from the hypertrophied ventricles. Isolated cells appear to give responses representative of the function of the whole heart.

Animals↗
PubMedDate not supplied

Insufficiency of hypertrophied heart.

There are two types of compensatory hypertrophy of the heart. In valvular diseases, systemic hypertension and pulmonary arterial hypertension, the resultant hypertrophy compensates the increased load on the organ and is designated as hypertrophy due to overload. In ischemic disease, hereditary cardiomyopathies and myocarditis, the hypertrophy compensates for the functional insufficiency of the damaged myocardial tissue and is designated as hypertrophy due to damage. It is shown in this paper that increase in cardiac mass in both types of compensatory hypertrophy prevents acute cardiac insufficiency but at the same time is a non-balanced form of growth. As a result, in severe hypertrophy a disturbance of normal proportions at all levels of cardiac structural integration occurs. Disturbances of this type which gradually become causes of cardiac insufficiency are the main subject of this paper.

Cardiomegaly↗
PubMed1998

Spin-spin relaxation times in myocardial hypertrophy induced by endocrine agents in rat.

Magnetic resonance techniques afford a significant advantage for noninvasive diagnosis of cardiovascular pathology. The purpose of our present study was to assay the proton nuclear magnetic resonance (1H-NMR) sensitivity in the differential diagnosis of certain endocrine cardiovascular complications. In this context, we investigated the water state and content in the hypertrophied myocardium. Male and female Wistar rats were treated with different hormones (hydrocortisone acetate, testosterone, estradiol, thyroid hormones) in combination with isoproterenol (a synthetic catecholamine that induces myocardial ischemia and hypertrophy). The animals were sacrificed after 20 days of treatment and samples of integral myocardium and left ventricular myocardium were analyzed on a 1H-NMR AREMI spectrometer (0.6 T; proton resonance at 25 MHz). The estimation of T2 was made by Carr Purcell-Meiboom-Gill pulse sequence. The data were fitted to a bi-exponential curve, yielding short (T21) values for bound water and long (T22) values for free water. In order to evaluate the myocardial hypertrophy, the following ratios were calculated: integral myocardium to body weight; left ventricle to body weight; left ventricle to integral myocardium. The first two ratios were also calculated for dried tissue, in order to estimate its contribution to myocardial hypertrophy. Our findings demonstrate that myocardial hypertrophy is associated with a decrease of T22, as a consequence of the increase in the dried component (i.e. proteins) of the tissue, while the total tissue water (H2Ot%), measured by gravimetry) was not significantly modified. Nevertheless, it is reasonable that the increase in the protein content would be proportional with the increase in H2Ot%. The decrease of T21 seems to be proportional with the level of left ventricle hypertrophy in female groups. The 1H-NMR measurements were much sensitive for the differential diagnosis of myocardial hypertrophy in the case of left ventricle.

Adrenergic beta-Agonists↗
PubMed1997

Reduction of angiotensin II-induced activation of mitogen-activated protein kinase in cardiac hypertrophy.

Mitogen-activated protein (MAP) kinases play a role in cell growth and are activated in the heart by cardiac stretch and various growth factors, but their role in signal transduction pathways once the heart has undergone hypertrophy is uncertain. To investigate the regulation of MAP kinases in the heart in response to angiotensin II (ang II), once cardiac hypertrophy has become established, ventricular and skeletal muscle explants were studied from Dahl S salt-sensitive and Dahl R salt-resistant rats that were on a high (6% NaCl) salt supplement in their diet. Cardiac hypertrophy was produced in the Dahl S but not R rat through NaCl-induced hypertension. MAP kinases were assayed by myelin protein phosphotransferase activity in MonoQ fractions of cell extracts. Ang II increased MAP kinases mainly in extracts from nonhypertrophic ventricles of Dahl R rats on a high-salt diet. Immunoblots revealed predominantly p44ERK1 with lower amounts p42MAPK in rat ventricle, and no apparent changes with hypertrophy. In hypertrophied hearts, ang II-induced MAP kinase activity was less markedly increased and more rapidly fell to baseline levels in comparison to the response in nonhypertrophied hearts. Prolonged ang II exposure did not produce the same effect on MAP kinase activity in ventricles from Dahl S rats on a low-salt diet, or skeletal muscle from salt-fed Dahl R and S rats. The ability of phorbol myristate acetate to simulate MAP kinase and ang II to simulate translocation of protein kinase C from the cytosole to the membrane was similarly compromised in hypertrophied ventricles. These results are consistent with a disturbance in the regulation of cell-signalling pathways in cardiac hypertrophy in which the MAP kinase response to ang II is dramatically altered.

Angiotensin II↗
PubMed2001

Cardiac isoform of alpha-2 macroglobin, a novel serum protein, may induce cardiac hypertrophy in rats.

Earlier studies from this laboratory have identified a novel high molecular weight (182 kDa) serum protein suggested to be involved in the development of cardiac hypertrophy. In the present case the role of this novel serum protein in the development of pressure-induced cardiac hypertrophy and the molecular events associated with it in experimental rats has been investigated. Multiple injections of this purified protein intravenously (through tail vein) into the normal animals lead to the development of cardiac hypertrophy and this is accompanied by an induction of muscle specific genes such as that of MLC2 and beta-MHC characteristic of pressure overloaded heart. Further, the hypertrophy-specific serum protein has been found to be identical to rat alpha-2 macroglobulin (alpha-2M) in molecular weight (182 kDa) and in its appearance in blood serum. alpha-2M is an acute phase serum protein that increases markedly after inflammatory stimuli in hepatocytes in liver and gets secreted into the blood. The studies at present suggest that the 182kDa serum protein that appeared during the early stage of development of cardiac hypertrophy in aorta constricted rats is a glycoprotein localized in the heart that showed immunological cross reactivity with alpha-2M and is expressed in the heart as evinced by Northern blot analysis. Further this protein showed certain differences from rat alpha-2M under denaturing conditions in isoelectric focusing and partial peptide mapping. Partial peptide sequencing of the internal peptides of tryptic digest of 182 kDa showed 100% identity of the sequences with alpha-2M sequences. Rat alpha-2M does not, however, have any influence on the development of cardiac hypertrophy and its antibody does not cross react with the 182 kDa protein. These data suggest that the 182 kDa protein that may play an indispensable role in the development of cardiac hypertrophy in experimental rats is cardiac specific, and may be an isoform of liver alpha-2M belonging to macroglobulin family.

Amino Acid Sequence↗
PubMed1985

Increased injury of hypertrophied myocardium with ischemic arrest: preservation with hypothermia and cardioplegia.

Many patients undergoing cardiac surgery have some degree of myocardial hypertrophy. To assess the response of hypertrophied myocardium to simulated cardiac surgery, left ventricular hypertrophy was induced in rats by aortic banding, and ventricular function was measured by means of the isolated, isovolumic heart perfusion technique. The hypertrophied hearts had a greater susceptibility to ischemic injury than nonhypertrophied control hearts, as manifested by a greater degree of diastolic contracture during the recovery period after 30 minutes of ischemic arrest at 37 degrees C. Hypothermia without cardioplegia during a 2-hour arrest did not completely preserve diastolic function in the hypertrophied hearts, but cardioplegia combined with hypothermia completely protected the hypertrophied hearts against 2 hours of ischemia. The results suggest a need for both hypothermic and cardioplegic preservation techniques in patients with myocardial hypertrophy who have cardiac surgical procedures requiring a significant period of myocardial ischemia.

Animals↗