Search PubMed⌕ Search

Biomedical subjects

S Futaki

Publications and source records attributed to S Futaki.

At least 127 records · Page 7Linked to original sources
PubMed1988

Efficiencies from consumed O2 and pressure-volume area to work of in situ dog heart.

We studied the efficiencies from oxygen consumption (VO2) to external mechanical work (EW), from VO2 to the systolic pressure-volume area (PVA), and from PVA to EW, and the effects of cardiac output and contractility index (Emax) on these efficiencies in the left ventricle of open-chest, right-heart-bypassed dogs. PVA is an intermediate form of energy between VO2 and EW. PVA, EW, and Emax were determined by an abrupt occlusion of the ascending aorta. The right-heart bypass allowed us to collect all coronary venous return for VO2 measurement. The EW/VO2 efficiency ranged between 4 and 21%, the PVA/VO2 efficiency ranged between 5 and 27%, and the EW/PVA efficiency ranged between 60 and 95%. At a given Emax, EW/PVA efficiency was independent of cardiac output, but PVA/VO2 and EW/VO2 efficiencies increased with cardiac output. An increase in Emax by dobutamine increased EW/PVA efficiency, but decreased PVA/VO2 and EW/VO2 efficiencies. We could theoretically account for these changes in EW/PVA, PVA/VO2, and EW/VO2 efficiencies of the in situ heart by the VO2-PVA relation and its dependence on Emax that we had observed.

Animals↗
PubMed1987

Proteolysis of human C-reactive protein produces peptides with potent immunomodulating activity.

We have studied the ability of human C-reactive protein to modulate the immune response in vitro. Whereas native C-reactive protein did not induce phagocytic leukocytes to chemotax or to produce superoxide, treatment of purified C-reactive protein with human neutrophil-derived acid proteases produced substances with potent effects on leukocyte function. Close examination of the primary structure of human C-reactive protein revealed three regions evenly distributed throughout the protein each of which contain peptide sequences closely resembling the amino acid sequence of the immunomodulator peptide tuftsin, Thr-Lys-Pro-Arg. We have synthesized the three peptides which include Thr-Lys-Pro-Leu ([Leu4]tuftsin), Gly-Lys-Pro-Arg ([Gly1]tuftsin), and Thr-Lys-Pro-Gln ([Gln4]tuftsin) and assayed them for biological activity. The three synthetic peptides were found to stimulate phagocytic leukocytes to chemotax, produce superoxide, and induce mononuclear cells to produce interleukin 1 in vitro at concentrations similar to those concentrations required for tuftsin to induce these phenomena. These results support a potentially important role for C-reactive protein as a possible immunomodulator during inflammation.

Amino Acid Sequence↗
PubMed1987

Mechanism of inhibition of mammalian DNA topoisomerase I by heparin.

We have previously shown that heparin is a potent inhibitor of a mammalian DNA topoisomerase I. We have now investigated the mechanism of its inhibition. This was carried out first by scrutinizing the structural features of heparin molecules responsible for the inhibition. Commercial heparin preparation was fractionated by antithrombin III-Sepharose into non-adsorbed, low-affinity and high-affinity fractions, of which only the high-affinity fraction of heparin is known to contain a specific oligosaccharide sequence responsible for the binding to antithrombin III. These fractions all exhibited essentially similar inhibitory activities. Furthermore, when chemically sulphated to an extent comparable with or higher than heparin, otherwise inactive glycosaminoglycans such as heparan sulphate, chondroitin 4-sulphate, dermatan sulphate and neutral polysaccharides such as dextran and amylose were converted into potent inhibitors. Sulphated dermatan sulphate, one of the model compounds, was further shown to bind competitively to the same sites on the enzyme as heparin. These observations strongly suggested that topoisomerase inhibition by heparin is attributable primarily, if not entirely, to the highly sulphated polyanionic nature of the molecules. In a second series of experiments we examined whether heparin inhibits only one or both of the topoisomerase reactions, i.e. nicking and re-joining. It was demonstrated that both reactions were inhibited by heparin, but the nicking reaction was more severely affected than was the re-joining reaction.

Antithrombin III↗
PubMed1987

Prospective prediction of O2 consumption from pressure-volume area in dog hearts.

Systolic pressure-volume area (PVA) is the area circumscribed by the end-systolic pressure-volume (PV) line, the end-diastolic PV curve, and the systolic PV trajectory of the ventricle. PVA represents the total mechanical energy generated by ventricular contraction. Myocardial O2 consumption (VO2) linearly correlates with PVA under different pre- and afterloads in the dog left ventricle. The linear VO2-PVA relation parallel shifts with changes in contractility index Emax. We have retrospectively obtained VO2 = A X PVA + B . Emax + C, where A, B, and C are regression coefficients. We used this equation to prospectively predict VO2 from measured PVA and Emax in a new group of dog left ventricles. Coefficient of determination (CD) of measured VO2 from predicted VO2 was 0.86 +/- 0.09 (SD) in individual hearts, but decreased to 0.72 when data of the five hearts were pooled. These prospective CDs in individual hearts and all hearts were smaller than retrospective CDs in the individual hearts (0.90 +/- 0.06). Inter-individual variations of A,B, and C caused the lower prospective predictability.

Animals↗
PubMed1987

Relation between oxygen consumption and pressure-volume area of in situ dog heart.

We studied the relation between O2 consumption (VO2) and the systolic pressure-volume area (PVA) in the left ventricle of open-chest dogs. PVA and the slope (Emax) of the end-systolic pressure-volume line were determined by an abrupt occlusion of the ascending aorta. VO2 linearly correlated with PVA in control contractile state, where Emax was 15.8 +/- 4.4 (SD) mmHg/ml with intact reflexes and 11.5 +/- 1.2 mmHg/ml with blocked reflexes. Emax and the VO2 axis intercept of the VO2-PVA line were greater in the in situ heart than in the excised cross-circulated dog heart in our previous study. Enhancement of contractile state by dobutamine increased Emax by 60-80% and shifted the VO2-PVA line upward, increasing the VO2 axis intercept by 38% with intact reflexes and by 79% with blocked reflexes. The slope had a tendency to increase with dobutamine, but the increase was statistically insignificant. We conclude that PVA and Emax obtained by the aortic-occlusion method can account for changes in VO2 with changes in loading conditions and contractility in an in situ dog heart.

Animals↗
PubMed1987

Left ventricular O2 consumption and pressure-volume area in puppies.

We studied the relation between O2 consumption (VO2) and systolic pressure-volume (PV) area (PVA) in the left ventricles of eight puppies (2-4 mo old). PVA is the area circumscribed by the end-systolic and end-diastolic PV curves and systolic PV trajectory. We assumed PVA to represent the total mechanical energy generated by ventricular contraction. We produced isovolumic contractions at different volumes in the left ventricles isolated and cross-circulated with adult dogs. VO2 closely correlated with PVA in each of control contractile state, an enhanced contractile state with epinephrine, and a depressed contractile state with propranolol in each heart. The slope of the regression line of VO2 on PVA was not significantly affected by epinephrine and propranolol. The regression line shifted upward with epinephrine and downward with propranolol. These characteristics of the puppy's VO2-PVA relation were comparable to those of the adult dog. These results suggest that similar relations hold between myocardial mechanics and energetics in both the puppy and adult dog despite the differences in the heart size and contractile properties.

Animals↗
PubMed1987

Force-time integral decreases with ejection despite constant oxygen consumption and pressure-volume area in dog left ventricle.

We have shown that systolic pressure-volume area (PVA), which is equivalent to the total mechanical energy generated by ventricular contraction, correlates linearly with myocardial oxygen consumption, VO2, in canine left ventricle. Systolic force-time integral, FTI, also correlates with VO2. In this study, stroke volume was increased from 0 (isovolumic) in isolated cross-circulated canine left ventricle in a stable contractile state while keeping PVA constant with a servo pump. Ventricular total force was calculated from ventricular pressure and volume by the force-equilibrium equation and was integrated from the end of diastole to the end of systole as identified with the time of Emax to yield FTI. Under the conditions of constant PVA, FTI significantly (p less than 0.001) decreased by 10 +/- 7% and 25 +/- 8% with increases in stroke volume from 0 to 8 +/- 4 ml and 17 +/- 3 ml and in ejection fraction from 0 to 0.24 +/- 0.10 and 0.61 +/- 0.05, respectively, while VO2 and Emax remained constant. Therefore, we conclude that in a stable contractile state, it is possible to keep PVA constant even when stroke volume and ejection fraction are varied and that under such conditions, FTI no longer predicts VO2. PVA remains a reliable predictor of VO2 regardless of ventricular loading conditions.

Animals↗
PubMed1987

Intact chordae tendineae increase ventricular volume measurement error by the balloon method.

We assessed the accuracy of the intraventricular balloon method of left ventricular volume measurement with all chordae tendineae intact and then severed. The space between the endocardium and the balloon is the source of the volume measurement error. We assessed the volume errors at different intra-balloon pressures between 50 and 250 mmHg, using formalin fixed canine left ventricles. The volume error with all chordae tendineae intact was significantly greater than with all chordae tendineae severed at any balloon pressure. The difference of the volume errors under these two conditions amounted to 1.9-3.3 ml regardless of intra-balloon pressures. We visually confirmed that this difference predominantly originated from the space behind the tense chordae tendineae.

Animals↗
PubMed1987

Dissociation of pressure-rate product from myocardial oxygen consumption in dog.

Although the pressure-rate product (double product; DP) is generally recognized as a good index of myocardial oxygen consumption (VO2), catecholamines are reported to change the VO2-DP relationship. However, the separate influences of chronotropism and inotropism on the VO2-DP relation have not been studied. Therefore, we examined these influences in anesthetized open-chest dogs by cardiac pacing and dobutamine infusion. We observed two different VO2-DP lines under the separate chronotropic and inotropic changes. We interpreted such VO2-DP relations by the concept of the pressure-volume area (PVA). PVA is a measure of total mechanical energy for ventricular contraction and is a specific area in the ventricular pressure-volume (P-V) diagram circumscribed by the end-systolic and end-diastolic P-V relation curves and the systolic segment of the P-V trajectory. The empirical VO2-PVA relation that had been obtained in our previous studies reasonably simulated the dissociation of DP from VO2 under separate changes in chronotropism and inotropism.

Animals↗
PubMed1987

[Non-invasive assessment of the peak pressure gradient between the aorta and pulmonary artery in patent ductus arteriosus].

The validity of continuous wave Doppler ultrasound estimation of the peak pressure gradient between the aorta (Ao) and pulmonary artery (PA) in patients with patent ductus arteriosus (PDA) was evaluated. Ten patients, all without other anomalies, underwent cardiac catheterization and cine-angiography, and the peak pressure gradient between the Ao and PA (dP(C)) was measured during catheterization. In all cases the mean PA pressure was less than 35 mmHg. According to the angiographic findings, the patients were categorized as Group A, consisting of seven patients whose features of the ductus were wedge- or tube-like in configuration; Group B, consisting of two patients whose features were termed "orifice-like" stenosis including one with abrupt narrowing on the PA side of the ductus and the other with a short segmental ductus. Group C consisted of one patient who had a long curved segmental ductus. The maximum velocity of ductus flow was measured by continuous wave Doppler ultrasonography, and the estimated peak pressure gradient between the Ao and PA by Doppler (dP(D] was calculated using the simplified Bernoulli equation (dP = 4V2). In group A, dP(D) was overestimated compared to dP(C) in all patients by 19 to 51 mmHg (mean 34 mmHg). However, in group B, the difference between dP(D) and dP(C) was small, 5 mmHg and 7 mmHg, respectively. In group C, dP(D) was underestimated as opposed to dP(C). Thus, in the limited cases, the simplified Bernoulli equation could be used in estimating the peak pressure gradient between the Ao and PA. However, this equation leads to overestimation in many cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗
PubMed1986

Exercise capacity of patients with post-operative tetralogy of Fallot.

Twenty-one patients with tetralogy of Fallot following intracardiac repair underwent a treadmill test for evaluation of their exercise capacity. They were divided into two groups according to their post-operative hemodynamic status, the good result group and the poor result group. The maximum oxygen consumption during exercise was significantly decreased in the poor result group, but that of the good result group showed no significant difference from the control group. However, the maximum heart rate in both the good and the poor result groups was significantly lower than that of the control group. Thus, the exercise tolerance in post-operative tetralogy patients was found to be within the normal range as long as their hemodynamic operative result was satisfactory, but the limited capability of increasing heart rate with exercise could present a potential problem in the long-term prognosis.

Adolescent↗
PubMed1986

[Pulsed Doppler echocardiographic estimation of pressure gradient across a ventricular septal defect: with particular reference to potential factors of error].

The clinical validity and some problems concerning pulsed Doppler echocardiography (PD) in non-invasive estimates of pressure difference (delta P) across a ventricular septal defect were studied. The maximum velocity (max V) of the left to right shunt flow in the right ventricle was converted to delta P using the simplified Bernoulli equation: delta P = 4V2. We also used the equation: delta P = 4(V2(2) - V1(2)) to estimate the delta P in cases who had left to right shunt flows of high velocity in the left ventricle. Simulatenous recordings of both left and right ventricular pressures and PD were obtained during cardiac catheterization of 11 cases. Accurate Doppler estimates of delta P only from the maximum velocity of the left to right shunt flow in the right ventricle were impossible in nine cases whose actual delta P's were large (more than 41 mmHg) and also in eight cases whose right ventricular systolic pressure was high (either equal to or higher than left ventricular systolic pressure). Besides these 17 cases, delta P estimated by PD using the simplified Bernoulli equation in 39 cases, with pansystolic left to right shunt flows in the right ventricle, correlated well with the actually measured delta P (Y = 0.99X + 2.77, r = 0.91, p less than 0.01). The difference in the maximal instantaneous pressure gradient and Doppler delta P was considered insignificant (between 0 and 7 mmHg, mean 4 mmHg). In nine cases, the left to right shunt flows of relatively high speed (0.63 approximately 2.00 m/sec, mean 1.31 m/sec) were observed also in the left ventricle, and calculated delta P using the simplified Bernoulli equation overestimated the actually measured delta P by 2 to 16 mmHg (Y = 1.52X + 4.88, r = 0.95, p less than 0.01). However, if the delta P is estimated by using the equation, delta P = 4(V2(2) - V1(2)), without ignoring the maximum speed in the left ventricle (V1), it correlates well with the actually measured delta P (Y = 1.07X + 0.76, r = 0.98, p less than 0.01). Thus, in cases with left to right shunt flows with high speeds in the left ventricle, the equation: delta P = 4(V2(2) - V1(2)) was more accurate in estimating the delta P by pulsed Doppler echocardiography.

Blood Pressure↗