Aging changes in the optic tectum of the guppy Poecilia (Lebistes) reticulatus

Histological surveys of the brains of guppies throughout their lifespan showed no overall loss of tissue with advancing age. Brain and body increased in size at a similar rate throughout adult life in male fish. In old females after the age of two years, brain growth apparently ceased, although body growth continued at a low rate. In both sexes there was a loss of neurones from the stratum griseum periventriculare in the midbrain roof in old age; the decrease in size was significant. The midbrain is a major correlative center concerned with spatial orientation. How far neuronal loss may contribute to functional behavioral disorder in old age is unknown, but a loss of orientation could render the older fish more susceptible to predation.     

The development of thyroid neoplasia in old age in the amazon molly, Poecilia formosa

In a previous paper we have described the appearance of a thyrotrophin sensitive thyroid neoplasm in an few senile individuals from a laboratory population of guppies, Lebistes reticulatus (Peters). Material has now been examined from the closely related species, Poecilia formosa, the Amazon molly, in which the incidence of thyroid neoplasms in the senile fish of our clones approaches 100%. The spontaneous growth seen in the old mollies was large, occupying much of the pharyngeal region. It was formed of three zones; at the center were inactive follicles with flattened epithelial cells, enclosing a dense, uneroded colloid. Peripherally, there was an area which microfollicles predominated and, the follicular epithelial cells frequently were swollen and balloon-like. The outermost area of the growth contained many afollicular groups of epithelial cells, lying amongst a great deal of loose connective tissue. The thyroid tissue was invasive, destroying muscle and bone. We have suggested that the spontaneous thyroid neoplasia in old P. formosa and L. reticulatus arise in a similar way. They develop as a result of the inability of the aging thyroid to respond to thyrotrophic hormone. Under continued pituitary stimulation the thyroid cells greatly proliferate and hypertrophy, and form a neoplasia. The appearance is described of massive thyroid growths which were experimentally induced by the injection into young mollies of cells with damaged DNA. There were striking differences between the induced and the spontaneous thyroid growths. The neoplasia of old fish was highly variable in structure, but the induced neoplasia had a regular appearance. Neoplastic tissue closely resembled normal thyroid tissue—but the growth was exuberant and highly invasive. We suggest that the differences between the neoplasm of old age and the induced neoplasm may reflect a different hormonal status.     

Aging changes in the kidneys of two poeciliid fishes,the guppy Poecilia reticulatus and the Amazon molly P. formosa

Histological surveys of the kidneys of two poeciliid fishes, the Amazon molly Poecilia formosa and the guppy P. reticulatus, throughout their lifespans showed no regular aging trends. Few kidney lesions were found in the Amazon molly until very late in life, 60 months or more, when obsolescent glomeruli and dilated renal tubules occurred. Guppies showed involutional changes of the renal system earlier, and the lesions became more severe with age, particularly in male fish. Hemopoietic tissue was reduced in amount in older fish of both species. Guppies of a year and older had marked accumulation of melanin in the melanomacrophage centers of the kidney, and the amount present increased with age. By contrast, there was little melanin deposition in mollies until almost the end of the lifespan. Hyaline droplets were consistently seen in the renal tubules of the mollies, but were rare in guppies. The degenerative changes in the kidneys of these two teleosts are similar to those seen in the kidneys of aging mammals. Despite the loss of normal structure in older fish, it seemed unlikely that degeneration of the kidney was directly involved in aging and death.     

Myocardial DNA content, ploidy level and cell number in geriatric hearts: post-mortem examinations of human myocardium in old age

A reduced adaptation rate of the myocardium must, in many cases, be made responsible for heart insufficiency of old patients. The present investigations are aimed towards the question whether heart in old age is accompanied by a loss of myocardial cells and whether a polyploidisation of heart muscle cells takes place thus indicating an adaptive process. A total of 40 human hearts obtained from autopsy material were studied, among them 30 geriatric hearts. Following preparation of the hearts, the myocardium was weighed and the total amount of DNA was determined biochemically. By means of Feulgen cytophotometry the ploidy levels of the heart muscle nuclei were detected. We have used a special method for estimating the total number of heart muscle cells and connective tissue cells in the individual hearts. It could be shown that the total amount of DNA in the myocardium is correlated with the myocardial weight and not with the age of the individual. Instead, DNA synthesis occurs in the heart muscle cells of all age groups depending on the functional activity of the heart. The degree of polyploidisation is closely correlated with myocardial hypertrophy without any influence of age. In hypertrophic hearts the number of connective tissue cells increases from normally 4 to 5 X 10(9) to 12 X 10(9) (in hearts weighing more than 700 g); in hearts with interstitial fibrosis these values are even higher. In normal hearts 1.8 to 2.1 X 10(9) heart muscle cells can be estimated; in hearts weighing more than 500 g numerical hyperplasia of the heart muscle cells is produced, reaching a maximum number of 4.8 X 10(9) muscle cells in excessively hypertrophied hearts weighing more than 800 g. No correlation between age and myocardial cell number (i.e. heart muscle cells or connective tissue cells) could be observed. This means that no agespecific changes occur in the myocardium with regard to the DNA content and cell number. The structural changes found in the hearts of old individuals are produced by extracardial influences (i.e. arteriosclerosis, hypertension, etc.) leading to myocardial hypertrophy. Polyploidisation and augmentation of heart muscle cells in cardiac hypertrophy or decrease in the number of heart muscle cells in heart atrophy may occur at any time of life and are not age-specific.     

Anatomic obstruction of the right ventricular outflow tract in transposition of the great arteries

In 126 hearts with transposition of the great arteries (TGA), morphologic features of the right ventricular (RV) outflow tract were analyzed. Distinct anatomic outflow tract obstruction was found in 15 of the 55 hearts with a ventricular septal defect (VSD) (27%): 12 had a perimembranous defect (predominantly extending into the infundibulum), 2 had an inlet, and 1 had an infundibular defect. In 12 hearts, outflow tract obstruction was caused by anterior displacement of infundibular septum and ventriculoinfundibular fold; in 3 hearts, it was caused by bulging of the trabecula septomarginalis or ventriculoinfundibular fold, or both. Of 71 hearts with an intact ventricular septum, only 2 (3%) had RV outflow tract obstruction: 1 had a trabecula in front of the aortic ostium and in the other an aberrant hypertrophic muscle bundle crossed the RV cavity, obstructing the entrance to the infundibulum. Associated malformations included aortic arch malformations (6 cases) and tricuspid valve anomalies (6 cases). Thus, anatomic RV outflow tract obstruction may constitute a complicating factor in TGA, notably in cases with VSD. A systemic RV blood pressure may trigger hypertrophy, resulting in progression of the obstruction; establishing normal RV pressure by a “switch” procedure might prevent this progression.     

Prevention by hypothermia of paradoxical calcium necrosis in cardiac muscle

Isolated rat hearts were perfused with calcium-free medium at either 37° or 4°C, and electrical and mechanical phenomena recorded. The calcium-free perfusion of the isolated rat heart at 37°C for periods in excess of 3 min, caused quick cessation of contractile activity with electro-mechanical dissociation. When calcium was restored to the perfusate at 37°C irreversible electro-mechanical dissociation and myocytolysis occurred, accompanied by a massive efflux of intracellular constituents into the perfusate. When the isolated rat heart was perfused with calcium-free medium at 4°C, both the electrocardiogram and contractility disappeared within 15–20 s. The restoration of calcium to these hearts perfused with calcium-free medium at 4°C, permitted rapid recovery of cardiac function upon warming to 37°C. Electron microscopy of hearts perfused with calcium after calcium-free perfusion at 37°C and 4°C showed that at 37°C extensive alteration and lysis of the cardiac organelles occurred, whereas at 4° they were well protected. Uptake of ⁴⁵Ca²⁺ by the myocardium subsequent to calcium-free perfusion at 37°C was approximately 20 times greater than that observed in hearts subjected to calcium deprivation at 4°C. These findings lend support to the view that the paradoxical calcium necrosis of cardiac muscle at 37°C is due to the massive influx of calcium into the cardiac muscle cells following damage to the sarcolemma. It is suggested that the damage to the sarcolemma observed at 37° consists of loss of membrane-bound proteins responsible for the physiologic “calcium channel”. At 4°C their escape from the bilayer appears to beretarded by a more sluggish shift in conformation from the calcium-bound to the calcium-free state, and a more crystalline membrane.     

Fatty acid metabolism via triglyceride in the salmon heart.

The composition of heart lipids was analyzed and the metabolism of heart triglycerides investigated in pre- and post-spawning pink salmon (Oncorhyncus gorbuscha). Comparison of the two kinds of fish indicated that the latter have smaller hearts containing less total lipid. The most notable finding involved virtually complete loss, on average 94%, of heart triglycerides during the fresh water migration to the spawning grounds. In vivo palmitate-1-¹⁴C incorporation into heart triglycerides, as well as heart slice incubations, revealed the triglyceride pathway as an active metabolic route even in post-spawning fish that were only hours from death. The heart took up and retained fatty acid from the serum more readily than liver, skeletal muscle or brain. Following intravenous injection of the label, maximum specific activity of heart triglycerides was achieved in approximately one hour. The rapid turnover of the glyceride pool coupled with its diminishing mass is evidence of a substantial fatty acid flow through this intermediate in the heart muscle.     

Evidence for a role of immunoproteasomes in regulating cardiac muscle mass in diabetic mice

The ubiquitin-proteasome system plays an important role in regulating muscle mass. Inducible immunoproteasome subunits LMP-2 and LMP-7 are constitutively expressed in the heart; however, their regulation and functions are poorly understood. We here investigated the hypothesis that immunoproteasomes regulate cardiac muscle mass in diabetic mice. Type 1 diabetes was induced in wildtype mice by streptozotocin. After hyperglycemia developed, insulin and the proteasome inhibitor epoxomicin were used to treat diabetic mice for 6 weeks. Isolated mouse hearts were perfused with control or high glucose solution. Catalytic proteasome β-subunits and proteolytic activities were analyzed in the heart by immunoblotting and fluorogenic peptide degradation assays, respectively. Insulin and epoxomicin blocked loss of heart weight and improved cardiac function in diabetic mice. LMP-7 and its corresponding chymotryptic-like proteasome activity were increased in diabetic hearts and high glucose-treated hearts. Myosin heavy chain protein was decreased in diabetic hearts, which was largely reversed by epoxomicin. High glucose decreased LMP-2 protein levels in perfused hearts. In diabetic hearts, LMP-2 expression was downregulated whereas expression of the phosphatase and tensin homologue deleted on chromosome ten (PTEN) and the muscle atrophy F-box were upregulated. Moreover, mice with muscle-specific knockout of PTEN gene demonstrated increased cardiac muscle mass, while mice with LMP-2 deficiency demonstrated PTEN accumulation, muscle mass loss, and contractile impairment in the heart. Therefore, we concluded that high glucose regulates immunoproteasome subunits and modifies proteasome activities in the heart, and that dysregulated immunoproteasome subunits may mediate loss of cardiac muscle mass in experimental diabetic mice.     

Heart myosin adenosine triphosphatase and light subunits in experimental chronic aortic insufficiency in the rabbit

Cardiac myofibrillar and myosin ATPases were studied in experimentally induced aortic insufficiency in the rabbit, in order to elucidate the pathogenesis of the defect in myofibrillar ATPase shown in chronically hypertrophied and/or failing hearts. The rabbits were killed 345 ± 32 days after the operation; 24% of them had clinical or anatomical signs of failure. They all had hypertrophic hearts (mean degree of hypertrophy, 64%) with dilatation.Heart myofibrillar Ca²⁺ ATPase was found to be lowered in aortic insufficiency. Three different preparations of myosin were also studied. The purity of these preparations was assessed by urea or SDS polyacrylamide gel electrophoresis or by measuring Mg²⁺-ATPase in a medium of low ionic strength. The first preparation (homogenized muscle) was highly contaminated by thin-filament proteins; the second (minced muscle) was rather pure but still contaminated by a nucleoprotein; the latter was separated by chromatography in the third preparation. Myosin Ca²⁺-ATPase measured in a medium of low or high ionic strength at pH 7.0 was decreased in aortic insufficiency when all three preparations were tested.On electrophoresis myosin light subunits were normal in aortic insufficiency. The search for an inhibitor was unsuccessful: the two myosin ATPase activities were additive and ribonuclease treatment did not normalize hypertrophied heart myosin. The “nucleoprotein” peak separated from myosin during chromatography had an inhibitory effect on myosin ATPase but was present in controls as well as in aortic insufficiency.This work suggests that myosin itself is abnormal in chronic aortic insufficiency, but an abnormality residing in a very closely associated factor could not definitely be excluded. Because myosin subunits were only studied by electrophoresis, their structures and relative amounts would need more detailed study before final conclusions could be reached.     

Lactate dehydrogenase subunit activities in hearts of aging rats

Diets with 40% of calories as fat with poly-unsaturated to saturated ratios of either 0.2 beef tallow (BT) diet or 1.0 mix (M) diet were fed to rats of both sexes. Groups were killed at 9, 12, 15, 18, and 21 mo. of age. To estimate the effects of age, sex and dietary fat on lactate dehydrogenase (LDH), activities of muscle type and heart type subunits were assayed biochemically in heart homogenates using differential substrate concentrations of 1.0 × 10⁻² M and 3 × 10⁻⁴ M pyruvate, respectively. For comparison of methods, LDH activity was also determined histochemically in frozen sections of hearts, using lactate as a substrate. Age significantly (p < 0.05) affected heart type activity, which was highest in males at 9 mo. and females at 12 mo., and lowest in 15 mo. old rats. Activities of heart type LDH were similar in hearts from rats at 9 and 21 mo. of age. Age also significantly (p < 0.05) affected muscle type activity, which generally increased to a maximum in 18 mo. old rats. Histochemical LDH activity was significantly (p <.001) greater in hearts of 9 and 12 mo. old rats than in those of 15 mo. old rats. Fluctuations in the activities of muscle type and heart type LDH subunits seemed to follow a pattern indicative of myocardial damage.     

The influence on sarcopenia of muscle quality and quantity derived from magnetic resonance imaging and neuromuscular properties

The relative contributions of intrinsic and extrinsic neuromuscular factors on sarcopenia are poorly understood. The associations among age-related declines of strength, muscle mass, and muscle quality in response to motor unit (MU) loss have not been systematically investigated in the same groups of subjects. The purpose was to assess MU loss, MRI-derived muscle cross-sectional area (CSA), muscle protein quantity (MPQ), and normalized strength of the dorsiflexors in one group of young (~25 years) adult males compared with two groups of healthy men aged 60–85 years. Muscle strength was assessed on a dynamometer and was ~25 % lower in both older groups, but CSA was less only in the older (>75 years) men, with no differences between the young and old (60–73 years). Normalized strength tended to be lower in both groups of aged men compared to young. For MPQ, only the older men showed ~8 % lower values than the young and old men. Older men had fewer functioning MUs than old, and both groups of aged men had fewer MUs than young men. Muscle quality appears to be maintained in the old likely due to compensatory MU remodeling, but in the older group (>75 years), MU loss was higher and MPQ was lower.     

Effects of propafenone on anisotropic conduction properties within the three-dimensional structure of the canine ventricular wall

Background Structural complexities of the intact ventricular wall cause a very complex spread of activation. The effects of regional tissue damage and of antiarrhythmic drugs on directional differences in activation should help to further elucidate intramural conduction patterns. Methods and results In 10 healthy dogs and in 5 dogs with subacute anterior wall infarction, 6 parallel rows of 6 needle electrodes with 4 bipolar electrode pairs per needle were inserted into the left anterior ventricular wall. Using a computerized multiplexer-mapping system, the spread of activation in epi-, endo- and midmyocardial muscle layers and in the surviving epicardium, respectively, was reconstructed. Marked differences in conduction velocities relative to fiber orientation were evident in the surviving epicardium of infarcted hearts. Directional differences in conduction velocities, although less pronounced, were still preserved throughout the intact ventricular wall. Epicardial transverse conduction in intact hearts was significantly faster than transverse conduction in infarcted hearts (0.87 ± 0.11 m/s vs 0.68 ± 0.1 m/s). In normal hearts, propafenone (2 mg/kg) decreased conduction velocities primarily in longitudinal directions (−27 ± 10%), but also moderately in transverse directions (−13 ± 7%) of all muscle layers, with no significant effect on straight (−4 ± 8%), but on oblique transmural conduction (−33 ± 18%). In infarcted hearts propafenone decreased conduction particularly in longitudinal direction (−23 ± 14%) without affecting conduction transverse to the fiber orientation (+3 ± 6%). Conclusions Longitudinal intramural shortcircuits reduce directional differences in activation. Transmural infarction results in a loss of alternative intramural pathways, unmasking marked anisotrophy in the surviving epicardium. Conduction delay in intramural pathways explains the effects of propafenone on transverse and oblique transmural conduction. Primarily longitudinal conduction delay results in reduced tissue anisotropy. Received: 8 June 2000, Returned for revision: 4 July 2000, Revision received: 20 September 2000, Accepted: 9 October 2000     

Comparison of the handling of norepinephrine in the myocardium of adult and old rats.

The handling of norepinephrine was compared in the myocardium of adult and old rats. Endogenous norepinephrine levels were significantly lower in the hearts of old animals. Following intravenous injection of 3H-norepinephrine [3H-NE] the initial uptake was slightly higher in the old animals; subsequently, however, there was a more pronounced and prolonged fall in 3H-NE specific activity in the myocardium of the old rats. The increased turnover rate was associated with normal catecholamine synthesis. Studies of the subcellular distribution of 3H-NE showed an inability of the myocardium from ageing rats to retain norepinephrine in the storage granules with subsequent loss of the soluble fraction.     

Evidence for a sustained effectiveness of sodium-channel activators in failing human myocardium.

Elevation of cytosolic sodium is thought to be correlated with an increase in force of contraction due to an activation of sodium-calcium exchange. We investigated the inotropic response mediated by the new sodium-channel activator BDF 9148 (0.01-100 mumol/l) on failing human myocardium. Force of contraction was studied using electrically driven human papillary muscle strips from moderately (NYHA II-III, mitral valve replacement) and terminally (NYHA IV, heart transplantation) failing hearts. We also investigated the effects in auricular trabeculae from non-failing hearts (aortocoronary bypass operation). Results were compared with inotropic responses to DPI 201-106 (DPI, 0.1-3 mumol/l), Ca2+ (1.8-15 mmol/l) and isoprenaline (0.001-1 mumol/l). Carbachol (100 mumol/l) and adenosine (1000 mumol/l) were examined in the presence of BDF 9148 and isoprenaline. Both sodium-channel activators, BDF 9148 and DPI 201-106, increased force of contraction in a dose-dependent manner in papillary muscle strips as well as in auricular trabeculae. BDF 9148 and DPI 201-106 were more effective (max. PIE NYHA II-III 1.6 +/- 0.2 mN, NYHA IV 5.9 +/- 0.7 mN, P less than 0.05) and more potent (EC50 (in mumol/l): NYHA IV 0.35, 0.19-0.66; NYHA II-III 1.85, 1.37-2.41) in terminally failing as compared to moderately failing left ventricular myocardium. Moreover, the positive inotropic effects of BDF 9148 were greater than those of DPI 201-106 in NYHA IV (max. PIE 2.7 +/- 0.3 mN, P less than 0.05). In NYHA IV, BDF 9148 was as effective as CA2+ (max. PIE 5.1 +/- 0.4 mN). In the same hearts, the positive inotropic effects of isoprenaline were reduced in NYHA IV (max. PIE 2.1 +/- 0.3 mN) compared to NYHA II-III (max. PIE 3.4 +/- 0.4 mN, P less than 0.05). Adenosine as well as carbachol did not affect the positive inotropic response of BDF 9148 or DPI 201-106 but reduced the effectiveness of isoprenaline (P less than 0.05). In myocardial membranes, BDF 9148 was 1000-fold less effective in competition experiments with 3H-ouabain than ouabain. We conclude that (1) sodium-channel activators may produce a significant cAMP-independent positive inotropic effect in left ventricular myocardium from failing human hearts; (2) the inotropic effect of sodium-channel activators were more potent and more effective in NYHA IV as compared to NYHA II-III. The degree of myocardial failure does not reduce the effectiveness of the sodium-channel activator BDF 9148.     

Nuclear-cytoplasmic interactions affecting DNA synthesis during induced cardiac muscle growth in the rat

Nuclear-cytoplasmic interactions affecting DNA synthesis during induced cardiac muscle growth were examined in 29 to 46 day old rats. DNA synthesis was examined in vitro using isolated nuclei from rat heart and adult X. laevis spleen. Cytoplasmic extract (CE) was obtained from a 105 000 g supernatant of rat heart and fetal liver homogenates. To measure DNA synthesis we utilised DNA within the isolated quiescent nucleus as the template and measured the effect of CE on the incorporation of 3H-TTP into an acid precipitable product. In a homologous system of rat heart nuclei from weanling rats and CE from cardiac muscle undergoing induced growth, no stimulation of 3H-TTP incorporation was observed. Cardiac muscle CE however, did possess stimulatory factor(s) since quiescent X. laevis nuclei could be stimulated with the rat heart CE. Furthermore, CE from hearts undergoing induced growth had greater activity than extract from control hearts. While cardiac muscle nuclei were not stimulated by heart CE, they showed substantial stimulation by CE from fetal rat liver, which contains a large population of proliferating cells. Stimulation by fetal rat liver was greater with nuclei obtained from hearts undergoing induced growth than from control hearts. Stimulatory factor(s) in CE was distinct from DNA polymerase-alpha activity, as shown by separation of the two activities on a 5 to 15% glycerol gradient.     

K201 improves aspects of the contractile performance of human failing myocardium via reduction in Ca<Superscript>2+</Superscript> leak from the sarcoplasmic reticulum

In heart failure, intracellular Ca²⁺ leak from cardiac ryanodine receptors (RyR2s) leads to a loss of Ca²⁺ from the sarcoplasmic reticulum (SR) potentially contributing to decreased function. Experimental data suggest that the 1,4-benzothiazepine K201 (JTV-519) may stabilise RyR2s and thereby reduce detrimental intracellular Ca²⁺ leak. Whether K201 exerts beneficial effects in human failing myocardium is unknown. Therefore, we have studied the effects of K201 on muscle preparations from failing human hearts. K201 (0.3 μM; extracellular [Ca²⁺]_e 1.25 mM) showed no effects on contractile function and micromolar concentrations resulted in negative inotropic effects (K201 1 μM; developed tension ?9.8 ± 2.5% compared to control group; P < 0.05). Interestingly, K201 (0.3 μM) increased the post-rest potentiation (PRP) of failing myocardium after 120 s, indicating an increased SR Ca²⁺ load. At high [Ca²⁺]_e concentrations (5 mmol/L), K201 increased PRP already at shorter rest intervals (30 s). Strikingly, treatment with K201 (0.3 μM) prevented diastolic dysfunction (diastolic tension at 5 mmol/L [Ca²⁺]_e normalised to 1 mmol/L [Ca²⁺]_e: control 1.26 ± 0.06, K201 1.01 ± 0.03, P < 0.01). In addition at high [Ca²⁺]_e, K201 (0.3 μM) treatment significantly improved systolic function [developed tension +27 ± 8% (K201 vs. control); P < 0.05]. The beneficial effects on diastolic and systolic functions occurred throughout the physiological frequency range of the human heart rate from 1 to 3 Hz. Upon elevated intracellular Ca²⁺ concentration, systolic and diastolic contractile functions of terminally failing human myocardium are improved by K201.     

Post-anoxic recovery of myocardial performance in senescent mice

In studies with intact open-chested male mice, the ability of the myocardium to maintain left ventricular pressure (LVP) during and subsequent to 3 min of anaerobic respiration has been studied. The hearts of young (6 months) and old (24 months) animals revealed dissimilar pressure profiles throughout the anoxic and recovery periods. Uppon re-establishment of aerobic respiration, only old animals were able to restore LVP to pre-anoxic levels. Indices of external myocardial work were similar in young and old hearts prior to anoxia and declined significantly more in young animals during anoxia and recovery.In order to localize the energy source for the recovery of myocardial performance by old animals myocardial and hepatic levels of glycogen and phosphorylase were assessed. Cardiac glycogen and phosphorylase levels were similar in both young and old animals prior to the recovery period. Upon recovery from anoxia, old animals were able to restore myocardial glycogen content and phosphorylase activity towards pre-anoxic levels while the hearts of young animals failed to do so. Pre-anoxic hepatic glycogen content in old animals was significantly greater than young animals while phosphorylase levels were similar in both groups prior to anaerobic respiration. Hepatic glycogen utilization and phosphorylase activation throughout the respiratory period were similar to that seen in the myocardium from both young and old animals with old animals displaying a greater utilization of glycogen and a greater activation of phosphorylase during anoxia and a greater tendency to return to pre-anoxic levels during the recovery period. In addition, blood glucose levels during anoxia were significantly lower in young animals when compared to values obtained from old animals. Under these conditions, increases in liver glycogen may be responsible for the maintenance of myocardial performance during and after anoxia by old mice.     

Myocyte nuclear and possible cellular hyperplasia contribute to ventricular remodeling in the hypertrophic senescent heart in humans

Objectives. The present investigation was designed to evaluate the growth reserve capacity of the aged and senescent myocardium.Background. Aging affects the ability of the heart to sustain alterations in ventricular loading, and this phenomenon may be coupled with attenuation of the hypertrophic reaction of the myocardium. However, because myocyte cellular hyperplasia has been documented experimentally in the old heart, a similar adaptation may also occur in humans and play a role in this process.Methods. The changes in number and size of ventricular myocytes were measured quantitatively in pathologic hearts of elderly subjects. Morphometric methodologies were applied to the analysis of 13 hypertrophic hearts obtained at autopsy from patients 80 ± 4 (mean ± SD) years old. An identical number of nonhypertrophic hearts collected from subjects 76 ± 7 years old were used as control hearts.Results. A 71% increase in left ventricular weight was associated with a 33% increase in average myocyte cell volume per nucleus and a 36% augmentation in the total number of myocyte nuclei in the ventricular myocardium. However, a 55% increase in right ventricular weight was the result of a 59% increase in the aggregate number of myocyte nuclei, with no change in myocyte cell volume. These cellular processes were associated with a 95% and 83% enlargement of the myocardial interstitium in the left and right ventricle, respectively.Conclusions. Myocyte nuclear and possibly cellular hyperplasia appear to be the prevailing growth mechanism of the overloaded aging myocardium. Proliferation of myocyte nuclei and connective tissue accumulation are the major determinants of ventricular remodeling in the hypertrophic senescent heart.     

Age-related changes in catalase activity and its inhibition by manganese (II) chloride in the brain of two species of poikilothermic vertebrates

Two species of poikilothermic vertebrates, a teleost fish (Channa punctatus) and the garden lizard (Calotes versicolor) were used to study the effect of age on brain catalase (CT) activity and its inhibition by manganese (II) chloride (MnCl(2)). While in fish the CT activity of brain remained unchanged throughout the lifespan, the enzyme activity decreased during maturation and then showed an increase during aging in the garden lizard. MnCl(2) at a concentration of 333 muM in incubating medium significantly inhibited the CT activity of the brain of both fishes and lizards of all the three age groups (young, middle-aged and old), the degree of inhibition showing a trend of increase with advancing age. However, statistical significance was observed when fishes of the young age group were compared either with those of middle-aged or old counterparts, and between young versus old and middle-aged versus old lizards. Increased susceptibility to Mn(2+) during aging suggests changes in regulation of CT.