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PERIPHERAL VASCULAR HEMODYNAMICS IN THE BULBAR CONJUNCTIVA OF SUBJECTS WITH HYPERTENSIVE VASCULAR DISEASE Richard E. Lee, Elizabeth A. Holze J Clin Invest. 1951;30(6):539-546. https://doi.org/10.1172/JCI102470. Research Article Find the latest version: https://jci.me/102470/pdf PERIPHERAL VASCULAR HEMODYNAMICS IN THE BULBAR CONJUNCTIVA OF SUBJECTS WITH HYPERTENSIVE VASCULAR DISEASE 1" 2 3 By RICHARD E. LEE AND ELIZABETH A. HOLZE (From the Departnteiif of Medicine, The New York Hospital, and Cornell University Medical Center, New York, N. Y.; and the Federal Security Agency, U. S. Public Health Serzice, National Institutes of Health, National Heart Institute, Bethesda, Md.) (Submitted for publication October 11, 1950; accepted, March 19, 1951) Within recent years, methods have been devel- It should be emphasized that no single feature oped for direct observational studies concerned of those which were selected to be followed in ani- with functional aspects of the muscular vessels in mals could be described as "characteristic" of any the capillary bed of living small mammals of sev- of these experimental syndromes. Vasoconstric- eral species (1-3). With these technics, it has tion, or elevated epinephrine responses, or slug- been found that certain objective criteria of periph- gishness of blood flow, etc., were often found in eiral vascular reactivity can be selected and fol- various and differing situations. The specificity lowed during repeated examinations of the termi- of the hemodynamic state became apparent only nal vessels with the microscope.- Comparisons of when all of the functional criteria used were con- the several different overall hemodynamic disturb- sidered together. ances in the experimental animal (i.e., hyperten- The observational methods and technics of sion, acute hemorrhage, prolonged hypotension) eliciting peripheral vascular responses to stimuli with their co-existent phenomena in the peripheral during examinations of the vessels with the micro- vascular system have shown that each separate scope have been adapted, with modifications, to condition thus far investigated has had a distinc- the study of metarterioles, capillaries and collect- tive status reflected in the capillary bed of the ing venules in the conjunctiva of man. The de- mesentery. For example, acute hemorrhage was scription of the microscope and apparatus, which accompanied by widespread arteriolar and metar- are comparable to those used by others (7), to- teriolar constriction, capillary ischemia, and poor gether with the procedures and observations on venular return. The reactivity of metarterioles young adults without known disease, have been and precapillary sphincters to topically applied previously published (8). Since then the survey epinephrine was augmented. Terminal prolonged has been extended to include patients with hyper- hemorrhagic or traumatic hypotension, on the tensive vascular disease. It is the purpose of this other hand, had a dilated capillary bed, with slug- report to describe certain peripheral vascular gish arteriolar and venular blood flow, plethoric hemodynamic responses in these patients and to capillaries and diminished epinephrine responses compare them with findings in normotensive (2, 4, 5). The mesenteric vascular bed in experi- subjects. mental renal hypertension was predominantly con- METHODS stricted, with ischemic arterioles and capillaries and a similar elevation of epinephrine response. In The technics employed in this study were those used and described in the previous report (8). In brief, the addition, it had a marked "hyperplasia" of vascu- bulbar conjunctiva in each eye was examined with a slit- lar elements (6). lamp microscope in a manner similar to that used in routine ophthalmological practice. After establishing that 1This work was supported in part by the Nutrition conjunctival disease per se was absent, the general state Foundation, New York, N. Y. of the capillary bed was noted (i.e., ischemic, plethoric, 2Apparatus used for the study of the conjunctiva was euvascular, etc.). In certain cases, the velocity of blood obtained through a grant in aid from the American Philo- flow was measured in the metarterioles, capillaries and sophical Society, Philadelphia, Pa. collecting venules with the method previously described 3 The authors gratefully acknowledge the stimulating (8). This procedure consisted of repeated determina- interest and encouragement of Dr. Ephraim Shorr and tions with an ocular micrometer in the microscope, and Dr. Benjamin William Zweifach. a fast stopwatch, of the durations of the passage of red 539 540 RICHARD E. LEE AND ELIZABETH A. HOLZE blood cells over a measured length of vessel. At the mag- nifications used (47 X), single red blood cells, and cell ag- gregations can readily be seen and followed. In meas- urement of flow speed, vessels were selected (arterioles, capillaries and venules) that were as straight as could be found, over a distance of at least 75-100 microns. After a minimum of practice, the method has been found to fur- nish comparable data with different observers. In a total of 30 subjects, the incidence of spontaneous vasomotor activity 4 in the precapillary sphincters was estimated. Metarteriolar and precapillary sensitivity to directly applied epinephrine in known concentration was then measured. It proved important to begin with the most diluted solution (1: 800,00-1: 400,000 epinephrine) and use progressively stronger concentrations (at in- FIG. 1. THE CONJUNCTIVAL CAPILLARY BED OF A NOR- tervals of three minutes) until the threshold precapillary MOTENSIVE SUBJECT WITHOUT DISEASE constrictions were obtained. This avoided sen- possible A = terminal arteriole, from which the true capillaries sitization of the vascular smooth muscle cells by re- (C) arise. These latter vessels are of uniform caliber peated exposure to epinephrine solutions of greater than and in general follow a smooth, sinuous pathway over the threshold strength. A vasoconstrictor response to cold conjunctiva. Two capillaries in the right half of the can be measured by applying an ice pack to the closed lid picture, however, are slightly tortuous or coiled. The for progressively greater intervals until precapillary con- collecting venules (V) drain the capillaries, then form striction is seen. This type of response may also be tested larger venules which are frequently situated approximate by routine use of a short of exposure period to ice (10 to the arteriole, as shown. The small seconds) which is without subsequent vascular change in venules in the left portion of the picture display the venular loopings which a large series of controls, yet which is followed by vaso- in are not uncommon in normotensive individuals (120 X). constriction certain disease states (cirrhosis, multiple (This is another photograph of the same field shown in myeloma). The latter method was employed in this Figure 1 of the previous study. publication.) To date, examinations of the bulbar conjunctiva in hy- pertensive individuals have been made on 14 men and 31 received a wide variety of clinic and laboratory studies. women. The mean age was 31 years, with age distribution Those of each subject were appropriate only to his specific from three to 78 years.5 During repeated studies over illness. The vascular findings in this group are there- periods of from two to three months, the blood pressures fore representative of a random sampling in a diseased were consistenly greater than 140/100 in all subjects. Only population and are included only for the purpose of com- those cases were selected who had no history of renal or paring their variability with the relatively consistent hepatic disease or cardiac incompetency. P.S.P. tests, phenomena displayed by the blood vessels of the patients urine concentrating and diluting capacities and blood urea with "essential hypertension." The results of the survey nitrogen concentrations in all cases demonstrated no on 72 normotensive subjects without evidence of dis- renal insufficiency. Intravenous pyelograms were carried ease are also included in the data. out on 20 subjects and retrograde pyelograms were made on three others. These X-rays revealed no evidence of RESULTS renal abnormality. In addition, similar conjunctival observations were The capillary bed and its reactions in the con- made on 33 patients with various normotensive systemic junctiva of normotensive subjects has been pre- diseases, such as multiple myeloma, cirrhosis, peptic ulcer, viously described (8). Its topographical arrange- polycythemia; and with psychosomatic disorders. None ment in shown in Figures 1 and 2. The terminal of them had a history of hypertension. These cases had arterioles, usually accompanying larger collecting 4 Vasomotion is an apparently spontaneous variation in venules, frequently extend radially from the orbital caliber resulting from contraction and relaxation of the margins. Capillaries arise from these vessels to vascular smooth muscle. It is usually irregular in rate, in form the blood capillary network of the conjunc- degree and in duration of dilated and constricted phases. These vessels become confluent to form 5 The Department of Pediatrics at Cornell University tiva. the Medical College and The New York Hospital has been most peripheral system of collecting venules, which very interested and cooperative in this study. The au- in turn empty into the larger venules accompany- thors are very grateful to the department, and to Dr. Sarah ing the nutrient arterioles

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