It has been reported that many of the effects of digitalis glycosides could be mediated partly through the central nervous system. In this study the effects of ouabain given directly into the lateral ventricle of the brain on the renal function of the rabbit were investigated. Intraventricular ouabain elicited antidiuresis in doses ranging from 0.1 to $3\;{\mu}g$, exhibiting a rough dose-response relationship, and decreased the renal plasma flow, glomerular filtration rate and urinary excretion of sodium and potassium, concomitant with the decrease of urine flow. These decreases in urine flow, excretory rate of electrolytes significantly correlated with the decrease in renal plasma flow or glomerular filtration rate, suggesting that the antidiuresis might have been induced by the hemodynamic changes. Intravenous ouabain in a dose of $1\;{\mu}g$ did not affect the renal function. Systemic blood pressure as well as cardiac activity was not affected by the intraventricular ouabain. Effects of the intraventricular ouabain on renal function were abolished by the intravenous phentolamine-pretreatment but not affected by intraventricular phentolamine-pretreatment. Neither vasopressin infusion nor hydration did affect the renal effects of intraventricular ouabain. From these observations, it is suggested that the antidiuresis of intraventricular ouabain is induced by the increased sympathetic influence to the kidney.
The action of debrisoquine on renal function in rabbits was studied. 1. When debrisoquine was given into ear vein, it did not affect on renal functin with smaller doses of 0.1 or 0.3mg/kg, while with higher dose of 1.0mg/kg it elicited the significant decrease of urine flow, renal plasma flow and glomerular filtration rate, and the increase of filtration fraction, and at the same time sodium excreted in urine, FENa (fractional excretion of sodium) and osmolar clearance were significantly decreased, and then it exhibited the increase of $K^+/Na^+$ ratio and no changes of $T^cH_2O$. 2. Debrisoquine (1.0mg/kg), when injected repeatedly into a vein, produced a more marked decrease of urine flow. 3. Debrisoquine induced-antidiuretic action was not affected by pretreatment with phentolamine (2mg/kg, i.v.), alpha-sympathetic blocking agent. 4. Debrisoquine given intracerebroventricularly did not produce a significant change on renal function in dose of 0.1mg/kg. These results suggest that debrisoquine produce the antidiuretic effect in rabbit, and the mechanism of its action is due to dual actions that are the decrease of hemodynamic effect and the facilitation of reabsorption of sodium in renal tubules.
With the improvement of hemodialysis, the course of the disease in patient with endstage renal disease has been clearly improved. Nevertheless, among several shortcomings to our present mode of renal replacement therapy, cardiovascular complications have been the leading cause of morbidity and mortality. Several factors such as anemia, arteriovenous shunting of blood, intermittent extracorporeal circulation and hypertension may be contributing. But little is known about the quantitative cardiac hemodynamic characteristics occurred during hemodialysis. The purpose of this study is to observe the sequential hemodynamic changes before, during and after the hemodialysis and to investigate reliable parameters in the detection of ventricular dysfunction. In the present study, equilibrium radionuclide cardiac angiography was performed and left and right ventricular volume indices, ejection phase indices of both ventricular, performance were measured in the 16 stable patients with chronic renal failure treated with maintenance hemodialysis sequentially i.e. before, during (early and late phase) and after the hemodialysis. The results obtained were as follows; 1) The indices of the left ventricular function were not changed during the hemodialysis but increased after the hemodialysis. 2) The indices of the right ventricular function(EF, SVI) were significantly decreased in the early phase (15, 30 minutes after starting extracorporeal circulation) but recovered after the hemodialysis. 3) The ratio of right ventricular to left ventricular ejection fraction was significantly decreased in the early phase and the lung volume indices were significantly increased at the same phase. As a conclusion, hemodialysis improves left ventricular function maybe due to increased contractility, and effects on the right ventricular function maybe due to the increased lung volume in the early phase of hemodialysis.
The pharmacological actions to methanol extract(PME) obtained from Plantaginis semen were examined in the rabbit. 1) PME, when administered into the vein of rabbit, produced the fall of blood pressure and stimulation of respiration. The former action was inhibited by atropine but the latter not affected by atropine. 2) PME caused contraction in both isolated intestinal and uterus strips, atropine blocked the contraction of intestinal strips while did not the uterus contraction. 3) PME decreased the heart rate of rabbit anesthetized with urethane. 4) PME elicited antidiuresis with doses ranging from 10mg/kg. The antidiuresis appeared to be related to the hemodynamic changes decreases in the renal plasma flow and glomerular filtration rate. Urinary sodium and potassium decrease in the renal plasma flow and glomerular filtration rate. Urinary sodium and potassium decrease in relation to the diminished filtration.
The action of serotonin (5-Hydroxytryptamine) on the excretory function of the kidney was investigated in the dog, utilizing the clearance method and the stop-flow technique. It was shown that serotonin, $10{\mu}g/kg/min$, i. v., exerts a marked antidiuretic effects and elicits a marked hemodynamic changes in the kidney: a highly significant decrease of the glomerular filtration rate and a tendency of decrement in the renal plasma flow. Little change in the systemic blood pressure was noted, and the participation of the antidiuretic hormone in the antidiuretic action was ruled out by adding vasopressin to the infusion fluid. The stop-flow analysis showed that there is no evidence of altered activity in the tubules by serotonin. It was thus concluded that serotonin elicits anti diuresis in the dog by decreasing glomerular filtration rate, which results from the constriction of Vas afferens in the glomeruli.
The patterns of renogram in patients with Korean hemorrhagic fever were evaluated with clinical course and renal hemodynamic changes in various clinical stages. The renal plasma flow was measured by hippuran blood clearance using $^{131}I$-ortho-iodohippurate and hippuran renogram was analysed by means of quantitative and qualitative methods in 26 patients of Korean hemorr hagic fever. The results obtained with this study were as follows; 1. During the oliguric phase of Korean hemorrhagic fever, the renogram showed non-functioning (flat) or obstructive pattern. The group of patients with non-functioning pattern of renogram had more severe impairement of renal function and grave prognosis than the group with obstructive pattern of renogram. 2. During the diuretic phase, the renogram showed obstructive or dysfunction or normal pattern, which was related with the recovery of renal function. Obstruction pattern of renogram was observed till the 2nd week of diuretic phase. Normal pattern of renogram began to appear by the 2nd week of diuretic phase. 3. During the convalescent phase of Korean hemorrhagic fever, 40% of patients showed dysfunnction pattern of renogram, and the recovery of abnormal renogram in Korean hemorrhagic fever was more delayed than the recovery of clinical features and laboratory findings. 4. The renogram showed normal pattern 6 months after onset of Korean hemorrhagic fever in all cases. 5. There was significant correlationship between the pattern of renogram and the decreace of renal plasma flow in the patients with Korean hemorrhagic fever. The decreace of renal plasma flow was maked in the patients with non-functioning pattern of renogram and was least in the patients with dysfunction pattern of renogram. All above results suggested that the renogram reflects the effective renal plasma flow and degree of renal impairement, and the renogram may be one of the important indexes which could give us a more precise prognosis in Korean hemorrhagic fever.
Dopamine when given icv induces antidiuresis along with transient natriuretic tendency, and it has been suggested that both subtypes of central dopamine receptors may influence renal function differentially. This study was undertaken to delineate the role of central $D_2$ receptors employing domperidone (DOM), a selective $D_2$ antagonist. DOM icv elicited antidiuresis and antinatriuresis in doses ranging from 15 to $135{\mu}g/kg$. GFR and RPF as well as sodium excretion decreased. Systemic blood pressure increased slightly. Intravenous DOM did not elicit significant changes in sodium excretion. Denervation of the kidney abolished the hemodynamic change induced by icv DOM, but sodium excretion decreased on both innervated and denervated kidneys. No diuretic tendency was uncovered by the denervation. Dopamine, $150{\mu}g/kg$ icv, produced antidiuresis along with decreases in hemodynamics. These effects were not affected by DOM-pretreatment, and no natriuretic tendency was unveiled. Bromocriptine, a $D_2$ receptor agonist, $200{\mu}g/kg$ icv, elicited marked diuresis and natriuresis, which were completely abolished by DOM-pretreatment. Apomorphine, another prototype of $D_2$ agonist, $150{\mu}g/kg$ icv, produced diuresis and natrituresis with increases in renal hemdoynamics, followed by decreases in all parameters. DOM-pretreatment did not affect the renal hemodynamic effects, wherease the increases in urine flow and sodium excretion were markedly reduced by DOM, Present study suggests that central $200{\mu}g/kg$ receptors mediate natriuretic and diuretic influence to the kidney, possibly through mediation of natriuretic humoral factor, and provide further evidence supporting the hypothesis that central $200{\mu}g/kg$ receptors mediate antidiuretic influence via nerve pathway, whereas natriuresis are brought about through mediation of central $200{\mu}g/kg$ receptors.
Ischemia-reperfusion (I/R) injury is associated with an increased risk of acute rejection, delayed graft function and long-term changes after kidney transplantation. The reperfusion models remain unsolved complications such as vascular obstruction and blood leakage. We developed an alternative model of isolated hemoperfusion in porcine kidneys. In the present study we introduced a newly developed reperfusion method. A connector was used instead of surgical suture for the vascular anastomosis on the inguinal region in which main femoral vessels are parallel and big enough to perfuse the kidney. To assess renal perfusion quality of the modified hemoreperfusion model, we analyzed both hemodynamic values and patterns of I/R injury following a renal reperfusion. Following unilateral nephrectomy, the kidneys were preserved for 0, 24 and 48 hours at $4^{\circ}C$ with histidine-tryptophan ketogluatarate (HTK) solution and reperfused for 3 hours by vascular anastomosis connected to the femoral artery and vein in inguinal region. Histolopathological examinations were assessed on kidney biopsy specimens, taken after each cold storage and reperfusion. No differences of hemodynamic values were observed between aorta and femoral artery. The average warm ischemia time before reperfusion start was $7.0{\pm}1.1$ minutes. There were no complications including vascular obstruction and blood leakage during the reperfusion. I/R injury of the perfused kidneys in this model was dependent upon the cold ischemia time. The results support that the modified perfusion model is simple and appropriate for the study of early renal I/R injury and transplant immunology.
Cardiac output, plasma volume and renal plasma flow were determined to evaluate hemodynamic changes in 29 patients with cirrhosis of the liver. The results obtained were as follows. 1. The mean plasma volume was 3793+895ml and it was significantly higher than the normal controls. The mean blood volume ($5266{\pm}1222ml$) and blood volume per kg body weight ($95.7{\pm}23.41ml$) were also increased significantly. The mean plasma volume per kg body weight ($69.1{\pm}19.1ml$) showed increased tendency and the mean difference between blood volume and plasma volume per kg body weight ($26.4{\pm}7.05ml$) was in lower limit of normal range. 2. The mean cardiac output was $7708{\pm}2652ml/min$ and it was significantly increased. The mean cardiac index ($4924{\pm}1998ml/min/M^2$), stroke volume ($96.2{\pm}34.2ml/beat$), stroke index ($62.3{\pm}27.34ml/M^2$) and fractional cardiac index ($1.54{\pm}0.577$) were also increased significantly. The mean total -peripheral resistance was $1664{\pm}753.8\;dynes\;sec\;cm^{-5}M^2$ and it was significantly lower than the normal controls. 3. The mean renal plasma flow was $537{\pm}146.8ml/min/1.73M^2$ and it was normal to decreased tendency. The mean endogenous creatinine clearance ($66.7{\pm}23.0ml/min/1.73M^2$) was significantly decreased. Filtration fraction was variable, but it was slightly lower than normal in most cases. The mean renal fraction of cardiac output ($11.4{\pm}6.27%$) was relatively decreased. 4. Although renal plasma flow was normal or decreased in general, it was definitely diminished in patients with creatinine clearance less than $60ml/min/1.73M^2$, resistant ascites, and signs of azotemia (elevated BUN and serum creatinine). 5. Diminished glomrular filtration rate with low filtration fraction and decreased renal fraction of cardiac output observed strongly supported increased renal afferent arteriolar resistance. 6. Renal circulatory impairment preceded azotemia or oroliguria in cirrhosis. 7. Clinical findigns and liver function were not correlated with hemodynamic changes, except for esophageal varices associated with high cardiac output obsedved. 8. No definite correlation of renal hemodynamics with plasma volume or cardiac output was found.
Journal of The Korean Society of Clinical Toxicology
/
v.19
no.2
/
pp.133-138
/
2021
Glufosinate-containing herbicides is a non-selective herbicide commonly used worldwide. As the use of them increased gradually since paraquat was banned in 2012, the number of suicides by their ingestion is also increasing continuously. Complications of glufosinate-containing herbicide poisoning include various central nervous system (CNS) toxicities such as convulsions, loss of consciousness, memory impairment, and respiratory depression, which may be accompanied by hemodynamic changes such as bradycardia and hypotension. However, it is very rare that arrhythmias other than bradycardia occurred and Takotsubo cardiomyopathy was combined due to cardiotoxicity. A 71-year-old female patient was transferred to our hospital after ingesting 500 mL of glufosinate-containing herbicide and receiving 5 L of gastric lavage at a local hospital. A few hours later, she presented stuporous mentality, respiratory depression, and convulsions, and was accompanied by hypotension and bradycardia. On the second day of admission, electrocardiogram (ECG) showed bradycardia and QTc prolongation with hemodynamic Instability. Accordingly, we conducted the early treatment with continuous renal replacement therapy (CRRT) and the application of temporary cardiac pacemaker. An echocardiogram demonstrated decreased ejection fraction (EF) and Takotsubo cardiomyopathy on the third day of admission. Then, she was discharged safely with conservative treatment. At the follow-up after 1 year, Takotsubo cardiomyopathy, EF and QTc prolongation were recovered on echocardiogram and ECG. Because cardiac toxicity after glufosinate-containing herbicide poisoning may cause life-threatening consequences, caution is required while treating the patient. Therefore, if electrocardiogram changes are seen in the elderly with a large amount of glufosinate herbicide ingestion, additional cardiac function test through echocardiography should be concerned, and early treatment through CRRT or artificial cardiac pacing should be considered.
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