David Spiro

Cellular basis for volume related wall thickness changes in the rat left ventricle

Abstract Nine arrested rat hearts fixed by glutaraldehyde perfusion of the coronary arteries were studied in vertical cross-sections of the left ventricle by phase contrast microscopy. The number of fibers per unit area in the wall and the number of fibers between the epicardium and endocardium were measured and correlated with ventricular volume and wall thickness. Average center to center fiber separation was derived from these measurements. Increasing ventricular volume is associated with a decrease in wall thickness and fiber diameter which follows theoretical predictions. The relationship between these measurements, however, presents a dimensional paradox in that the decreases in wall thickness are 3 to 4 times greater than the decrease observed in separation of fiber centers. Thus, an increase in fixation volume from 0.03 to 0.60 ml results in a 68% decrease in wall thickness, while center to center fiber separation decreases only 20%. Changes in wall thickness are therefore mainly accounted for by internal rearrangement of the disposition of fibers composing the ventricular wall. A mechanism for such rearrangements is illustrated by low magnification cross-sections of the ventricular wall which demonstrate open spaces or sliding planes between groups of muscle fibers. A volume related alteration in the orientation of these sliding planes is noted.

Electron Microscopic Alterations at the Alveolar Level in Pulmonary Edema

The electron microscopic alterations of the alveolar septum in advanced hemodynamin and alloxan-induced pulmonary edema were compared. Pulmonary edema was produced in anesthetized dogs by means of increased lefy atrial pressure and hemodilution and by allocan administration. Sections of pulmonary tissue from these dogs and similarly anesthetized controls were processed for and examined by light and electron microscopy. In the hemodynamic form of edema the interstitial fluid collects only in the collagen-containing portions of the septum. The endothelium, epithelium, their respective basement membranes and large portions of the air-blood barrier are unaffected. Alloxaninduced edema, in contrast, is characterized by degeneration of both endothelium and epithelium and by the appearance of fibrin within the alveoli. The hemodynamic type of pulmonary edema appears to result from an accentuation of the normal process of fluid exchange within the lung. Allocan-induced edema, on the other hand, is a pathologic process. The functional implications of these results are discussed.

Ultrastructural studies of muscle in McArdle's disease.

An electron microscopic study of the flexor carpi radialis muscle from 2 patients with MeArdles disease is presented. Glycogen accumulation occurred primarily in the intermyofibrillar space of the I band and under the sarcolemma. Increased amounts of glycogen were also noted between the thin filaments within the I band and. occasionally, between filaments in the A band. The most significant alteration in the muscle fiber, in terms of muscle fiber function, was disorganization of the myofibrils at the level of the I band. This was due to compression of the myofibrils by excess glycogen in the inter-myofibrillar space and displacement or replacement of thin filaments within the myofibrils by glycogen deposits. It is suggested that these alterations in myofibril structure, due to glycogen deposition, may lie one of the causes of the permanent weakness that has been observed in the later stages of McArdles disease. The distribution of excels glycogen in McArdles disease may provide indirect evidence for tile localization of skeletal muscle phosphorylase. Electron microscopic study of phosphorylase deficient muscle in physiological contracture, removed 30 minutes after the onset of ischemic exercise, revealed mitochondrial alterations and dilatation of portions of the sarco-plasmic reticulum.

The ultrastructural basis of Starling's law of the heart. The role of the sarcomere in determining ventricular size and stroke volume

Abstract The relation of the ultrastructure of heart muscle to ventricular function has been discussed. The fact that the length of the sarcomere, the unbiquitous unit of contraction, is a function of muscle length allows the formulation of a sarcomere length-tension curve. This forms the ultrastructural basis of “Starlings law of the heart.” The limits of sarcomere shortening are discussed (2.2 to 1.5 μ), and the normal range of contraction under afterloaded conditions has been delimited (2.1 to 1.7 μ), thus allowing for a 20 per cent sarcomere shortening. It has been shown that this 20 per cent sarcomere shortening accounts for the ventricular muscle shortening necessary to explain known ventricular performance in the cat, dog, and man. On this basis, it has been suggested that the initial size of the ventricle required to produce a given stroke volume depends on the structural and functional limits of the sarcomere.

Structure of the cardiac muscle cell

Abstract 1.1. An electron microscopic study of the papillary muscles of rat and dog hearts is reported. The ultrastructural features of the sarcolemma, intercalated disc, myocardial nuclei and mitochondria, sarcoplasmic reticulum, myofibrils, and other cytoplasmic components are described. 2.2. The observations of other investigators and their interpretations are discussed in relation to these findings. 3.3. The intercalated disc is defined as a distinctive complex consisting of modified cell membranes with an interposed intercellular space. The concept of a morphologic syncytium is discarded. 4.4. The sarcoplasmic reticulum is interpreted as a system of anastomosing, membrane-limited channels which traverse the interior of the myocardial cell and come into close relationship with other intracellular structures. 5.5. The myofibril is conceived as an ordered integrated system composed of thick and thin myofilaments which interdigitate at A band levels. The structural similarity to skeletal muscle is discussed.

Electron microscope studies in experimental thrombosis

Abstract Thrombi were produced experimentally in rats and studied at various stages of organization with the electron microscope. Fibrin, which is a prominent constituent of the early thrombus, was virtually absent after 4 days. There was evidence of collagen formation within the wall at 2 days, and there was extensive fibrogenesis within the thrombus at 4 days. The thrombi were first recanalized by solid cell cylinders which were converted into mature capillaries by a process of growth and fusion of extracellular spaces between adjacent endothelial cells. Other significant features and problems relating to the organization of thrombi are briefly discussed.

CYTOCHEMICAL LOCALIZATION OF CHOLINESTERASE IN EMBRYONIC RABBIT CARDIAC MUSCLE

Cardiac muscle of rabbit embryos from day 9 through day 18 of gestation was studied by a modification of the Koelle-Friedenwald copper thiocholine technique for the localization of cholinesterase activity. In the earlier stages of development a cholinesterase, presumed to be acetylcholinesterase from its substrate and inhibitor specificity, is found in the abundant, randomly dispersed rough surfaced endoplasmic reticulum of the myoblast. Cytochemical end product is also occasionally found in the nuclear envelope, Golgi complex and subsarcolemmal cisternae. The localization of the enzyme first in the rough surfaced endoplasmic reticulum and Golgi complex and at later stages in the sarcoplasmic reticulum is significant with regard to the differentiation of the cardiac myocyte. Furthermore, the presence of this enzyme in contractile tissue before the appearance of nerves or nerve endings demonstrates an acetylcholine-cholinesterase system of myogenic origin.