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Biomedical subjects

M Fukunami

Publications and source records attributed to M Fukunami.

At least 37 records · Page 2Linked to original sources
PubMed1993

New approach to the estimation of the extent of myocardial fibrosis in patients with dilated cardiomyopathy: use of signal-averaged electrocardiography.

To determine whether the extent of myocardial fibrosis in dilated cardiomyopathy could be estimated noninvasively, signal-averaged electrocardiograms were recorded in 32 patients with dilated cardiomyopathy, followed by left ventricular endomyocardial biopsy. The root mean square voltage for the last 40 msec (V40), the duration of the filtered QRS complex (fQRSd) and the duration of low amplitude signals < 40 microV (LAS) were obtained by signal-averaged electrocardiography. The extent of fibrosis in all biopsy samples was measured by the point-counting method. The extent of myocardial fibrosis closely correlated with fQRSd (r = 0.623, p < 0.001), LAS (r = 0.570, p < 0.001), and V40 (r = -0.355, p < 0.05). When fibrosis was classified into intercellular and interfascicular types, the extent of intercellular fibrosis more closely correlated with fQRSd (r = 0.695, p < 0.0001), LAS (r = 0.640, p < 0.0001), and V40 (r = -0.533, p < 0.005). These results suggest that signal-averaged electrocardiograms might be useful for estimation of the extent of myocardial fibrosis, especially intercellular fibrosis in patients with dilated cardiomyopathy.

Adult↗
PubMed1993

[Pathophysiology of cytoskeleton and extracellular matrix in failing myocardium].

Cytoskeleton of myocytes and extracellular matrix play an essential role for maintaining cellular function. Alterations in humoral factors observed in heart failure, e.g., excess of plasma norepinephrine and angiotensin II, injure the microtubule structure probably through Ca overload and increase the collagen synthesis of the cardiac fibroblast. Recent studies demonstrated that network structures of microtubules and intermediate filaments are disrupted in the myocardium obtained from patients with heart failure. Changes in cytoskeletons and extracellular matrix may affect the contractile function, since they organize the intra- and inter-cellular architectures. Pathophysiological roles of cytoskeletons and extracellular matrix in failing hearts deserve further studies.

Angiotensin II↗
PubMed1992

Characteristics of frequency content of atrial signal-averaged electrocardiograms during sinus rhythm in patients with paroxysmal atrial fibrillation.

To clarify the characteristics of the frequency content of atrial signal-averaged electrocardiograms (ECGs) during sinus rhythm in patients with paroxysmal atrial fibrillation, P wave-triggered signal-averaged ECGs were recorded in 28 patients with and 34 control patients without paroxysmal atrial fibrillation. Fast Fourier transform analysis was performed on the 100-ms segment starting 75 ms before the end of the P wave. An area ratio (AR50) was calculated by dividing the area under the spectrum curve between 20 and 50 Hz, multiplied by 100, by the area between 0 and 20 Hz. Magnitude ratios (MR20, MR30, MR40 and MR50) were calculated by dividing the magnitude at 20, 30, 40 and 50 Hz, respectively, multiplied by 100, by the maximal magnitude of the entire signal. AR50 was significantly greater in patients with than without paroxysmal atrial fibrillation (62.3 +/- 34.2 vs. 42.4 +/- 18.4). MR20 and MR30 were also significantly greater in patients with than without paroxysmal atrial fibrillation (MR20 76.1 +/- 15.2 vs. 60 +/- 20.2; MR30 41 +/- 18.8 vs. 26.6 +/- 14.4), although no significant differences in MR40 or MR50 were observed between the two patient groups. The difference in MR30 between groups remained significant even after taking into account the presence of organic heart disease. It is concluded that, irrespective of the presence of organic heart disease, the terminal portion of the P wave contained significantly more components in the 20- to 50-Hz range, especially around 30 Hz, in patients with than in patients without paroxysmal atrial fibrillation. These results suggest that frequency analysis could characterize atrial signal-averaged ECGs of patients at risk for paroxysmal atrial fibrillation.

Adult↗
PubMed1992

Effect of flosequinan on exercise capacity and cardiac function in patients with chronic mild heart failure: a double-blind placebo-controlled study.

Although beneficial effects of a new vasodilating agent, flosequinan, have been demonstrated in patients with severe heart failure, its efficacy has not been studied in patients with a less severe form of chronic heart failure. In this study, the effects of 4 weeks' administration of flosequinan, 50 mg daily, and placebo on exercise capacity, cardiac function, and symptoms of heart failure were investigated in 24 patients with chronic mild heart failure (New York Heart Association functional class, mainly class II) in a double-blind clinical trial. When the parameter changes during the treatment period of the flosequinan and placebo groups were compared, no significant difference was found in any of the measurements except for left ventricular fractional shortening determined from M-mode echocardiograms; it was increased by 2.9 +/- 1.3% in the flosequinan group whereas it was decreased by 1.3 +/- 0.9% in the placebo group (P less than 0.05 vs flosequinan treatment). However, when compared to baseline values, flosequinan significantly increased exercise time in the symptom-limited maximal exercise test (704 +/- 103 to 763 +/- 107 s, P less than 0.05) and the oxygen uptake at the anaerobic threshold (13.8 +/- 1.3 to 16.7 +/- 1.4 ml/min kg, P less than 0.05), and improved symptoms assessed with a new heart failure severity classification (a median value of 2.0-1.5, P less than 0.05). These improvements were not observed in the placebo group. Serious adverse effects were not observed in either group. These results suggest that flosequinan is useful for the treatment of chronic mild heart failure as well as severe heart failure.

Adult↗
PubMed1992

Dynamic process between the clotting and the lytic activities on intracardiac thrombi--its relationship with systemic embolization.

To clarify the relationship between clotting and lytic activities of intracardiac thrombi, and to elucidate whether this could be used to evaluate the embolic risk the ratio of indium-111 radioactivity accumulated on thrombi to that in the blood pool using dual-tracer technique %IE as a parameter of the clotting activity, and D-dimer, which is a fibrin specific degradation product, as a parameter of lytic activity were measured in 37 patients with intracardiac thrombi. Fifteen of the 37 patients had past histories of arterial embolization. The values of D-dimer correlated significantly with those of %IE (r = 0.758, p less than 0.01), e.g., the higher the values of D-dimer the higher the values of %IE. 37 patients were divided into 2 groups using the regression line for the D-dimer and %IE domains. Eleven patients above the regression line had thrombosis in excess of fibrinolysis but the remaining 26 patients under the regression line had fibrinolysis in excess of thrombosis. The incidence of past embolic episodes was 82% (9/11) in patients with thrombosis in excess of fibrinolysis but 23% (6/26) in patients with fibrinolysis in excess of thrombosis. These results demonstrated that intracardiac thrombi were under the dynamic process between the clotting and the lytic activities and moreover patients with intracardiac thrombi and thrombosis in excess of fibrinolysis had a substantial risk of arterial embolization.

Aged↗
PubMed1992

[Late potentials in dilated cardiomyopathy in relation to ventricular tachycardia and cardiac function: their significance].

We assessed the usefulness of ventricular late potentials (VLP) for detecting ventricular tachycardia (VT), and of the relationship between VLP and left ventricular dysfunction. The subjects consisted of 21 patients with dilated cardiomyopathy (DCM) not accompanied with ventricular conduction disturbances. Signal-averaged electrocardiograms were recorded by using VCM-3000. The signals of 200 or more beats were averaged through the 40-300 Hz band-pass filter until the noise level was reduced to less than one microvolt (microV). The duration (fQRSd) and the root mean square voltage (LP40) for the last 40 msec of the filtered QRS complex were calculated. The left ventricular diastolic dimension (LVDd), systolic dimension (LVDs) and the ejection fraction (EF) were obtained by echocardiography. Five of 21 patients had VT. fQRSd was significantly longer in patients with VT than in those without VT (158.8 +/- 8.6 vs 126.5 +/- 10.4 msec, p < 0.01). LP40 was significantly less in patients with VT than in those without VT (8.7 +/- 2.7 vs 24.1 +/- 12.3 microV, p < 0.01). If the presence of "fQRSd > or = 120 msec" or "LP40 < or = 20 microV" was defined as VLP positive, as in patients with old myocardial infarction, the criteria sensitivity was 100% and their specificity was 25% for detecting VT. If the presence of both "fQRSd > or = 135 msec" and "LP40 < or = 20 microV" was defined as VLP positive, the criteria sensitivity was 100%, and their specificity, 88%.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1991

Effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy--echocardiographical follow-up.

To evaluate the effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy (DCM), two groups (Group I: 18 patients, Group II: 17 patients) with DCM divided by the order at the entry were followed echocardiographically for 16.9 +/- 3.0 months in Group I and 21.4 +/- 3.9 months in Group II. Metoprolol (final dose: 60 mg/day) was administered in Group I, but not in Group II (the control), although the conventional treatment for heart failure was continued. The left ventricular end-systolic dimension and ejection fraction assessed by echocardiography improved significantly after 6 months in Group I, but not in Group II, even after 48 months, although there were no significant differences in baseline data between the two groups. The end-diastolic dimension decreased significantly after 12 months in Group I only. It was estimated, using the point count method on a left ventricular endomyocardial biopsy specimen taken at entry, that the improvement (delta EF) of the ejection fraction 12 months after metoprolol administration inversely correlated (r = -0.677, p less than 0.01) with percent fibrosis, indicating that the more myocardium remains, the more improvement is expected. These findings suggested a favorable effect of beta blockade in DCM, especially in cases with less fibrosis, showing that the endomyocardial biopsy could be of clinical use in selecting candidates for chronic beta-blocker therapy in DCM.

Adrenergic beta-Antagonists↗
PubMed1991

Detection of patients at risk for paroxysmal atrial fibrillation during sinus rhythm by P wave-triggered signal-averaged electrocardiogram.

To determine whether patients at risk for paroxysmal atrial fibrillation could be detected while in sinus rhythm, the signal-averaged electrocardiogram triggered by P waves was recorded in 42 patients with paroxysmal atrial fibrillation (Paf group) and in 50 control patients. The root mean square voltages (LP10, LP20, and LP30) for the last 10, 20, and 30 msec and the duration (Ad) of filtered (40-300 Hz) P wave of the spatial magnitude were measured. LP10 and LP20 were significantly lower in the Paf than in the control group (LP10, 1.92 +/- 0.58 versus 2.49 +/- 0.78 microV, p less than 0.001; LP20, 2.47 +/- 0.78 versus 3.46 +/- 1.20 microV, p less than 0.0001), although no significant difference in LP30 was found between groups. Ad was also significantly longer in the Paf than in the control group (137.0 +/- 14.3 versus 118.6 +/- 11.3 msec, p less than 0.001). These differences between the Paf and control groups remained significant even after dividing by the presence or absence of organic heart diseases. The criteria of "LP20 = 3.5 microV or less" and "Ad greater than 120 msec" as defining "atrial late potential" gave a sensitivity of 91% and a specificity of 76%. These findings suggest that patients at risk for paroxysmal atrial fibrillation could be detected while in sinus rhythm by using the P wave-triggered signal-averaged electrocardiogram.

Algorithms↗
PubMed1991

Delayed end ejection increases isovolumic ventricular relaxation rate in isolated perfused canine hearts.

We sought to determine the ejection variables that are principally responsible for increases in isovolumic ventricular relaxation rate observed with increases in stroke volume. In nine isolated canine hearts, left ventricular ejection was controlled by patterns specially designed to isolate the ejection parameters most critical to isovolumic relaxation rate. When stroke volume was augmented by increases in end-diastolic volume (EDV) with end-systolic volume (ESV) held constant, isovolumic ventricular relaxation rate was unchanged, as gauged by the time constants of single-exponential fits to decaying pressure. In contrast, when ESV was decreased with EDV held constant, isovolumic relaxation time constants decreased significantly, from approximately 100 to 70 msec (protocol I). The important difference in these two situations might have been that the time of end ejection was delayed in the case with faster isovolumic relaxation. To rule out other parameters that may have influenced isovolumic relaxation, ejection velocity was varied in another protocol (protocol II) by either delays in time of the onset of ejection or advances in end-ejection time, always with constant ESV and EDV. Here isovolumic relaxation was progressively slowed as end ejection occurred earlier, whereas isovolumic relaxation rate was insensitive to changes in the onset of ejection, consistent with the unique importance of end ejection to isovolumic relaxation. In fact, our analysis reveals the remarkable finding that changes in isovolumic relaxation time constant produced by either protocol I or protocol II could be related quantitatively to end ejection by a single curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Increased intracardiovascular clotting in patients with chronic atrial fibrillation.

To clarify whether the formation of thrombi could be induced by atrial fibrillation itself or by factors predisposing to atrial fibrillation such as mitral stenosis, plasma D-dimer levels (cross-linked fibrin degradation products) were measured in 73 patients without atrial fibrillation (Group 2). In Group 1, 49 of the 73 patients had factors predisposing to atrial fibrillation such as valvular heart disease, and the remaining 24 had lone atrial fibrillation. In Group 2, 16 patients had organic heart disease and the remaining 5 had a chest pain syndrome. The plasma D-dimer level was significantly higher in Group 1 (150 +/- 19 ng/ml) than in Group 2 (61 +/- 3 ng/ml) (p less than 0.01, mean +/- standard error of the mean). In both groups, there were no significant differences in plasma D-dimer level between patients with and without organic heart disease (146 +/- 18 versus 156 +/- 46 ng/ml in Group 1; 61 +/- 4 versus 59 +/- 10 ng/ml in Group 2). These findings indicate that atrial fibrillation itself may be more important than factors predisposing to atrial fibrillation in the development of intracardiovascular clotting.

Atrial Fibrillation↗
PubMed1989

The inotropic consequences of cooling: studies in the isolated rat heart.

To investigate the controversial effects of hypothermia on cardiac contractile performance, we have carried out ventricular volume-loading experiments in 23 perfused, paced (2 Hz), isolated rat hearts, contracting isovolumically at various temperatures. A water-filled, unstressed latex balloon was inserted into the left ventricle and its volume was controlled with a microsyringe. Left ventricular pressure (LVP), its first derivative (dP/dt) and coronary flow were recorded. One group of hearts (n = 7) were perfused at 37 degrees C over 2 h. Another group of hearts (n = 16) were cooled in a stepwise manner from 37 degrees C to 21 degrees C, with 10-min perfusion at each of seven different temperatures, and then rewarmed to 37 degrees C. Emax, an index of contractility, calculated as the slope of the regression line of the end-systolic pressure-volume relationship, was found to increase as temperature fell (3.9, 4.6, 4.9, 5.5, 5.5, 6.2, and 6.3 cm H2O/microliters at 37 degrees, 34 degrees, 31 degrees, 29 degrees, 27 degrees, 24 degrees and 21 degrees C, respectively) while it remained constant over the 2-h perfusion in the normothermic perfusion group. By contrast, peak positive dP/dt/peak-developed pressure (+dP/dt/DP) progressively decreased during cooling without any change in the normothermic perfusion group. The results indicate that hypothermia can be designated as a positive inotropic intervention in terms of force-generation (Emax) but as a negative inotropic intervention in terms of shortening velocity of contractile element in Hill's model (+dP/dt/DP).

Animals↗
PubMed1988

Assessment of warfarin therapy under full dose using indium-111 platelet scintigraphy in patients with intracardiac thrombi.

Twenty patients in whom intracardiac thrombi were detected by indium-111 platelet scintigraphy (the first platelet scintigraphy) were prospectively studied to examine the effect of warfarin therapy under full dose on the intracardiac thrombogenicity. Eleven patients (group I) who received 2-6 mg/day of warfarin and 9 patients (group II) who did not receive warfarin had the second platelet scintigraphies 14-71 days after the first platelet scintigraphies. In group I, 10 platelet scintigraphies became negative and one remained positive for intracardiac thrombi after administration of warfarin, while in group II 8 platelet scintigraphies remained positive and only one changed to negative. The incidence of negative image at the second platelet scintigraphy was significantly lower in group II than that in group I. In group I, the degree of accumulation of platelets onto the surface of the thrombus (%IE), showed significant reduction (0.69 +/- 0.48 to 0.11 +/- 0.21) after warfarin therapy, while in group II %IE at the second scintigraphy (1.07 +/- 1.03) were not significantly different from those at the first scintigraphy (1.13 +/- 0.79). These results indicated that warfarin therapy under full dose inhibited the deposition of platelets on the intracardiac thrombi and thrombogenicity in the patients with intracardiac thrombi which were detected by indium-111 platelet scintigraphy.

Adult↗
PubMed1987

Spatial and temporal characteristics of the transmural distribution of collateral flow and energy metabolism during regional myocardial ischemia in the dog.

To characterize the temporal and spatial characteristics of transmural gradients of flow, ATP and CP, dogs (n = 17) were subjected to coronary artery ligation for either 30 minutes or 24 hours. Different radioactive microspheres were given at the onset and end of the ischemic period. Simultaneous multiple transmural biopsies (up to 20 per heart) were obtained (in situ freezing) from central ischemic and surrounding normal tissue after either 30 minutes or 24 hours of elapsed ischemia. After lyophilization each biopsy was divided into up to 6 transmural sub-fragments, each of which was analysed for flow, ATP and CP. At the onset of ischemia flow declined to less than 15% throughout the ischemic zone and there was a slight transmural gradient of flow from epi- to endocardium (12.4 +/- 1.6, 13.5 +/- 2.0, 11.0 +/- 1.8, 10.3 +/- 1.7, 8.5 +/- 1.9 and 8.3 +/- 3.1% of non-ischemic tissue). After 30 minutes of ischemia, collateral flow to the epicardial tissue had increased substantially but endocardial flow remained unchanged, the epi- to endo- gradient was 20.8 +/- 2.5, 18.9 +/- 2.4, 13.7 +/- 2.1, 10.8 +/- 1.5, 8.5 +/- 1.2, 7.6 +/- 1.7. After 24 hours there were further increases in the epi- and mid- myocardial regions but the endocardial flow remained severely depressed, the epi- to endo- gradient was 23.9 +/- 3.2, 24.5 +/- 3.0, 23.6 +/- 4.8, 16.4 +/- 3.3, 9.8 +/- 2.9, 5.8 +/- 2.9%. ATP and CP were severely depressed after 30 minutes of ischemia and reflected flow closely with sharp linear epi- to endo- gradients (17.5 to 10.9 muMol/g dry wt for ATP and 7.4 to 3.1 muMol/g dry wt for CP). After 24 hours, the decline in ATP had been slowed and there was a striking recovery of CP in the epi- and mid- myocardial regions which had experienced increasing collateral flow. CP in the endocardium remained severely depressed. Progressive supplementation of collateral flow early and throughout a 24 hour period of regional myocardial ischemia and the selective delivery of this flow to subepi- and mid- myocardial tissue accounts in part for the natural salvage of this tissue and the deterioration of the endocardium to necrosis. Gradients of flow and metabolism further influence these events and account for the "wave front" of cell death.

Adenosine Triphosphate↗
PubMed1986

Simulation of T wave based on cardiac model of electrical activity: effects of anisotropy of myocardium and inhomogeneity of ventricular gradient on QRS-T angle.

To investigate the effects of the excitation propagation and the inhomogenous distribution of action potential duration (APD) on QRS-T angle and T wave polarity, mathematical analysis and computer simulation of QRS-T wave were performed in a cardiac model of the electrical activity. A rectangular solid model with the conduction system on the subendocardial surface simulated a part of the free wall of the left ventricle. In our previous studies we assumed isotropy of the myocardium and linear ventricular gradient. In the present study, we obtained the quantitative relationship between the ventricular gradient (beta) (intramural gradient of action potential duration) and the QRS-T angle (theta) in the models with anisotropy of the myocardium and inhomogenous ventricular gradient. The directions of progress of depolarization and repolarization were different between with presence and absence of anisotropy. However, the beta-theta relationship was minimally influenced by anisotopy. Furthermore, the present study demonstrated that the total T vector is determined by the difference of APD between endocardium and epicardium, and is not influenced by the inhomogeneity of APD in the middle layer of the ventricular wall. These results support the validity of our previous cardiac model in which we assumed isotropy of the myocardium and the homogenous ventricular gradient. Moreover we demonstrated that the propagation velocity and the cardiac hypertrophy may largely influence the T wave polarity by the simulation study of electrocardiograms.

Computer Simulation↗
PubMed1985

An increase in afterload augments ventricular relaxation rate in isolated perfused canine hearts.

The afterload dependency of relaxation rate was reappraised in isolated canine hearts both in isovolumic and isobaric contractions by using the reliable exponential method in which the asymptote LV pressure (P chi) is variable. This method provided a closer correlation (r = 0.999 +/- 0.001) between the measured LV pressure decay and the model estimate than the semilogarithmic method assuming P chi = 0 (r = 0.992 +/- 0.001). Time constants of isovolumic LV pressure decay obtained by the exponential method demonstrated a significant (p less than 0.01) decrease during volume loading both in isovolumic and isobaric contractions, indicating that the relaxation rate is augmented as afterload increases. In contrast, if we assume P chi = 0, the time constant of LV pressure decay was independent of peak LV pressure as previously reported. Thus, we conclude that the load insensitive relaxation rate implied by the semilogarithmic method (P chi = 0) may be erroneous due to an invalid assumption, ie, P chi = 0, but the relaxation rate is augmented as afterload increases both in isovolumically contracting and isobarically ejecting isolated canine hearts.

Animals↗
PubMed1985

Temperature-dependency of nifedipine as a protective agent during cardioplegia in the rat.

An isolated working rat heart preparation was used to characterise the temperature-dependency of the anti-ischaemic properties of nifedipine. In this study hearts were subjected to pre-ischaemic infusion with the St Thomas' cardioplegic solution with or without added nifedipine (0.075 mumol X litre-1). Hearts were then rendered globally ischaemic for various periods, (35, 42, 48, 56, 55, 65, 80, 105 or 130 min) at various temperatures (37.0, 35.5, 34.0, 32.5, 31.0, 29.0, 27.0, 24.0 or 20.0 degrees C, respectively). The duration of ischaemia at each temperature was selected to produce a post-ischaemic (37 degrees C) recovery of aortic flow that was approximately 50% of its pre-ischaemic (37 degrees C) control. In addition to functional indices (aortic flow, cardiac output, coronary flow, aortic pressure and heart rate) creatine kinase leakage during reperfusion was measured. At all temperatures at or above 31 degrees C the addition of nifedipine enhanced significantly (maximal value = 43%) the post-ischaemic recovery of aortic flow and other indices of pump function, while at the same time reducing significantly (by up to 56%) enzyme leakage. At ischaemic temperatures below 31 degrees C nifedipine failed to afford any significant additional protection when assessed functionally or enzymatically. It would therefore appear that hypothermia either blocks the action of nifedipine or, by acting on some common mechanism, renders the actions of the drug redundant.

Animals↗