Increased ventricular vulnerability during haemodialysis.
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Biomedical subjects
Publications and source records attributed to T Omae.
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The mechanism of polyuria associated with paroxysmal supraventricular tachycardia (SVT) was investigated in 8 patients. SVT was induced artificially and sustained for 60 minutes. Urine and blood samples were collected every 30 minutes. During the latter half of SVT, urine flow increased twofold in the control subjects before SVT. Urinary sodium excretion increased significantly (p less than 0.01) within 30 minutes after SVT. Urinary excretion of antidiuretic hormone (ADH) decreased (p less than 0.01) during the latter half of SVT and increased (p less than 0.01) after SVT, respectively. Plasma level of ADH did not change during SVT but increased (p less than 0.05) after SVT. The concentration of plasma atrial natriuretic polypeptide (ANP) increased significantly (p less than 0.05) before SVT ended. Urinary excretion of prostaglandin E2 increased significantly (p less than 0.05) after termination of SVT. The percent changes in the urinary excretion of prostaglandin E2 were correlated (r = 0.713, p less than 0.001) with those of ADH. There was also a correlation (r = 0.6, p less than 0.001) between the percent changes in the urinary excretion of prostaglandin E2 and those of sodium. Their findings suggest that the polyuria during SVT is attributed mainly to the inhibition of ADH release and that the natriuresis after SVT is due not only to the increased ANP but also to the increased renal prostaglandin E2 probably stimulated by ADH.
The effects of brain natriuretic peptide (BNP) on renin secretion were evaluated in normal and hypertonic saline-infused kidneys of anesthetized dogs. In the normal kidney (N = 5), intrarenal infusion of porcine BNP-(1-26) (pBNP) at a dose of 50 ng/kg per min attenuated the renin secretion rate significantly to 9 +/- 27% of control without exerting a significant effect on mean arterial pressure (MAP), renal blood flow (RBF) or glomerular filtration rate (GFR); urine flow (V) was significantly increased to 260 +/- 33% of control and urinary excretion of sodium (UNaV) to 480 +/- 140% of control. In the hypertonic saline infusion group (N = 6), intrarenal infusion of hypertonic saline (20% w/v) at 0.5, 0.8, and 1.0 mEq NaCl/min caused a decrease in GFR and natriuresis in a dose-dependent manner. The renin secretion rate was attenuated by hypertonic saline infusion (1 mEq NaCl/min) to 87 +/- 31% of control. In another group (N = 6), administration of pBNP at a dose of 50 ng/kg per min during hypertonic saline infusion (1 mEq NaCl/min) increased the renin secretion rate to 196 +/- 57%, increased RBF to 160 +/- 13%, increased GFR to 137 +/- 22%, increased V to 221 +/- 29%, and increased UNaV to 218 +/- 29% of the values measured during hypertonic saline infusion. Our results indicate that BNP inhibits renin secretion through sodium delivery to the macula densa and effectively inhibits the tubuloglomerular feedback response that is activated by intrarenal hypertonic saline infusion.
For evaluating hepatic tumors, ultrasonograms using carbon dioxide by arterial injection (CO2US) was performed in 37 patients, including 28 hepatocellular carcinomas, 11 hepatic metastases, and 3 hepatic hemangiomas. Hepatic tumors were enhanced by CO2US and easily identified. CO2US of hepatic tumors were classified into six patients. Generally, on CO2US hepatocellular carcinomas were well enhanced, and hepatic metastases had ring-like enhancement. Hepatic hemangiomas showed peripheral patchy enhancement. In the patients with hepatocellular carcinoma, the primary tumors were better identified on CO2US than conventional sonography. The daughter nodules with hepatocellular carcinoma were also better demonstrated than other examinations. CO2US is helpful in evaluating and differentiating hepatic tumors.
Two hundred sixty-six patients took part in a multicenter comparative study of doxazosin and prazosin. Both drugs produced a significant reduction (p less than 0.001) in blood pressure and no increase in heart rate. Blood pressure was considered "markedly decreased" or "decreased" in 70.8% of patients treated with doxazosin and 70.0% of patients treated with prazosin. No statistically significant between-group differences in antihypertensive efficacy were observed. Both doxazosin and prazosin were well tolerated; seven patients (5.6%) in each group had the therapy withdrawn.
Split intrarenal hemodynamics in stenotic and contralateral kidneys of unilateral renovascular hypertension (RVH) were estimated by Gomez's formulae. Forty patients with essential hypertension and 40 patients with RVH were studied. Split para-amino hippurate and inulin clearances were measured by ureteral catheterization as indexes for effective renal plasma flow and glomerular filtration rates, allowing the estimation of intrarenal hemodynamics such as afferent arteriolar resistance (RA), efferent arteriolar resistance (RE) and glomerular hydrostatic pressure (PG) in each kidney. Normal values of intrarenal hemodynamic parameters were obtained in 24 normotensive subjects without ureteral catheterization, assuming each kidney had the half function of both kidneys. Systemic mean arterial pressure did not differ between essential and renovascular hypertension (141 +/- 3 vs. 148 +/- 3 mm Hg). Effective renal plasma flow and glomerular filtration rates were decreased in the stenotic kidney of RVH (98 +/- 8, 24 +/- 2 ml/min/m2), while increased in the contralateral kidney (195 +/- 11, 48 +/- 2), compared with the right kidney of essential hypertension (162 +/- 8, 33 +/- 1). Although effective renal plasma flow rate was not different from normal (191 +/- 8), glomerular filtration rate was significantly higher in the contralateral kidney of RVH than in normal (38 +/- 1). RA was elevated due to the stenotic lesion in the stenotic kidney (28,500 +/- 1,900 dyns.sec.cm-5), while the elevation in the contralateral kidney (10,800 +/- 600) was less than in the right kidney of essential hypertension (14,900 +/- 1,200). RE (5,800 +/- 300) in both kidneys of RVH was higher than in the right kidney of essential hypertension (4,500 +/- 200).(ABSTRACT TRUNCATED AT 250 WORDS)
Delapril, a new angiotensin converting enzyme (ACE) inhibitor discovered in the laboratory of Takeda Chemical Industries, Ltd., is the result of drug design based on the structure-activity relationships of ACE inhibitors. Delapril is an antihypertensive agent with a relatively long duration of action and no SH moiety in its structure. Following administration, it is converted into two active metabolites. Delapril effectively lowered blood pressure in 73% of 1,008 patients with hypertension during clinical trials in Japan. Efficacy rates were 73% for essential hypertension, 85% for renal hypertension, and 80% for renovascular hypertension. Excellent hypotensive response was observed in all age groups, from young to elderly patients. Side effects during administration of delapril, based on subjective evidence, were reported in 80 out of the 1,008 cases (7.9%). The main symptoms included orthostatic dizziness (1.7%), dizziness (1.3%), and nausea (1.1%). Dry cough, which has attracted attention in recent years as a side effect of ACE inhibitors, was reported at a low incidence of 1.1%. In a double-blind, controlled study in patients with mild to moderate essential hypertension in which captopril served as a positive control, delapril showed superior hypotensive effect and greater safety. Data derived from the Japan Study Group on Delapril indicate that this ACE inhibitor has excellent hypotensive effects and a high level of safety. It is suitable as a first-line drug in both monotherapy and combined therapy.
The antihypertensive response to nicardipine was analyzed in 467 hypertensive patients who had participated in four similarly designed double-blind clinical studies in which the effectiveness of nicardipine was evaluated. This population was divided into five age groups. The difference in response rates between the youngest (less than or equal to 39 years) and oldest group (greater than or equal to 70 years) of patients was less than 5%. After 12 weeks of treatment with nicardipine, the rate of response for each decade ranged from 65% to 77%. The per cent decrease in blood pressure was not age dependent, but did correlate with the pretreatment systolic and diastolic blood pressure (P less than 0.001). No age-related trend in side effects was observed. The incidence of side effects ranged between 0% among the oldest patients to 17.3% in patients 50-59 years of age. No adverse metabolic effects were found in any age groups. These results indicate that nicardipine, a calcium entry-blocker, is effective and useful in adult hypertensive patients of all ages.
We studied the effects of ouabain and verapamil on endothelin-1(ET-1)-induced contraction of the mesenteric artery in prehypertensive spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto (WKY) rats. Rings of mesenteric artery of SHRs and WKY rats aged 4 weeks were superfused with physiological saline solution and isometric tension was measured. ET-1 (10(-9) or 10(-8) M)-induced contractions were significantly larger in WKY rats than in SHRs. ET-1 (10(-7) M)-induced contractions were not significantly different between SHRs and WKY rats. Verapamil markedly inhibited ET-1 (10(-7) M)-induced contractions both in SHRs and in WKY rats. Although the percent inhibition tended to be larger in SHRs than in WKY rats, the difference was not significant. Ouabain significantly increased ET-1 (10(-7) M)-induced contraction in the presence of verapamil both in SHRs and in WKY rats. The increase was significantly greater in SHRs than in WKY rats. As a result, ET-1 (10(-7) M)-induced contractions were significantly greater in SHRs than in WKY rats in the presence of verapamil and ouabain. These results suggest that in ET-1-induced arterial contraction, [Na+]i-mediated [Ca2+]i regulation such as the Na+/Ca2+ exchange system might be greater in SHRs than in WKY rats, and that this might be, at least in part, involved in the pathogenesis or maintenance of hypertension in SHRs.
Responses of blood pressure to intravenous (i.v.) or intracerebroventricular (i.c.v.) endothelin-1 (ET-1) in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were investigated. Conscious male SHRs and WKY rats were used for the experiments. ET-1 (300-1,000 ng/kg) was injected intravenously in the i.v. experiments, or 30 and 100 ng/kg of ET-1 were injected into the lateral ventricle in the i.c.v. experiments. The initial depressor response to i.v. ET-1 was greater in SHRs (n = 10) than in WKY rats (n = 10) at 1,000 ng/kg (-54 +/- 6 vs. -41 +/- 3 mm Hg, mean +/- SEM, p less than 0.05). The subsequent pressor response to i.v. ET-1 was smaller in SHRs than in WKY rats (3.5 +/- 0.8 vs. 7.0 +/- 0.9 mm Hg at 300 ng/kg, p less than 0.05, and 11 +/- 2 vs. 17 +/- 2 mm Hg at 1,000 ng/kg, p less than 0.05). Pressor responses to i.c.v. ET-1 were not different in SHRs (n = 8) and WKY rats (n = 8) at both doses (10 +/- 4 vs. 10 +/- 3 mm Hg at 30 ng/kg, and 46 +/- 10 vs. 49 +/- 10 mm Hg at 100 ng/kg). A greater initial depressor response and a smaller subsequent pressor response to i.v. ET-1 were observed in SHRs than in WKY rats. The attenuated pressor response to intravenously administered ET-1 may be unique since vasoconstrictor responses to other known vasoactive substances such as angiotensin, catecholamines, or vasopressin are reportedly augmented in SHRs. We did not find any difference in responsiveness to i.c.v. ET-1 between SHRs and WKY rats.
To investigate the possible role of brain endothelin-1 (ET-1) in hypertension of spontaneously hypertensive rats (SHRs), we measured immunoreactive (ir) ET-1 contents in brain regions as well as plasma ir-ET-1 levels in SHRs aged 4-5 and 12-14 weeks and age-matched Wistar-Kyoto rats (WKY) with a radioimmunoassay for ET-1. Systolic blood pressures of SHR aged 4-5 and 12-14 weeks were significantly higher than those of corresponding WKY. Significant amounts of ir-ET-1 were detectable throughout the discrete brain regions analyzed in both strains; higher ir-ET-1 contents in structures such as thalamus, hypothalamus, midbrain, pons, medulla, and cerebellum, with the lowest in cerebral cortex, were observed. A reverse-phase high-performance liquid chromatography of the brain extracts revealed the presence of both a major component identical to the elution position of synthetic ET-1 and a minor component possibly corresponding to its oxidized form. When compared, ir-ET-1 contents in all brain regions analyzed were lower in SHRs than in WKY rats. This strain-related change of ir-ET-1 contents was significant in the medulla at 4-5 weeks of age, and in all brain regions except hypothalamus at 12-14 weeks of age. Plasma ir-ET-1 levels, in contrast, were comparable between SHRs and WKY rats. These results suggest that brain ET-1 may be involved in the development and the maintenance of hypertension in SHRs.
To evaluate the significance of endogenous endothelin (ET) in the maintenance of blood pressure in hypertensive and normotensive conditions, we examined the acute and chronic effects of anti-ET-1 antibody in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. Immunoglobulin (Ig) solution purified from anti-ET-1 rabbit serum was injected intravenously in conscious rats aged 12-14 weeks (SHR: n = 7, WKY: n = 7). In the control group (SHR: n = 5, WKY: n = 4), Ig prepared from nonimmune rabbit serum was administered. One week after the first injections of Ig, second intravenous injections were given. After the intravenous injections of ET-1 antibody, there were no significant changes in directly measured blood pressure (BP) for up to 60 min in both strains. On the first, third, and seventh days after the first administration of ET-1 antibody, as well as on the first, third, and seventh days after the second injection, there were no appreciable differences in BP between SHR treated with anti-ET-1 antibody and SHR with control Ig. No significant changes in BP were observed throughout the observation period in WKY groups. Plasma levels of immunoreactive ET-1 were similar in SHR and WKY. This study suggests that circulating ET may not play a significant role in the maintenance of hypertension in SHRs or in the regulation of blood pressure in WKY rats.
OBJECTIVE: To investigate the relation between intracardiac thrombus and blood coagulability in patients with mitral stenosis. DESIGN: Prospective study. Cross sectional echocardiography and plasma concentrations of the D-dimer fragment of fibrin were used concurrently to detect intracardiac thrombus in patients with mitral stenosis. SETTING: Department of Medicine, National Cardiovascular Centre, Osaka, Japan. PATIENTS: 63 patients with mitral stenosis. None of them had been receiving any anticoagulants or antiplatelet agents. MAIN OUTCOME MEASURES: Plasma concentrations of D-dimer in patients with a mobile intracardiac thrombus, those in patients with a non-mobile intracardiac thrombus, and those in patients without an intracardiac thrombus. RESULTS: A mobile intracardiac thrombus was found in 10 patients and a non-mobile thrombus in eight. The remaining 45 patients had no intracardiac thrombi. Plasma concentrations of D-dimer in the 10 patients with a mobile thrombus were all greater than 300 ng/ml (mean 983.3, 95% confidence interval 498.9 to 1467.7 ng/ml) and they were significantly higher than those in the patients with a non-mobile thrombus (226.2, 33.6 to 418.8 ng/ml) and the patients without an intracardiac thrombus (147.2, 110.4 to 184 ng/ml). CONCLUSIONS: A high plasma concentration of D-dimer seemed to reflect a hypercoagulable intracardiac state and may be a helpful indicator of the possible presence of mobile intracardiac thrombus in patients with mitral stenosis.
Supraventricular tachycardia was induced in 10 patients by programmed cardiac stimulation through esophageal lead. Blood pressure, heart rate, renal function, and hormonal factors were measured before, during, and after tachycardia. The patients were divided into two groups, depending on whether antinatriuresis occurred during tachycardia; one group (n = 5) with antinatriuresis during tachycardia associated with a decrease in blood pressure and the other group (n = 5) with neither antinatriuresis nor changes in blood pressure. The urinary sodium excretion tended to increase after tachycardia only in the latter group. On the other hand, urine volume and free water clearance increased during or after tachycardia in both groups. Plasma levels of atrial natriuretic peptide significantly increased and the urinary vasopressin excretion significantly decreased during tachycardia in both groups. During tachycardia, natriuresis due to atrial natriuretic peptide secretion seems to be hampered by hypotension, but polyuria is preserved despite the fall in blood pressure probably related to suppression of vasopressin release.
The hematologic disorders in patients with acute cardioembolic stroke are not fully understood, and no reliable measures are available to identify patients at high risk for recurrent embolism. We analyzed coagulation and fibrinolytic functions in 22 patients with cardiogenic cerebral embolism less than or equal to 24 hours after onset and in 25 age-matched controls. The levels of antithrombin III, protein C, and alpha 2-plasmin inhibitor were significantly lower in the patients than in the controls (p less than 0.001, 0.02, and 0.05, respectively). In contrast, the plasma concentrations of thrombin-antithrombin III complex and crosslinked D-dimer were markedly higher in the patients than in the controls (p less than 0.01 and 0.001, respectively). At the time of admission, the plasma concentrations of thrombin-antithrombin III complex and crosslinked D-dimer in the eight patients at high risk for recurrent embolization (one with prodromal embolism, three with intracardiac thrombi, and four with recurrent embolization) were 2.8 and 3.5 times, respectively, higher than those in the 14 patients without recurrence or thrombus formation. The lowest concentration of crosslinked D-dimer in the eight patients at high risk for recurrent embolization was 600 ng/ml on admission. Our results suggest that patients with acute cardioembolic stroke have various degrees of consumption coagulopathy and that the plasma concentrations of thrombin-antithrombin III complex and crosslinked D-dimer can be useful indicators of those who are prone to recurrent embolization during this stage.
Using ryanodine and verapamil, we compared the relative contributions of SR Ca2+ release and gated Ca2+ entry in arterial contractions induced by norepinephrine (NE) between spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Aortic rings of 10 SHR and 10 WKY aged 10-12 weeks were superfused in small water-jacketed tissue chambers with physiological salt solution and isometric tension was measured. The inhibition of the NE (3 x 10(-8) M)-induced contraction of aortic rings by ryanodine (10 microM) was significantly greater in WKY (40.1 +/- 6.9%) than in SHR (2.2 +/- 9.0%) (p less than 0.01). The inhibition of the NE-induced contraction by verapamil (10 microM) in the presence or absence of ryanodine (10 microM) was significantly greater in SHR than in WKY. The residual ryanodine and verapamil-insensitive component of NE-induced contraction was significantly greater in WKY than in SHR. Caffeine (5 mM)-induced contraction in the presence of verapamil and phentolamine was significantly smaller in SHR than in WKY. These results suggest that gated Ca2+ entry plays a more important role in Ca2+ control and that ryanodine-sensitive Ca2+ store is smaller, or the ryanodine receptor is altered in these tissues of SHR compared with those of WKY.
Split intrarenal hemodynamics in stenotic and contralateral kidneys of unilateral renovascular hypertension (RVH) were estimated by Gomez's formulae. Ten patients with RVH were studied. Split para-amino hippurate and inulin clearances were measured by ureteral catheterization as indexes for renal plasma flow and glomerular filtration rates, allowing the estimation of intrarenal hemodynamics such as preglomerular arteriolar resistance, postglomerular arteriolar resistance and glomerular hydrostatic pressure in each kidney. Renal plasma flow and glomerular filtration rates were lower in the stenotic kidney (83 +/- 12, 19 +/- 2 ml/min/m2) than in the contralateral kidney (170 +/- 19, 43 +/- 4). Preglomerular arteriolar resistance was elevated due to the stenotic lesion in the stenotic kidney (30,900 +/- 4,500 dyns.sec.cm-5) while the elevation in the contralateral kidney (11,300 +/- 1,000) was less. Postglomerular arteriolar resistance was high in both kidneys. Glomerular pressure was lowered in the stenotic kidney (54 +/- 1 mmHg), while elevated in the contralateral kidney (71 +/- 3). Although the stenotic kidney of RVH was protected from systemic hypertension (138 +/- 6 mmHg) by stenosis of the renal artery, the increase in preglomerular arteriolar resistance in the contralateral kidney was not sufficient, making glomerular pressure elevated. Thus, glomerular hypertension and hyperfiltration were demonstrated in the contralateral kidney of RVH.
Blood pressure (BP) becomes more sodium and body fluid sensitive as renal function deteriorates. Thus, hypertension in chronic renal failure is mostly of the sodium sensitive type. We studied whether the increased sodium sensitivity (SS) can be restored to normal on the maintenance phase of hemodialysis (HD) therapy. Body weight (BW) and BP (specifically, mean arterial pressure [MAP]) were measured after HD and before the next HD, and the body fluid sensitivity (BFS) was calculated as the ratio of changes in these factors on both introduction and maintenance phases in HD patients (n = 56) who were not taking any antihypertensive drugs (BFS = delta MAP/delta BW). In a preliminary study, the amount of interdialytic sodium intake (QNa+) was measured (n = 30), and SS was calculated as the ratio of the change in MAP to QNa+ (SS = delta MAP/QNa+). Interdialytic BW gain (3.1 +/- 0.1 kg) was correlated with the amount of sodium intake (136 +/- 17 mEq), resulting in a positive relationship between BFS and SS (r = 0.79, P less than .0001). Therefore, BFS was used as an index of SS. As a whole, BFS decreased from the introduction to the maintenance phase (6.5 +/- 1.0 to 3.5 +/- 0.6 mm Hg/L, P less than .01). This decrease was marked (6.2 +/- 1.1 to 2.9 +/- 0.6 mm Hg/L, P less than .01) in patients (n = 46) whose BP was normalized in the maintenance phase, while not significant (7.9 +/- 1.9 to 6.3 +/- 1.3 mm Hg/L) in patients (n = 10) whose BP was still high.(ABSTRACT TRUNCATED AT 250 WORDS)