Toshiaki Mochizuki

Background: Conventional hands-on chest compression, in cardiopulmonary resuscitation, is often inadequate, especially when the rescuers are weak or have a small physique. Objectives: This study aimed to investigate the potential of leg-foot chest compression, with and without a footstool, during cardiopulmonary resuscitation. Methods and Results: We prospectively enrolled 21 medical workers competent in basic life support. They performed cardiopulmonary resuscitation on a manikin for 2 min using conventional hands-on compression (HO), leg-foot compression (LF), and leg-foot compression with a footstool (LF + FS). We analyzed the compression depths, changes in the rescuers' vital signs, and the modified Borg scale scores after the trials. The compression depth did not differ between the cases using HO and LF. In the case of LF + FS, compression depths > 5 cm were more frequently observed (median, inter-quartile range: 93%, 81%-100%) than in HO (9%, 0%-57%, p < 0.01) and LF (28%, 11%-47%, p < 0.01). The increase in the heart rate or modified Borg scale scores, after the trials, did not differ between the HO and LF group; however, the values were the lowest in the case of LF + FS (49 +/- 18 beats/min and 5 (4-7) in HO, 46 +/- 18 and 6 (5-7) in LF, and 32 +/- 11 and 2 (1-3) in LF + FS, respectively, p < 0.01). However, the increase in blood pressure, SpO(2), and respiratory rate were not different among each group. The increases in the heart rate and modified Borg scale scores negatively were correlated with the rescuers' body size, in the case of HO and LF, but not LF + FS. Conclusion: LF can be used as an alternative to HO, when adequate HO is difficult. LF + FS could be used when rescuers are weak or have a small physique and when the victims are bigger than the rescuers.

Background: Hypocapnia induced following the accidental intravenous infusion of a local anesthetic can mitigate anesthetic toxicity, but the effects of hypocapnia induced prior to local anesthetic infusion are unknown. In this study, we examined the effects of prior hypocapnia on bupivacaine-induced cardiotoxicity in rats. Methods: Eighteen Sprague-Dawley rats were randomly divided into two groups: one receiving sevoflurane with normal ventilation (Control Group) and the other receiving sevoflurane with hyperventilation to induce hypocapnia (Hypocapnia Group). After 30 min, both groups received continuous intravenous infusions of 0.25% bupivacaine at 2 mg . kg(-1) . min(-1). The time taken to reach 25% and 50% reductions in heart rate (HR; HR-25%, HR-50%) and mean arterial pressure (MAP; MAP-25%, MAP-50%) from the start of bupivacaine infusion were recorded. The difference between HR-25% and MAP-25% was calculated. The times of the first ventricular premature beat (VPB) and final systole were also recorded. Results: In the Hypocapnia Group, HR-50%, MAP-25%, and MAP-50% were prolonged compared with the Control Group (P &lt; 0.001). Furthermore, the interval between HR-25% and MAP-25% and the times between the first VPB and final systole were prolonged in the Hypocapnia Group (P &lt; 0.001). Conclusion: In rats under sevoflurane anesthesia, prior hypocapnia delayed the onset of bupivacaine-induced cardiotoxicity. Prior hypocapnia should be avoided during continuous bupivacaine nerve block under general anesthesia, because it may delay the detection of cardiotoxicity.

In this study, we aimed to compare the effects of low-and high-quality cardiopulmonary resuscitation (CPR) on cardioprotection by induced hypothermia (IH) at 34 degrees C and examine whether extracellular signal-regulated kinase or endothelial nitric oxide synthase mediates this cardioprotection. Left ventricle infarct sizes were evaluated in six groups of rat hearts (n = 6) following Langendorff perfusion and triphenyltetrazolium chloride staining. Controls underwent 30 min of global ischemia at 37 degrees C, followed by 10 min of simulated low-or high-quality CPR reperfusion and 90 min of reperfusion at 75 mmHg. The IH groups underwent IH at 34 degrees C during reperfusion. The U0126 group received U0126 (60 mu M)-an extracellular signal-regulated kinase inhibitor-during reperfusion at 34 degrees C. The L-NIO (N-5-(1-iminoethyl)-L-ornithine dihydrochloride) group received L-NIO (2 mu M)-an endothelial nitric oxide synthase inhibitor-5 min before global ischemia at 37 degrees C to the end of reperfusion at 34 degrees C. Infarct size did not significantly differ between the control and IH groups receiving low-quality CPR. However, IH with high-quality CPR reduced the infarct size from 47.2% +/- 10.2% to 26.0% +/- 9.4% (P = 0.005). U0126 reversed the IH-induced cardioprotection (45.9% +/- 9.4%, P = 0.010), whereas L-NIO had no significant effect. Cardiopulmonary resuscitation quality affects IH-induced cardioprotection. Extracellular signal-regulated kinase may mediate IH-induced cardioprotection.

Aim: Therapeutic hypothermia (TH) is widely used as a cardioprotective treatment for cardiac arrest. TH at 30-32 degrees C during ischaemia and reperfusion has a cardioprotective effect. The aims of the study were to examine whether TH at 34 degrees C with late induction (immediately after the start of reperfusion) has a cardioprotective effect and to determine if this effect is mediated by nitric oxide (NO) and phosphatidylinositol 3'-kinase (PI3K). Methods: Langendorff perfusion of Sprague-Dawley rat hearts was initiated at 75 mmHg at 37 degrees C. Left ventricle infarct sizes were evaluated by triphenyltetrazolium chloride staining after Langendorff perfusion in 6 groups (each n = 7): control group; ischaemia group, with 34 degrees C TH during ischaemia for 30 min and reperfusion for 180 min; reperfusion group, with 34 degrees C TH induced solely during the reperfusion period; the L-NAME (NO synthase inhibitor), LY294002, and wortmannin (PI3K inhibitors) groups, which were treated similarly to the reperfusion group with the addition of each compound. Results: TH reduced the left ventricle infarct size from 54.2 +/- 14.8% of the control group to 11.9 +/- 6.3% (ischaemia group, p &lt; 0.001) and to 23.5 +/- 10.5% (reperfusion group, p &lt; 0.001). L-NAME, LY294002, and wortmannin reversed the cardioprotective effect of TH induced during reperfusion to 42.5 +/- 10.6% (p = 0.009), 40.9 +/- 4.1% (p = 0.021), and 51.9 +/- 13.0% (p &lt; 0.001), respectively. Circulatory temperatures reached 34 degrees C within 5 min in all groups subjected to TH. Conclusions: TH of 34 degrees C showed a cardioprotective effect even with late initiation of cooling during reperfusion. The effect was mediated by NO and PI3K. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Purpose: Systemic alkalinization is recommended for resuscitation from local anesthetic-induced cardiotoxicity. It has been suggested that inducing hypocapnic alkalosis, prior to exposure to toxic concentrations of local anesthetics, may minimize cardiotoxicity. However, it remains unclear whether inducing severe hypocapnic alkalosis after administration of local anesthetics will minimize the duration of bradycardia. We used isolated rat hearts to investigate the effects of hypocapnic alkalosis on heart rate (HR) recovery from bupivacaine or levobupivacaine-induced bradycardia. Methods: We measured the time required for the HR in 24 isolated rat hearts, respectively, to attain 90% of the baseline HR (recovery time) following bradycardia induced by 1 mu g.mL(-1) and 10 mu g.mL(-1) concentrations of either bupivacaine or levobupivacaine. Normal pH perfusate (bupivacaine or levobupivacaine with normal pH washout groups) or severe hypocapnic alkalosis perfusate (bupivacaine or levobupivacaine with hypocapnic alkalosis washout groups) were reperfused after exposure to the local anesthetics. Results: Severe hypocapnic alkalosis prolonged the recovery time from 273 coproduct 122 sec, at the 1 mu g.mL(-1) bupivacaine concentration with normal pH washout, to 1203 coproduct 540 sec, in the bupivacaine with hypocapnic alkalosis washout (P = 0.029). Severe hypocapnic alkalosis also prolonged the recovery time from 1153 +/- 644 sec, at a 10 mu g.mL(-1) bupivacaine concentration in the normal pH washout group, to 2065 +/- 617 sec, in the bupivacaine with hypocapnic alkalosis washout group (P = 0.032). With levobupivacaine 10 mu g.mL(-1) in the normal pH washout group, HR recovery time increased from 863 +/- 186 sec to 1565 +/- 567 sec, compared to the hypocapnic alkalosis washout group (P = 0.045). Conclusions: Severe hypocapnic alkalosis prolonged the recovery time from bupivacaine or levobupivacaine-induced bradycardia in isolated rat hearts. When bradycardia occurs after intravascular bupivacaine or levobupivacaine administration, maintenance of normocapnia may minimize the duration of bradycardia.

Purpose. Our purpose was to investigate whether the NO donor, 3-(2-hydroxy-1-methyl-2-nitroso-hydrazino)-N-methyl-1-propanamine (NOC7), restored cardiac function following global ischemia in an isolated rat heart model and whether intracellular messengers were involved in its effect. Methods. Isolated rat hearts (n = 36) were randomly divided into six groups. The sham control group was perfused with modified Krebs-Henseleit bicarbonate buffer (KHB) alone. The ischemic control group and the NOC7 groups were subjected to 35 min of global ischemia, followed by 30 min of reperfusion with KHB alone, or reperfusion with KHB including NOC7 at 0.2, 2, 20, or 200 mu M, respectively. Left ventricular developed pressure (LVDP), the maximum and the minimal rate of rise in LVP (+/- dP/dt), and coronary flow were measured continuously. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were measured in myocardium homogenate, using enzyme immunoassay (EIA) methods. Results. NOC7 at 2 and 20 mu M rescued myocardial performance (LVDP, 111.9 +/- 10.5% and 124.3 +/- 12.5% of baseline, respectively; P &lt; 0.05 vs ischemic control) at 30 min after reperfusion. However, NOC7 at 200 mu M reduced the LVDP to 55.3 +/- 6.0% of baseline. Coronary flows remain unchanged. The cAMP levels increased significantly from 0.83 +/- 0.44 pmol.mg(-1) protein in the ischemic control group to 1.79 +/- 0.39, 1.86 +/- 0.25, and 2.63 +/- 0.24 pmol.mg(-1) protein, in the groups with NOC7 at 2, 20, and 200 mu M, respectively (P &lt; 0.05). The cGMP level increased from 1.49 +/- 0.61 pmol.mg(-1) protein in the ischemic control group to 3.92 +/- 0.66 pmol.mg(-1) protein in the group with NOC7 at 200 mu M alone (P &lt; 0.05). Conclusion. NOC7 appeared to exert a biphasic effect on the contractile force of the isolated rat heart after 35-min global ischemia. The balance between intracellular cAMP and cGMP levels seemed to be involved in its mechanism.

Bleeding after cardiopulmonary bypass (CPB) is related to multiple factors. Excess protamine weakens clot structure and decreases platelet function; therefore, an increased activated clotting time (ACT) after protamine reversal of heparin may be misinterpreted as residual heparin anticoagulation. We evaluated the effects of protamine, recombinant platelet factor 4 (rPF4), and hexadimethrine on ACT in blood obtained after CPB. Ln addition, we examined the effect of protamine on in vitro platelet aggregation. Incremental doses of protamine, rPF4, and hexadimethrine were added to heparinized blood from CPB, and ACTs were performed. Incremental concentrations of protamine were added to heparinized platelet-rich plasma, and aggregometry was induced by adenosine diphosphate (ADP) and collagen. The mean heparin concentration at the end of CPB was 3.3 U/mL. Protamine to heparin ratios &gt;1.3:1 produced a significant prolongation of the ACT that was not seen with rPF4 and was observed only with 5:1 hexadimethrine to heparin ratios. ADP-induced platelet aggregation was reduced with protamine administration greater than or equal to 1.3:1. Excessive protamine reversal of heparin prolongs ACT and alters ADP-induced platelet aggregation in a dose-dependent manner in vitro. Additional protamine administered to treat a prolonged ACT may further increase clotting time, reduce platelet aggregation, and potentially contribute to excess bleeding after CPB. Implications: We found that excess protamine prolonged the activated clotting time and altered platelet function after cardiopulmonary bypass, whereas heparin antagonists, such as recombinant platelet factor 4 and hexadimethrine, exhibited a wider therapeutic range without adversely affecting the activated clotting time. Approaches to avoid excess protamine or use of alternative heparin antagonists after cardiopulmonary bypass may be beneficial.

Coagulopathies in children after cardiopulmonary bypass (CPB) are complex. There are very limited data correlating coagulation tests with postoperative bleeding. We evaluated coagulation changes after CPB and after the administration of coagulation products to 75 children. Baseline coagulation tests were obtained and repeated after protamine administration, after transfusion of individual coagulation products, and on arrival in the intensive care unit (ICU). Regression analysis demonstrated no baseline coagulation test to predict postoperative chest tube drainage. Weight and duration of CPB were determined to be the only predictors of bleeding. Further analyses demonstrated that children &lt;8 kg had more bleeding and required more coagulation products than children &gt;8 kg. Postprotamine platelet count and fibrinogen level correlated independently with 24-h chest tube drainage in children &lt;8 kg, whereas postprotamine platelet count and thrombelastographic values did so in patients weighing &gt;8 kg. Platelet administration alone was found to restore effective hemostasis in many patients. With ongoing bleeding, cryoprecipitate improved coagulation parameters and limited blood loss. Fresh-frozen plasma administration after platelets worsened coagulation parameters and was associated with greater chest tube drainage and more coagulation product transfusions in the ICU. Objective data to guide post-CPB component therapy transfusion in children are suggested. Implications: Children &lt;8 kg can be expected to have more severe coagulopathies, require more coagulation product transfusions, and bleed more after cardiopulmonary bypass. Correlations between coagulation tests and postoperative chest tube drainage are defined. Platelets and, if necessary, cryoprecipitate optimally restore hemostasis. Fresh-frozen plasma offers no benefits in correcting postcardiopulmonary bypass coagulopathies in children.