[Abnormal intracellular calcium handling as a cause of diastolic dysfunction in the failing myocardium].
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Biomedical subjects
Publications and source records attributed to Y Kihara.
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A case of renal cell carcinoma with erythrocytosis is presented. A 51-year-old man was referred to us for evaluation of left renal mass. Laboratory data revealed marked erythrocytosis and elevated serum erythropoietin level. These data were normalized after removal of the left kidney. Pathological diagnosis was adenocarcinoma of clear cell type.
In the construction of a Kock continent ileal reservoir for urinary diversion, significantly high rates of late postoperative complications regarding nipple valves, the efferent limb in particular, have been reported. There are only a few reports on afferent nipple valve malfunction. A total of 42 patients who underwent a Kock pouch operation and were observed for more than 12 months (mean 38 months) was evaluated in terms of afferent nipple valve malfunction. Late afferent nipple valve complications were observed in 10 of the 42 patients (24%). These complications included erosion of the polyester fiber fabric used as a collar (5 patients), stenosis of the afferent limb (2) and obstruction of the afferent nipple by a mucous plug or fungus ball (3). The latter 2 complications were due to mechanical or dynamic obstruction of urine flow caused by a nonabsorbable collar. None of the 10 patients had problems with efferent nipple valve function. Our results suggest that the peristaltic direction of the intestine and the use of nonabsorbable material as a collar are primarily responsible for the late afferent nipple valve complications. Further modifications are needed to produce a stable nipple valve. Otherwise, simpler and more reliable alternative techniques of antireflux anastomosis should be considered.
We tested the hypothesis that mechanical alternans of the heart is due to alternations in intracellular calcium (Cai2+) levels. Eight papillary muscles were isolated from the right ventricles of male ferrets and were chemically loaded with aequorin to record cytoplasmic Cai2+. To produce a steady-state mechanical alternans, the preparations were perfused with a physiological salt solution containing a low calcium concentration (0.25 mM), at 22 degrees C, and stimulated at 0.5-1.0 Hz in the presence of carbachol and propranolol. The aequorin signal (Cai2+) and isometric contraction were simultaneously recorded. In each muscle, the strong beats (beats with higher peak tension) were associated with larger Ca2+ transients than the weak beats. The relationships between peak Cai2+ and peak tension, both during strong and weak beats, were similarly modified by short-term frequency responses. On the other hand, the time courses of the isometric contractions and Ca2+ transients during strong beats and weak beats were superimposable. These data indicate that mechanical alternans is caused by an alternate change of Cai2+ available for activation of the myofilaments. Prolongation of the time for recycling Ca2+ by the sarcoplasmic reticulum, i.e., a depressed uptake function of the Ca2+ pump with concomitant slow transportation of Ca2+ from the uptake compartment to the release compartment in the sarcoplasmic reticulum, is suggested as a cause of the abnormal Cai2+ handling during mechanical alternans.
The incidence of the 7 tumor markers carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), squamous cell carcinoma-related antigen (SCC), neuron-specific enolase (NSE), CA 125, CA 19-9 and CA 15-3 was studied before and after hemodialysis (HD) in 144 uremic patients who had no malignancies. Before HD, of all tumor markers, the mean concentration of SCC only exceeded the normal value. The positive rate was highest in SCC (95.1%), and that of CEA and NSE was 25.7 and 10.6%, respectively. However, AFP was within the normal range in all cases. Among CA antigens, the positive rate of CA 125 was 7.6%, of CA 19-9 was 6.3% and of CA 15-3 was 3.5%. After HD, the incidence as well as the mean concentration of all tumor markers increased. A parallel increment of total protein was observed after HD. The membrane filter used in HD appears to be insufficient to remove tumor marker proteins during HD. It is necessary to consider the clinical interpretation of elevated tumor markers in patients with uremia.
To elucidate the role of changes in [Ca2+]i in the induction of ventricular fibrillation (VF), Ca2+i signals, epicardial electrical potentials, and isovolumic left ventricular pressure were simultaneously recorded in isolated intact ferret hearts loaded with aequorin, a bioluminescent protein. When the preparations were perfused with 3 microM acetylstrophanthidin and 8 mM Ca2+, or with a low Na+ solution (18 mM Na+, 100 mM Li+), spontaneous transitions to the VF state were consistently observed within a short period of time. The initiation of spontaneous VF was preceded by development of a Ca2+i overload state, coincidental with the ascending phase of diastolic Ca2+i oscillations, and was followed by further elevation in Ca2+i levels, which were associated with augmented Ca2+i oscillations of a saw-toothed pattern. Pretreatment with 10 microM ryanodine, which blocked Ca2+i oscillations in the preparation, did not eliminate inducibility of VF by means of AC electrical stimulations; however, VF no longer occurred spontaneously, and the threshold for VF induction increased markedly. In the absence of a state of Ca2+i overload, spontaneous defibrillation occurred within a minute after the initiation of VF. We conclude that 1) VF can be induced in the absence of Ca2+i oscillations; however, 2) Ca2+i oscillations play a crucial role as a trigger for VF and therefore are an important determinant of the vulnerability to VF; and 3) the augmented Ca2+i oscillations after the transition to VF state may support the maintenance of this type of arrhythmia.
The purpose of this study was to test the hypothesis that systolic and diastolic dysfunction in left ventricular pressure-overload hypertrophy is caused by abnormal intracellular calcium handling. Experiments were performed with intact, buffer-perfused, isovolumic ferret hearts (n = 9 hypertrophied, n = 9 control) that were loaded with the bioluminescent indicator aequorin to monitor changes in cytoplasmic calcium. In each experiment, left ventricular pressure and intracellular calcium transients were simultaneously recorded. Compared with their age-matched controls, significant hypertrophy of the left ventricle developed 4 weeks after postvalvular aortic banding; at the time the animals were killed, the left ventricular weight/body weight ratio was increased in the banded animals (5.3 x 10(-3) versus 3.6 x 10(-3), p less than 0.001). As indicated by the diastolic pressure-volume relation, left ventricular distensibility was significantly diminished in the hypertrophied hearts. In comparison to the controls, the hypertrophied hearts demonstrated a prolonged duration of isovolumic contraction (time to 90% decline from peak: 278 +/- 5.4 versus 247 +/- 10.2 msec, p less than 0.05), but a marked decrease in peak systolic midwall stress (22.4 +/- 5.0 versus 38.6 +/- 5.7 g/cm2, p less than 0.05). The increased duration of isovolumic contraction correlated with a similar prolongation of the calcium transient (time to 90% decline from peak: 245 +/- 19.5 versus 127 +/- 13.2 msec, p less than 0.05), indicating that the rate of sequestration and perhaps release of calcium by the sarcoplasmic reticulum is decreased in hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
Computed tomographic (CT)-guided biopsies of the lesions in paraaortic region were performed for three urologic disease conditions: retroperitoneal fibrosis, lymph node metastases of transitional cell carcinoma of renal pelvis and lymph node metastasis of renal cell carcinoma. The biopsies were performed without complications using the Bard Biopty biopsy gun with a Bard Biopty-Cut needle. Every biopsy specimen we obtained by the Biopty rendered an excellent biopsy core from which a definite histopathological diagnosis was made. CT-guided biopsy is considered to be safe and useful for diagnosis of the disease of the paraaortic region, even when ultrasonography guided biopsy is difficult. The use of the Biopty for CT-guided biopsy provides a high quality specimen for histopathological diagnosis.
The AMS Hydroflex penile prosthesis was implanted in 34 organic impotence patients between June 20, 1986 and Aug. 6, 1990. Patients ages ranged between 26 and 71 with an average of 50.5. The causes of impotences were; 17 cases of post-radical pelvic surgery, 7 cases of injury, 6 cases of diabetes and 4 of others. First evaluation was made after 12 weeks of implantation in terms of patient satisfaction with sexual intercourse and post operative complication. Sixteen patients (47.1%) were highly satisfied with intercourse, 13 (38.2%) satisfied with intercourse, 2 (5.9%) slightly dissatisfied even with successful intercourse, 1 (2.9%) with no improvement and 2 (5.9%) could not follow. Utility of the prosthesis, e.g. effectiveness and safety was; high utility in 20 (58.8%), good utility in 11 (32.4%), slight utility in 1 (2.9%), no favorable in 1 (2.9%) and no judgement in 1 (2.9%). The overall effectiveness and safety of the Hydroflex was demonstrated based on the above findings. Long term evaluation was made from the initial implantation of the device up to the termination of the trial with average of 19.2 months and was mentioned altogether.
Chronic pancreatitis is known to cause vascular disorders including pseudoaneurysm of peripancreatic arteries. Although the incidence of pseudoaneurysms due to pancreatitis detected by angiography has been reported as high as 10% in western literature, they are still considered rare in Japan. We reported two cases of pseudoaneurysm caused by chronic pancreatitis, one in splenic artery and the other in gastroduodenal artery, successfully treated by embolization. The embolizations were performed by occluding proximal splenic artery for splenic arterial aneurysm and gastroduodenal artery distal and proximal to the orifice for the aneurysm of gastroduodenal artery with stainless steel coils. Since the surgical therapy has high mortality rate, we consider transcatheter embolization is the treatment of choice for pseudoaneurysms caused by chronic pancreatitis.
The right caudocranial oblique (RACCO) view which is obtained by tilting the image intensifier 25 degrees caudally and 30 degrees to the right while the patients lie in supine position is proposed for improved depiction of the portal venous system. Transarterial portography with digital subtraction angiography was performed in the RACCO and posteroanterior (PA) views in 32 patients. Comparison of the two views revealed that the RACCO view was superior to the PA view of the left main branch in 25 patients (78%) and of the right posterior lobe branch in 24 (75%) patients. Visibility of more distal portal branches, however, did not always improve by RACCO view. RACCO view will be useful for the evaluation of portal systems of primary and secondary hepatic neoplasms as a special view following portogram in PA projection when more detailed information is necessary on proximal portal branches.
Construction of a continent ileal urinary reservoir (Kock pouch) is associated with a high incidence of late complication because of malfunction of the nipple valve, the efferent limb in particular. We have so far experienced several types of afferent nipple malfunction. We herein report on the unexpected complications of the afferent nipple valve in patients with a post operative observation of 1 year or more. From 1984 through 1989, urinary diversion via a Kock pouch was performed on 47 patients at Kyoto University Hospital and Public Toyooka Hospital. The study group comprises 42 patients with a mean observation of 40 months (range 14 to 60 months). The late complications of the afferent nipple valve were observed in 11 of the 42 (26%) patients. These included erosion of Dacron fabric used as a collar (5 patients), afferent nipple stenosis (3 patients) and afferent nipple obstruction by mucous plug or fungus ball (3 patients). Removal of Dacron collar was performed in 4 of the 5 patients with collar erosion and in 1 of the 3 patients with nipple stenosis. Nipple obstruction was relieved by endoscopic manipulation or diuresis. All of the 11 patients had no problems with their efferent nipples. Our results suggest that the use of nonabsorbable material as a collar and peristaltic direction of the afferent limb are mainly involved in the complications of the afferent nipple. A more reliable and simpler procedure for antireflux anastomosis should be considered.
We report two cases of primary paraganglioma of the urinary bladder. Case 1. A 61-year-old man was hospitalized with the chief complaints of gross hematuria, dysuria and headache. The patient had a history of hypertension. Cystoscopy disclosed a nonpapillary, sessile tumor in the retrotrigonum of the bladder. An attack of paroxysmal hypertension was induced by bimanual palpation of the tumor, and paraganglioma was suspected. Partial cystectomy with staging pelvic lymphadenectomy was performed. Case 2. A 65-year-old man was hospitalized with the chief complaints of gross hematuria and urinary retention. The patient had no history of hypertension. Cystoscopy disclosed a nonpapillary tumor in the right lateral wall of the bladder. Transurethral resection was performed with no cardiovascular complication. Prostatic needle biopsy showed the histological evidence of prostatic adenocarcinoma. Radical retropubic prostatectomy with limited lymphadenectomy was performed. There was no histological evidence of lymph node involvement of paraganglioma or adenocarcinoma. The histological and biochemical examinations revealed a chromaffin positive, functioning and non-malignant tumor in Case 1, and a chromaffin negative, non-functioning and non-malignant tumor in Case 2. In total, 29 cases of primary paraganglioma of the urinary bladder have been so far reported in Japan. The tumor recurrence, multiple or metastases were recorded in 8 of 29 cases (27.6%), mainly in regional lymph node metastases. We recommend lymphadenectomy at the initial operation, irrespective of pathological finding of the primary paraganglioma of the urinary bladder.
We compared the results of loading the bioluminescent Ca++ indicator aequorin by standard microinjection techniques to those obtained with two new chemical approaches to loading that utilize low concentrations of Ca++ chelator; i.e., 1) Immersion and 2) Macroinjection. After loading with the immersion and macroinjection methods, twitch tension returned to pre-load values indicating lack of damage to the muscles. The aequorin signals obtained with all three methods were similar and converted to similar quantitative values for [Ca++]i. Our data suggest that chemical loading (in particular macroinjection) may be preferable to microinjection, particularly in muscles with increased connective tissue content.
We studied the inotropic and lusitropic responses to MCI-154 in 12 right or left ventricular trabeculae carneae isolated from 7 organ donors (non-cardiac) without known cardiovascular disease who met accepted criteria for brain death. Isometric tension was recorded from muscles superfused with a physiologic salt solution at 30 degrees C, and stimulated to contract at three-second intervals. Concentration-response curves were developed over a range of MCI-154 organs bath concentrations (10(-7) M to 3 x 10(-4) M; n = 9). Six experiments were conducted using 10(-6) M carbachol, a muscarinic agonist, in the presence of a maximally effective concentration of MCI-154 to test for dependence of tension development on cyclic adenosine monophosphate. Three experiments were conducted with MCI-154, 3 x 10(-5) M, in muscles loaded with the bioluminescent calcium indicator aequorin. MCI-154 produced a concentration-dependent rise in peak tension in the human muscle (positive inotropic effect), equivalent to 70% of the maximal response to calcium (P less than 0.001). Relaxation was enhanced (positive lusitropic effect), as evidenced by a fall in the time to 80% relaxation from 311 +/- 13 ms (baseline) to 248 +/- 15 ms at 10(-5) M (P less than 0.01). Aequorin studies showed the increase in tension to be accompanied by large increases in cystolic calcium, the principal mechanism of action. Carbachol caused MCI-154--induced maximum peak tension to decrease by 5 +/- 1%. While not excluding a cyclic adenosine monophosphate--mediated MCI action, this modest carbachol inhibition suggests the existence of additional mechanism(s) of action. MCI-154 had a negative lusitropic effect at high concentrations (greater than 10(-4)M) which may have been due to intracellular calcium overload, evidenced by the large amplitude aequorin signals. This does not exclude sensitization of the myofilaments to calcium as a possibility. Extrapolated to the in vivo setting, these experiments suggest that MCI-154 may be an effective positive inotropic agent in man.
1. We used the bioluminescent protein aequorin, which emits light when it combines with Ca2+, to test the hypothesis that the inotropic and lusitropic actions of DPI 201-106 are due to changes in intracellular Ca2+ handling in papillary muscles from ferrets and guinea-pigs. 2. DPI 201-106 increased peak isometric tension (T) in a dose-dependent manner, with an 83% increase in T as the concentration of DPI 201-106 was increased to 1 x 10(-5) M; however, peak [Ca2+]i did not increase significantly until the concentration of DPI 201-106 reached 3 x 10(-6) M, suggesting a sensitization of the contractile apparatus to Ca2+. 3. Tetrodotoxin (1 x 10(-6) M), which did not reduce the tension response significantly before DPI 201-106, decreased both [Ca2+]i and T in the presence of 1 x 10(-5) M DPI 201-106, suggesting involvement of a sodium channel activation mechanism; however, tetrodotoxin did not completely reverse the calcium sensitization. 4. The shift of the [Ca2+]i versus T relationship was not observed in the presence of another sodium channel agonist, veratridine (3 x 10(-7)-1 x 10(-6) M). 5. In the guinea-pig, DPI 201-106 markedly prolonged relaxation of tension (increase of 60% in the time from peak to 50% tension regression), which was accompanied by the appearance of a second component in the aequorin light signal; effects on relaxation were less prominent in the ferret. 6. Tension prolongation and the second component of the [Ca2+]i transient in the guinea-pig were exacerbated by increased [Ca2+]o and decreased by tetrodotoxin. Ryanodine (3 x 10(-7) M) markedly diminished the calcium transient in controls and the initial component of the calcium transient in the presence of DPI 201-106, but had only a modest effect on the second component. 7. We conclude that although sodium agonism plays a role, sensitization of the contractile apparatus to Ca2+ is an important mechanism in the positive inotropic action of DPI 201-106. 8. The negative lusitropic action of DPI 201-106 varies between ferret and guinea-pig, possibly reflecting differences between these two species in subcellular Ca2+ handling.
In studies of ischemia and reperfusion, a major experimental problem has been the inability to measure intracellular ionized calcium ([Ca2+]i) in the intact heart. We have developed a new approach in which the bioluminescent calcium indicator aequorin is used to measure [Ca2+]i in the isolated, coronary-perfused ferret heart. Aequorin is loaded into subepicardial myocytes of the left ventricle, and the signals are recorded simultaneously along with isovolumic left ventricular (LV) pressure at a constant pacing rate. This system shows 1) no attenuation or change of time course of LV pressure development or coronary perfusion pressure after aequorin loading; 2) consistent responses to physiological interventions and drugs; 3) individual aequorin and pressure signals that do not require signal averaging for analysis; and 4) [Ca2+]i levels comparable with those reported in tissue or isolated myocyte cell preparations. During 5 minutes of hypoxia, diastolic [Ca2+]i and LV diastolic pressure increased while the systolic values of both [Ca2+]i and pressure decreased. The peak-to-peak systolic [Ca2+]i versus LV isovolumic pressure relation remained close to the control curve. In contrast, during 3 minutes of global ischemia, LV systolic and diastolic pressures fell rapidly, while [Ca2+]i increased substantially. The [Ca2+]i versus pressure relations for both systole and diastole shifted to the right, indicating desensitization of the contractile apparatus to [Ca2+]i. These results provide evidence that different primary mechanisms determine the systolic and diastolic responses to acute hypoxia versus ischemia. During hypoxia, changes in [Ca2+]i handling probably play a major role, while during ischemia, changes in the Ca2+ sensitivity of the myofilaments appear to be of primary importance in the modulation of contractile dysfunction.
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