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Biomedical subjects

H Suga

Publications and source records attributed to H Suga.

At least 199 records · Page 11Linked to original sources

Variable series elasticity accounts for Fenn effects of skeletal and cardiac muscles.

The Fenn effect differs between skeletal and cardiac muscles in the magnitude of energy consumption of shortening contraction relative to isometric contraction at the same preload. The former is typically greater than the latter in the skeletal muscle, whereas the former is smaller than the latter in the cardiac muscle. The present theoretical study examined whether the different Fenn effects could be accounted for by different compliances of the series elasticity (SE) in different muscles. A two-element model consisting of an idealized contractile element (CE) and an SE was used. The compliance of the SE was assumed to be variable. Results show that the skeletal Fenn effect can be simulated when SE is stiff and the cardiac Fenn effect can be simulated when SE is compliant. Moreover, when SE is compliant the total work of CE approximates for force-length area, which has been proposed as a measure of the total mechanical energy and shown to correlate linearly with myocardial oxygen consumption.

Biomechanical Phenomena↗

Simulation of mechanoenergetics of asynchronously contracting ventricle.

We simulated mechanoenergetics of ventricular asynchronous contraction using a model comprising two compartmentalized asynchronous time-varying elastic elements, E1 and E2. Their elastances [e1(t) and e2(t)] waxed and waned cyclically with a variable time lag (tau). The pressure-volume area (PVA1 or PVA2) circumscribed by the maximum (emax) and minimum e1(t) or e2(t) lines and the contracting pressure-volume trajectory of E1 or E2 quantifies the mechanical energy generated by a contraction of E1 or E2. Similarly, the PVA circumscribed by the resultant Emax (ventricular contractility index) line, the end-diastolic pressure-volume (P-V) line, and the systolic P-V trajectory quantifies the mechanical energy of the entire ventricle. PVA of the ventricle is equal to the sum of PVA1 and PVA2. We found that Emax decreased with increases in tau despite constant emax, and hence ventricular PVA decreased with increases in tau. This simulation helps us to better understand the mechanism of decreased oxygen consumption with increasing ventricular asynchrony reported in the literature.

Animals↗

Effects of bigeminies and paired-pulse stimulation on oxygen consumption in dog left ventricle.

In 10 excised, cross-circulated, isovolumically beating dog left ventricles, we examined the effects of bigeminy, including paired-pulse stimulation, on cardiac oxygen consumption (VO2) and evaluated whether the VO2 versus pressure-volume area (PVA) relation obtained from regularly beating hearts in our previous studies could account for the changes in VO2 during bigeminies with various coupling intervals. The extrasystolic interval (ESI) was decreased in four steps from 300 msec (regular rhythm) to paired-pulse stimulation (less than or equal to 210 msec). The sum of ESI and the postextrasystolic interval was always held constant (600 msec); therefore, the number of excitations was 200/min at any ESI. Both VO2 and PVA were measured in four runs: a small volume run at a ventricular volume of 13 ml, a large volume of 12 ml, a calcium run in which contractility was enhanced by CaCl2 at a small volume of 12 ml, and a verapamil run in which contractility was depressed by verapamil at a large volume of 20 ml. In any run, both VO2 and PVA were unchanged at long ESIs (greater than or equal to 250 msec) from each control value at regular rhythm, but VO2 markedly increased at short ESIs (less than or equal to 230 msec). VO2s during bigeminies with various ESIs were comparable with the theoretical VO2 values that were calculated by the VO2-PVA relation at regular rhythm. However, the theoretical VO2 values underestimated the measured VO2 values at the shortest ESIs under a high volume loading and in a high contractile state. This indicates that the PVA concept can be expanded to various arrhythmias unless ESI becomes very short.

Animals↗

Energetics of the time-varying elastance model, a visco-elastic model, matches Mommaerts' unifying concept of the Fenn effect of muscle.

It is generally believed that the Fenn effect contradicts all visco-elastic models of muscle, including the new elastic body and the time-varying elastance models. Although it is clear that the new elastic body model can be discarded, the Fenn effect does not preclude the time-varying elastance model. Although no visco-elastic models can simulate the extra energy utilization for work above the level of the energy utilized for the maximal isometric contraction, the extra energy observed by Fenn is not generally observed, even in skeletal muscles. However, work-related extra energy utilization, above the isometric energy utilization at equivalent force (Mommaerts' unifying concept of the Fenn effect), is generally observed in both skeletal and cardiac muscles. This unifying concept of the Fenn effect in cardiac muscle can be simulated by a simple time-varying elastance model. This study demonstrates the essential difference in energetics between the new elastic body model and the time-varying elastance model.

Elasticity↗

New method to determine oxygen cost for contractility.

We developed a new method to determine the oxygen cost for myocardial contractility and applied it to epinephrine in the excised cross-circulated dog heart. We utilized the relation between myocardial oxygen consumption (VO2) and the systolic pressure-volume area (PVA) which represents the total mechanical energy generated by contraction. We first obtained a reference VO2-PVA relation in a baseline contractile state. Then, the end-diastolic and stroke volumes were fixed constant and a global index of ventricular contractility, Emax, was enhanced by infusing epinephrine. The VO2-PVA data point was shifted linearly right-upward with the increases in Emax. From the slopes of both the reference VO2-PVA relation line and the regression line of VO2 on PVA during the gradually increased Emax, we calculated the oxygen cost for contractility, i.e., the ratio of the elevation of the VO2-PVA relation to enhanced Emax in each heart. The ratio was 0.00095 +/- 0.00013 ml O2.ml.mmHg-1.beat-1.100 g LV-2. The result indicates that the oxygen cost for contractility can be reliably and efficiently determined by this new method.

Animals↗

Heart-rate-proportional oxygen consumption for constant cardiac work in dog heart.

We studied whether there is an optimal heart rate (HR) that would minimize myocardial oxygen consumption (MVO2) per min for a constant minute cardiac work. We measured minute MVO2 (ml O2/min) of the left ventricle paced at increasing rates (100-200 beats/min) in 10 right-heart-bypassed dogs. In each experiment, cardiac output was kept constant with a constant-flow bypass pump, and mean aortic pressure was also kept constant by inflation or deflation of an intra-aortic balloon. Minute cardiac work was thus kept constant. Minute MVO2 was obtained as the product of mean coronary arteriovenous O2 difference and mean coronary blood flow drained from the collapsed right ventricle. Both left ventricular Emax (contractility index defined as the slope of the left ventricular end-systolic pressure-volume relation) and PVA (pressure-volume area as a measure of total mechanical energy of contraction) were obtained by an abrupt aortic occlusion method. The obtained-minute MVO2-HR relationship showed a good linear positive correlation (r = 0.824-0.995) in every heart. We accounted for this relationship by the changes in PVA and Emax that we had proposed as primary determinants of MVO2. We conclude that minute MVO2 for a constant minute cardiac work increased monotonically with increases in HR from 100 to 200 beats/min, being minimum at the lowest HR, and that this relation was ascribable to the HR-proportional increase in the MVO2 component for the excitation-contraction coupling.

Animals↗

Comparison between Bretschneider's total myocardial energy demand (Et) and our total mechanical energy (PVA) as a predictor of cardiac oxygen consumption in dogs.

We compared the predictive capability of two indexes of ventricular oxygen consumption (VO2) in excised cross-circulated dog hearts. One of the indexes was Bretschneider's Et, formulated as the sum of energies for 5 different mechanical and nonmechanical activities of myocardium. The other one was the left ventricular systolic pressure-volume area (PVA), originally proposed by Suga. PVA is a measure of total mechanical energy and has been combined with Emax (ventricular contractility index) to predict VO2 in different inotropic states. When all data sampled from different hearts under various loading and inotropic conditions were pooled, both VO2 (Bret) predicted from Bretschneider's index and VO2 (Suga) predicted from Suga's index correlated well with the measured VO2 (VO2 (Measured)). However, VO2 (Bret) was more affected by the contraction mode as compared with VO2 (Suga), because the former includes ejection period as a parameter. Among the 5 terms of VO2 (Bret), the major correlate of VO2 (Measured) was found to be tension development energy term E3 which includes dP/dtmax as a parameter. VO2(Suga), as a predictive index of VO2 (Measured), was more reliable in each heart than in pooled data from all the hearts because of the interindividual variations of the coefficients. We conclude that both indexes have usefulness and limitations, and should be chosen depending on the application.

Animals↗

A low CA++ level in effluent as a risk factor for the peritonitis in CAPD patients.

In vitro, some studies revealed the importance of the CA++ level in peritoneal macrophage functions in CAPD patients. We therefore retrospectively studied the relationship between the frequency of peritonitis and the concentration of Ca, Ca++, Interferon-r (IFN-gamma), Interleukin-1B (IL-1B) in the Pd effluent. Samples were taken during a peritonitis-free period. In a group of patients without peritonitis, the mean Ca++ level in the Pd effluent was 2.25 +/- 0.20 mEq/L, while in the other group with frequent episodes of peritonitis (more than one episode per 20 patient-months), the mean Ca++ level in PD effluent was 2.01 +/- 0.13 mEq/L which was significantly lower than the former (p less than 0.05). The mean Ca concentration in Pd effluent was also lower in the group with the high frequent peritonitis than the peritonitis-free group, but not significantly. The level of IFN-gamma is lower and IL-1B is higher in the group with frequent peritonitis than in the peritonitis-free group, although these differences were not significant. These evidences suggest that lower Ca++ level in the effluent of the frequent peritonitis group may impair the peritoneal macrophage function and peritoneal cell-mediated immune function and may increase a risk of the peritonitis. These results may offer a new approach for prophylaxis of peritonitis in CAPD patients.

Calcium↗

Cardiac mechanics and energetics--from Emax to PVA.

After these seven decades of cardiac mechanics, through the windows of Starling's cardiac output curve followed by Sonnenblick's myocardial force-velocity relation and Vmax, Frank's ventricular pressure-volume (P-V) relationship has revived as a window of cardiac mechanics over the past two decades following the proposal of the Emax concept by Suga and Sagawa. Emax is a physically sound measure of ventricular contractile compressibility or time-varying volume elastance at end systole. Although the original Emax concept has been slightly modified to improve its fitness to reality, the Emax concept has successfully survived over two decades as a basic conceptual framework of ventricular contraction in physiological, pathophysiological and clinical studies. An important expansion of the Emax concept was introduced by Suga a decade ago, and a new window for cardiac energetics was opened up by the concept of PVA as a measure of the total contractile energy generated by ventricular contraction. PVA correlates with ventricular oxygen consumption, with Emax as a decisive parameter. Moreover, Emax and PVA combined with effective arterial elastance Ea as a new afterload parameter proposed by Sunagawa and Sagawa have enabled us to predict cardiac energetics under a variety of loading and contractile conditions. The key advances of the Emax and PVA concepts are reviewed mainly in the biomedical engineering aspects by the proposer of these concepts himself.

Animals↗

Assessment of left ventricular regional work under ischemia.

The wall tension-regional area (T-A) loop method, a new approach assessing regional contractile function of the left ventricle, has been developed in experiments performed on the isolated dog heart. Regional work is quantitatively determined by the area within a T-A loop with physically correct dimensions of energy (Joule) and regional contractility can be reliably assessed by the end-systolic T-A relation (ESTAR). During global ischemia, both the T-A loop area and the slope of the linear ESTAR decreased in proportion to the decreases in left ventricular stroke work and contractility. During regional ischemia, the T-A loop area in an ischemic region decreased to near zero, and the ESTAR markedly shifted to the right with a decreased slope and an increased regional area intercept. In contrast, the T-A loop in a non-ischematic region showed an increase in systolic area shrinkage and a decrease in regional work, demonstrating hyperkinesis due to regional afterload reduction. In addition, the ESTAR in a non-ischemic region remained almost unchanged. Thus, using the T-A loop method we can reliably assess regional work and contractility of a left ventricular region under ischemia.

Animals↗

Effect of ouabain on the relation between left ventricular oxygen consumption and systolic pressure-volume area (PVA) in dog heart.

We studied the effect of ouabain (digitalis) on the relation between left ventricular (LV) O2 consumption (VO2) and pressure-volume (P-V) area (PVA) in 7 excised cross-circulated canine heart preparations. PVA is a measure of the total mechanical energy generated by LV contraction and was obtained as the specific area in the P-V diagram circumscribed by the end-systolic P-V line, end-diastolic P-V curve, and the systolic P-V trajectory. Ouabain (0.11 mg, intracoronary-arterially) increased Emax (LV contractility index) by 58 +/- 44% (mean +/- SD) from 7.8 +/- 3.4 to 12.0 +/- 4.8 mmHg/(ml/100 g LV). PVA correlated linearly with LV VO2 per beat in either the control (r greater than 0.97) or the ouabain run (r greater than 0.96) in individual hearts. Ouabain increased the VO2-axis intercept of the regression line of VO2 on PVA from 0.029 +/- 0.004 in the control run to 0.036 +/- 0.009 ml O2/beat/100 g LV without significantly changing the slope [(1.53 +/- 0.24).10(-5) ml O2/(mmHg/ml)] of the regression line. This slope is equivalent to the contractile efficiency value of 44 +/- 6% from the excess VO2 above unloaded VO2 to PVA. The parallel elevation of the VO2-PVA relation with ouabain was similar to the results produced by epinephrine and Ca2+ in our previous studies. Ouabain, like epinephrine and Ca2+, did not change the contractile efficiency from the PVA-dependent fraction of VO2 to PVA.

Animals↗

Minor preload dependence of O2 consumption of unloaded contraction in dog heart.

We studied whether end-diastolic volume (EDV) would affect myocardial oxygen consumption (VO2) of mechanically unloaded contraction in the cross-circulated dog heart, as expected from the concept of the myocardial length-dependent activation. We made preloaded but maximally unloaded contractions from different EDVs by quickly releasing ventricular volume to eliminate systolic pressure development and hence to minimize the VO2 for mechanical load during the contraction. We then studied the relation between VO2 and EDV. The VO2 of the almost unloaded contraction from a relatively large EDV slightly exceeded the VO2 of the isovolumic contraction at V0, where V0 is the volume at which peak isovolumic pressure was zero. However, the excess VO2 could be ascribed to the residual systolic pressure-volume area (PVA) adversely produced from the large EDV, where PVA is a measure of the total mechanical energy generated during contraction. Therefore, we considered that VO2 was practically little dependent on EDV. We interpreted this finding as an indication that an increase, if any, in VO2 due to the length-dependent activation of the excitation-contraction coupling was practically negligible in the whole heart preparation.

Animals↗

Arteriovenous oximeter for O2 content difference, O2 saturations, and hemoglobin content.

We combined two spectrophotometric oximeters to measure continuously and simultaneously arteriovenous O2 content difference (AVOD) as well as arterial and venous oxyhemoglobin saturations (SaO2, SvO2) and total hemoglobin concentration (Hb). AVOD of the flowing arterial and venous whole blood was determined by the method of Guyton et al. (J. Appl. Physiol. 10: 158-163, 1957) and Shepherd and Burgar [Am. J. Physiol. 232 (Heart Circ. Physiol. 1): H437-H440, 1977]. The new arteriovenous oximeter was tested in dog experiments in which SaO2, SvO2, Hb, and AVOD were variously changed by temporary suffocation, electric muscle stimulation, hemorrhage and transfusion, and hemodilution with saline. AVOD, SaO2, SvO2, and Hb were compared with the data of the arterial and venous blood sampled near the oximeter cuvettes and measured with an IL282 CO oximeter. In one dog experiment and one in vitro blood experiment, AVOD data of the same arterial and venous blood were compared by connecting the present oximeter in series with an A-VOX Systems oximeter developed by Shepherd and Burgar. The results showed that the new arteriovenous oximeter can continuously measure AVOD, SaO2, SvO2, and Hb over wide ranges with reasonable accuracy.

Animals↗

Time-invariant oxygen cost of mechanical energy in dog left ventricle: consistency and inconsistency of time-varying elastance model with myocardial energetics.

We studied whether the oxygen cost of mechanical energy is time-invariant in the excised, cross-circulated canine heart. The total mechanical energy generated by ventricular contraction can be quantified by the total pressure-volume area (PVA) according to the time-varying elastance model. In this model, mechanical energy generated until a specified time (t) during systole can be quantified by the partial pressure-volume area, PVA(t). PVA(t) was obtained by quickly releasing ventricular volume at a varied time during isovolumic contraction. The quick release aborted further development of mechanical energy. We found that PVA(t) at a constant end-diastolic volume linearly correlated with myocardial oxygen consumption (VO2). This indicates that the oxygen cost of mechanical energy is time-invariant. However, we also found that the slope of the VO2-PVA(t) relation decreased with increasing quick-release speed. This indicates a decrease in VO2 by the quick release despite the same PVA(t). The time-invariant oxygen cost of mechanical energy is consistent with the time-varying elastance model of the ventricle, but the decreased VO2 with increasing quick-release speed despite the same PVA(t) is not.

Animals↗

The linear relation between oxygen consumption and pressure-volume area can be reconciled with the Fenn effect in dog left ventricle.

We studied the Fenn effect in 12 excised cross-circulated dog left ventricles in control contractility and in a contractility enhanced by dobutamine or depressed by propranolol. The additional oxygen consumption (Vo2) in an ejecting contraction compared with that found in an isovolumic contraction at a comparable end-systolic pressure was considered to constitute the cardiac Fenn effect. We examined whether this load-dependent Vo2 could be reconciled with the linear relation between Vo2 and pressure-volume area (PVA) common for both ejecting and isovolumic contractions that has so far been consistently observed and was presently confirmed. PVA is a specific area in the pressure-volume diagram, represents the total mechanical energy generated by each contraction, and consists of external mechanical work (EW) and mechanical potential energy. Because potential energy is common in the isovolumic and ejecting contractions producing the same end-systolic pressure, PVA of the ejecting contraction is greater by EW than that of the isovolumic contraction. Despite this difference in PVA by EW, the Vo2-PVA relation was always linear and load independent regardless of the isovolumic and ejecting contractions in a given heart in any given contractile state. By contrast, the upward convex Vo2-end-systolic pressure relation was higher for ejecting contractions than the downward convex Vo2-end-systolic pressure relation for isovolumic contractions in each contractile state. The difference of Vo2 between the ejecting and isovolumic contractions was proportional to EW at comparable end-systolic pressure. The slope of the additional Vo2 of ejecting contractions plotted against their EW had a slope close to the slope of the Vo2-PVA relation. Thus, the load-independent linear Vo2-PVA relation can be reconciled with the cardiac Fenn effect.

Animals↗