Renal hemodynamics in epidemic hemorrhagic fever

의학과/박사[한글] Renal Hemodynamics in Epidemic Hemorrhagic Fever Joung Ho Park Department of Medical Science The Graduate School, Yonsei University (Directed by Drs. P.H Lee and H.J. Choi) Epidemic hemorrhagic fever(E.H.F.) is an acute infectious disease of unknown etiology which is characterized by widespread abnormalities of blood vessels, chiefly arterioles, venules and capillaries. The vascular abnormalities lead to impairment of function in a number of organs(Cugell, 1954; Froeb and McDowell, 1954; Earle, 1954 ; Mayer, 1952). The renal lesions are an outstanding feature in E.H.F. resulting in various symptoms that simulate the clinical picture of acute renal failure. Early in the disease renal involvement makes its appearance with microscopic or gross hematuria (Barbero et al., 1953; Earle, 1954). Along with the development of hypotension or shock, a progressive fall in urine volume, even anuria, occurs and continues for two to several days with marked elevation of blood non-protein nitrogen and creatinine, electrolyte abnormalities, acidosis and finally uremia(Barbero et al., 1953; Chiu et al., 1959; Earle, 1954, Hunter et al, 1954 ; Leedham, 1953). Through systematic studies on renal functions in E. H. F. 1 month after the onset, it was found that glomerular filtration rate and renal plasma flow (Proeb and McDowell, 1954; Park et al., 1968, 1969), tubular reabsorptive and secretory capacity and renal concentrating ability (Park et al., 1968, 1965) were decreased to one-half or less of normal. Although the direct causes and underlying mechanisms in the reduction of renal function has not been clearly elucidated at present, they are, in general, related to the tubular destruction. On the basis of the finding that the degree of reduction in tubular function is in a parallel relationship with the degree of renal hemodynamic changes, Park et al(1969), suggested a possibility that renal hemodynamic changes, rather than tubular destruction itself, might play an important role: in the impairment of renal functions. Recently several lines of evidence have suggested that intrarenal hemodynamic chanties play a determining role in the control of renal tubular functions(Birtch et al., 1967; Deetjen and Boylan, 1968; Deetjen and Sonnenberg, 1965; Earley, 1966; Epstein et at., 1971 : Hollenberg et al., 1977; Pomeranf et al.,1968 : Thurau, 1964 b, 1969), as well as the evidence that adrenergic mechanisms are involved in the control of intrarenal blood flow distribution(Aukland, 1968; Pomeranz et al., 1968). However, there is no available information in the literature on the recovery process of impaired renal functions in E. H. F. Hence, the present investigation was undertaken as an attempt to study: a) the degree of reduction and recovery process of renal hemodynamic changes. b) intrarenal blood flow and its distribution and c) the role played by sympathetic nerves on the decrease and distribution of intrarenal blood flow through rental vasoconstriction in E. H. F. Studies were carried out on 30 patients with typical epidemic hemorrhagic fever who were admitted to the Epidemic Hemorrhagic Fever Research Center, ROK Army, from 1969 through 1970. In the first series of experiments glomerular filtration rate and renal plasma flow were estimated in 10 patients 1 and 6 months after the onset of illness by measuring clearances of inulin and p-aminohippuric acid. Both clearance rates were determined by 3∼4 periods of 10 min. each by the constant infusion method outlined by Smith(1945). In the second series of experiments with 20 patients intrarenal blood flow and its distribution was measured by the radioactive xenon wash-out technique as described by Thorburn et al. (1963) and by Ladefoged(1966). In brief, after renal artery catheterization via left brachial artery under the image intensifier, about 0.5mc Xe**l33 in 10㎖ saline was injected as a bolus and its disappearance from the kidney was followed on a scintilltion detector coupled to a ratemeter and linear recorder. The resulting disappearance curves were graphically analyzed by the method of Van Liew (1967). A third series of experiments with the same 20 patients of the second series was carried out after completion of the barre line. Intrarenal blood flow and its distribution was remeasured after intrarenal injection of Isuprel(2㎍/min for 10-20 min) in 5 patients, Dibenamine(20-3Omg) in 4 patients, Inderal(1.5mg) in 4 patients, Thorazine (25mg) in 2 patients, furosemide (10-2Omg) in 2 patients and after sublingual administration of Nitro히ycerin(0.3mg) in 3 patients. The result may be summarized as follows: (1) One month after the onset of the illness, glomerular filtration rate ranged from 25 to 75㎖/min with an average of 48.2±4.9㎖/min, while renal plasma flow ranged from 100 to 391㎖/min averaged to 294.1±25.6 ㎖/min. Both glomerular filtration rate and renal plasma flow, on the average, decreased to 50% or less of normal. (2) Sin months later, glomerular filtration rate and renal plasma flow averaged to 88.6±8.6㎖/min and 443.5±38.4㎖/min, respectively. Thus, good recovery of renal hemodynamics was obtained but still remained below the lower limit of the normal. (3) On the contrary, the values of filtration fraction ware 0.17±0.01 and 0.20±0.71 for one and six mouths after the onset, respectively, and were within normal limit. (4) One month after the onset intrarenal blood flow and its distribution was 186.60±15.32m11100gm1min representing 74.78±3.20% for compartment Ⅰ and 38.93±8.71㎖/100gm/min representing 20.66±2.26% for compartment Ⅱ. These values indicate that intrarenal blood flow for both compartment Ⅰ and Ⅱ was decreased to 50% of the normal without changed in its distribution. (5) a. The values of intrarenal blood flow and its distribution for compartment Ⅰ was 116.0±24.6㎖/100gm/min representing 87.2±2.1% after administration of Dibenamin;, respectively. In compartment Ⅱ there was no changes in the intrarenal blood flow and its distribution. b. After, administration of Isuprel intrarenal blood flow for compartment Ⅱ was increased by 20% from 182±37.8 to 215±16.5㎖/100gm/min, which is not statisticaly significant, along with no changes in its distribution while compartment Ⅱ was significantly decreased from 32.1±7.4 to 20.8±8.0㎖/100gm/min with corresponding decrease in its distribution. c. After administration of propranolol intrarenal blood flow for compartment Ⅰ was significantly increased from 141 ±10.7 to 203±22.4㎖/100gm/min without changes in its distribution. There was no chanties in intrarenal blood flow and. its distribution for compartment Ⅱ. d. There was no consistent effects of Thorazine, furosemide and Nitroglycerin. On the basis of the above results it is expected that the decrease in the renal hemodynamics in the early phase of E.H.F. would be severe and that it takes at least 6 months or more to recover. The intrarenal blood flow was also decreased without changes in its distribution, a pattern similar to that induced by renal artery stenosis. The pathological changes observed in the blood. vessels in E.H.F. suggest that the renal hemodynamic changes in E.H.F might be caused by a narrowing of the renal vasculature. In addition, gympathetic nerves in the renal vasculature would have some role in the reduction of renal blood flow as evidenced by the increase in renal blood flow by both Dibenamine and Isuprel, although the statistical significance of the effects of adrenergic agonist and antagonist may be somewhat doubtful because of the limited number of observed patients. [영문] Epidemic hemorrhagic fever(E.H.F.) is an acute infectious disease of unknown etiology which is characterized by widespread abnormalities of blood vessels, chiefly arterioles, venules and capillaries. The vascular abnormalities lead to impairment of function in a number of organs(Cugell, 1954; Froeb and McDowell, 1954; Earle, 1954 ; Mayer, 1952). The renal lesions are an outstanding feature in E.H.F. resulting in various symptoms that simulate the clinical picture of acute renal failure. Early in the disease renal involvement makes its appearance with microscopic or gross hematuria (Barbero et al., 1953; Earle, 1954). Along with the development of hypotension or shock, a progressive fall in urine volume, even anuria, occurs and continues for two to several days with marked elevation of blood non-protein nitrogen and creatinine, electrolyte abnormalities, acidosis and finally uremia(Barbero et al., 1953; Chiu et al., 1959; Earle, 1954, Hunter et al, 1954 ; Leedham, 1953). Through systematic studies on renal functions in E. H. F. 1 month after the onset, it was found that glomerular filtration rate and renal plasma flow (Proeb and McDowell, 1954; Park et al., 1968, 1969), tubular reabsorptive and secretory capacity and renal concentrating ability (Park et al., 1968, 1965) were decreased to one-half or less of normal. Although the direct causes and underlying mechanisms in the reduction of renal function has not been clearly elucidated at present, they are, in general, related to the tubular destruction. On the basis of the finding that the degree of reduction in tubular function is in a parallel relationship with the degree of renal hemodynamic changes, Park et al(1969), suggested a possibility that renal hemodynamic changes, rather than tubular destruction itself, might play an important role: in the impairment of renal functions. Recently several lines of evidence have suggested that intrarenal hemodynamic chanties play a determining role in the control of renal tubular functions(Birtch et al., 1967; Deetjen and Boylan, 1968; Deetjen and Sonnenberg, 1965; Earley, 1966; Epstein et at., 1971 : Hollenberg et al., 1977; Pomeranf et al.,1968 : Thurau, 1964 b, 1969), as well as the evidence that adrenergic mechanisms are involved in the control of intrarenal blood flow distribution(Aukland, 1968; Pomeranz et al., 1968). However, there is no available information in the literature on the recovery process of impaired renal functions in E. H. F. Hence, the present investigation was undertaken as an attempt to study: a) the degree of reduction and recovery process of renal hemodynamic changes. b) intrarenal blood flow and its distribution and c) the role played by sympathetic nerves on the decrease and distribution of intrarenal blood flow through rental vasoconstriction in E. H. F. Studies were carried out on 30 patients with typical epidemic hemorrhagic fever who were admitted to the Epidemic Hemorrhagic Fever Research Center, ROK Army, from 1969 through 1970. In the first series of experiments glomerular filtration rate and renal plasma flow were estimated in 10 patients 1 and 6 months after the onset of illness by measuring clearances of inulin and p-aminohippuric acid. Both clearance rates were determined by 3∼4 periods of 10 min. each by the constant infusion method outlined by Smith(1945). In the second series of experiments with 20 patients intrarenal blood flow and its distribution was measured by the radioactive xenon wash-out technique as described by Thorburn et al. (1963) and by Ladefoged(1966). In brief, after renal artery catheterization via left brachial artery under the image intensifier, about 0.5mc Xe**l33 in 10㎖ saline was injected as a bolus and its disappearance from the kidney was followed on a scintilltion detector coupled to a ratemeter and linear recorder. The resulting disappearance curves were graphically analyzed by the method of Van Liew (1967). A third series of experiments with the same 20 patients of the second series was carried out after completion of the barre line. Intrarenal blood flow and its distribution was remeasured after intrarenal injection of Isuprel(2㎍/min for 10-20 min) in 5 patients, Dibenamine(20-3Omg) in 4 patients, Inderal(1.5mg) in 4 patients, Thorazine (25mg) in 2 patients, furosemide (10-2Omg) in 2 patients and after sublingual administration of Nitro히ycerin(0.3mg) in 3 patients. The result may be summarized as follows: (1) One month after the onset of the illness, glomerular filtration rate ranged from 25 to 75㎖/min with an average of 48.2±4.9㎖/min, while renal plasma flow ranged from 100 to 391㎖/min averaged to 294.1±25.6 ㎖/min. Both glomerular filtration rate and renal plasma flow, on the average, decreased to 50% or less of normal. (2) Sin months later, glomerular filtration rate and renal plasma flow averaged to 88.6±8.6㎖/min and 443.5±38.4㎖/min, respectively. Thus, good recovery of renal hemodynamics was obtained but still remained below the lower limit of the normal. (3) On the contrary, the values of filtration fraction ware 0.17±0.01 and 0.20±0.71 for one and six mouths after the onset, respectively, and were within normal limit. (4) One month after the onset intrarenal blood flow and its distribution was 186.60±15.32m11100gm1min representing 74.78±3.20% for compartment Ⅰ and 38.93±8.71㎖/100gm/min representing 20.66±2.26% for compartment Ⅱ. These values indicate that intrarenal blood flow for both compartment Ⅰ and Ⅱ was decreased to 50% of the normal without changed in its distribution. (5) a. The values of intrarenal blood flow and its distribution for compartment Ⅰ was 116.0±24.6㎖/100gm/min representing 87.2±2.1% after administration of Dibenamin;, respectively. In compartment Ⅱ there was no changes in the intrarenal blood flow and its distribution. b. After, administration of Isuprel intrarenal blood flow for compartment Ⅱ was increased by 20% from 182±37.8 to 215±16.5㎖/100gm/min, which is not statisticaly significant, along with no changes in its distribution while compartment Ⅱ was significantly decreased from 32.1±7.4 to 20.8±8.0㎖/100gm/min with corresponding decrease in its distribution. c. After administration of propranolol intrarenal blood flow for compartment Ⅰ was significantly increased from 141 ±10.7 to 203±22.4㎖/100gm/min without changes in its distribution. There was no chanties in intrarenal blood flow and. its distribution for compartment Ⅱ. d. There was no consistent effects of Thorazine, furosemide and Nitroglycerin. On the basis of the above results it is expected that the decrease in the renal hemodynamics in the early phase of E.H.F. would be severe and that it takes at least 6 months or more to recover. The intrarenal blood flow was also decreased without changes in its distribution, a pattern similar to that induced by renal artery stenosis. The pathological changes observed in the blood. vessels in E.H.F. suggest that the renal hemodynamic changes in E.H.F might be caused by a narrowing of the renal vasculature. In addition, gympathetic nerves in the renal vasculature would have some role in the reduction of renal blood flow as evidenced by the increase in renal blood flow by both Dibenamine and Isuprel, although the statistical significance of the effects of adrenergic agonist and antagonist may be somewhat doubtful because of the limited number of observed patients.restrictio