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Biomedical subjects

H Komai

Publications and source records attributed to H Komai.

At least 55 records · Page 3Linked to original sources
PubMed1993

Increased lung injury in pulmonary hypertensive patients during open heart operations.

To investigate lung injury in adult open heart operations during extracorporeal circulation, we measured plasma chemiluminescence levels. Nineteen patients were divided into two groups depending on preoperative pulmonary artery pressure: a pulmonary hypertension group (n = 11) and a control group (n = 8). Plasma samples were taken simultaneously from arterial and central venous lines at six different points during and early after operation. Arteriovenous difference of chemiluminescence (counts/10 seconds) increased significantly only in the pulmonary hypertension group (from -19.1 +/- 8.3 at the end of cross-clamping to 23.7 +/- 12.4 at the end of bypass; p < 0.01). There was a positive correlation between peak values of arterial plasma chemiluminescence and postoperative respiratory index in the pulmonary hypertension group (p < 0.05). In addition, during the first 12 hours postoperatively, arteriovenous difference of chemiluminescence in the pulmonary hypertension group changed significantly from negative to positive values (p < 0.05). These data suggest that free radical activity (detected by chemiluminescence) was deeply involved in lung injury during and also early after open heart operations, especially in pulmonary hypertensive patients.

Adult↗
PubMed1993

Effects of inhibition of transsarcolemmal calcium influx by nickel on force of postrest contraction and on contracture induced by rapid cooling.

OBJECTIVE: The aim was to characterise the influence of a decrease in transsarcolemmal calcium influx on the calcium content of the sarcoplasmic reticulum and on the force of postrest contraction, which is largely activated by calcium released from the sarcoplasmic reticulum. METHODS: Isometric force of postrest contractions in isolated rabbit papillary muscles was measured in the absence and in the presence of ryanodine (1 microM). The force measured in the presence of ryanodine was used as an index of transsarcolemmal calcium influx. The calcium content of the sarcoplasmic reticulum was estimated by rapid cooling induced contracture measurements. Nickel (Ni2+) was used to decrease the calcium influx, and the results were compared to those obtained by lowering the extracellular calcium concentration. RESULTS: The addition of Ni2+ or lowering extracellular Ca2+ markedly decreased the force of postrest contraction measured in the presence of ryanodine, and moderately decreased the force of postrest contraction measured in the absence of ryanodine. Neither the addition of Ni2+ nor lowering extracellular Ca2+ decreased maximum rapid cooling induced contracture; this was actually increased in the presence of Ni2+ even though a larger number of stimuli was required in the presence than in the absence of Ni2+ for the force of the subsequently elicited contracture to reach the maximum level. CONCLUSIONS: The results suggest: (1) that a decrease in the calcium influx reduces the force of the postrest contraction by decreasing the amount of calcium required to trigger the release of calcium from the sarcoplasmic reticulum, without decreasing its maximum calcium content; and (2) that Ni2+ decreases the rate of filling of sarcoplasmic reticular calcium stores even though the calcium content of the sarcoplasmic reticulum after a sufficiently large number of beats is higher in the presence of Ni2+ than in its absence.

Animals↗
PubMed1993

Increased plasma levels of endothelin-1 after cardiopulmonary bypass in patients with pulmonary hypertension and congenital heart disease.

The plasma level of the potent vasoconstrictor endothelin-1 was measured in children who underwent cardiac operations. Forty-five patients were divided into two groups, those with a high pulmonary blood flow (HF group; n = 23) and those with a normal or low flow (NF group; n = 22). Seven blood samples were taken: immediately before cardiopulmonary bypass, immediately after removing the aortic cross-clamps, immediately after discontinuing bypass, and at 20 minutes and 3, 6, and 24 hours after termination of bypass. The plasma levels of endothelin-1 were similar in both groups before bypass. From the time the aortic crossclamps were removed, the plasma endothelin-1 levels in both groups increased significantly, to reach a peak level at 3 to 6 hours. The increase was significantly greater in the HF than in the NF group, and the maximum values in the two groups were 12.6 +/- 1.1 and 9.6 +/- 0.8 fmol/ml, respectively (mean +/- standard error of the mean, p < 0.05). The value 20 minutes after bypass showed a positive correlation with the mean pulmonary arterial pressure measured at the preoperative cardiac catheterization study (r = 0.41, p < 0.05). In addition, a significant positive correlation was obtained between endothelin-1 3 hours after bypass and the maximum pulmonary/systemic arterial pressure ratio during the first 12 hours after operation (r = 0.86, p < 0.05). These results suggest that cardiopulmonary bypass is associated with an immediate postoperative increase in circulating endothelin and that patients who had a high pulmonary blood flow before the operation are particularly vulnerable, bypass having a more injurious effect on a lung with preexisting endothelial dysfunction. A high level of circulating endothelin may predispose to pulmonary vascular lability and pulmonary hypertensive crises in the postoperative period.

Adolescent↗
PubMed1993

[Clinical application of recombinant human SOD for the protection of ischemia reperfusion injury during open heart surgery].

We have applied recombinant human superoxide dismutase (RH-SOD) to prevent ischemia reperfusion injury in the patients who received open heart surgery. Twenty-four patients were divided into 2 groups; group A had no treatment as control and group B received bolus injection of RH-SOD (35,000 IU/kg) into cardiopulmonary bypass 5 minutes before reperfusion. Arterial and coronary sinus blood was collected to measure chemiluminescence (ChL) value, SOD activity, lactate and pyruvate level, and several parameters of myocardial oxygen metabolism after reperfusion. Arterio-venous difference of ChL value showed the tendency of less ChL generation of the heart in group B compared with those in group A. But no other parameters showed significant difference between the two groups. Our data suggested that this way of the administration of RH-SOD failed to improve the myocardial protection during open heart surgery. Further investigation, such as dose response study, might be required to determine whether RH-SOD possess beneficial effects or not in the clinical setting.

Heart Arrest, Induced↗
PubMed1991

Contribution of the known subcellular effects of anesthetics to their negative inotropic effect in intact myocardium.

The results of these studies suggest that halothane, in addition to its effect of reducing the trans-sarcolemmal Ca2+ influx, has a direct effect on the function of the sarcoplasmic reticulum by making the organelle leaky to Ca2+ and reducing the amount of Ca2+ stored. Isoflurane, on the other hand, does not appear to make the sarcoplasmic reticulum leaky to Ca2+. In fact, our observations suggest that isoflurane makes the sarcoplasmic reticulum less leaky to Ca2+. Halothane may enhance the reduction in the myofibrillar response to activator Ca2+ when the muscle fiber length is shortened. Thiopental appears to reduce the trans-sarcolemmal Ca2+ influx without reducing the amount of Ca2+ stored in the sarcoplasmic reticulum.

Anesthetics↗
PubMed1991

Harmful effects of inotropic agents on myocardial protection.

Using an isolated working rat heart model, the pretreatment effects of positive inotropic agents on ischemia-reperfusion injury were investigated. The experiment consisted of (1) working control perfusion; (2) working perfusion with isoproterenol (I), milrinone (M), a combination of these drugs (I + M) and dibutyl-cyclic adenosine monophosphate (DB) followed by ischemic arrest for 33 minutes at 37 degrees C or 150 minutes at 20 degrees C and Langendorff reperfusion; and (3) working perfusion. Under conditions of normothermic ischemia, percent recoveries of postischemic cardiac output (mean +/- standard error of the mean) in the I, M, I + M, and DB groups were 37.8% +/- 12.7%, 61.3% +/- 3.1%, 0%, and 53.1% +/- 5.2%, respectively. Under conditions of hypothermic ischemia, the percent recoveries in I + M and DB groups were 10.9% +/- 7.9% and 29.8% +/- 9.5%; they were all significantly lower than that in the control group. The addition of diltiazem or ryanodine at several concentrations and lowering of the Ca2+ concentration in the St. Thomas' cardioplegic solution did not prevent I + M-induced injury. Our data suggest that pretreatment by I + M aggravated ischemia-reperfusion injury, and adjustments in Ca2+ concentration were not sufficient to prevent that injury.

Animals↗
PubMed1991

Effects of thiopental and halothane on spontaneous contractile activity induced in isolated ventricular muscles of the rabbit.

To see if the known properties of thiopental of reducing Ca2+ and K+ fluxes across the myocardial sarcolemma account for its arrhythmogenic action, we have evaluated the effect of the anesthetic on spontaneous contractile activity induced in isolated rabbit papillary muscles. Thiopental (20 mg/l) prolonged the duration of sustained automaticity induced by stimulation at 1-2 Hz in the presence of 1 mumol/l isoproterenol. Thiopental (10, 20 mg/l) shortened the delay before the onset of Ba(2+)-induced automaticity, which involves a decrease in a K+ current. The minimum concentration of Ba2+ required to induce automaticity was lowered by thiopental. Whether spontaneous activities were induced by high frequency stimulation in the presence of isoproterenol or by Ba2+, thiopental lowered the frequency of spontaneous beats. Thus, thiopental appears to have both arrhythmogenic and antiarrhythmic actions, and the former may be unmasked when catecholamines counteract the latter by increasing Ca2+ influx. Like thiopental, halothane (1.0%) decreased the frequency and force of Ba(2+)-induced automatic beats but, unlike thiopental, prolonged the delay before the onset of Ba(2+)-induced automaticity, indicating that halothane acts as a purely antiarrhythmic agent in this type of automaticity.

Animals↗
PubMed1991

[The effects of calcium concentration of reperfusion solution upon myocardial protection].

The effects of several calcium concentrations in reperfusion solution were studied. Experimental time course was as followed: 20 min working perfusion, 3 min cardioplegic infusion with St. Thomas cardioplegic solution (STS) followed by global ischemia for 30 min at 37.5 degrees C, 15 min early Langendorff reperfusion with reperfusion solution and 5 min late reperfusion with Krebs Henseleit bicarbonate buffer [( Calcium] = 2.5 mM), followed by 20 min working perfusion. Percent recoveries of aortic flow at the Ca concentration of 0, 0.1, 0.6, 1.2, 1.8, 2.5 mM were 0, 14 +/- 1, 43 +/- 4, 64 +/- 3, 55 +/- 2, 59 +/- 1 (%), respectively. Our data indicated that reperfusion solution with less than 1.2 mM calcium reduced the protective properties of STS.

Animals↗
PubMed1990

Direct effect of halothane and isoflurane on the function of the sarcoplasmic reticulum in intact rabbit atria.

The negative inotropic effect of halothane and isoflurane on potentiated-state contractions of isolated rabbit atria in a normal Ca2+ (2.5 mM) medium was compared with the force depression in low Ca2+ media without an anesthetic. When this comparison was made in the presence of 1 microM ryanodine so that the force of contraction was dependent only upon transsarcolemmal Ca2+ influx with no Ca2+ contribution from the sarcoplasmic reticulum (SR), the force of contraction was depressed equally by 0.6% halothane in a normal Ca2+ medium and by a 1.5 mM Ca2+ medium without the anesthetic. Similarly, 1.0% halothane or 1.5% isoflurane and a 1.0 mM Ca2+ medium were equally depressant as were 2.4% isoflurane and a 0.5 mM Ca2+ medium. In the absence of ryanodine, where the atrial contractile activity is largely dependent on Ca2+ released from the SR, 0.6% halothane in the normal Ca2+ medium depressed contractile force by 32%, whereas the force was depressed by only 16% in the 1.5 mM Ca2+ medium without the anesthetic. Similar results were obtained when the effects of 1.0% halothane and of 1.0 mM Ca2+ were compared. In contrast, the force of contraction measured in the absence of ryanodine was not at all inhibited by 1.5% isoflurane and minimally (11%) inhibited by 2.4% isoflurane. Consequently, the force depression by isoflurane was less than that found in the low Ca2+ media.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Negative inotropic effect of ketamine in rabbit ventricular muscle.

The effect of ketamine on myocardial contractile force was examined in rabbit papillary muscles in order to determine the underlying mechanism of action of the anesthetic. Ketamine HCl (20 and 40 mg/L) inhibited rested-state contractions that are dependent on the transsarcolemmal influx of Ca2+ for activation and reduced the upstroke velocity of the slow action potential, which reflects Ca2+ influx through the slow Ca2+ channel. On the other hand, ketamine had a relatively small effect on potentiated-state contractions and no effect on rapid cooling induced contractures, both of which are activated by the release of Ca2+ stored in the sarcoplasmic reticulum. These results suggest that ketamine inhibition of transsarcolemmal Ca2+ influx plays a major role in the negative inotropic action of the anesthetic.

Animals↗
PubMed1990

[Changes in lymphocyte subsets, neutrophil function and complement levels in patients with complications following open heart surgery].

In order to evaluate the immune response during and after open heart surgery, we have studied 34 patients who received open heart surgery under extracorporeal circulation. Age range of these patients were from 41 to 76 years. These patients were divided into three groups, depending upon existence of multiple organ failure (MOF), low output syndrome (LOS) and non-LOS and non-MOF diagnosed from our criteria. The following cytological and immunological study has been performed pre-operatively, immediately after and on 1, 2, 7 and 14th postoperative day; 1) the leukocyte differential cell count, 2) function test of neutrophils, 3) lymphocyte subpopulation and subsets, 4) serum level of complement fractions (C3, C4) and CH 50. By lymphocytes analysis, postoperative early reduction of OKT 3 (CD 3) and OKT 4 (CD 4) was observed in patients with poor prognosis. Patients with the postoperative high activity of NBT reduction test was developed into MOF. Complement activity (C3, C4, CH50) decreased during surgery and recovered to preoperative level in patients without LOS and MOF. However in MOF patients, these values showed lower level than that of patients without LOS and MOF. Our data suggested that lymphocytes and leukocytes tests were useful to evaluate the prognosis in open heart surgery.

Adult↗
PubMed1989

Isoflurane and halothane inhibit tetanic contractions in rabbit myocardium in vitro.

Rabbit right ventricular papillary muscles were tetanized by rapid stimulation in the presence of 1 microM ryanodine, an inhibitor of sarcoplasmic reticular function. Tetanic contractions elicited in this manner increased in strength as extracellular calcium concentration [Ca+2]ext was raised from 0.5 to 5 mM, exhibited saturation behavior above [Ca+2]ext = 5 mM, and were blocked by nifedipine. Accompanying membrane potentials depolarized to +10 mV and repolarized to -60 mV between stimuli. These data suggest that rabbit myocardial tetany is supported in large part by extracellular calcium influx via slow (L-type) calcium channels, consistent with similar recent findings in the ferret. At [Ca+2]ext = 2.5 mM, isoflurane (0.6-2.3%, gas phase) and halothane (0.4-1.5%) inhibited the strength of tetanic contractions in dose-dependent fashion. At [Ca+2]ext = 20 mM neither isoflurane (1.2%) nor halothane (0.8%) inhibited tetanic contraction strength. These data demonstrate that isoflurane and halothane inhibit contractile activity that is dependent on transsarcolemmal calcium influx via pathways independent of the ryanodine-sensitive sarcoplasmic reticulum. The exact sites of inhibition (e.g., slow channel vs. intracellular transit vs. myofibrillar binding) are not identified, but inhibition by either anesthetic may be competitively reversed by high extracellular calcium concentrations.

Animals↗
PubMed1989

Effects of isoflurane and halothane on rapid cooling contractures in myocardial tissue.

The effects of isoflurane and halothane on the availability of Ca2+ stored in and released from the sarcoplasmic reticulum (SR) were studied in isolated rabbit papillary muscles by measuring the effects of the anesthetics on rapid cooling contractures, which are known to be activated by Ca2+ released from the SR. Isoflurane (0.3%) reduced the force of the rapid cooling contracture to 57% of control with a marked slowing of the average rate of contracture development and increased the force of the first contraction after rewarming to 133% of control. In contrast, 1.7% halothane, which reduced the rapid cooling contracture to 51% of control (comparable to the value in the presence of 0.3% isoflurane), had little effect on the rate of contracture development and strongly inhibited the first contraction after rewarming to 5% of control. Halothane, but not isoflurane, strongly inhibited postrest potentiated-state contractions, which are also known to be activated by Ca2+ released from the SR. These results suggest that 1) isoflurane inhibits rapid cooling-induced Ca2+ release from the SR without inhibiting Ca2+ release triggered by rapid depolarization as occurs in the potentiated-state contraction, and 2) halothane inhibits contractile activity dependent on Ca2+ released from the SR regardless of mechanism involved.

Animals↗
PubMed1988

Differential effects of inhalation anesthetics on myocardial potentiated-state contractions in vitro.

The effects of enflurane, halothane, and isoflurane on myocardial potentiated-state contractions were examined in a study in which each of the anesthetics was presented, in random order, to each of eight isolated rabbit papillary muscles. Post-rest potentiated-state contractions were elicited by imposing a stimulus at precisely timed intervals following a 2-Hz steady-state stimulus train. The strength of these contractions is known to be highly dependent on sarcoplasmic reticulum (SR) Ca2+ release. The increment in tension developed in potentiated state, as compared to the steady state, is directly attributed to the potentiation process, and is defined here as potentiated-state strength (PSS). Effects of enflurane, halothane, and isoflurane on the time course of development of the potentiated state were characterized, as were the effects of incremental doses of these anesthetics on PSS. Anesthetic gas phase concentrations that produced 50% depression of contractile tension at 0.05 Hz steady-state stimulation were 0.6% halothane, 1.4% isoflurane, and 1.6% enflurane. Muscles exhibited maximal PSS of 0.91 +/- 0.01 g/mm2 in the absence of anesthetics. Halothane (0.6%) and enflurane (1.6%) caused significant depression of PSS to 0.45 +/- 0.06 and 0.61 +/- 0.06 g/mm2, respectively, while isoflurane (1.4%) preserved PSS at 0.95 +/- 0.09 g/mm2. Concentration profiles showed that the depression of PSS by halothane and enflurane was dose dependent. Isoflurane, up to 2.3%, failed to depress PSS. The time interval for development of optimum PSS, 1.5 to 2.0 s, was unaffected by any of the anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Anesthetic depression of myocardial contractility: a review of possible mechanisms.

The bulk of experimental evidence indicates that anesthetics do not produce their negative inotropic effect via an inhibitory action on mitochondrial electron transport. Anesthetics decrease energy need, rather than energy production. Anesthetics also decrease the rate of sequestration of Ca2+ by mitochondria, but, again, this appears not to be an important cause of reduced myocardial contractility. The role played by direct anesthetic depression of the myofibrils in reducing contractility is uncertain. Most experimental evidence now available suggests that significant myofibrillar depression, measured in terms of inhibition of actomyosin ATPase activity or inhibition of force production, occurs only at anesthetic concentrations which are high compared to concentrations employed clinically. This would seem to indicate that the myofibrils are not an important target for anesthetics in regard to the production of depressed myocardial contractility. However, the experimental act of removing myofibrils from their intracellular environment, or of removing the sarcolemma or making it hyperpermeable, appears to prevent some regulatory myofibrillar phosphorylation reactions from taking place. As stated by Winegrad, "certain forms of regulation of the cardiac myofibril are fragile and can be seen only when cellular constituents and structure are maintained." It is possible that this type of regulation is susceptible to inhibition by anesthetics. Methods for preserving this regulation are available, and will need to be employed before a depressant action of anesthetics on the myofibril can be definitely dismissed as a significant cause of the inhibition of cardiac contractility. A single study, of intracellular Ca2+ levels in the intact cell (where myofibrillar regulation was presumably preserved), has indicated that halothane may decrease myofilament Ca2+ sensitivity. However, for reasons stated above, this study cannot be taken as unequivocal proof of such an action. Despite the fact that the normal action potential is little affected by anesthetics, the sarcolemma appears to play a pivotal role in the production of anesthetic-induced contractile depression. Significant depression of the rate of upstroke of the slow (Ca2+-mediated) action potential by clinical concentrations of both inhalation and intravenous anesthetics has been demonstrated by several workers. This has been interpreted to mean that anesthetics inhibit the influx of Ca2+ through the slow channel, and such has been confirmed (to date, for halothane and thiamylal) by direct measurement of the slow inward Ca2+ current using a voltage clamp technique.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthetics↗
PubMed1987

Negative inotropic effects of isoflurane and halothane in rabbit papillary muscles.

The possibility that the negative inotropic effect of isoflurane is primarily due to a competitive inhibition of the influx of extracellular Ca2+ with little effect on the availability of Ca2+ stored intracellularly in the sarcoplasmic reticulum was examined in rabbit papillary muscle. The negative inotropic effect of isoflurane (1.4%) on steady state contractions (primarily dependent on the influx of extracellular Ca2+) was significantly greater than that on potentiated-state contractions (primarily dependent on Ca2+ released from the sarcoplasmic reticulum). In previous work from this laboratory we found that halothane has an opposite effect in this regard. Increasing stimulation frequency in the presence of isoproterenol (0.1, 1 microM) completely reversed the negative inotropic effect of isoflurane (1.4%) but not that of halothane (0.6%). These results suggest that isoflurane inhibits Ca2+ influx with little effect on the availability of activator Ca2+ stored in and released from the sarcoplasmic reticulum, and that the effect of isoflurane but not that of halothane can be effectively counteracted by conditions that are known to increase Ca2+ influx in the absence of an anesthetic. These properties of isoflurane may in part account for the minimal myocardial depressant effect of the anesthetic on the intact heart in the presence of a functional autonomic system.

Animals↗
PubMed1986

Calcium and thiopental-induced spontaneous activity in rabbit papillary muscle.

Isolated rabbit papillary muscles exposed to 20 to 30 mg/l of thiopental developed spontaneous contractile activity. The spontaneous activity often appeared following the cessation of high frequency stimulation. The maximum rate of spontaneous beating decreased in parallel with the force of contraction when the extracellular Ca2+ concentration was lowered or when ryanodine, an inhibitor of sarcoplasmic reticular function, was added. Stretching of the muscles increased the incidence of thiopental-induced spontaneous activity. These results suggest that intracellular Ca2+ influences thiopental-induced spontaneous activity, analogous to arrhythmias associated with afterdepolarization.

Animals↗