• The Korean Journal of Physiology and Pharmacology
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• 제8권1호
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• pp.43-50
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• 2004

Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. Amrinone, a specific inhibitor of phosphodiesterase 3, has an antioxidant activity against PMNs. Therefore, we hypothesized that amrinone could attenuate PMNs-Induced cardiac dysfunction by suppression of reactive oxygen species (ROS) produced fby PMNs. In the present study, we examined the effects of amrinone on isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. Amrinone at $25\;{\mu}M$, given to hearts during the first 5 min of reperfusion, significantly improved coronary flow, left ventricular developed pressure (P<0.001), and the maximal rate of development of left ventricular developed pressure (P<0.001), compared with ischemic/reperfused hearts perfused with PMNs in the absence of amrinone. In addition, amrinone significantly reduced myeloperoxidase activity by 50.8%, indicating decreased PMNs infiltration (p< 0.001). Superoxide radical and hydrogen peroxide production were also significantly reduced in fMLP- and PMA-stimulated PMNs pretreated with amrinone. Hydroxyl radical was scavenged by amrinone. fMLP-induced elevation of $[Ca^{2+}]_i$ was also inhibited by amrinone. These results provide evidence that amrinone can significantly attenuate PMN-induced cardiac contractile dysfunction in the ischemic/reperfused rat heart via attenuation of PMNs infiltration into the myocardium and suppression of ROS release by PMNs.

• Journal of Chest Surgery
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• 제29권2호
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• pp.191-198
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• 1996

암리논은 환식-AMP 분해 효소인 포스포다이에스트라제-F-III를 선택적으로 차단하는 비카테콜아민 계통의 약물로 심근세포내 환식-ATP의 양을 증가시켜 심근수축을 촉진한다. 이번 연구에서는 개심술을 시행한 40명의 환자에서 술후 암리논과도파민을 정맥주사하여 혈역학성 변화, 혈액성분변화, 합병증 들을 비교분석하였다. 혈역학성 변화로는 심박수, 수축기와 이완기 혈압, 심박출 계수, 폐동맥 쐐기압, 체혈관 저항 등을 수술직후부터 30분, 1시간, 3시간, 6시간, 12시간, 24시간, 48시간에 측정하였다. 암리논은 처음 초기 용량으로 1.5~2mg/kg을 주사한 후 유지량은 5~ 20ug/kg/min으로 주사하였다. 암리논에서 심박출계수는 수술직후 3.73$\pm$1.39 L/min/m2에서 술후 48시간에 5.44 $\pm$ 2.65 L/min/m2으로 증가하였고(p<0.05) 체혈관 저항은 1237.5 $\pm$ 637.7dyne/sec/cm2에서 1000.8 $\pm$ 608.5 dyne/sec/cm2으로 감소하였다. 도파민군에서 술후 12시 간에 심 박수가 92.1 $\pm$ 13.0/min에서 101.0 $\pm$ 13.1/min으로 증가하고 체혈관 저항도 1058.5 $\pm$ 234.6dyne/sec/cm2에서 1979.7 $\pm$ 759.2dyne/sec/cm2으로 증가하며 심 박출 계수는 3.40 $\pm$ 0.50L/min/m2에서 2 53 $\pm$ 1.15L/min/m2으로 감소하였다(p<0.05). 암리논을 사용한 군에서 도파민군과 비교하여 높은 심박출 계수와 낮은 체혈관 저항을 나타내어 혈역학성 동태에서 더 좋은 결과를 보였다. 술후 암리논의 사용이 좋은 혈역학성 동태를 유지하여 심근 보호 및 심장 기능회복에 좋을 것으로 생각한다.

• Journal of Chest Surgery
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• 제33권2호
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• pp.117-124
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• 2000

Background: Nucleoside transport inhibitor(NTI) Keeps AMP, ADP, ATP levels high in myocytes by inhibiting adenosine cataboilsm so that it may preserve the myocardial contractability during ischemia In this study we investigated the effects of cyclic AMP phosphodiesterase inhibor(C-AMP PDSI) and S-P-nitrobenzyl-6 -thioniosine(NBT; a sort of NIT) on myocadial preservation and changes of constituent enzyme. Material and method: Twenty-six isolated rabbit hearts were perfused with Krebs-Henseleit buffer solution for 20 minutes arrested for 20 minutes and ten reperfused for 30 minutes. The following four groups were prepared and hemodynamic changes coronary effluent lactate dehydrogenase (LDH) a-hydroxybutylic accid(a-HBD) levels and myocardial LDH creatine kinase-MB (CK-MB) adenosine deaminase(ADA) a-HBD levels and myocardial LDH creatine kinase-MB (CK-MB) adenosine deaminase(ADA) a-HBD levels were analysed before and after cardiac arest ; Group I(control) ; the heart was only perfused with K-H ; Group II ; the heart was perfused with K-H including C-AMP PDSI(Amrinone 25mg/L); Group III ; the heart was perfused with K-H including NBT(4.19mg/L) ; Group IV ; the heart was perfused with K-H including C-AMP PDSI + NBT. Result : Left venticular developed pressure(LVDP) at 10 minutes of the equilibrium was significantly higher in group III(72.1$\pm$5.3 mmHg p<0.01) and group III(72$\pm$5.6 mmHg P<0.025) as compared with group I (40.8$\pm$4.7mmHg) and LVDP at 20 minutes of the reperfusion was significantly higher in group II(74$\pm$5.3mmHg p<0.01) and group III(72$\pm$5.6mmHg p<0.025) as compared with group I (44.2$\pm$4.6mmHg). Percentage recovery of LVDP at the reperfusion was the highest in group II(123.3%) Percentage recovery of coronary flow at the equilibrium reperfusion were higher in group II(310%, 270%) group III(230%, 290%) group IV(310%, 280%) as compared with group I (100%) respectively. Myocadial LDH level was significant lower in group IV(33495$\pm$1802 IU/gm p<0.04) as compared with group I(48767$\pm$1421 IU/gm) Myocadial CK-MB level was significant higher in group II(74820$\pm$1421 IU/gm) compared with group I (45450$\pm$1737 IU/gm) Myocadial ADA level was significant higher group IV(1215$\pm$8 IU/gm p<0.05) compared with group I(125$\pm$15 IU/gm) but there was no significant difference between group I and group II ,III, IV in changes of coronary effluent LDH, a-HBD levels. Conclusion: C-AMP PDSI solely appears to have a better effect on myocardial preservation after ischemia than NBT but with no synergistic effect and it could keep CK-MB leve high in myocardial tissues.