J.B. Gavin

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.

The nature and progression of injury in the organ of Corti during ischemia

This study has defined the nature and sequence of ultrastructural changes in the organ of Corti following severe, total cochlear ischemia. Afferent nerve endings of IHC became swollen within 15 min and eventually ruptured. Outer hair cells were swollen within 30 min and showed alterations to mitochondria, endoplasmic reticulum and the nucleus whereas IHC remained unchanged for up to 60 min. Both efferent and afferent nerve endings of OHC were unaltered until after 60 min ischemia. Regardless of the type, cells in the base of the cochlea developed abnormalities more rapidly than those in the apical turns. These results imply a differential susceptibility to ischemic damage both among the different cell types and along the organ of Corti.

Cardiovascular implant calcification: a survey and update.

Calcification of cardiovascular prosthetic implants is a common and important problem. This review provides an update based upon the Conference on Cardiovascular Implant Calcification held as part of the 13th World Congress of the International Society for Heart Research, 1989. A variety of cardiovascular prostheses are affected clinically by calcification, including bioprosthetic heart valves, aortic homografts and trileaflet polymeric valve prostheses. In addition, experimental studies have demonstrated calcification of artificial heart devices in ventricular assist systems in long-term calf studies. The pathophysiology of this disease process is incompletely understood. A common element between the various types of cardiovascular implant calcification is the localization of calcific deposits to devitalized cells and membranous debris. Prevention of cardiovascular implant calcification by either biomaterial modifications or regional drug therapy (controlled release) is being investigated.

The intima of human coronary arteries

Intimal thickness relative to that of the media (r) was measured in coronary and internal mammary arteries from 300 human subjects. Whereas this ratio remained low (less than 0.17) in the mammary arteries, coronary arteries showed progressive intimal thickening (r = 4.10 by 60 years). The intimal surfaces of 70 pairs of arteries were compared by light, transmission, and scanning electron microscopy. The mammary arteries had a continuous endothelial lining, but the coronary arteries showed incomplete coverage of the thickened intima. In affected vessels the endothelial cells showed loss of attachment to adjacent cells and to the underlying tissue. It was concluded that the progressive intimal thickening of the human coronary artery, which develops early in life and is associated with defects in the internal elastic lamina, is also associated with endothelial cell separation and detachment, with the formation of denuded areas on the intimal surface.

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.

Histological assessment of orthotopic aortic valve leaflet allografts: its role in selecting graft pre-treatment

Summary Histopathological studies of human cardiac valve grafts recovered at autopsy or re‐operation, together with long‐term clinical follow‐up of valve graft recipients, have indicated that the success of grafts is largely dependent upon the extent to which they are replaced by host fibrous connective tissue. To find the valve preparation technique with least inhibitory effect on tissue ingrowth after grafting, various sterilizing and storage procedures were evaluated using a series of aortic valve leaflet allografts in dogs. To facilitate evaluation, a method for rapidly assaying relative degrees of colonization of grafts was first devised. Application of this method has unequivocally identified a newly‐formulated antibiotic solution as the pre‐treatment most compatible with host tissue ingrowth.

The effect of ischaemia on the function and fine structure of the microvasculature of myocardium.

Summary Seventeen mongrel dogs were subjected to ligation of the circumflex branch of the left coronary artery. At intervals from 10 to 300 minutes after ligation, 10 ml of a sodium fluorescein and colloidal thorium hydroxide solution were injected via an intra‐arterial catheter placed distal to the ligature. Up to 20 minutes after ligation this tracer solution evenly perfused the left ventricular wall including the posterior papillary muscle (PPM). During 25 to 50 minutes there was a progressive patchy loss of perfusion into the PPM although the sub‐epicardial region was evenly perfused. After 60 or more minutes of ischaemia it was not possible to inject this tracer solution into the subendocardial region. Electron microscopic examination indicated that this loss of vascular competence was possibly due to vasospasm of some vessels in the marginal zone between the perfused and non‐perfused areas and was unlikely to be due to intravascular thrombosis, endothelial cell swelling, or to compression of vessels due to cell or tissue oedema.

A scanning electron microscope study of lymphocyte-erythrocyte binding in three types of rosette

Summary Three types of union between lymphocytes and erythrocytes were examined by scanning electron microscopy. Specific antigen‐binding rosette‐formation between immunoglobulin on mouse lymphocytes and sheep red blood cells (SRBC) formed a strong union with narrow bands uniting the two cells. Human T lymphocytes bound SRBC non‐specifically by large areas of contact. Human B lymphocytes united with erythrocytes through the receptor for the third component of complement and the union showed multiple small points of contact between the erythrocyte and fine processes extending from lymphocyte surfaces. In general, the B lymphocyte surface had many fine villi or processes while T lymphocytes showed a smoother surface. But this distinction was not absolute as some B lymphocytes have large smooth areas while many T lymphocytes showed irregular surfaces.

Effects of glutamic acid on cardiac function and energy metabolism of rat heart during ischaemia and reperfusion

The effects of exogenous glutamate (20 mM) on myocardial energy metabolism and cardiac function during low-flow ischaemia and subsequent reperfusion were studied in isolated working rat hearts. Hearts were made severely ischaemic for 60 min by reducing the perfusion rate to 0.17 ml/min, and then reperfused for 30 min. Low-flow ischaemia resulted in a 50% reduction of myocardial ATP, a 70% reduction of both creatine phosphate (CP) and GTP, and a 250% rise in AMP. After reperfusion, CP was restored to normal levels but ATP and GTP remained significantly low. All hearts failed completely to recover cardiac pump function. The addition of glutamate to the perfusate during low-flow ischaemia had no significant effect on myocardial high-energy phosphates (HEP) but slightly increased succinate production. Subsequent reperfusion without added glutamate resulted in the recovery of 62% of pre-ischaemic aortic flow rate, as well as restoration of myocardial ATP and GTP to 70% of their control values and of creatine phosphate to supranormal levels. Reperfusion with added glutamate did not raise HEP levels any further but did increase recovery of cardiac function to 92% or more of pre-ischaemic values. Thus, by mechanism(s) which are not yet clear but which may include an increase in HEP via anaerobic succinate production, elevated levels of exogenous glutamate exert a highly beneficial effect on the post-ischaemic recovery of cardiac function.

The pathogenesis of stereocilia abnormalities in acoustic trauma

Stereocilia abnormalities develop in anesthetized guinea pigs within two minutes of exposure to loud sound (3 kHz, 125 dB SPL). Displacement, fracture, fusion and membrane rupture were observed well before the development (after 10 or more minutes) of fine structural changes to other cytoplasmic organelles within the hair cells. Thus stereocilia abnormalities can arise very rapidly due to the direct effects of noise on their microfilaments, cross linkages and limiting membranes. Such abnormalities are thus not necessarily secondary to changes in the body of the affected hair cells.