Comprehensive Physiology Wiley Online Library

Cellular Basis of Physiological and Pathological Myocardial Growth

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Morphometric Analysis of Cell Size and Number in the Ventricular Myocardium
1.1 Myocyte Dimensional Properties and Number: Methodological Considerations
1.2 Confocal Microscopic Measurements of Myocyte Cell Volume
2 Morphometric Analysis of the Coronary Vasculature
3 Physiological Myocardial Growth: Maturation of the Heart
3.1 Ventricular Remodeling
3.2 Myocyte Adaptations
3.3 Cytoplasmic Adaptations in Myocytes
3.4 Capillary Adaptations
3.5 Conclusions
4 Aging of the Heart
4.1 Aging and Ventricular Remodeling
4.2 Aging and Myocyte Number
4.3 Aging and Myocyte Reactive Hypertrophy
4.4 Aging and the Coronary Arterial and Capillary Tree
4.5 Conclusions
5 Pressure and Volume Overload Hypertrophy
5.1 Cardiac Hypertrophy and Ventricular Remodeling
5.2 Cardiac Hypertrophy and Myocyte Size, Shape, and Number
5.3 Cardiac Hypertrophy and Volume Composition of Myocytes
5.4 Cardiac Hypertrophy and the Coronary Arterial and Capillary Tree
5.5 Conclusions
6 Ischemic Cardiomyopathy
6.1 Ischemic Cardiomyopathy and Ventricular Remodeling
6.2 Ischemic Cardiomyopathy, Myocyte Cell Loss, and Ventricular Function
6.3 Ischemic Cardiomyopathy and Myocyte Cellular Hypertrophy and Hyperplasia
6.4 Ischemic Cardiomyopathy and Volume Composition of Myocytes
6.5 Ischemic Cardiomyopathy and the Coronary Capillary Tree
6.6 null
Figure 1. Figure 1.

Schematic graph of equation .

Figure 2. Figure 2.

Sections of plastic‐embedded tissue of ventricular myocardium with myofibers oriented transversely (A) and longitudinally (B).

several myocyte nuclear profiles (arrows) are seen in the center of transversely sectioned cells.

Mid‐sections of myocyte nuclei are shown. The nuclear envelope is defined at both ends, and clusters of mitochondria are visible at the nuclear poles. Methylene blue and safranin staining.

A and B: bars = 10 μm.

Figure 3. Figure 3.

Three‐dimensional optical section reconstruction by confocal microscopy of a left ventricular myocyte from a dog heart and

a right ventricular myocyte from a rat heart.

Fluorescein and propidium iodide staining. A and B: bars = 50 μm.

Figure 4. Figure 4.

Confocal microscopic images of cross‐sectional areas of two rat ventricular myocytes on the surface of a microscopic slide. These images were obtained by three‐dimensional optical reconstruction in the Z‐plane of the cell. A and B: bars = 10 μm.

Figure 5. Figure 5.

Schematic representation of a vessel profile in the myocardium and

its projection on sectioning plane.

L, major axis; D, minor axis. See text for details.

Figure 6. Figure 6.

Effects of postnatal development on wall thickness, mural number of myocytes, myocyte diameter, and aggregate length of myocytes in the left ventricle of the rat heart. Results are presented as mean ± SD.

Figure 7. Figure 7.

Effects of postnatal development on the capillary properties implicated in tissue oxygenation in the rat left ventricle. Results are presented as mean ± SD.

Figure 8. Figure 8.

Light microscopic tissue sections of methacrylate‐embedded left ventricular myocardium collected from a 74‐year‐old woman.

Two small foci of replacement fibrosis located in the subendocardial region of the wall.

An area of interstitial fibrosis separating individual myocytes. Hematoxylin and eosin staining.

A: bar = 50 μm. B: bar = 10 μm.

Figure 9. Figure 9.

Effects of aging on the number of mononucleated and binucleated myocytes in the left and right ventricles of the male and female heart. Male heart: left ventricle = mononucleated myocytes: y = 6.4 − 0.05 ×; r = 0.84, p = 0.0001; binucleated myocytes: y = 0.3 − 0.005 ×; r = 0.63; p = 0.0001; right ventricle = mononucleated myocytes: y = 2.2 − 0.02 ×; r = 0.84; p = 0.0001; binucleated myocytes: y = 0.16 + 0.001 ×; r = 0.45; p = 0.0003. Female heart: left ventricle = mononucleated myocytes: y = 3.8 − 0.002 ×; r = 0.09; p = 0.5; binucleated myocytes: y = 0.7 − 0.0004 ×; r = 0.08; p = 0.5; right ventricle: mononucleated myocytes: y = 1.07 − 0.0002 ×; r = 0.03; p = 0.82; binucleated myocytes: y = 0.36 − 0.00008 ×; r = 0.03; p = 0.82.

Figure 10. Figure 10.

Effects of aging on myocyte cell volume in the left and right ventricles of the female and male human heart. Female heart: left ventricle: y = 19,718 + 0.5 X; r = 0.0049; p = 0.97; Right ventricle: y = 17,204 + 10.6 X; r = 0.057; p = 0.68. Male heart; left ventricle: y = 19,406 + 158 X; r = 0.45; p = 0.001; Right ventricle: y = 15,106 + 167 X; r = 0.63; p = 0.0001.

Figure 11. Figure 11.

Changes in the volume fraction of capillary lumen, capillary luminal surface per unit volume of myocytes, and diffusion distance for oxygen in the left and right ventricular myocardium of Sprague‐Dawley rats at 3, 11, and 19 months of age. *Indicates a statistically significant difference from 3‐month‐old rats. **Indicates a statistically significant difference from 11‐month‐old rats. Results are presented as mean ± SD.

Figure 12. Figure 12.

Effects of age on length density of arterioles 6–20 μm in diameter in the principal layers of the left ventricular wall. *Indicates a statistically significant difference from 4‐month‐old rats. **Indicates a statistically significant difference from 12‐month‐old rats. Results are presented as mean ± SD.

Figure 13. Figure 13.

Mitotic index in myocytes from control hearts (Controls), and hearts affected by ischemic cardiomyopathy (IC) and idiopathic dilated cardiomyopathy (IDC). Results are presented as means ±SD. *Indicates a statistically significant difference from controls.

Reproduced from ; copyright © 1998 National Academy of Sciences, USA
Figure 14. Figure 14.

Papillary muscle hypertrophy, eight days after abdominal aortic stenosis (AAS) in rats. Relationships between the anatomical characteristics of the papillary muscle and the structural properties of myocytes. *Indicates a statistically significant difference between sham‐operated (SO) and aorticbanded rats. Results are presented as mean ± SD.

Figure 15. Figure 15.

Effects of chronic pulmonary artery banding (PAB) on wall thickness, myocyte diameter, and transmural number of myocytes in the right ventricular wall. *Indicates a statistically significant difference between sham operated (SO) and PAB rats. Results are presented as mean ± SD

Figure 16. Figure 16.

Effects of chronic pulmonary artery banding (PAB) on the ratio of capillary profiles to myocyte profiles, number of capillaries across the wall, and aggregate length of capillaries in the right ventricle. * Indicates a statistically significant difference between sham‐operated (SO) and PAB rats. Results are presented as mean ± SD

Figure 17. Figure 17.

Effects of occlusion of the left main coronary artery on left ventricular chamber diameter, ventricular wall (open bars), and septal (hatched bars) thickness, and number of myocytes and capillaries across the wall and septum. * Indicates a statistically significant difference between infarcted and sham operated (SO) rats. Results are presented as mean ± SD.

Figure 18. Figure 18.

Effects of chronic coronary artery narrowing on left ventricular wall thickness and chamber diameter, at six subsequent levels from the basal to the apical region of the heart. Sham‐operated animals (open circles). Coronary artery narrowed animals with left ventricular failure (solid circles). *Indicates a value that is statistically significantly different from the corresponding value in sham‐operated rats. Results are presented as mean ± SD.

Figure 19. Figure 19.

Ischemic cardiomyopathy in humans: Relative amounts of segmental, replacement, and interstitial fibrosis in the myocardium. *Indicates a value that is statistically significantly different from the corresponding value in control hearts. Results are presented as mean ± SD.

Figure 20. Figure 20.

Ischemic cardiomyopathy in humans: Total number of myocyte nuclei in the ventricle. LV: Left Ventricle; RV: Right Ventricle. *Indicates a value that is statistically significant different from the corresponding value in control hearts. Results are presented as mean ± SD.

Figure 21. Figure 21.

Graphic comparison of myocyte cell volume measured in the border and remote regions of infarcted left ventricles. The upper linear regression line corresponds to the data collected in the border zone, whereas the lower regression line represents the values obtained in the remote region. Comparison of the two regression lines demonstrates a statistically significant difference between the two slopes (p < 0.001).

Figure 22. Figure 22.

Effects of coronary artery narrowing (CAN) on the total number of mononucleated and binucleated myocytes in the right and left ventricles. *Indicates a statistically significant difference between CAN and sham‐operated (SO) rats. Results are presented as mean ± SD.



Figure 1.

Schematic graph of equation .



Figure 2.

Sections of plastic‐embedded tissue of ventricular myocardium with myofibers oriented transversely (A) and longitudinally (B).

several myocyte nuclear profiles (arrows) are seen in the center of transversely sectioned cells.

Mid‐sections of myocyte nuclei are shown. The nuclear envelope is defined at both ends, and clusters of mitochondria are visible at the nuclear poles. Methylene blue and safranin staining.

A and B: bars = 10 μm.



Figure 3.

Three‐dimensional optical section reconstruction by confocal microscopy of a left ventricular myocyte from a dog heart and

a right ventricular myocyte from a rat heart.

Fluorescein and propidium iodide staining. A and B: bars = 50 μm.



Figure 4.

Confocal microscopic images of cross‐sectional areas of two rat ventricular myocytes on the surface of a microscopic slide. These images were obtained by three‐dimensional optical reconstruction in the Z‐plane of the cell. A and B: bars = 10 μm.



Figure 5.

Schematic representation of a vessel profile in the myocardium and

its projection on sectioning plane.

L, major axis; D, minor axis. See text for details.



Figure 6.

Effects of postnatal development on wall thickness, mural number of myocytes, myocyte diameter, and aggregate length of myocytes in the left ventricle of the rat heart. Results are presented as mean ± SD.



Figure 7.

Effects of postnatal development on the capillary properties implicated in tissue oxygenation in the rat left ventricle. Results are presented as mean ± SD.



Figure 8.

Light microscopic tissue sections of methacrylate‐embedded left ventricular myocardium collected from a 74‐year‐old woman.

Two small foci of replacement fibrosis located in the subendocardial region of the wall.

An area of interstitial fibrosis separating individual myocytes. Hematoxylin and eosin staining.

A: bar = 50 μm. B: bar = 10 μm.



Figure 9.

Effects of aging on the number of mononucleated and binucleated myocytes in the left and right ventricles of the male and female heart. Male heart: left ventricle = mononucleated myocytes: y = 6.4 − 0.05 ×; r = 0.84, p = 0.0001; binucleated myocytes: y = 0.3 − 0.005 ×; r = 0.63; p = 0.0001; right ventricle = mononucleated myocytes: y = 2.2 − 0.02 ×; r = 0.84; p = 0.0001; binucleated myocytes: y = 0.16 + 0.001 ×; r = 0.45; p = 0.0003. Female heart: left ventricle = mononucleated myocytes: y = 3.8 − 0.002 ×; r = 0.09; p = 0.5; binucleated myocytes: y = 0.7 − 0.0004 ×; r = 0.08; p = 0.5; right ventricle: mononucleated myocytes: y = 1.07 − 0.0002 ×; r = 0.03; p = 0.82; binucleated myocytes: y = 0.36 − 0.00008 ×; r = 0.03; p = 0.82.



Figure 10.

Effects of aging on myocyte cell volume in the left and right ventricles of the female and male human heart. Female heart: left ventricle: y = 19,718 + 0.5 X; r = 0.0049; p = 0.97; Right ventricle: y = 17,204 + 10.6 X; r = 0.057; p = 0.68. Male heart; left ventricle: y = 19,406 + 158 X; r = 0.45; p = 0.001; Right ventricle: y = 15,106 + 167 X; r = 0.63; p = 0.0001.



Figure 11.

Changes in the volume fraction of capillary lumen, capillary luminal surface per unit volume of myocytes, and diffusion distance for oxygen in the left and right ventricular myocardium of Sprague‐Dawley rats at 3, 11, and 19 months of age. *Indicates a statistically significant difference from 3‐month‐old rats. **Indicates a statistically significant difference from 11‐month‐old rats. Results are presented as mean ± SD.



Figure 12.

Effects of age on length density of arterioles 6–20 μm in diameter in the principal layers of the left ventricular wall. *Indicates a statistically significant difference from 4‐month‐old rats. **Indicates a statistically significant difference from 12‐month‐old rats. Results are presented as mean ± SD.



Figure 13.

Mitotic index in myocytes from control hearts (Controls), and hearts affected by ischemic cardiomyopathy (IC) and idiopathic dilated cardiomyopathy (IDC). Results are presented as means ±SD. *Indicates a statistically significant difference from controls.

Reproduced from ; copyright © 1998 National Academy of Sciences, USA


Figure 14.

Papillary muscle hypertrophy, eight days after abdominal aortic stenosis (AAS) in rats. Relationships between the anatomical characteristics of the papillary muscle and the structural properties of myocytes. *Indicates a statistically significant difference between sham‐operated (SO) and aorticbanded rats. Results are presented as mean ± SD.



Figure 15.

Effects of chronic pulmonary artery banding (PAB) on wall thickness, myocyte diameter, and transmural number of myocytes in the right ventricular wall. *Indicates a statistically significant difference between sham operated (SO) and PAB rats. Results are presented as mean ± SD



Figure 16.

Effects of chronic pulmonary artery banding (PAB) on the ratio of capillary profiles to myocyte profiles, number of capillaries across the wall, and aggregate length of capillaries in the right ventricle. * Indicates a statistically significant difference between sham‐operated (SO) and PAB rats. Results are presented as mean ± SD



Figure 17.

Effects of occlusion of the left main coronary artery on left ventricular chamber diameter, ventricular wall (open bars), and septal (hatched bars) thickness, and number of myocytes and capillaries across the wall and septum. * Indicates a statistically significant difference between infarcted and sham operated (SO) rats. Results are presented as mean ± SD.



Figure 18.

Effects of chronic coronary artery narrowing on left ventricular wall thickness and chamber diameter, at six subsequent levels from the basal to the apical region of the heart. Sham‐operated animals (open circles). Coronary artery narrowed animals with left ventricular failure (solid circles). *Indicates a value that is statistically significantly different from the corresponding value in sham‐operated rats. Results are presented as mean ± SD.



Figure 19.

Ischemic cardiomyopathy in humans: Relative amounts of segmental, replacement, and interstitial fibrosis in the myocardium. *Indicates a value that is statistically significantly different from the corresponding value in control hearts. Results are presented as mean ± SD.



Figure 20.

Ischemic cardiomyopathy in humans: Total number of myocyte nuclei in the ventricle. LV: Left Ventricle; RV: Right Ventricle. *Indicates a value that is statistically significant different from the corresponding value in control hearts. Results are presented as mean ± SD.



Figure 21.

Graphic comparison of myocyte cell volume measured in the border and remote regions of infarcted left ventricles. The upper linear regression line corresponds to the data collected in the border zone, whereas the lower regression line represents the values obtained in the remote region. Comparison of the two regression lines demonstrates a statistically significant difference between the two slopes (p < 0.001).



Figure 22.

Effects of coronary artery narrowing (CAN) on the total number of mononucleated and binucleated myocytes in the right and left ventricles. *Indicates a statistically significant difference between CAN and sham‐operated (SO) rats. Results are presented as mean ± SD.

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Piero Anversa, Giorgio Olivetti. Cellular Basis of Physiological and Pathological Myocardial Growth. Compr Physiol 2011, Supplement 6: Handbook of Physiology, The Cardiovascular System, The Heart: 75-144. First published in print 2002. doi: 10.1002/cphy.cp020102