Biomedical subjects

J Araki

Publications and source records attributed to J Araki.

At least 19 recordsLinked to original sources

PubMed2001

Coupling interval from slow to tachycardiac pacing decides sustained alternans pattern.

We discovered that the coupling beat interval from a slow to a tachycardiac pacing period considerably affected the pattern of the beat-to-beat alternation of the tachycardia-induced sustained contractile alternans. We analyzed the relationship between the coupling interval and the pattern and amplitude of the alternans in the isovolumic left ventricle of canine blood-perfused hearts. The alternans pattern and amplitude varied transiently over the first 30-50 beats and became gradually stable over the first minute in all 12 hearts. We discovered that stable alternans, even under the same tachycardiac pacing, had three different strong-weak beat patterns depending on the coupling interval. A relatively short coupling interval produced a representative sustained alternans of the strong and weak beats. A relatively long coupling interval produced a similar sustained alternans but in a reversed order of even- and odd-numbered beats counted from the coupling interval. However, sustained alternans disappeared after 1-3 specific coupling intervals. We conclude that ventricular pacing rate does not solely determine the pattern and amplitude of sustained contractile alternans induced by tachycardia.

Action Potentials↗

PubMed2001

New calculation of internal Ca(2+) recirculation fraction from alternans decay of postextrasystolic potentiation.

In our previous studies, we calculated the internal Ca(2+) recirculation fraction (RF) after obtaining the beat decay constant (tau(e)) of the monoexponential component in the postextrasystolic potentiation (PESP) of the alternans decay by curve fitting. However, this method sometimes suffers from the sensitive variation of tau(e) with small noises in the measured contractilities of the 5th and 6th postextrasystolic (PES) beats in the tail of the exponential component. We now succeeded in preventing this problem by a new method to calculate RF without obtaining tau(e). The equation for the calculation in the new method expresses an alternans decay of PESP as a recurrence formula of PESP. It can calculate RF directly from the contractilities of the 1st through the 4th PES beats without any fitting procedure. To evaluate the reliability of the new method, we calculated RF from the alternans decay of PESP of the left ventricle (LV) of the canine excised cross-circulated heart preparation by both the original fitting and the new method. Although there was no significant difference in the mean value of the obtained RF between these two methods, the variance of RF was smaller with the new method than with the original method. Thus the new method proved useful and more reliable than the original fitting method.

Animals↗

PubMed2001

Cardiovascular beneficial effects of electroacupuncture at Neiguan (PC-6) acupoint in anesthetized open-chest dog.

Neiguan (PC-6) is a traditional acupoint in the bilateral forearms, overlying the median nerve trunk. Neiguan electroacupuncture (EA) has been believed to affect cardiovascular function and used in traditional Chinese medicine to improve or treat a wide range of health conditions and diseases, including angina pectoris, myocardial infarction, hypertension, and hypotension. However, few physiological studies have assessed the beneficial effects of Neiguan EA on the cardiovascular function. In the present study, we investigated its effects on the cardiovascular function in normal open-chest dogs under pentobarbital and fentanyl anesthesia. We also obtained left ventricular (LV) pressure-volume (P-V) data with a micromanometer catheter and a volumetric conductance catheter. Mean arterial pressure, end-diastolic volume, heart rate, stroke volume, cardiac output, and end-systolic pressure gradually decreased by 5 to 10% over 1.5 h without Neiguan EA. Neiguan EA at 40 Hz, however, increased these cardiovascular variables by 10 to 15%, especially end-systolic elastance (Ees) by 40% (p<0.05) over 15 to 60 min. After Neiguan EA was stopped at 1 h, these facilitated cardiovascular variables decreased below the pre-EA level. This beneficial effect of electroacupuncture may contribute to the effectiveness of the acupuncture in Chinese medicine.

Adjuvants, Anesthesia↗

PubMed2001

Frank-Starling mechanism retains recirculation fraction of myocardial Ca(2+) in the beating heart.

Myocardial Ca(2+) handling in excitation-contraction coupling is the second primary determinant of energy or O(2) demand in a working heart. The intracellular and extracellular routes remove myocardial Ca(2+) that was released into the sarcoplasma with different Ca(2+): ATP stoichiometries. The intracellular route is twice as economical as the extracellular route. Therefore the fraction of total Ca(2+) removed via the sarcoplasmic reticulum, i.e., the recirculation fraction of intracellular Ca(2+) (RF), determines the economy of myocardial Ca(2+) handling. RF has conventionally been estimated as the exponential decay rate of postextrasystolic potentiation (PESP). However, we have found that PESP usually decays in alternans, but not exponentially in the canine left ventricle beating above 100 beats/min. We have succeeded in estimating RF from the exponential decay component of an alternans PESP. We previously found that the Frank-Starling mechanism or varied ventricular preload did not affect the economy of myocardial Ca(2+) handling. Then, to account for this important finding, we hypothesized that the Frank-Starling mechanism would not affect RF at a constant heart rate. We tested this hypothesis and found its supportive evidence in 11 canine left ventricles. We conclude that RF at a constant heart rate would remain constant, independent of the Frank-Starling mechanism.

Action Potentials↗

PubMed2001

Total Ca2+ handling for E-C coupling in the whole heart: an integrative analysis.

We assessed total Ca2+ handling (transport, flux) in excitation-contraction (E-C) coupling in a beating left ventricle (LV). We developed a new integrative analysis method that utilizes the internal Ca2+ recirculation fraction (RF), O2 consumption (V(O2)) for Ca2+ handling, and O2 cost of Emax (contractility index) of the LV. We obtained the RF from the beat constant of the exponential decay component of the postextrasystolic potentiation, and the O2 cost of Emax from V(O2) measured at different Emax. Our equation calculated the unknown total Ca2+ handling, futile Ca2+ cycling, and Ca2+ reactivity of Emax from the RF and Ca2+ handling V(O2). The calculated total Ca2+ handling fell between 30 and 110 micromol/kg, depending on Emax and pathological conditions. Our method also allowed an assessment of futile Ca2+ cycling and Ca2+ reactivity of Emax in a beating LV. These data are not available using conventional methods. Our method can be used to better understand the pathophysiology of total Ca2+ handling in a beating heart.

Animals↗

PubMed2000

[An imported case of primary pulmonary coccidioidomycosis].

Coccidioides immitis is a causative agent of coccidioidomycosis, which is one of the most dreadful mycosis because of its infectious and pathogenic nature. The endemic areas are in the southwestern parts of the United States and other semi-arid regions throughout the Western Hemisphere. During the early 1990s, the incidence of coccidioidomycosis in California increased dramatically, resulting in recognition for this mycosis as a reemerging infectious disease in the United States. The patients included a large number of non-informed visitors from non-endemic countries. Our report is on an imported case of primary pulmonary coccidioidomycosis. A 35-year-old Japanese male, after living in the United States for nine months, suffered from a combination of headache and fever. He was given a serological examination, and a chest radiograph in Phoenix, Arizona in the United States and was diagnosed as coccidioidomycosis. A daily dosage of 400 mg of fluconazole was administered and he returned to Japan. His headache and skin rash persisted and he was admitted to our hospital to evaluate the severity of his disease. There were no fungi cultured from neither bronchoalveolar nor cerebrospinal fluid and he was discharged. The patient had been treated with fluconazole and his symptoms, high-resolution CT and serological antibody titer were monitored. After 18 months, his clinical and radiological evolution was favorable and his serological IgM titer was below its sensitivity medication was stopped and there were no relapses.

Adult↗

PubMed2000

Energy-wasteful total Ca(2+) handling underlies increased O(2) cost of contractility in canine stunned heart.

Postischemic myocardial stunning halved left ventricular contractility [end-systolic maximum elastance (E(max))] and doubled the O(2) cost of E(max) in excised cross-circulated canine heart. We hypothesized that this increased O(2) cost derived from energy-wasteful myocardial Ca(2+) handling consisting of a decreased internal Ca(2+) recirculation, some futile Ca(2+) cycling, and a depressed Ca(2+) reactivity of E(max). We first calculated the internal Ca(2+) recirculation fraction (RF) from the exponential decay component of postextrasystolic potentiation. Stunning significantly accelerated the decay and decreased RF from 0.63 to 0. 43 on average. We then combined the decreased RF with the halved E(max) and its doubled O(2) cost and analyzed total Ca(2+) handling using our recently developed integrative method. We found a decreased total Ca(2+) transport and a considerable shift of the relation between futile Ca(2+) cycling and Ca(2+) reactivity in an energy-wasteful direction in the stunned heart. These changes in total Ca(2+) handling reasonably account for the doubled O(2) cost of E(max) in stunning, supporting the hypothesis.

Animals↗

PubMed2000

Postextrasystolic contractile decay always contains exponential and alternans components in canine heart.

In isolated, blood-perfused canine hearts, postextrasystolic potentiation (PESP) decays monotonically after a noncompensatory pause following a spontaneous extrasystole (ES). The monotonic PESP decay yields myocardial internal Ca(2+) recirculation fraction (RF). We have found that after a compensatory pause (CP), PESP decays in alternans, consisting of an exponential and a sinusoidal decay component. We have proposed that this exponential component also yields RF. In the present study, we examined the reliability of this alternative method by widely changing the ES coupling interval (ESI), CP, and heart rate in the canine excised, cross-circulated left ventricle. We found that all PESP decays consisted of the sum of an exponential and a sinusoidal decay component of variable magnitudes whether a CP existed or not. Their decay constants as well as the calculated RF were independent of the ESI and CP. This confirmed the utility of our alternative RF determination method regardless of the ESI, CP, and heart rate. Direct experimental evidence of Ca(2+) dynamics supportive of this alternative method, however, remains to be obtained.

Animals↗

PubMed2000

Kamegainema cingulum (Linstow, 1902) n. gen., n. comb. (Nematoda: Dracunculidae), a subcutaneous parasite of cryptobranchids (Amphibia: Caudata).

The monotypic Kamegainema n. gen. is proposed for Filaria cingula, a subcutaneous parasite of cryptobranchids. Examination of female specimens recently collected from the Japanese giant salamander, Andrias japonicus, revealed that it belongs to Dracunculidae. Kamegainema is closest to Protenema Petter and Planelles, 1986, the only other dracunculid genus known from Amphibia, but is readily distinguished by having prominent cuticular bosses. Kamegainema cingulum is redescribed.

Animals↗

PubMed2000

Mechanoenergetics characterizing oxygen wasting effect of caffeine in canine left ventricle.

Caffeine causes a considerable O(2) waste for positive inotropism in myocardium by complex pharmacological mechanisms. However, no quantitative study has yet characterized the mechanoenergetics of caffeine, particularly its O(2) cost of contractility in the E(max)-PVA-VO(2) framework. Here, E(max) is an index of ventricular contractility, PVA is a measure of total mechanical energy generated by ventricular contraction, and VO(2) is O(2) consumption of ventricular contraction. The E(max)-PVA-VO(2) framework proved to be powerful in cardiac mechanoenergetics. We therefore studied the effects of intracoronary caffeine at concentrations lower than 1 mmol/l on left ventricular (LV) E(max) and VO(2) for excitation-contraction (E-C) coupling in the excised cross-circulated canine heart. We enhanced LV E(max) by intracoronary infusion of caffeine after beta-blockade with propranolol and compared this effect with that of calcium. We obtained the relation between LV VO(2) and PVA with E(max) as a parameter. We then calculated the VO(2) for the E-C coupling by subtracting VO(2) under KCl arrest from the PVA-independent (or zero-PVA) VO(2) and the O(2) cost of E(max) as the slope of the E-C coupling VO(2)-E(max) relation. We found that this cost was 40% greater on average for caffeine than for calcium. This result, for the first time, characterized integratively cardiac mechanoenergetics of the O(2) wasting effect of the complex inotropic mechanisms of intracoronary caffeine at concentrations lower than 1 mmol/l in a beating whole heart.

Animals↗

PubMed2000

Logistic time constant of isometric relaxation force curve of ferret ventricular papillary muscle: reliable index of lusitropism.

We have found that a logistic function fits the left ventricular isovolumic relaxation pressure curve in the canine excised, cross-circulated heart more precisely than a monoexponential function. On this basis, we have proposed a logistic time constant (tau(L)) as a better index of ventricular isovolumic lusitropism than the conventional monoexponential time constant (tau(E)). We hypothesize in the present study that this tau(L) would also be a better index of myocardial isometric lusitropism than the conventional tau(E). We tested this hypothesis by analyzing the isometric relaxation force curve of 114 twitches of eight ferret isolated right ventricular papillary muscles. The muscle length was changed between 82 and 100% L(max) and extracellular Ca(2+) concentrations ([Ca(2+)](o)) between 0.2 and 8 mmol/l. We found that the logistic function always fitted the isometric relaxation force curve much more precisely than the monoexponential function at any muscle length and [Ca(2+)](o) level. We also found that tau(L) was independent of the choice of the end of isometric relaxation but tau(E) was considerably dependent on it as in ventricular relaxation. These results validated our present hypothesis. We conclude that tau(L) is a more reliable, though still empirical, index of lusitropism than conventional tau(E) in the myocardium as in the ventricle.

Animals↗

PubMed2000

2,3-Butanedione monoxime suppresses primarily total calcium handling in canine heart.

Whether 2,3-butanedione monoxime (BDM, < or = 5mmol/l) suppresses primarily crossbridge cycling or total Ca(2+) handling in the blood-perfused whole heart remains controversial. Although BDM seems to suppress primarily total Ca(2+) handling in canine hearts, more evidence is lacking. We therefore analyzed the cardiac mechanoenergetics, namely, E(max) (contractility), PVA (total mechanical energy), and O(2) consumption of canine BDM-treated hearts by our recently developed integrative method to assess myocardial total Ca(2+) handling. This method additionally required the internal Ca(2+) recirculation fraction. We obtained this from the beat constant of the exponential decay component of the postextrasystolic potentiation. Our analysis indicated significant decreases in both internal Ca(2+) recirculation fraction and total Ca(2+) handling in the BDM-treated heart, but virtually no change in the reactivity of E(max) to total Ca(2+) handling. This result corroborates the view that BDM suppresses primarily total Ca(2+) handling rather than crossbridge cycling in the canine blood-perfused heart.

Animals↗

PubMed2000

Effective arterial elastance of irregular beats during atrial fibrillation in canine left ventricle.

Effective arterial elastance (E(a)) was originally defined as the end-systolic pressure (ESP)/stroke volume (SV) ratio of the left ventricle (LV). E(a) combined with LV contractility (E(max)), E(a)/E(max), proved to be powerful in analyzing the ventriculo-arterial coupling of normal and failing hearts in regular beats. However, E(a) sensitively changes with LV E(max), preload, and afterload widely changing among irregular beats. This has discouraged the use of E(a) during arrhythmia. However, we hypothesized that E(a) could serve as the effective afterload (not always arterial) elastance against ventricular ejection under arrhythmia. We tested this hypothesis by analyzing beat-to-beat changes in E(a) of irregular beats during electrically induced atrial fibrillation (AF) in normal canine in situ hearts. We newly found that during AF in each heart: 1) E(a) changed widely among irregular beats and became markedly high in weak beats with small SVs; 2) E(a) and E(a)/E(max) distributed non-normally with large skewness but 1/E(a) distributed more normally; 3) 1/E(a) correlated closely with end-diastolic volume, E(max) and preceding beat intervals; and 4) the reciprocal of mean 1/E(a) closely correlated with mean ESP/mean SV. These results support our hypothesis that E(a) can serve as the effective afterload elastance against ventricular ejection on a per-beat basis during AF. E(a)/E(max) can also quantify the ventriculo-afterload (not arterial) coupling on a per-beat basis. This study, however, warns that mean E(a) and mean E(a)/E(max) of irregular beats cannot necessarily represent their averages during AF.

Animals↗

PubMed2000

[Pilot study of dose intensive weekly chemotherapy followed by cisplatin plus etoposide with concurrent thoracic irradiation for limited-disease small-cell lung cancer. West Japan Thoracic Oncology Group].

It was reported from a previous randomized trial (NEJM 329: 1848, 1993) that a moderate increase in the initial dose of cyclophosphamide and cisplatin improves the survival of patients with LDSCLC. Rapid administration of several active agents over a short treatment period, such as the CODE regimen, is a potentially usefully strategy for increasing the initial dose intensity. Based on these findings, we conducted a pilot study of CODE (C: 25 mg/m2, day 1, weeks 1-4, O: 1 mg/m2, day 1, weeks 2, 4, D: 40 mg/m2, day 1, weeks 1, 3, E: 80 mg/m2, days 1-3, weeks 1, 3) chemotherapy for the first 4 weeks followed by PE therapy (P: 80 mg/m2, day 1, E: 100 mg/m2, days 1-3, for 3 cycles) with concurrent TRT (1.5 Gy bid x 30 fr., total 45 Gy) to treat LDSCLC. From June 1996 through September 1996, 23 patients (pts) were enrolled, among whom 22 were eligible. The patients' characteristics were as follows: median age 65; M/F, 15/7; PS, 0/1/2,9/9/4; Stage II/IIIA/IIIB, 3/8/11. The relative dose intensities in the CODE phase for patients who received this treatment were 107% for P and 156% for E, compared with standard PE therapy. No treatment related death occurred in this series. Myelosuppression was the most frequent toxicity in both treatments. Grade 3 and 4 leukopenia and neutropenia occurred in 73% and 86% of patients in the CODE phase, and in 83% and 91% in the PE phase, respectively. Thrombocytopenia occurred in 14% of the patients in the CODE phase and in 37% in the cisplatin-etoposide phase. Other non-hematological toxicities were mild. There was no severe esophagitis or pneumonitis following radiation therapy. CR was observed in 13 (59%) of the 22 patients, and 9 (41%) patients showed PR, giving an overall response rate of 100%. A median survival time has not yet been ascertained. Our preliminary results indicate that CODE therapy followed by PE therapy with concurrent TRT has very high activity with acceptable toxicities. This treatment regimen should be compared with PE therapy and concurrent TRT in a randomized trial.

Adult↗

PubMed1999

Total Ca handling in canine mild Ca overload failing heart.

We analyzed total Ca handling of the left ventricle (LV) in the mildly failing heart preparation induced by a temporary intracoronary Ca overloading intervention in eight excised and cross-circulated canine hearts. This Ca intervention consisted of interruption of coronary blood perfusion by Ca-free oxygenated Tyrode perfusion for 10 min followed by high-Ca (16mmol/l) oxygenated Tyrode perfusion for 5 min. This intervention decreased the LV contractility index, Emax (end-systolic maximum elastance), by 40% after restoration of the blood cross-circulation. We expected a Ca overload or paradox failing heart resembling the postischemic stunned heart and being characterized by an increased O2 cost of Emax. However, LV O2 consumption under mechanically unloading conditions decreased by 30% from control without increasing the O2 cost of Emax. To obtain a mechanistic view of this failing heart, we investigated cardiac total Ca handling by our integrative analysis method. In this method, we obtained the internal Ca recirculation fraction (RF) from the decay beat constant of the postextrasystolic potentiation following each sporadic spontaneous extrasystole in these failing LVs. We combined the RF with the decreased Emax and the unchanged O2 cost of Emax in our recently developed formula of total Ca handling. We found that these failing LVs had a slightly but significantly increased RF accompanied by either a slightly increased futile Ca cycling or a slightly decreased Ca reactivity of Emax, or both. Any of these three possible changes can account for the unchanged O2 cost of Emax. This result indicates that the present mildly failing heart has not yet fallen into a typical Ca overload or paradox by the temporary Ca overloading intervention.

Animals↗

PubMed1999

Myocardial mechanical restitution and potentiation partly underlie alternans decay of postextrasystolic potentiation: simulation.

We have reported that the postextrasystolic potentiation (PESP) decays in alternans or monotonically, respectively, depending on whether the first postextrasystolic beat interval has a compensatory pause or not, in the canine left ventricle. To get better mechanistic insight into the alternans PESP decay, we hypothesized that the myocardial mechanical restitution and potentiation could partly account for both types of PESP decay. To test this hypothesis, we simulated PESP decay on a computer using a documented equation combining myocardial mechanical restitution and potentiation. We changed the first postextrasystolic beat interval after a fixed extrasystolic beat interval without changing regular and other postextrasystolic beat intervals. The simulated PESP decayed in alternans or monotonically as a function only of the first postextrasystolic beat interval. Thus, the myocardial mechanical restitution and potentiation could partly account for both alternans and monotonic decay of PESP. We conclude that myocardial mechanical restitution and potentiation may partly underlie the initial two alternating beats, the first beat being the most potentiated and the second beat being the most depressed, of alternans PESP decay in the canine heart.

Animals↗

PubMed1999

O(2) cost of contractility but not of mechanical energy increases with temperature in canine left ventricle.

We investigated the effects of myocardial temperature on left ventricular (LV) mechanoenergetics in the excised, cross-circulated canine heart. We used the framework of the LV contractility (E(max))-pressure-volume area (PVA; a measure of total mechanical energy)-myocardial oxygen consumption (VO(2)) relationship. We have shown this framework to be useful to integrative analysis of the mechanoenergetics of a beating heart. In isovolumic contractions at a constant pacing rate, increasing myocardial temperature from 30 to 40 degrees C depressed E(max) and increased the oxygen cost of E(max), which was enhanced by dobutamine, in a linear manner. However, the slope of the VO(2)-PVA relation (reciprocal of contractile efficiency) and its VO(2) intercept remained constant. Q(10) values of E(max), the oxygen cost of E(max), and the oxygen cost of PVA were 0.4, 2.1 and 1.0, respectively, around normothermia. We conclude that the temperature-dependent processes of cross-bridge cycling and Ca(2+) handling integratively depress E(max) and augment its oxygen cost without affecting the oxygen cost of PVA as myocardial temperature increases by 10 degrees C around normothermia.

Animals↗

PubMed1999

Weibull distribution function for cardiac contraction: integrative analysis.

The Weibull distribution is widely used to analyze the cumulative loss of performance, i.e., breakdown, of a complex system in systems engineering. We found for the first time that the difference curve of two Weibull distribution functions almost identically fitted the isovolumically contracting left ventricular (LV) pressure-time curve [P(t)] in all 345 beats (3 beats at each of 5 volumes in 23 canine hearts; r = 0.999953 +/- 0.000027; mean +/- SD). The first derivative of the difference curve also closely fitted the first derivative of the P(t) curve. These results suggest the possibility that the LV isovolumic P(t) curve may be characterized by two counteracting cumulative breakdown systems. Of these, the first breakdown system causes a gradual pressure rise and the second breakdown system causes a gradual pressure fall. This Weibull-function model of the heart seems to give a new systems engineering or integrative physiological view of the logic underlying LV isovolumic pressure generation.

Animals↗