To determine the therapeutic effects of glucose-insulin-potassium () solution, 5 control dogs and 5 -treated dogs were investigated 24 hours after coronary artery occlusion by use of myocardial creatine phosphokinase (CK) activity and myocardial thallium-201 uptake. There was no significant difference in myocardial blood flow estimated by thallium-201 uptake between the control and the group, but myocardial CK activity in the ischemic zone of -treated animals was significantly higher than that of the control group. This suggests that administration of solution is effective in protecting myocardial tissue in the central ischemic area and that this protecting action of seems to be independent of myocardial blood flow.

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As glucose-insulin-potassium solution () has been used as clinical cardioplegia during open heart surgery, we studied the fundamental effects of on the electrical and mechanical activities of the bullfrog atrial muscle under voltage clamped and unclamped conditions by the double sucrose-gap method. produced an immediate disappearance of the action potential and twitch tension with pronounced depolarization accompanied by transient contracture. Reperfusion with normal Ringer's solution after perfusion (30-180min) resulted in recovery of the action potential, with an initial lengthening followed by a sustained shortening in duration. Recovery of twitch tension was incomplete, and perfusion with for a longer period caused stronger suppression. Voltage clamp studies revealed that after removal of , the slow inward current (I_s) and I_s-dependent tension were markedly depressed, while the delayed outward current (I_x) was augmented. The fast inward current (I_Naf), background current (I_k1), and I_s-independent tension gradually recovered to the control levels. Perfusion with low Ca Ringer's solution or verapamil Ringer's solution for 10min at the initial reperfusion phase significantly improved the recovery of I_s and the I_s-dependent tension. These results indicate that the after-effects of are mainly governed by Ca influx at the initial reperfusion phase. Therefore, a lowering of the Ca influx in this period is expected to produce a beneficial effect on cardiac function after treatment.

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Background -²⁰¹Tl imaging reportedly improves the detection of viable myocardium, so the present study evaluated whether it can detect myocardial viability after acute myocardial infarction (AMI). Methods and Results Resting ²⁰¹Tl and ^99mTc-pyrophosphate (PYP) dual single photon emission computed tomography (SPECT) and ²⁰¹Tl SPECT after ²⁰¹Tl with (10% glucose, insulin 5 U, and KCl 10 mmol) infusion (-²⁰¹Tl) were performed in 25 AMI patients within 10 days of admission. -²⁰¹Tl SPECT images were obtained immediately and 4 h after infusion. Left ventriculography (LVG) was performed within 3 weeks and at 6 months when follow-up ²⁰¹Tl SPECT was also performed. From 20 SPECT segments, both the summed defect score (RDS) and the number of defect segments (ES) were calculated. The infarcted area was defined as ^99mTc-PYP uptake segments. Wall motion was estimated in 7 LVG segments. The ES of R-²⁰¹Tl (5.5±2.8), immediate -²⁰¹Tl (4.0±2.3), and 4-h -²⁰¹Tl (5.6±2.7) were lower than that of ^99mTc-PYP (7.5 ±4.1) (p<0.05), and the ES had significantly declined 6 months later on ²⁰¹Tl (3.5±2.8) (p<0.05). Although the RDS of R-²⁰¹Tl (11.3±7.9) and 4-h -²⁰¹Tl (11.2±6.3) were greater than at the 6-month ²⁰¹Tl (7.1±6.5), immediate -²⁰¹Tl (7.4±6.5) was equivalent to follow-up ²⁰¹Tl. The sensitivity of immediate -²⁰¹Tl was highest among the imaging methods. Conclusion To detect myocardial viability after AMI, early imaging with -²⁰¹Tl is more useful than resting ²⁰¹Tl imaging. (Circ J 2004; 68: 348 - 354)

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We have performed a comparative study on the effects of intravenous (Glucose-Insulin-Kalium) infusion by hemodynamic investigations mainly on cardiac output, administering to 3 calves with total artificial heart implantation and 3 calves with natural heart. The dosis of infused was 20% glucose; 5ml kg, K; 0.2mEq/kg and Regular insulin; 0.6units/kg.
We have obtained the following conclusions. 1) The aortic pressure and cardiac output were significantly increased by intravenous infusion of in the calves with intact natural heart. 2) No significant hemodynamic changes were observed by intravenous infusion in the calves with total artificial heart replaced. 3) Consequently the hemodynamic effect of was proved mainly due to the mechanism directly activated on the natural heart.

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The accumulation of intermediates subsequent to impaired oxidation of free fatty acids has been suggested as a cause of cellular damage in ischemic myocardium. Many reviews have supported the theory that glucose-insulin-potassium () solution has a beneficial effect on the ischemic myocardium. We evaluated the effects of solution on intermediates of free fatty acid metabolism in ischemic myocardium. The left coronary artery was occluded for 40 minutes in twelve dogs. In six dogs, 10 minutes before coronary artery occlusion, solution (50 per cent of glucose, 50 units/liter of regular insulin, 50 mEq/ liter of potassium) was given at the rate of 0.1 ml/kg per minute until the time of excision of the hear. In the ischemic area, adenosine triphosphate (ATP) level in the group (3.80±1.34 μmole/g) was significantly higher than that in the control group (2.04±0.68, p<0.05). The free carnitine level was significantly increased was in both ischemic and nonischemic areas (p<0.05). In the control group, the long chain acyl coenzyme A (CoA) level in the ischemic area (23.0±7.0 nmole/g) was significantly higher than that in the nonischemic area (1.71±3.5, p< 0.05). On the other hand, prevented the increase in the long chain acyl CoA in the ischemic area (17.8±5.6). This study suggests that has a protective effect on ischemic myocardium, probably by preventing the accumulation of long chain acyl CoA by improving free fatty acid metabolism.

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This investigation was designed to explore the metabolic, hemodynamic, and electrocardiographic effects of glucose-insulin-potassium () solution in a model of segmental myocardial ischemia with significant but incomplete restriction of coronary blood flow. An open-chest anesthetized canine model was utilized including 11 and 6 saline control experiments. The anterior descending coronary artery (LAD) was partially occluded causing an average 71% reduction in its blood flow. Thirty min following occlusion or saline was infused for 30min at 3ml/min into a femoral vein. Statistically significant effects of included: increased glucose uptake by the ischemic myocardium, reduced arterial free fatty acid (FFA) concentration, reduced myocardial FFA uptake, decreased coronary arterio-venous oxygen content difference, increased myocardial lactate extraction, decreased myocardial potassium egress, and reduced epicardial ST segment elevation. Heart rate, aortic and left ventricular end-diastolic pressures, and developed force in the ischemic area were unchanged. The results indicate a potentially favorable effect of on the metabolism of the ischemic myocardium which may be due to the shift of substrate utilization from free fatty acids to glucose.

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To identify and quantify the amount of viable hibernating myocardium in patients with chronic coronary artery disease, resting ²⁰¹Tl single photon emission computed tomography (SPECT) was compared with ^99mTc-methoxyisobutyl isonitrile (MIBI) SPECT after nitrate infusion (nitrate-^99mTc-MIBI) and ²⁰¹Tl SPECT after ²⁰¹Tl with glucose-insulin-potassium infusion (²⁰¹Tl-) in 25 patients. Twenty-one patients also underwent completely left ventriculography beforehand and 5±4 months afterwards. SPECT images were divided into 9 segments and scored visually from 0 (normal uptake) to 3 (absent). The defect score was calculated as the summation of the total scores (TDS) in each patient. The TDS of nitrate-^99mTc-MIBI images (6.3±4.3) and ²⁰¹Tl- images (5.8±4.2) were significantly lower than the 7.4±4.3 of resting ²⁰¹Tl images (p<0.01). Based on the improvement of wall motion after coronary revascularization, the sensitivity of ²⁰¹Tl- imaging (85%) was significantly higher (p<0.05), and that of nitrate-^99mTc-MIBI imaging (79%) also tended to be higher (p=0.08), than that of ²⁰¹Tl imaging (62%) in detecting viable myocardium. The specificity of the 3 methods was almost the same. The nitrate-^99mTc-MIBI and ²⁰¹Tl- methods were more useful than the resting ²⁰¹Tl method for evaluating viable hibernating myocardium. Furthermore, the ²⁰¹Tl- method may provide a more accurate estimate of the amount of viable myocardium than the nitrate-^99mTc-MIBI method.

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Influence of myocardial protection method to the postoperative hemodynamics was studied in two groups of infants under 12 months of age who had undergone a radical operation for congenital heart disease. The daily doses of diuretic were slightly different between the group of 9 patients who had recieved cold (K: 20mEq/L, Insulin: 10 unit) injection after aoatic clamping at the operation, and the non group of 11 patients who had received intermittent aortic cross-clamping. Both methods were effective.

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持続冠灌流時の液と冷却人工心肺血の流量、灌流圧の差を定量的に検索した。冠灌流回路のポンプ圧は100～120mmHgに維持したのに対し、大動脈壁に挿入した冠灌流カニューレより直接測定した大動脈基部圧は液32.6±1.4mmHg, 人工心肺血34.5±5.7mmHgであり、有意差は認めなかった。同時に測定した流量は液345±12.2ml/min、人工心肺血238±24.8ml/minと持続血液冠灌流時では有意に低下していた。大動脈基部圧および流量より計算された冠灌流圧抵抗は液95.8±70mmHg/1/min、人工心肺血144.4±16.0mmHg/1/minとなり持続血液冠灌流では有意に増大していた。冠灌流圧抵抗から推定される冠血管床の開存率は、持続血液冠灌流時は液注入時に対し95.8/144.4≒0.66になると推定される。これは人工心肺血と液の粘性等の影響による。

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To evaluate the myocardial protective effects of various cardioplegic infusates, 104 isolated working rat hearts were studied. Following normothermic (37 C) cardioplegic arrest (30 minutes) and hypothermic (21 C) cardioplegic arrest (60 minutes), the recovery course of cardiac function were observed.
At hypothermic condition, St. Thomas'Hospital solution (ST), glucose insulin potassium solution (), lactate Ringer's potassium solution (LRK) showed significantly better restoration of aortic flow than modified Roe's solution. GK solution and Young's solution. ST added solution exhibited the highest and most lasting functional recovery in mean values. On the other hand, simple external cooling, Kirsch's solution, and lactate Ringer's GK solution resulted in marked deterioration of cardiac function. At normothermic condition, ST was significantly superior than LRK. Groups of simple aortic occlusion, and Young's solution followed by could not recover after the reperfusion.
These results indicate that balanced electrolyte solution contained Mg ^_??_ (ST) may have a superior myocardial preservative action, insulin may present an inotropic effect following global ischemia at hypothermic condition, and excessively hypertonic solution (LRGK, Kirsch) may be damaging to the myocardium. It seems also that perfusion experiment of isolated working rat heart is very useful as a screening test of cardioplegic solutions, because the isolated heart has no extracoronary collateral flow and their net effect on myocardium can be clearly observed.

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開心術時の心筋保護法として,常温体外循環下にretrograde continuous warm blood cardioplegiaを5例に使用した。心筋保護液基調液として,高濃度カリウム液および低濃度カリウム液を用い,これらの液を1に対し,人工肺酸素加血液を4の割合で混合した後,34℃ に加温し心温し心筋保護液とした。高濃度カリウム心筋保護液の順行性投与で速やかな心停止が得られ,低濃度カリウム心筋保護液の逆行性持続投与で充分な心停止維持が可能であった。本法を施行することにより,体外循環時間の短縮も得られ,良好な術後心機能および心筋由来血清酵素活性値の推移からも,有効な心筋保護法と考えられた。

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教室における体外循環の工夫について報告した。教室では体外循環に際して、(1)血小板凝集抑制を目的として、gabexate-mesilateを点滴投与する。(2)DM症例においては糖代謝を改善し、且つ高血糖を避ける目的で通常の (; 2:1:4)より糖を減らした1:1:4のを用いている。(3)ACB症例及びAVR症例の如く右心系を開く必要のない手術では一本脱血法を用いて溶血を少なくする。(4)症例によりECUMを施行し、体外循環中の水分バランスの改善及び輸血量節減をはかる。
この結果、(1)のgabexate-mesilateの効果については決定的な有効性を見出し得なかった。(2)DM症例に対する1:1:4の投与は高血糖を避け、且つ糖代謝の改善に有効であった。(3)一本脱血法では溶血が少なかったが、RAA系への効果は明確ではなかった。(4)ECUMは体外循環中の水分バランスの改善に有用且つ輸血量の節減効果も認められた。

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植物は動物とは異なり、一生を通して幹細胞を維持し、その生長は幹細胞の絶え間ない増殖と分化のバランスに支えられている。従って植物はたとえ体の大半を失ったとしても、分化しつつある細胞が脱分化し幹細胞を再生することで、継続的な生長を維持することができる。私たちは、これまで記述されながらも分子機構の理解がほとんど進んでいなかった植物分裂組織の再生現象に着目し、植物幹細胞の可塑性と器官再生を動的な生命システムとして解明することを目指している。シロイヌナズナにおいてはホメオボックスタンパク質WUSCHELが幹細胞の維持に必要であることが示されている。WUSは茎頂、花序、花芽すべての分裂組織において機能し、特に花芽においては特定の領域に決まった数の花器官原基を形成した幹細胞の機能は消失する。私たちは核タンパク質の一つであるGIANT KILLER ()が花序および花芽においてWUSの発現を抑制する機能を持つこと見つけた。は核マトリクスに結合するタンパク質であり、WUSをエピジェネティックな制御により抑制していた。さらに一過的なの発現誘導により、消失した幹細胞は時間変化とともに2つ、もしくは3つの分裂組織として再生した。本発表ではによるWUSの抑制機構、分裂組織の再生へといたる機構について論じたい。

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人工弁置換例7例,その対照として軽症な開心術症例5例について,術前日と術後3～4週目にGlucose-Insulin-Kalium()溶液を短時間に静注し,その溶液注入前後で心拍出量,動脈血ガス分析,血清電解質,尿量,尿中電解質を測定し,それらの値に認められる変動から,弁膜疾患患者が人工弁置換によって受けた影響を評価出来るか否かを検討した.心拍出量は注入前値に比べ人工弁置換群で術前1.2倍,術後1.7倍に,対照群ではそれぞれ1.7倍,1.3倍となった.
動脈ガス分析上,PaO₂は人工弁置換群で術前,術後で有意に増加し,base excessは術前2.1±3.4mEq/Lから1.0±4.6mEq/L,術後では2.9±2.4mEq/Lから2.5±2.4mEq/Lと変化し,対照群のこれらの値の変化は著明でなかった.
血清電解質の変動は人工弁置換群で術前Clの増加とIPの減少,術後はKとClの増加,IPの減少が示された.対照群で術後IPにのみ減少が認められたに過ぎない.点滴期間中の尿量のみが対照群の術前,術後期間で有意の差が得られたに過ぎなかった.尿中電解質排泄は人工弁置換群で術後K,Clで増加した.
以上対照群の病態がより好ましい状態として負荷に対する反応を考察すると,人工弁置換後3ないし4週間の時点では水分,電解質を調整する機能はまだ充分に回復していないと推測された.

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長時間の体外循環時間を要し, 大量の心筋保護液を使用する開心術例では, その液を回路内に回収すると血液希釈率が異常に高くなり水分バランスの維持を困難にすることがある。この余分な水分を術中積極的に排出するため, 限外濾過法を10例(I群)に併用した結果,その有用性を認めたので, 非併用9例(II群)と比較し検討した。使用量はI群30.7±10.5ml/kg, II群19.3±6.3, 限外濾過量は30.0±8.1ml/kgであった。ICU入室時バランスはI群+44.6±17.9ml/kg, II群+43.6±25.7とI群では循環時間が長く, 使用量も多かったにもかかわらず, 両群に差は認めなかった。また膠質浸透圧も両群とも同様の推移を示し, 血漿浸透圧はほぼ一定の値を示した。本法は細胞外液(組織間)に貯留すべき水分を濾過するものと思われ, 簡便なだけでなく, 心筋保護法の徹底, 術後の水分管理についてなど種々の利点をもつものと思われた。

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