P.B. Herdson

Plasma Exchange in Goodpasture’s Syndrome

The clinical course and levels of anti-glomerular basement membrane (GBM) antibody were compared in 20 patients with Goodpastures syndrome treated with plasma exchange and immunosuppression (8 patients), immunosuppression alone (4 patients) or no specific therapy (8 patients). There was a more rapid fall in the level of anti-GBM antibody and pulmonary hemorrhage was less protracted in the 8 patients treated with plasma exchange and immunosuppression. In this group, 1 patient who presented with severe renal failure showed a marked improvement of renal function and there was no progression of disease in the 4 with milder renal involvement. 2 of the 4 patients treated with immunosuppression alone, and only 2 of the 8 patients who received no specific therapy, maintained normal renal function. In the group which received no specific therapy, 1 of the 6 patients who progressed to renal failure had mild renal involvement initially. There was a significant correlation between the level of anti-GBM antibody and the severity of the morphological changes seen at renal biopsy but not between the level of anti-GBM antibody and the severity of lung hemorrhage. The course and outcome of the disease in those patients not treated, or treated with immunosuppression alone, was better than that described in early reports of this disease, while those patients with plasma exchange and immunosuppression fared even better. An adequately stratified controlled trial of immunosuppression and plasma exchange versus immunosuppression alone is in order.

The relationship of ischemic contracture to vascular reperfusion in the isolated rat heart

Abstract Isolated Langendorff rat heart preparations were used to measure ischemic contracture of the left ventricle by means of an intraventricular balloon catheter connected to a pressure recorder. After various times of global ischemia, the extent of reflow to the ventricles was visualized by perfusion with 1% fluorescein solution. The onset of ischemic contracture was accelerated and its magnitude increased by preischemic perfusion with 0.5 m m iodoacetate (IAA). Conversely, its onset was delayed and magnitude decreased by preischemic perfusion with buffer containing only 0.05 m m calcium. Compared with control hearts, those pretreated with the low calcium buffer showed more extensive reflow, whereas IAA-treated hearts showed a greater loss of vascular competence in the early stages of reperfusion. Although the reperfusion defect developed after ischemic contracture, its ultimate extent correlated closely with the force of contracture. It is proposed that subendocardial blood vessels closed by the tension generated in ischemic contracture, eventually lose their ability to dilate and allow reperfusion as compliance of the myocardium is reduced by the development of rigor mortis.

Scanning Electron Microscopy Of The Endocardial Endothelium Overlying Early Myocardial Infarcts

Summary Using scanning electron microscopy, the endothelium of normal left ventricle was compared with that overlying experimentally‐induced myocardial infarcts in dogs. Ten minutes after coronary artery ligation there was no apparent difference, but at intervals from 20 to 360 minutes, patches of altered endothelium were evident over the ischaemic muscle. In affected areas there was separation of endothelial cells along intercellular boundaries and the loss of many, but not all, endothelial cells. Up to two hours after coronary ligation the depressions left by the missing cells were smoothly rounded with prominent intercellular lines separating them. However, after six hours, the bases of these depressions were rough and the intercellular lines indistinct due to the loss of a layer of supporting material originally lying between the endothelial cells and underlying connective tissue fibres.

Changes in vascular morphology associated with the no-reflow phenomenon in ischaemic myocardium

To investigate the pathogenesis of the reperfusion defect which develops in ischaemic myocardium, intravascular casts were prepared by injection of methyl methacrylate into the coronary arteries of isolated heparinised rat hearts. Using a scanning electron microscope, the vascular morphology following 60 min of global ischaemia at 37° C was compared to that of non-ischaemic control hearts injected immediately after stopping perfusion with oxygenated Krebs-Henseleit buffer. Complete casts were obtained from control hearts and from all parts of ischaemic hearts except the subendocardial half of the left ventricular wall of ischaemic hearts where the blood vessels were not filled. At the border between the perfused subepicardial and unperfused left subendocardial regions, the resin which filled the radial penetrating arteries and their branches projected from the filled capillary plexus to an extent proportional to their diameter. Intravascular events such as erythrocyte plugging and thrombosis were excluded as causative factors by the use of a cell-free perfusate. Also, there was no morphological evidence that endothelial cell swelling or constriction of any particular population of vessels was involved. The observed pattern of vascular occlusion suggests that, during global ischaemia, blood vessels in the endocardial half of the left ventricular myocardium lose their ability to be reperfused because of extravascular compression.

Fine structural changes in rat myocardium induced by daunorubicin

Summary Rats were injected intravenously with the anti‐leukaemic drug daunorubicin to determine the morphological basis of its cardiotoxic effects. Although changes were not observed by light microscopy in either atrial or ventricular myocardium, significant fine structural changes were seen by electron microscopy in both. They appeared earlier and were most striking in the ventricle. Membranous whorls within or adjacent to the mitochondria appeared within 24 hours and increased in both number and size up to the fifth day after injection. On the fifth day the lumina of many capillary vessels were partly occluded by swollen endothelial cells. This latter change may well lead to hypoxia and so accelerate the degenerative changes present in the muscle fibres.

A Quantitative Study of the Sequence of Topographical Changes in the Organ of Corti Following Acoustic Trauma

The organs of Corti of 30 guinea pigs were examined quantitatively by scanning electron microscopy either immediately or 1, 3, 7 or 14 days after exposure to 3 kHz at 125 dB SPL for 30 min. Lesions (0.1-4.15 mm in length) were observed in 70% of the organs of Corti. There was no significant change in lesion length with recovery from the exposure. Early changes in hair cells consisted of stereocilia abnormalities, predominantly amongst inner hair cells and the first row of outer hair cells. The proportion of affected cells increased towards the centre of lesions, where supporting cells were affected also. Subsequent to exposure, affected hair cells were either lost or remained with stereocilia abnormalities but did not recover. Regions showing supporting cell damage were replaced within 3 days by inner sulcus and Claudius cells. Despite similar changes to stereocilia, inner hair cells were more resistant to necrosis than outer hair cells, suggesting that the nature of stereocilia damage does not necessarily indicate the fate of hair cells.

Experimental Autoimmune Glomerulonephritis in the Rat I. Factors Influencing Induction

Summary Albino Holtzman, albino Wistar and hooded HS rats were injected fortnightly for 14 weeks with human glomerular basement membrane (GBM) emulsified in Freunds complete adjuvant. Half of the rats were pretreated with Freunds complete adjuvant and some were unilaterally nephrectomized. Anti‐GBM antibody glomerulonephritis, characterized by proteinuria (>100 mg/16 h) and a diffuse linear deposition of host immunoglobulin along the glomerular basement membrane, was first detected in Holtzman rats 4 weeks after treatment with GBM had begun, and had developed in 69% of these rats by 15 weeks. In contrast, none of the similarly treated Wistar or HS rats became proteinuric at any time, although a few showed weak glomerular fluorescence at the end of the experiment. Thus Holtzman rats are susceptible, and HS and Wistar rats are resistant to experimental anti‐GBM antibody glomerulonephritis. Pretreatment with Freunds complete adjuvant apparently shortened the induction period of the experimental disease in the Holtzman rats whereas unilateral nephrectomy appeared to decrease their susceptibility to it.

The pathology of chemically-sterilized human heart valve allografts

Summary Fourteen human heart valve allografts were examined by light and electron microscopy following their surgical removal 26 to 65 months after insertion. Cusp rupture was the most common reason (78.5%) for replacement of the allografts, which had been sterilized either with beta propiolactone or ethylene oxide before insertion. The deep surface of the grafts showed invasion by lymphocytes, plasma cells, macrophages and capillary loops. A sheath of host tissue extended from the margin of the orthotopic aortic grafts toward, and sometimes just onto, the base of the cusps. Although most of the allograft tissue lacked intact fibroblasts or endothelial cells, it contained widely scattered cell debris. Focal collections of mononuclear cells including macrophages, lay in zones of homogeneous eosinophilic matrix in the cusps of all but one graft, and infiltration by fibrin, erythrocytes and leucocytes was common. These changes were present in all but one of the cusps which had ruptured. It is suggested that local factors may permit infiltration by mononuclear cells and deposition of fibrin, which coincidentally weaken the cusp, predisposing to its rupture.

An experimental evaluation of staining techniques for the detection of early ischaemic injury to the myocardium.

Summary A series of experimental infarcts of the posterior papillary muscle of the canine heart was used to assess the value of 6 special stains in the histological detection of early myocardial infarction. The infarcts were of 5–720 min duration and were compared not only with normal control myocardium but also with normal myocardium autolyzed for similar periods of time. All tissue was stained with H & E, PAS, PAS‐diastase, PTAH, Massons trichrome, Connors modification of the acid fuchsin method, Puchtlers PAS‐navy blue, and Lies haematoxylin‐basic fuchsin‐picric acid. The zone of severely altered myofibres which separated normal from ischaemic tissue in infarcts aged 2 or more hours was demonstrated by all but PAS. Normal, border, and ischaemic zones of heart muscle were clearly differentiated only by PTAH and PAS‐navy blue. PAS distinguished normal from glycogen‐depleted ischaemic myocardium after only 40–60 min, but this change was also seen in autolyzed tissue.

Catecholamine-depletion and the no-reflow phenomenon in anoxic and ischaemic rat hearts

Abstract The effect of depleting catecholamines in myocardium on the extent of the no-reflow phenomenon was investigated in isolated Langendorff rat heart preparations. Catecholamines were depleted by pretreating the rats with reserpine. After ischaemia or anoxia the proportion of the ventricular walls perfused by 1% fluorescein was assessed, and compared with the changes in glycogen content, lactate production, ATP levels and general morphology. After 60 min of global ischaemia, 60% of the ventricular walls of both catecholamine-depleted and untreated hearts was not reperfused. A similar period of anoxia produced 30% no-reflow in untreated controls, but only 16% in catecholamine-depleted hearts. Reserpine pretreatment caused a doubling of glycolytically derived ATP in anoxic hearts. However, in catecholamine-depleted ischaemic hearts there was no increase in ATP because of an inhibition of glycolysis, presumably due to the fall in pH. These findings indicate that, in anoxia, catecholamine depletion delays the onset of no-reflow by prolonging anaerobic ATP generation due to increased glycogen stores, and in global ischaemia at least, the no-reflow phenomenon is not due to catecholamine-induced sustained contraction of coronary arteries.