Tunnel Capillaries of Cardiac Myocyte in Pressure-Overloaded Rat Heart—An Ultrastructural Three-Dimensional Study

Kobayashi, Mikio; Kawamura, Koichi; Honma, Makiko; Masuda, Hirotake; Suzuki, Yukiko; Hasegawa, Hitoshi

doi:10.1006/mvre.1999.2148

Cited by 6 publications

(6 citation statements)

References 13 publications

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“…This second possibility is described as the remodeling theory. 29 In both cases, the tunnel capillaries are present only within the hypertrophied cardiomyocytes. In our experiments we observed only sporadic scattered areas of cardiomyocyte hypertrophy (which means that only some of them were hypertrophied) in bortezomib-treated rats.…”

Section: Discussionmentioning

confidence: 97%

Cardiotoxicity of the Anticancer Therapeutic Agent Bortezomib

Nowis

Mączewski

Mackiewicz

et al. 2010

The American Journal of Pathology

120

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Recent case reports provided alarming signals that treatment with bortezomib might be associated with cardiac events. In all reported cases, patients experiencing cardiac problems were previously or concomitantly treated with other chemotherapeutics including cardiotoxic anthracyclines. Therefore, it is difficult to distinguish which components of the therapeutic regimens contribute to cardiotoxicity. Here, we addressed the influence of bortezomib on cardiac function in rats that were not treated with other drugs. Rats were treated with bortezomib at a dose of 0.2 mg/kg thrice weekly. Echocardiography, histopathology, and electron microscopy were used to evaluate cardiac function and structural changes. Respiration of the rat heart mitochondria was measured polarographically. Cell culture experiments were used to determine the influence of bortezomib on cardiomyocyte survival, contractility,

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Section: Discussionmentioning

confidence: 97%

Cardiotoxicity of the Anticancer Therapeutic Agent Bortezomib

Nowis

Mączewski

Mackiewicz

et al. 2010

The American Journal of Pathology

120

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“…It has also been shown that changes in T 1 values, caused by aldehyde fixation, are not a result of the presence of bulk fixative in the tissue per se , but of continued chemical reactions between fixative and tissue; therefore, washing samples after fixation does not reverse the reduction in T 1 relaxation times caused by the fixative (24). All samples in this study were perfusion fixed via the coronary vasculature, ensuring optimal and swift delivery of the fixative to all cells of the heart [each myocyte is surrounded by four to five capillaries in the myocardium of healthy Sprague Dawley rats (42)], and this was followed by immersion fixation for 24 h before embedding. However, the continued decay in T 1 values observed in Fomblin-embedded hearts is indicative of progressive effects of the fixative on the myocardium, after the sample has been removed from the fixative.…”

Section: Discussionmentioning

confidence: 99%

Progressive changes in T₁, T₂ and left‐ventricular histo‐architecture in the fixed and embedded rat heart

et al. 2010

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Chemical tissue fixation, followed by embedding in either agarose or Fomblin, is common practice in time-intensive MRI studies of ex vivo biological samples, and is required to prevent tissue autolysis and sample motion. However, the combined effect of fixation and sample embedding may alter tissue structure and MRI properties. We investigated the progressive changes in T 1 and T 2 relaxation times, and the arrangement of locally prevailing cardiomyocyte orientation determined using diffusion tensor imaging, in embedded ex vivo rat hearts fixed using Karnovsky's solution (glutaraldehyde-formaldehyde mix). Three embedding media were investigated: (i) standard agarose (n = 3 hearts); (ii) Fomblin (n = 4 hearts); and (iii) iso-osmotic agarose (n = 3 hearts); in the latter, the osmolarity of the fixative and embedding medium was adjusted to 300 mOsm to match more closely that of native tissue. The T 1 relaxation time in the myocardium showed a pronounced decrease over a 48-h period following embedding in Fomblin (−11.3 ± 6.2%; mean ± standard deviation), but was stable in standard agarose-and iso-osmotic agarose-embedded hearts. The mean myocardial T 2 relaxation time increased in all embedded hearts: by 35.1 ± 14.7% with standard agarose embedding, 13.1 ± 5.6% with Fomblin and 13.3 ± 1.4% with iso-osmotic agarose. Deviation in the orientation of the primary eigenvector of the diffusion tensor occurred in all hearts (mean angular changes of 6.6°, 3.2° and 1.9° per voxel after 48 h in agarose-, Fomblin-and iso-osmotic agarose-embedded hearts, respectively), indicative of progressive structural changes in myocardial histo-architecture, in spite of previous exposure to fast-acting tissue fixation. Our results suggest that progressive structural changes occur in chemically fixed myocardium, and that the extent of these changes is modulated by the embedding medium, and by osmotic gradients between the fixative in the tissue and the surrounding medium.

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“…Thus, a cubic mass, measuring 300 × 190 × 60 µm 3 for the control, the first, and the third animals and 220 × 180 × 60 µm 3 for the second animal was observed serially at a step of one unit (1.2 µm) each. After the contours of endothelial cells, endothelial cell nuclei, and pericytes nuclei were traced, 3‐D reconstruction of the capillary networks was performed using a computer analyzing system (TRI, Ratoc, Tokyo, Japan) 16 …”

Section: Methodsmentioning

confidence: 99%

“…This pattern of capillary formation is thought to be different from the intussusceptive vascular growth that involves abluminal invagination of the capillary wall and invasion by interstitial cellular elements 14,15 . To resolve these problems, we thought that ultrastructural and 3‐D studies of the sprouting process in the electrically stimulated skeletal muscle were important 16,17 …”

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confidence: 99%

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Physiological angiogenesis in electrically stimulated skeletal muscle in rabbits: Characterization of capillary sprouting by ultrastructural 3‐D reconstruction study

Ebina

Hoshi

Kobayashi

et al. 2002

Pathology International

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Physiological angiogenesis occurs in electrically stimulated skeletal muscles. It is known to start as capillary sproutings, but has not yet been well characterized as ordinary angiogenesis. To characterize the sprouting process during physiological angiogenesis, we carried out an ultrastructural 3-D reconstruction study for the extensor digitorum longus of three adult rabbits under electrical stimulation for 7 days. In addition, hemodynamic and morphological studies were carried out after stimulation for 3, 7, and 14 days. The electrical stimulation induced a twofold increase in femoral artery blood flow and tissue blood flow. This was associated with an increase in capillary density of the muscle by more than twofold at 7 and 14 days. Sproutings frequently appeared at 7 days (4.3 +/- 1.4 x 10(3) sproutings per mm3, 13.3 +/- 6.9 microm in length). All sprouting tips consisted of endothelial cytoplasmic protrusions (ECP). Besides sproutings, there were communicating networks consisting segmentally of ECP (11.6 +/- 5.6 x 10(3) networks per mm3). Endothelial cytoplasmic protrusions began to appear at 3 days, were frequent at 7 days, and disappeared at 14 days, which corresponded well to the changes in blood flow and capillary density. We consider that in physiological angiogenesis, sproutings start as ECP, which contact other capillaries to form networks and become hollowed to form new capillary networks.

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Tunnel Capillaries of Cardiac Myocyte in Pressure-Overloaded Rat Heart—An Ultrastructural Three-Dimensional Study

Cited by 6 publications

References 13 publications

Cardiotoxicity of the Anticancer Therapeutic Agent Bortezomib

Cardiotoxicity of the Anticancer Therapeutic Agent Bortezomib

Progressive changes in T₁, T₂ and left‐ventricular histo‐architecture in the fixed and embedded rat heart

Physiological angiogenesis in electrically stimulated skeletal muscle in rabbits: Characterization of capillary sprouting by ultrastructural 3‐D reconstruction study

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Tunnel Capillaries of Cardiac Myocyte in Pressure-Overloaded Rat Heart—An Ultrastructural Three-Dimensional Study

Cited by 6 publications

References 13 publications

Cardiotoxicity of the Anticancer Therapeutic Agent Bortezomib

Cardiotoxicity of the Anticancer Therapeutic Agent Bortezomib

Progressive changes in T1, T2 and left‐ventricular histo‐architecture in the fixed and embedded rat heart

Physiological angiogenesis in electrically stimulated skeletal muscle in rabbits: Characterization of capillary sprouting by ultrastructural 3‐D reconstruction study

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Progressive changes in T₁, T₂ and left‐ventricular histo‐architecture in the fixed and embedded rat heart