Myocardial cell damage during experimental infective endocarditis.

Infective endocarditis was induced in 15 catheterized rabbits by a single intravenous injection of Streptococcus viridans and the papillary muscles from the left ventricle were examined for histologic and ultrastructural changes at 3 and 6 days of infection. Papillary muscles from 10 normal and 12 catheterized uninfected animals were used for comparison. Catheterized animals, infected and uninfected, had cardiac hypertrophy and papillary muscles which showed an increase in myofiber size and some interstitial edema. The muscle from infected hearts had areas of focal necrosis, diffuse monocytic infiltration, and loss of normal myocardial architecture. The papillary muscles from catheterized uninfected animals showed some degree of mitochondrial and sarcotubular swelling as well as contracture of myofibrils; the infected myocardium exhibited dramatic changes in ultrastructure such as mitochondrial swelling and destruction, sarcotubular swelling, separation of the intercalated disc, and myofibrillar contracture and disruption. These histopathologic and ultrastructural changes in papillary muscles from rabbits with bacterial endocarditis are indicative of the presence of myocardial cell damage.     

Control of myocardial tissue components and cardiocyte organelles in pressure-overload hypertrophy of the cat right ventricle

Previous studies have demonstrated that there is a disproportionate increase in connective tissue in right ventricular myocardium subjected to pressure-overload hypertrophy associated with depressed cardiac contractility. While the myocardium is primarily responsive to load, the aim of the present study was to determine whether catecholamines also modulate the response of myocardial tissue components and cardiocyte organelles in pressure-overload-induced cardiac hypertrophy. Four experimental groups of cats were examined: (1) a sham-operated control group, (2) a group which had their pulmonary arteries banded in order to induce a pressure overload, (3) a group which had been subjected to the same pressure overload, but in addition had β-adrenoceptor blockade produced prior to and during the pressure overloading, and (4) a group which had been subjected to the same pressure overload, but in addition had α-adrenoceptor blockade produced prior to and maintained during the pressure overloading. As in our previous study, there was a significant and equivalent degree of right ventricular hypertrophy in all experimental groups with pressure overload when assessed either as the ratio of right ventricular weight to body weight or as cardiocyte cross-sectional area. At the light microscopic level, the disproportionate increase in the volume density of myocardial connective tissue seen in banded animals was completely prevented by either α- or β-adrenoceptor blockade. At the electron microscopic level, there was a reduction in the mitochondrial and myofibrillar volume fractions following β-adrenoceptor blockade. The results of this study provide evidence for a modulatory role of catecholamines in the control of myocardial connective-tissue proliferation in pressure-overload-induced cardiac hypertrophy. There is also evidence to support the role of the adrenergic nervous system in regulating cardiocyte subcellular organelles, independent of the regulation of cardiocyte size.     

The effects of beta adrenoceptor blockade with atenolol on myocardial cellular and subcellular hypertrophy in spontaneously hypertensive rats

In this study we investigated the effects of chronic β adrenoreceptor blockade with atenolol on cellular and subcellular hypertrophy in spontaneously hypertensive rats (SHR). Atenolol was injected subcutaneously (20 mg/kg) twice daily commencing in four-week-old rats. The treated animals (SHR-A) were compared to their nontreated controls and normotensive, Wistar-Kyoto (WKY) controls at the age of 16 weeks. A group of atenolol-treated WKY was also studied. Chronic drug treatment was effective in attenuating the rise in systolic blood pressure characteristic of SHR, but did not normalize the values to those of WKY. Cardiac hypertrophy, characteristic of SHR, was modified by drug treatment as evidenced by left ventricular weights as well as myocardial cell size. The cells from the subendocardium underwent selective hypertrophy in SHR which was attentuated by about 50% after atenolol treatment. Stereological analysis of electron micrographs showed that while relative mitochondrial volume was not affected by treatment, relative myofibrillar volume (%) decreased in both subepicardium (SHR = 63.28 ± 1.25; SHR-A = 56.72 ± 1.37) and subendocardium (SHR = 66.53 ± 1.27; SHR-A = 58.30 ± 1.51). This change raised the mitochondrial/myofibrillar volume ratio, which is characteristically low in SHR compared to WKY. Sarcoplasm, which included all cell constituents except mitochondria, increased with atenolol treatment, but water concentration remained unchanged. The data suggest that attenuation of hypertrophy in SHR after β blockade is associated with selective effects on the myocardial cell involving primarily the myofibrillar cell compartment.     

Hypertrophy and reversal of hypertrophy in rat pelvic ganglion neurons

Summary An experimental procedure which chronically reduces the lumen of the urethra in adult female rats produced distension of the bladder and conspicuous thickening of its wall, resulting within 6–8 weeks in a ten-fold increase in muscle weight (muscle hypertrophy). During this process, the neurons in the pelvic ganglion that innervate the bladder undergo a large increase in size (neuronal hypertrophy). The average neuronal volume increased by 83%; small neurons became less numerous and large neurons became more numerous than in controls, but there was no increase in the maximum neuronal size. Six weeks after re-operation and removal of the urethral obstruction, the weight of the bladder was reduced (although not quite to the control levels), while the average neuronal size reversed to values very close to controls.In separate experiments, the pelvic ganglion of one side was removed. The nerve fibres in the hemidenervated bladder sprouted, grew and spread to innervate the whole bladder. The neurons in the surviving pelvic ganglion hypertrophied, the average cell volume increasing by 50% in seven weeks.The experiments showed that: (i) the pelvic neurons of adult rats are capable of very extensive growth when the tissue they innervate (bladder muscle) undergoes hypertrophy; (ii) the neuronal hypertrophy is reversible. This was taken to imply that there are factors within the bladder, including trophic substances, that regulate nerve cell volume not only by inducing growth but also by inducing the opposite effect, a cell size reduction; (iii) unilateral ganglionectomy, which did not induce muscle hypertrophy but doubled the amount of muscle innervated by the contralateral ganglion, was followed by marked neuronal hypertrophy.     

Work-induced hypertrophy in exercised normal muscles of different ages and the reversibility of hypertrophy after cessation of exercise

1. Groups of male hamsters of different ages were subjected to a weight-lifting exercise regimen, and the biceps brachii, soleus and extensor digitorum longus (EDL) muscles examined for structural changes occurring in response to the increased workload. In addition, two groups of adult hamsters were left to recover from the exercise stimulus for 5 and 15 weeks respectively.2. All the exercised muscles exhibited muscle fibre hypertrophy, and the extent of the hypertrophy was greater in the younger animals. In all age groups, the biceps brachii and EDL showed more hypertrophy than did the soleus. There was no significant increase in fibre number after exercise.3. In both groups allowed to recover from the exercise stimulus, the fibre dimensions reverted back to those of the control muscles; this appeared to be complete after 15 weeks recovery.4. Electron microscopical studies of fibres from exercised and control biceps brachii revealed no significant changes with exercise in the proportions present of myofibrillar, mitochondrial and tubular components within muscle fibres of the same size.     

Norepinephrine-induced cardiac hypertrophy of the cat heart.

Norepinephrine administration causes progressive hypertrophy of the mammalian heart as measured by myocardial mass. The purpose of this study was to determine the growth response of the myocardial tissue components as well as the myocardial cell itself to norepinephrine. Young, adult cats were given low doses of norepinephrine in dextrose or dextrose alone twice daily for 15 days. On day 16, there were no changes in the animals body weight, right ventricular systolic pressure, right ventricular end-diastolic pressure, heart rate, cardiac index, or blood pressure. However, the right ventricle/body weight, the left ventricle/body weight and the total heart weight/body weight were increased significantly in the norepinephrine treated animals. The increase was on the order of 40%. The cardiac muscle cell was also significantly increased in size and both the right and left ventricular cardiac muscle cells exhibited a dramatic increase in size as measured by cross sectional area. Upon stereological examination it was found that the amount of hypertrophy as seen in the cardiac muscle cells was paralleled by the hypertrophy seen in the other tissue components of the myocardium. The volume density of the muscle cells, the interstitial components, as well as the blood vessel compartment were identical in the control and in the norepinephrine-treated groups. In conclusion, this study demonstrates that the response of the myocardium to norepinephrine is similar to that seen in response to a volume overload rather than that seen in response to pressure overload.     

Morphometry of myocardial apex in endurance-trained mice of different ages

Mitochondrial volume density, surface density of the outer mitochondrial membrane, the mean number and size of mitochondria, and the mean surface density of crista membranes together with the volume densities of myofibrils and sarcoplasmic space were morphometrically analyzed in cardiac muscle of two groups of sedentary control mice aged 3 and 7 months, and in two groups of mice trained either 1 month rather intensely or 4 months moderately. Of the calculated mitochondrial variables only the surface density of the outer mitochondrial membrane differed between the older controls and the older trained animals, the density being slightly smaller in the trained group. The myofibrillar volume density of the order controls was smaller than that of the younger controls, while the sarcoplasmic volume density was larger. The latter difference, possibly a function of age, was also observed in the trained groups. The results suggest that at a certain steady state level of exercise-induced cardiac muscle hypertrophy the muscle cells of trained mice do not differ markedly in ultrastructural properties from those of sedentary controls.     

Norepinephrine-induced cardiac hypertrophy of the cat heart

Norepinephrine administration causes progressive hypertrophy of the mammalian heart as measured by myocardial mass. The purpose of this study was to determine the growth response of the myocardial tissue components as well as the myocardial cell itself to norepinephrine. Young, adult cats were given low doses of norepinephrine in dextrose or dextrose alone twice daily for 15 days. On day 16, there were no changes in the animals body weight, right ventricular systolic pressure, right ventricular end-diastolic pressure, heart rate, cardiac index, or blood pressure. However, the right ventricle/body weight, the left ventricle/body weight and the total heart weight/body weight were increased significantly in the norepinephrine treated animals. The increase was on the order of 40%. The cardiac muscle cell was also significantly increased in size and both the right and left ventricular cardiac muscle cells exhibited a dramatic increase in size as measured by cross sectional area. Upon stereological examination it was found that the amount of hypertrophy as seen in the cardiac muscle cells was paralleled by the hypertrophy seen in the other tissue components of the myocardium. The volume density of the muscle cells, the interstitial components, as well as the blood vessel compartment were identical in the control and in the norepinephrine-treated groups. In conclusion, this study demonstrates that the response of the myocardium to norepinephrine is similar to that seen in response to a volume overload rather than that seen in response to pressure overload.     

Ultrastructure of the aging myocardium: A morphometric approach

Left ventricular tissue from adult and aging Syrian hamster heart was compared at the ultrastructural level, using both qualitative and morphometric electron microscopy. The aging myocardium often showed indented nuclei, lipid droplets and aggregations of dense bodies. The volume fractions of muscle cells occupied by mitochondria, lipid and lysosomes (including both primary lysosomes and residual bodies) was significantly greater in the old animals, while there was no significant difference in nuclear volume fraction or myofibrillar mass. Sarcoplasmic reticular volume and membrane surface area fell during aging. The area of mitochondrial inner membrane plus cristae per mitochondrial volume also fell. When sarcoplasmic reticular and mitochondrial area were expressed per myofibrillar volume fraction, the sarcoplasmic reticular ratio fell, while the mitochondrial parameter remained constant. Discoordinate aging of cellular components in the mammalian myocardium is proposed.     

Satellite cell response in rat soleus muscle undergoing hypertrophy due to surgical ablation of synergists

Although the role of satellite cells has been confirmed during skeletal muscle growth and regeneration, their involvement during work-induced muscle growth remains uncertain. In this study, chronically overloaded rat soleus muscles were ultrastructurally monitored following surgical ablation of synergists to examine cytological adaptations of satellite cells and myofibers. The left soleus muscle of 20 female Sprague-Dawley rats (7 weeks of age) was induced to hypertrophy by excising the contralateral plantaris and gastrocnemius muscles under pentobarbital anesthesia. Right limbs were sham-operated and served as controls. On days 3, 7, 14, 21, and 30 after surgery, the soleus muscles were removed and processed for electron microscopy. Two morphologically distinct phases were noted in the surgically overloaded muscles. The first stage (week 1) was characterized by a significant increase in the number of satellite cells, and by more than half of the experimental muscle fibers displaying myofibrillar disruptions, mitochondrial alterations and glycogen pooling. The second phase (weeks 2-4) featured mostly normal, although larger appearing muscle fibers, with the satellite cell frequency remaining slightly elevated. These findings suggest that muscle fiber structural abnormalities, rather than an increase in muscle activity, may play a more significant role in the early activation of satellite cells during compensatory hypertrophy, whereas activation of satellite cells during the later stages may be in response to increased levels of muscle activity.     

The role of satellite cells in muscle hypertrophy

The role of satellite cells in muscle hypertrophy has long been a debated issue. In the late 1980s it was shown that proteins remain close to the myonucleus responsible for its synthesis, giving rise to the idea of a nuclear domain. This, together with the observation that during various models of muscle hypertrophy there is an activation of the muscle stem cells, i.e. satellite cells, lead to the idea that satellite cell activation is required for muscle hypertrophy. Thus, satellite cells are not only responsible for muscle repair and regeneration, but also for hypertrophic growth. Further support for this line of thinking was obtained after studies showing that irradiation of skeletal muscle, and therefore elimination of all satellite cells, completely prevented overload-induced hypertrophy. Recently however, using different transgenic approaches, it has become clear that muscle hypertrophy can occur without a contribution of satellite cells, even though in most situations of muscle hypertrophy satellite cells are activated. In this review we will discuss the contribution of satellite cells, and other muscle-resident stem cells, to muscle hypertrophy both in mice as well as in humans.     

Muscle and nonmuscle cell RNA polymerase activities in early myocardial hypertrophy

RNA polymerase was solubilized from separated rat cardiac muscle and nonmuscle cells during the development of myocardial hypertrophy 1 or 3 days after sham operation or aortic constriction. Six fractions of enzymes designated IA, IB, IIA, IIB, IIIA, and IIIB were identified by DEAE-Sephadex chromatography in each cell population. Fractions designated IA and IB, IIA and IIB, and IIIA and IIIB were similar to RNA polymerase I, II, and III, respectively, found in other eukaryotes. Muscle cell enzyme activity from sham-operated and aortic-constricted rats did not significantly differ 1 day after intervention. By 3 days there was a significant increase in the activity of each enzyme fraction in muscle cells from aortic-constricted rats. There was a slight increase in IIA activity in nonmuscle cells from aortic-constricted rats at 1 day. By 3 days after aortic constriction RNA polymerase IIA, IIB, and IIIB activities increased in nonmuscle cells, but no change was noted in nonmuscle RNA polymerase IA, IB, and IIIA. Changes in RNA polymerase activities in cardiac muscle and nonmuscle cells occur during the development of myocardial hypertrophy but do not appear to correlate with reported changes in RNA synthesis. chromatin-template activity, however, did increase in cardiac muscle cells at both 1 and 3 days after aortic constriction. A similar increase was not seen in nonmuscle cell chromatin-template activity until 3 days. These data suggest that the initial increase in RNA synthesis during the development of myocardial hypertrophy is related to changes in chromatin-template activity in muscle cells. The activities of the RNA polymerase increase after a short delay and vary in their response.     

Morphometry of right ventricular hypertrophy induced by myocardial infarction in the rat.

The growth response of the right ventricle was studied in rats following ligation of the left coronary artery, which produced infarcts comprising approximately 40% of the left ventricle. A month after surgery the weight of the right ventricle was increased 30%, and this hypertrophic change was characterized by a 17% wall thickening, consistent with the 13% greater diameter of myocytes. Myocardial hypertrophy was accompanied by an inadequate growth of the microvasculature that supports tissue oxygenation. This was seen by relative decreases in capillary luminal volume density (-27%) and capillary luminal surface density (-21%) and by an increase in the average maximum distance from the capillary wall to the mitochondria of myocytes (19%). In contrast, measurements of the mean myocyte volume per nucleus showed a proportional enlargement of these cells (32%), from 16,300 cu mu in control animals to 21,500 cu mu in experimental rats. Quantitative analysis of the right coronary artery revealed a 33% increase in its luminal area, commensurate with the magnitude of ventricular hypertrophy.     

Myocardial concentration of cardiac troponin T as an early discriminator of mechanisms of cardiac hypertrophy

Measurement of myocardial concentration of the myofibrillar protein, cardiac troponin T (cTnT), was used as a biochemical correlate of myocardial myofibrillar volume fraction to confirm and extend results of histomorphometric studies of changes in myofibrillar density during hypertrophy. Rat models were used to study concentric cardiac hypertrophy due to pressure overload (spontaneous hypertension), eccentric cardiac hypertrophy due to volume overload (administration of minoxidil for 4 weeks), and mixed cardiac hypertrophy due to growth factor stimulation (administration of triiodothyronine for 4 weeks). Mean myocardial cTnT concentration was 583±60 g/g wet weight tissue in 40 control rats aged 10–20 weeks. We confirmed that pressure overload increased myofibrillar density by up to 30%, whereas volume overload decreased myofibrillar density, in our study, by up to 15%. Growth factor-induced hypertrophy was confirmed to occur by a mixture of processes; while myofibrillar density had increased by 31% at 1 week, it had normalised by 4 weeks. Minoxidil-induced hypertrophy was also confirmed to occur by a mixture of the processes, with myofibrillar density first decreased by 15% at 1 week before normalising by 4 weeks. Progressive, pathological hypertrophy, as modelled with spontaneous hypertension, was confirmed to be associated with abnormal myocardial myofibrillar density. We conclude that myocardial cTnT concentration may be used as a simple and precise biomarker of myofibrillar volume density, which, assessed over time, discriminates early physiological mechanisms involving myocyte thickening from those involving myocyte elongation and may discriminate between physiological and pathological hypertrophy.     

A morphometric study of the reversal of ACTH-induced hypertrophy of rat adrenocortical cells after cessation of treatment

The effect of a prolonged (7-day) ACTH administration on rat zona fasciculata cells and its reversal after cessation of treatment was investigated by morphometry. ACTH treatment caused a notable cell hypertrophy, which was mainly due to the increase in the volume of the mitochondrial compartment and to smooth endoplasmic reticulum (SER) proliferation, and a conspicuous rise in the basal level of corticosterone. After cessation of ACTH administration, rat zona fasciculata cells underwent a time-dependent atrophy, so that after 5 days they resembled those of control animals, and the blood concentration of corticosterone reverted to the base-line value. The cell atrophy was provoked by the decrease in the volumes of the mitochondrial compartment and SER, and was associated with a striking time-dependent accumulation of dense bodies. Stereology demonstrated that during the first two days after ACTH withdrawal the decrease of SER prevailed over that of the mitochondrial compartment, while the reverse occurred during the remaining three days. The increase in the volume of dense-body compartment, though largely due to the accumulation of residual bodies, was mainly coupled with a rise in the volume of the microautophagic-vacuole compartment during the first two days after ACTH cessation and with an increase in that of the macroautophagic-vacuole compartment during the following three days. The hypothesis is advanced that both micro- and macroautophagy play a role in the reversal of ACTH-induced hypertrophy of rat zona fasciculata cells after cessation of treatment, the first process being mainly involved in the elimination of SER, and the second one in the degradation of mitochondria.     

Cardiomegaly in chronic anemia in ratsman experimental study including ultrastructural, histometric, and stereologic observations.

Postweanling rats maintained on a milk-sugar diet develop a sideropenic anemia, the hemoglobin values falling to less than 30 per cent within 8 to 10 weeks. In that period the heart weight increases by more than 3 times, both ventricles enlarging proportionately. As in other forms of cardiac hypertrophy, a progressive increase in the numbers of connective tissue cells occurs. Ultrastructural and stereologic studies show an appreciable proliferation of the mitochondrial mass in myocardial cells, the mitochondrial fractional volume increasing from a normal of 0.38 to 0.48 per unit cell volume. This quantitative increase is accompanied by a progressive deterioration of the internal cristal structure and the appearance of abnormal, degenerating, and necrotic forms of mitochondria as congestive cardiac failure develops. Myofibrils remain normal. The heart of an anemic rat subjected to an additional workload produced by subdiaphragmatic aortic constriction shows an earlier deterioration of the mitochondrial ultrastructure and stereologic profiles. However, it does not become as large as the heart of the purely anemic animal. In anemic animals with an increased workload, the myofibrillar fractional volume increases from a normal of 0.52 to 0.57 per unit cell volume initially. The active sarcomerogenesis is achieved by Z-band proliferation, which was not observed in the heart of the purely anemic animal. These findings provide a structural basis for the functional and biochemical cardiac deterioration observed in the cardiomegaly induced by chronic anemia.     

Muscle hypertrophy and fast fiber type conversions in heavy resistance-trained women

Summary Twenty-four women completed a 20-week heavy-resistance weight training program for the lower extremity. Workouts were twice a week and consisted of warm-up exercises followed by three sets each of full squats, vertical leg presses, leg extensions, and leg curls. All exercises were performed to failure using 6–8 RM (repetition maximum). Weight training caused a significant increase in maximal isotonic strength (1 RM) for each exercise. After training, there was a decrease in body fat percentage (p<0.05), and an increase in lean body mass (p<0.05) with no overall change in thigh girth. Biopsies were obtained before and after training from the superficial portion of the vastus lateralis muscle. Sections were prepared for histological and histochemical examination. Six fiber types (1, IC, IIC, IIA, IIAB, and IIB) were distinguished following routine myofibrillar adenosine triphosphatase histochemistry. Areas were determined for fiber types 1, IIA, and IIAB + IIB. The heavy-resistance training resulted in significant hypertrophy of all three groups: I (15%), IIA (45%), and IIAB + IIB (57%). These data are similar to those in men and suggest considerable hypertrophy of all major fiber types is also possible in women if exercise intensity and duration are sufficient. In addition, the training resulted in a significant decrease in the percentage of IIB with a concomitant increase in IIA fibers, suggesting that strength training may lead to fiber conversions.     

Acute effects of ACTH on dissociated adrenocortical cells: Quantitative changes in mitochondria and lipid droplets

To study the role of certain organelles in steroidogenesis, dissociated rat adrenocortical cells were incubated for two hours with ACTH at a concentration that induces a high level of steroid production. Sections of ACTH treated and untreated cells were photographed in the electron microscope, and morphometric analysis was undertaken to assess possible ACTH-induced changes in total cell volume, volume density and numerical density of lipid droplets and mitochondria. There was no change in total cell volume. Lipid droplet volume density and numerical density decreased. Mitochondrial volume density did not change, but numerical density increased. The decrease in lipid droplet volume density indicates a rapid depletion of cholesterol for steroid production. This depletion is almost entirely due to the disappearance of lipid droplets, rather than to an overall diminution in their size, as shown by the decrease in lipid droplet numerical density. The mitochondrial data suggest that the adrenocortical cell has an adequate mitochondrial apparatus to respond to acute ACTH stimulation with increased steroid output without an increase in mitochondrial volume.     

The effect of verapamil cardioplegia on myocardial ultrastructure

The calcium channel blocker, verapamil, was evaluated as an adjunct to cold cardioplegia in 16 randomized patients with unstable angina pectoris who received saphenous vein bypass grafts. Myocardial biopsies taken before cardioplegia showed various degrees of ischemic change as assessed by ultrastructural parameters (mitochondrial swelling, matrix clearance, and sarcotubular dilatation). After reperfusion, the majority of the patients had progressive changes of ischemia, with marked mitochondrial and sarcotubular swelling, depletion of glycogen, chromatin clumping, and myofibrillar disruption; amorphous mitochondrial densities were occasionally seen. The ultrastructural changes after cardioplegia were dependent primarily on the extent of preexisting ischemic damage and did not correlate with the use of verapamil. Verapamil did not protect the ischemic myocardium during cold cardioplegia as assessed ultrastructurally.     

Hypertrophy of visceral smooth muscle

Summary Smooth muscles of viscera undergo a large increase in volume when there is a chronic, partial obstruction impairing the flow of lumenal contents. Hypertrophy of smooth muscle occurs in various medical conditions and several methods are available for inducing it experimentally in laboratory animals, especially in urinary bladder, small intestine and ureter. The hypertrophic response differs somewhat with the type of organ, the animal species, the age of the subject, and the experimental procedure.Ten- to fifteen-fold increases in muscle volume develop within a few weeks in the urinary bladder or the ileum of adult animals, a growth that would not have occurred in the lifespan of the animal without the experimental intervention. The general architecture of the muscle and the boundaries with adjacent tissues are well preserved. In intestinal hypertrophy, muscle cells increase in number: mitoses are found in mature, fully differentiated muscle cells. Cell division by full longitudinal splitting of muscle cells may also occur.Enlargement of muscle cells accounts for most of the muscle hypertrophy. The hypertrophic muscle cell has an irregular profile with deep indentations of the cell membrane, bearing caveolae and dense bands; however, the cell surface grows less than the cell volume (reduction of surface-to-volume ratio). The nucleus is crenated and is much less enlarged than the cell (reduction of the nucleo-plasmatic ratio). Mitochondria grow in number but in some muscles their spatial density decreases; intermediate filaments increase more than myofilaments. The spatial density of sarcoplasmic reticulum is generally increased. In the hypertrophic intestine, gap junctions increase in number and size; in the bladder, gap junctions are absent both in control and in hypertrophy. Thus the hypertrophic muscle cell is not only larger than a control cell, but has a different pattern of its structural components.Extensive neo-angiogenesis maintains a good blood supply to the hypertrophic muscle. The density of innervation is much decreased in the hypertrophic intestine, whereas it appears well maintained in the bladder. Neuronal enlargement is found in the intramural ganglia of the intestine and in the pelvic ganglion.The mechanisms involved in hypertrophic growth are unknown. Three possible factors, mechanical factors, especially stretch, altered nerve discharge, and trophic factors are discussed.