Ju Mizuno

A new integrative method to quantify total Ca2+ handling and futile Ca2+ cycling in failing hearts

Ca2+ handling in excitation-contraction coupling requires considerable O2 consumption (Vo 2) in cardiac contraction. We have developed an integrative method to quantify total Ca2+ handling in normal hearts. However, its direct application to failing hearts, where futile Ca2+ cycling via the Ca2+-leaky sarcoplasmic reticulum (SR) required an increased Ca2+handling Vo 2, was not legitimate. To quantify total Ca2+ handling even in such failing hearts, we combined futile Ca2+ cycling with Ca2+ handling Vo 2 and the internal Ca2+ recirculation fraction via the SR. We applied this method to the canine heart mechanoenergetics before and after intracoronary ryanodine at nanomolar concentrations. We found that total Ca2+ handling per beat was halved after the ryanodine treatment from ∼60 μmol/kg left ventricle before ryanodine. We also found that futile Ca2+ cycling via the SR increased to >1 cycle/beat after ryanodine from presumably zero before ryanodine. These results support the applicability of the present method to the failing hearts with futile Ca2+ cycling via the SR.

O2 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°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 2intercept remained constant. Q10values 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 Ca2+handling integratively depress E max and augment its oxygen cost without affecting the oxygen cost of PVA as myocardial temperature increases by 10°C around normothermia.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.

Encephalopathy and rhabdomyolysis induced by iotrolan during epiduroscopy.

PurposeWe describe a complication of epiduroscopy with encephalopathy and rhabdomyolysis associated with the contrast medium iotrolan.Clinical featuresA 76-yr-old man with failed back surgery syndrome underwent epiduroscopy. Sufficient lysis could not be achieved in the epidural space above the level of L4 due to dense adhesions and scar tissue. After epidural injections of iotrolan and mepivacaine, he developed motor weakness and hypoesthesia in both legs, which lasted for three hours. He also became confused, agitated, disoriented, and developed neck stiffness and tremors involving the head and legs. Computed tomography revealed diffuse contrast enhancement within the intracranial cerebrospinal fluid (CSF) spaces, indicating an intraoperative dural tear. Marked increases in serum creatinine phosphokinase and myoglobin indicated subsequent acute rhabdomyolysis. Crystalloid infusion and semi-recumbent positioning facilitated iotrolan absorption from the CSF, and the patient recovered uneventfully.ConclusionsDural tear during epiduroscopy may allow access of contrast media into the CSF. Neurotoxicity secondary to iotrolan within the CSF was a likely contributing factor to the encephalopathy and subsequent rhabdomyolysis. This is an instructive example of the importance of diagnosing inadvertent dural tear during epiduroscopy under iotrolan, for avoidance of adverse events such as encephalopathy and rhabdomyolysis.RésuméObjectifNous décrivons une complication survenue lors d’une épiduroscopie avec le produit de contraste iotrolan consistant en une encéphalopathie et une rhabdomyolyse.Eléments cliniquesUn homme de 76 ans présentant des séquelles d’un échec d’une chirurgie aux rachis a subi une épiduroscopie. Une lyse suffisante n’a pas pu être obtenue dans l’espace péridural au-dessus de L4 à cause d’adhésions denses et de tissus cicatriciels. Suite à des injections péridurales d’iotrolan et de mépivacaïne, il a développé une parésie ainsi qu’une hypoesthésie au niveau des membres inférieurs qui durèrent trois heures. Il est également devenu confus, agité, désorienté, et a développé une raideur du cou et des tremblements de la tête et des jambes. La tomodensitométrie a révélé un rehaussement diffus du produit de contraste dans les espaces intracrâniens du liquide céphalo-rachidien (LCR), indiquant une déchirure péropératoire de la dure-mère. Des augmentations significatives de la créatinine-phosphokinase sérique et de la myoglobine signalant une rhabdomyolyse aiguë ultérieure ont été observées. Une perfusion de cristalloïde ainsi qu’un positionnement semi-allongé ont facilité l’absorption de l’iotrolan du LCR, et le patient s’est rétabli sans problème.ConclusionsLa déchirure de la dure-mère durant l’épiduroscopie peuvent permettre l’injection de produit de contraste dans le LCR. Une neurotoxicité due à l’iotrolan dans le LCR est un facteur qui a possiblement contribué à l’encéphalopathie et à la rhabdomyolyse subséquente. Ceci est un exemple instructif de l’importance du diagnostic de la déchirure de la dure-mère commises par inadvertence durant l’épiduroscopie sous iotrolan, afin d’éviter des complications telles que l’encéphalopathie et la rhabdomyolyse.

Starling-effect-independent lusitropism index in canine left ventricle: logistic time constant.

The logistic time constant (&tgr;L) has been proposed as a better index of the rate of left ventricular (LV) relaxation or lusitropism than the conventional monoexponential time constant (&tgr;E). However, whether and how the Frank-Starling effect influences &tgr;L remains to be elucidated. We compared the effect of LV volume (LVV) loading on both logistic and monoexponential fittings. The isovolumic LV relaxation pressure curves from the maximum negative time derivative of pressure (-dP/dtmax) were analyzed at 3 different end-points at 4 LVVs of 10, 12, 14, and 16 mL in 8 excised, cross-circulated canine hearts. We found that the logistic fitting was superior to the monoexponential fitting at all LVVs and end-points. LVV loading did not affect &tgr;L but affected &tgr;E slightly. Although the advancing end-point increased both &tgr;L and &tgr;E, the increases were significantly smaller for &tgr;L than for &tgr;E at all LVVs. Moreover, the changes in both the amplitude constants and nonzero asymptotes with the advancing end-point were significantly smaller for the logistic fitting than for the monoexponential fitting. We conclude that &tgr;L served as a more reliable index of lusitropism that is independent of the change in LVV loading or the Frank-Starling effect.

Total Ca handling in canine mild Ca overload failing heart

SummaryWe 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 10min followed by high-Ca (16 mmol/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 ofEmax. However, LV O2 consumption under mechanically unloading conditions decreased by 30% from control without increasing the O2 cost ofEmax. 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 decreasedEmax and the unchanged O2 cost ofEmax 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 ofEmax, or both. Any of these three possible changes can account for the unchanged O2 cost ofEmax. 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.

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.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.

Male sex, height, weight, and body mass index can increase external pressure to calf region using knee-crutch-type leg holder system in lithotomy position

Background Well-leg compartment syndrome (WLCS) is one of the catastrophic complications related to prolonged surgical procedures performed in the lithotomy position, using a knee-crutch-type leg holder (KCLH) system, to support the popliteal fossae and calf regions. Obesity has been implicated as a risk factor in the lithotomy position-related WLCS during surgery. In the present study, we investigated the relationship between the external pressure (EP) applied to the calf region using a KCLH system in the lithotomy position and selected physical characteristics. Methods Twenty-one young, healthy volunteers (21.4±0.5 years of age, eleven males and ten females) participated in this study. The KCLH system used was Knee Crutch®. We assessed four types of EPs applied to the calf region: box pressure, peak box pressure, contact pressure, and peak contact pressure, using pressure-distribution measurement system (BIG-MAT®). Relationships between these four EPs to the calf regions of both lower legs and a series of physical characteristics (sex, height, weight, and body mass index [BMI]) were analyzed. Results All four EPs applied to the bilateral calf regions were higher in males than in females. For all subjects, significant positive correlations were observed between all four EPs and height, weight, and BMI. Conclusion EP applied to the calf region is higher in males than in females when the subject is supported by a KCLH system in the lithotomy position. In addition, EP increases with the increase in height, weight, and BMI. Therefore, male sex, height, weight, and BMI may contribute to the risk of inducing WLCS.

Factors that increase external pressure to the fibular head region, but not medial region, during use of a knee-crutch/leg-holder system in the lithotomy position

Background Paralysis of the common peroneal nerve is one of the relatively common nerve injuries related to the lithotomy position with the use of a knee-crutch/leg-holder system. Several risk factors have been implicated in lithotomy position-related common peroneal nerve paralysis during operation. Materials and methods In the present study, 21 young healthy volunteers participated in the investigation of the causes of the paralysis of the common peroneal nerve in the lithotomy position using a knee-crutch/leg-holder; Knee Crutch. We assessed the external pressure applied to the fibular head and medial regions using the Big-Mat pressure-distribution measurement system. Relationships between the peak contact pressure and physical characteristics, such as sex, height, weight, body mass index (BMI), and fibular head circumference, were analyzed. Results The peak contact pressure to the fibular head region was greater for males than for females. For all subjects, significant positive correlations were observed between the peak contact pressure to the fibular head region and weight, BMI, or fibular head circumference. However, there was no significant difference between the peak contact pressure to the fibular head region and height for any subjects. Moreover, there was no sex-related difference in the peak contact pressure to the fibular medial region, and no significant differences between the peak contact pressure to the fibular medial region and height, weight, BMI, or fibular head circumference. Conclusion External pressure to the fibular head region is greater for males than for females using a knee-crutch/leg-holder system in the lithotomy position. In addition, the external pressure to the fibular head region, but not the fibular medial region, increases with increasing weight, BMI, and fibular head circumference. Therefore, these patient-related characteristics may contribute to the risk of developing lower-extremity neuropathy, leading to injury or ischemia of the common peroneal nerve.

Effect of 2.5% sevoflurane, at PaCO2 30 mmHg for epileptic focus resection, on hemodynamics and hepatic and renal functions

* 1 * P < 0.05; 2* P < 0.001 compared with Pre; 3* P < 0.05 compared with 2 h; 4* P < 0.05 compared with 4 h Values are means ± SD (n = 5, excluding 8 h (n = 4)). The differences in heart rate, systolic blood pressure, and body temperature values among the five time points were compared by one-way repeated measures analysis of variance (RANOVA), following the PLSD test Pre, pre-anesthesia induction; 2 h, 2 h after anesthesia induction; 4 h, 4 h after anesthesia induction; 6 h, 6 h after anesthesia induction; 8 h, 8 h after anesthesia induction

Half-Logistic Function Model for First Half of Descending Phase of Cardiomyocyte Cytoplasmic Ca2+ Concentration ([Ca2+]i)-Time Curve (CaTCIII) in Isolated Aequorin-Injected Mouse Left Ventricular Papillary Muscle

BACKGROUND Myocardial contraction and relaxation are regulated by increases and decreases in cytoplasmic calcium concentration ([Ca(2+)]i). In previous studies, we found that a half-logistic (h-L) function, which represents a half-curve of a symmetrical sigmoid logistic function with a boundary at the inflection point, curve-fits the first half of the ascending phase and the second half of the descending phase of the [Ca(2+)]i transient curve better than a mono-exponential (m-E) function. In the present study, we investigated the potential application of an h-L function to analyse the first half of the descending phase of CaTC (CaTCIII). METHODS The [Ca(2+)]i was measured using the Ca(2+)-sensitive aequorin, which was microinjected into 15 isolated mouse left ventricular (LV) papillary muscles. The observed CaTCIII data in the interval from the point corresponding to the peak [Ca(2+)]i to the point corresponding to dCa/dtmin was curve-fitted using the h-L and m-E function equations by the least-squares method. RESULTS The mean correlation coefficient (r) values of the h-L and m-E function best curve-fits for 11 CaTCIIIs were 0.9986 and 0.9982, respectively. The Z transformation of h-L r (3.64 ± 0.45) was larger than that of m-E r (3.50 ± 0.33) (p < 0.05). CONCLUSIONS The h-L function can evaluate most CaTCIIIs more accurately than the m-E function in isolated aequorin-injected mouse LV papillary muscle. The three calculated h-L parameters i.e., amplitude constant, time constant, and non-zero asymptote, are more reliable indices than m-E for evaluating the magnitude and time course of the change in the decrease in [Ca(2+)]i. KEY WORDS Ca(2+) transient; Half-logistic amplitude constant; Half-logistic non-zero asymptote; Half-logistic time constant; Myocardial Ca(2+) handling.