Eye (1991) 5, 438-439

Response of Vessels to Ischaemia

G. A. GRESHAM

Cambridge

Ischaemia literally means the reduction or In addition a variety of metabolic products arrest of the blood supply to a tissue. The accumulate which are numerous and have result is a state of hypoxia in the territory sup­ diverse effects on the vascular wall. Hypoxia plied by the compromised blood vessel. The may result from causes other than vascular effects of hypoxia on blood vessels in the pul­ obstruction and in general the effects upon monary circulation have received consider­ the organ are similar to those produced by able attention in the past but the effects on ischaemia. Pulmonary disease, circulatory blood vessels in other parts of the body have shunts, anaemia and histotoxic agents can all not been so intensively studied.! Arteries, lead to hypoxia. veins and capillaries do not respond in the In some animals and particularly in man same way to hypoxia and arteries in some arteries are naturally hypoxic. This is largely organs, such as the lung, respond differently determined by the thickness of the vessel wall to arteries in other organs such as the heart. In and the number of lamellar units composed of the eye, arteries and veins respond differ­ elastin and smooth muscle that are present. In ently. In the hypoxic retina produced by sim­ thick walled vessels the hypoxic effects ulated high altitude conditions small arteries depends upon the adequacy of blood supply dilate, larger ones constrict and veins are to the vessel by the vasa vasorum. In the dog unaffected. Furthermore, the vascular vasa permeate the vessel wall as they do in response in the retina varies from one subject veins in many species. In man vasa supply a to another. 2 limited territory of the outer third of the To some extent the effects of ischaemia on artery. Spontaneously occurring atherosclero­ blood vessels depends upon their structure. sis in the dog is not described and extreme die­ The central retinal artery has features similar tary and other measures are needed to to those of arteries in skeletal muscle. After produce it experimentally. the first division of the retinal artery the inter­ The inner part of the media of human arter­ nal elastic lamina is lost. This affects the per­ ies is a vulnerable structure. It survives on dif­ meability of the vessel wall to substances such fusion from the capillary bed of the vasa and as lipid.3 The capillaries of the choroid have upon diffusion of nutrients from the lumen of highly fenestrated endothelial cells again the artery. It is a precarious existence and any affecting vascular permeability.4 limitation of diffusion of nutrients as for Ischaemia can be caused either by organic example by intimal thickening leads to disease of blood vessels such as atherosclero­ smooth muscle damage of the inner media. sis or thrombosis or by functional changes This is followed by a repair process which con­ such as vascular spasm or impaired blood flow sists of smooth muscle cell proliferation. This, due to changes in blood pressure or blood vis­ in turn, further thickens the arterial wall and cosity. The obvious effect of ischaemia is to aggravates the hypoxic state. Medial smootb produce defective oxygenation of the tissue. muscle cells that have proliferated migrate to

Correspondence to: G. A. Gresham, TD, MD, SeD, FRCPath, Professor of Morbid Anatomy and Histopathology, Department of Morbid Anatomy and Histopathology, John Bonnett Clinical Laboratories Addenbrooke's Hospital, Cambridge CB22QQ . RESPONSE OF VESSELS TO ISCHAEMIA 439 the intima and an atherosclerotic plaque is The effects of drugs and vasoactive agents on formed. the process are being studied. Using subcuta­ Intimal changes leading to atherosclerosis neous implants of plastic sponges in the rate of are the result of endothelial injury. The injury growth of new vessels in the sponges is being is hypoxic. Many agents damage endothelium investigated. Vascular development is but haemodynamic changes figure largely in measured by the rate of radioactive xenon the process. Increased intraluminal pressure clearance instilled into the centre of the leads to increased oxygen demand by the sponge and by morphometry using Ulex vessel wall. Rapid changes of pressure, either europeaus labelling of endothelial cells in his­ increase or decrease, reduce flow in the vasa tological sections. This is a useful model for vasorum producing hypoxic conditions. the study of promoters and inhibitors of vas­ Rapid flow can produce axial streamlining cular proliferation. Y effects of red blood cells with flow stagnation. Ischaemic damage is a common pathologi­ The localisation of atherosclerotic lesions is cal process which plays a part in many diseases best explained by haemodynamic forces.6 of degenerative, inflammatory and neoplastic Other factors contribute to the process, origins. The facts that come into play when diabetes: cigarette smoking and hyperlipid­ ischaemia develops are numerous and as yet aemia are examples. High low density lipo­ only partly elucidated. Changes in the walls of proteins (LDL) lead to transcellular and blood vessels made ischaemic are still pinocytotic uptake by endothelial cells. Oxi­ controversial. disation of imbibed LDL gives rise to histo­ toxic substances which aggravate the Bibliography atherosclerotic process. 1 Duke HN: Observations on the Effects of Hypoxia on the Pulmonary Vascular Bcd. 1 Physiol1957; Hypoxia leads to endothelial damage in a 135: 45-9, variety of ways. Enzyme activity is inhibited 2 Brinchmann-Hanscn 0 and Myhre K. February. Vas­ with a consequent fall in ATP reserves. This cular Response of Retinal Arteries and Veins to leads to impairment of sodium pump activity Acute Hypoxia at 8,000, 10,000, 12,500 and 15,000 Feet of Simulated Altitude. Aviation, and consequent swelling of endothelial cells. Space and Environmental Medicine 1990; More remote effects of hypoxia are on the 112-116. renin-angiotensin mechanism leading to J Noma A, Takahashi T and Wada T. Elastin Lipid hypertension which, as we have seen, has del­ Interaction in the Arterial Wall. Atherosclerosis eterious effects on endothelial cells. 1981; 38: 373-6. "Pedro R and Marano C. Chorioretinal Ischaemia. Even after the insult leading to hypoxia is Medicographia, 1988; 10: 10-13. reversed problems remain. Reperfusion of ) Gresham GA. Early Events in Atherogenesis. Lan­ previously obstructed vessels leads to the pro­ cet 1975; i: 614-17 duction of free radical products which are "Boxen I. Endothelial Hypoxia Induction of Athe­ cytotoxic. Another problem arises from the rosclerosis: An Explanation of Patency Rates for Internal Mammary Artery and Other Coronary stimulation of previously damaged endothe­ Artery Bypass Grafts. Medical Hyotheses 1989; lial cells leading to new vessel formation. 30: 157-65 Experimentally induced arterial constriction 7 Pasyk S, Schaper W, Schaper J, Pasyk K, Miskiewicz in the dog leads to endothelial damage fol­ G, Stcinscifer B. D.N.A. Synthesis in Coronary Collaterals After Coronary Artery Occlusion in lowed by endothelial cell regeneration as the Conscious Dog. Am 1 Physiol 1982; 242: shown by labelling with tritiated thymidine.7 1031-7 Mitoses occur subsequently in smooth muscle S Schapcr W, Hari S, Sharma MD, Qu inkler W, Mark­ cells and adventitial fibroblasts. A variety of ert T, Wunsch M, Schaper J. Molecular Biological Conccpts of Coronary Anastomoses. lACC 1990; growth factors derived from platelets, macro­ 15: 513-18 phages and fibroblasts produces this effect. � Y Andrade SP, Fan TPD, Lewis GP. Qu antatitative in Neovascularisation after hypoxia is an vivo Studies on Angiogenesis in a Rat Sponge important problem particularly in the eye. Model. Br 1 Exp Patho11987; 68: 755-8