• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.53-61
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• 1995

The experiments were performed to determine whether the cardiac depressant action of lidocaine is directly associated with the utilization of endogenous substrates in isolated rat atria, by using citrate and bicarbonate-free medium known as potent inhibitors of phosphofructokinases (PFK) enzyme step. Citrate and bicarbonate-free medium produced negative inotropic action of isolated rat atria incubated in normal Krebs-Ringer bicarbonate glucose medium. Pyruvate and acetate increased the force of contraction of atria depressed by citrate or bicarbonate-free medium, whereas fructose was without effect indicating the inhibitory effect of citrate and bicarbonate-free medium at some point in the glycolytic pathway such as the PFK step in atria. In the absence of exogenous substrate, citrate and bicarbonate-free medium produced a marked depression of the force of substrate-depleted atria indicating that utilization of endogenous substrate above the PFK step, probably cardiac glycogen, is also impaired by citrate or bicarbonate-free medium. Lidocaine produced further depression of the contractile force of atria depressed by citrate. These results argue strongly for an additional mechanism of cardiac depression caused by lidocaine involving the sites below the PFK.

• The Korean Journal of Pharmacology
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• v.12 no.1
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• pp.23-29
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• 1976

Aconiti tuber butanol fraction has been recently known to have stimulatory effect on myocardial contractility. In the present study, the possibility that the Aconiti tuber butanol fraction acts directly on contractile proteins of myocardium has been investigated using natural actomyosin extracted from dog heart. It revealed that Aconiti tuber butanol fraction in concentrations from $10^{-2}{\sim}10^{-7}\;gm/ml$ had no stimulatory effect on either the $Mg^{++}$ or $Ca^{++}$-activated adenosinetriphosphatase activity of cardiac actomyosin. And no direct $Ca^{++}$-like action of the drug on cardiac actomyosin was also found. Aconiti tuber butanol fraction in concentrations above $10^{-4}\;gm/ml$, however, was somewhat stimulatory on superprecipitation of actomyosin and markedly inhibited the membrane bound $Na^+-K^+$-activated ATPase activity. In these connections, the positive inotropic action of Aconiti tuber butanol fraction on myocardium thus does not seem to reflect a direct interaction with contractile proteins, but the drug seem to stimulate myocardial contractility through the actions on the membrane transport of $Ca^{++}$.

• Journal of Chest Surgery
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• v.21 no.2
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• pp.211-222
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• 1988

Tetralogy of Fallot is a cyanotic congenital heart disease characterized by large ventricular septal defect[VSD] and stenosis of right ventricular outflow tract[RVOT] and the degree of RVOT stenosis and the state of pulmonary arteries are the major determinant of prognosis of this anomaly after operation. The sum of blood flow through RVOT and collateral flow from systemic arteries determine the total pulmonary blood flow and it is drained to left atrium and left ventricle. Therefore the degree of development of left ventricle not only reflects pulmonary blood flow and the status of peripheral pulmonary arteries but also affects postoperative prognosis as a systemic ventricle. In this article, left ventricular volume and its influence on postoperative cardiac function in tetralogy of Fallot were studied in 34 patients operated on at Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital in 1985. Mean age of the patients was 5 1/12*3 9/12 years[range 9/12 - 14 8/12 years], mean body surface area[BSA] 0.65*0.20m2[range 0.38 - 1.22m2], mean body weight 15.6k6.48kg[range 7.0 - 36kg]and mean hematocrit 50.6*9.77%[range 32.0 - 73.5%]. Left ventricular end-diastolic volume[LVEDV] of them were from 11.2 to 113cc and there was a good linear correlation between BSA[m2, X]and LVEDV[cc, Y][Y= - 20.0+923x, r= 0.84, p < 0.005]. Mean LVEDV/m2 was [57.6 * 18.3 cc / m2[range 28.7 - 95.8 cc / m2] and there was a significant reduction of volume compared with normal value. As body surface increases, there was a increasing tendency in LVEDV/m2 but there was no statistical significance. Mean total amount of postoperatively infused dopamine in these 33 patients[except one who expired postoperatively] was 65.6*74.5mg / kg and it was 40.6*44.0mg / kg in routine RVOT widening group [Group I] and 205*49.3mg / kg in transannular RVOT widening group[Group II]. There was a statistically significant difference between two groups. In group I patients there was a good linear inverse correlation between dopamine total amount[mg / kg, Y] and LV volume[cc / m2, X] [Y = 150 - 1.89 X, r = - 0. 77, p < 0.005]. But there were no correlations between dopamine total amount and Hct, cardiopulmonary bypass time and aorta cross clamp time. In conclusion, the patient with small preoperative left ventricular volume required more amount of dopamine as an inotropic agent for the maintenance of a cardiac function in postoperative period. But this is a result of immediate postoperative period and does not reflect the long term effect of left ventricular volume in tetralogy of Fallot. There must be more study for the evaluation of its long term effect.

• Biomolecules & Therapeutics
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• v.9 no.3
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• pp.167-175
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• 2001

Recent studies have shown that cytokines are capable of modulating cardiovascular function and that some drugs used in the treatment of heart failure variably modulate the production of cytokines. Hige- namine, a positive inotropic isoquinoline alkaloid, has been used traditionally as cardiac stimulant, and reported to reduce nitric oxide (NO) and inducible nitric oxide synthase (iNOS) expression in LPS- and/or cytokine-activated cells in vitro and in vivo. Therefore, we investigated whether higenamine modulates the production of proinflammatory cytokines in myocardial infarction. In addition, effects of higenamine on antioxidant action and antioxidant enzyme expression (MnSOD) were studied. Myocardial infarction (MI) was confirmed by measuring left ventricular (LV) pressure after occlusion of the left anterior descending coronary artery (LAD) for 5 weeks in rats. Treatment of higenamine (10 mg/kg/day) reduced infarct size about 35 %, which accompanied by reduction of production TNF-$\alpha$, IL-6, but not IFN-${\gamma}$ and IL-1$\beta$ in the myocardium. The expression of TNF-$\alpha$ mRNA in infracted myocardium was significantly reduced by higenamine. Although iNOS mRNA was not detected, nitrotyrosine staining was significantly increased in myocardium of Ml compared to higenamine-treated one, Indicating that peroxynitrite-induced damage is evident in MI. Cytochrome c oxidation by peroxynitrite was concentration-dependently reduced by higenamine, an effect which was almost compatible to glutathion. Higenamine treatment did not affect the expression of MnSOD mRNA in myocardial tissues in MI. Taken together, higenamine may be beneficial in oxidative stress conditions such as ischemic-reperfusion injury and MI due to antioxidant action as well as modulation of cytokines.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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• pp.323-330
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• 1998

Tetrahydroisoquinoline (THI) alkaloids can be considered as cyclized derivatives of simple phenylethylamines. Many of them, especially with 6,7-disubstitution, demonstrate a relatively high affinity for catecholamines. Present study examines the pharmacological action of limited series of THI, using rats' isolated atria and aorta. In addition, a $[^3H]$ prazosin displacement binding study with THI compounds was performed, using rat brain homogenates to investigate whether these probes have ?${\alpha}$-adrenoceptor affinity. We also compared the vascular relaxation potency of these probes with dobutamine. YS 49, YS 51, higenamine and dobutamine, concentration-dependently, relaxed endothelium-denuded rat thoracic aorta precontracted with phenylephrine (PE, 0.1 ${\mu}M$) in which $pEC_{50}$ were $5.56{\pm}0.32$ and $5.55{\pm}0.21$, $5.99{\pm}1.16$ and $5.57{\pm}0.34$, respectively. These probes except higenamine also relaxed KCl (65.4 mM)-contracted aorta. In isolated rat atria, all THIs and dobutamine increased heart rate and contractile force. In the presence of propranolol, the concentration response curves of YS 49 and YS 51 shifted to the right and resulted in $pA_2$ values of $8.07{\pm}0.84$ and $7.93{\pm}0.11$, respectively. The slope of each compound was not deviated from unity, indicating that these chemicals are highly competitive at the cardiac ?${\beta}-adrenoceptors$. YS 49, YS 51, and higenamine showed ?${\alpha)-adrenoceptor$ affinity in rat brain, in which the dissociation constant $(K_i)$ was 2.75, 2.81, and 1.02 ${\mu}M$, respectively. It is concluded, therefore, that THI alkaloids have weak affinity to ${\alpha)_1-adrenoceptor$ in rat aorta and brain, respectively, while these probes show relatively high affinity for cardiac ${\beta}-adrenoceptors$. Thus, these chemicals may be useful in the treatment of congestive heart failure.

• Journal of Chest Surgery
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• v.29 no.2
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• pp.191-198
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• 1996

Amrinone is a non-glycosidic, non-adrenergic positive inotropic agent with peripheral and coronary vasodilator effect. It inhibits phosphodiesterase F-III, the cardiac cyclic-AMP specific phosphodiesterase, selectively and potently. In this study, the effects of IV administered amrinone and dopamine were compared in 40 patients who had open heart surgery. Amrinone was administered as a bolus of 1 5~2mglkg for several minutes, followed by continuous infusion at 5~1 Oug/kg/min. The hemodynamic measurements including heart rate, systolic and diastolic pressure, cardiac index, pulmonary wedge pressure, and systemic vascular resistance were recorded immediately for 12~24 hours awl 7th day following operation. In amrinone group, cardiac index increased from 3.73$\pm$1.39 L/min/m2 to 5.44$\pm$2.65 L/min/m2 at the time of posterative 48 hours (n=20, p< 0.05). The decrease in systemic vascular resistance from 1237.5 $\pm$ 637.7 dyne/sec/cm2 to 1000.8 $\pm$ 608.5 dyne/sec/cm2(p<0.05). In Dopamine group, the heart rate increased from 92.1 $\pm$ 13.0/min to 101.0 $\pm$ 13.1/min and the cardiac index decreased from 3.40 $\pm$ 0.50 L/min/m2 to 2.53 $\pm$ 1.15 L/min/m2 at the time of postoperative 12 hours(p<0.05). Systemic vascular resistance increased from 1058.5 $\pm$ 234.6 dyne/sec/cm2 to 1979.7 $\pm$ 759.2 dynelsec/cm2 The comparison of the hemodynamic effects of amrinone and dopamine, both drugs improved cardiac performance. But the administration of amrinone results in a higher cardiac index, diastolic blood pressure and lower systemic vascular resistance than those achieved with dopamine (p<0.05). The uniqueness of the action of amrinone on the heart and its sustained hemodynamic effect suggest it has clinical promise, pos operative care of cardiac surgery

• Journal of Chest Surgery
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• v.36 no.7
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• pp.483-488
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• 2003

There are still debates in the literature on the relative benefits of blood cardioplegia and crystalloid cardioplegia in pediatric cardiac surgery. We performed a clinical trial to compare the myocardial protective effect between HTK solution and blood cardioplegic solution in congenital heart surgery. Material and Method: 15 patients who underwent HTK solution cardioplegia (group 1) and 15 patients who underwent blood cardioplegia(group 2) were included in this study. Preoperative and postoperative serial serum cardiac enzyme levels (troponin I, CK-MB, LDH) were measured in all patients. Clinical data were analyzed and compared between the two groups. Result: There were no differences in age and body weight between the two groups. Operative diagnosis included ventricular septal defect (VSD, n＝4), atrial septal defect (ASD, n＝1), tetralogy of Fallot (TOF, n＝4), and other complex heart diseases (n＝6) in group 1, VSD (n＝7), ASD (n＝5), and TOF (n＝3) in group 2. Cardiopulmonary bypass times were 99.1$\pm$48.1 minutes in group 1, and 69.3$\pm$27.3 minutes in group 2 (p＝0,02). Aortic clamping times were 52.1$\pm$23.6 minutes in group 1, and 37.9$\pm$20.5 minutes in group 2 (p＝0.07). There was no mortality and spontaneous defibrillation was possible in all patients. No differences were observed in the serial enzyme levels between the two groups. There were no differences in the duration of inotropic support and ventilator time between the two groups. Conclusion: HTK solution provided comparable myocardial protection compared with blood cardioplegic solution. A single high dose of HTK solution may be safely and conveniently used for an extended periods as well in congenital heart surgery.

• Journal of Chest Surgery
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• v.40 no.10
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• pp.659-666
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• 2007

Background: Preserving the subvalvular apparatus after mitral valve replacement (MVR) results in better ventricular function and a better outcome. In conjunction, mitral valve repair (MVr) is associated with a better outcome, yet little is known about the hemodynamics and outcomes between patients undergoing MVr and MVR with chordal preservation. We prospectively evaluated the hemodynamic changes and outcomes of patients undergoing MVr and MVR with chordal preservation. Material and Method: Fifty-four patients with mitral regurgitation (MR) who under-went MVR with chordal preservation (n=21) or MVr (n=33) were studied. The patients' characteristics, the intra-and postoperative hemodynamics and the use of cardiac medications, the postoperative outcome and the complications were recorded during the hospital stay. All the patients were followed up for at least 6 months post-operatively for determining their morbidity and mortality. Result: The patients' characteristics were similar between the groups, except for the presence of atrial fibrillation and congestive heart failure which was more frequent in the MVR group. Also, the preoperative left ventricular ejection fraction was lower in the MVR group than in the MVr group ($64{\pm}9%$ versus $69{\pm}5%$, respectively, p=0.043). There were no significant differences of the hemodynamics between the groups. The use of inotropic drugs and pacemakers during the 12hrs postoperatively was more common in the MVR group than in the MVr group (48% versus 24%, p=0.025 and 52% versus 24%, p=0.035, respectively). The other postoperative outcomes were similar in both groups for at least the 6 months follow-up period. Conclusion: MVR with chordal preservation was comparable with regard to the hemodynamics and clinical outcomes, supporting the beneficial effect of preserving the subvalvular apparatus after MVR.

• The Korean Journal of Pharmacology
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• v.14 no.1_2
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• pp.1-11
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• 1978

The $Na^+$-and $K^+$-induced $Ca^{++}$ release was measured isotopically by Milipore filter technique in mitochondria isolated from rabbit ventricles. The release of $Ca^{++}$ from mitochondria could be induced by 1-3 mM of $Na^+$ added in incubating medium under the presence of 0.5mM EGTA to prevent the released $Ca^{++}$ from rebinding with mitochondrial membrane. The amount of $Ca^{++}$ released was increased by increasing the concentration of $Na^+$ added. 100mM $K^+$, in itself, did not induce the $Ca^{++}$ release from cardiac mitochondria, the $Na^+$-induced $Ca^{++}$ release, however, was potentiated by the presence of $K^+$. The potentiation of $Na^+$-induced $Ca^{++}$ release by $K^+$ was proportional to the $Na^+/K^+$ ratio presented in the incubating medium. Among the monovalent cations other than $Na^+$, the release of $Ca^{++}$ from cardiac mitochondria was shared only by $Li^+$. The $Na^+$-induced $Ca^{++}$ release could be also observed in the mitochondria isolated from liver and kidney. However, the $Na^+$ sensitivity was somewhat lower in liver and kidney mitochondria than in heart mitochondria. The release of $Ca^{++}$ induced by $Na^+$ in the mitochondria isolated from the experimentally produced failured heart was not different from that in the normal heart mitochondria, and was not directly modified by $10^{-6}{\sim}10^{-5}$ M of Ouabain. From the experiments, it was suggested that the $Ca^{++}$ released from mitochondria by $Na^+$ could be used in excitation-contraction coupling process to initiate the contraction of the cardiac myofibrils. Futhermore, it appeared that the phenomenon of $Ca^{++}$ release from cardiac mitochondria by $Na^+$ and $K^+$ might be related to the inotropic effect of digitalis glycoside which could bring about the increase of $Na^+$ or the reduction of $K^+$ intracellulary through the inhibition of $Na^+$, $K^+$-ATPase.

• Journal of Mushroom
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• v.3 no.4
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• pp.133-139
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• 2005

Fruiting bodies of Cordyceps have been regarded as popular folk and effective medicines to treat human diseases such as asthma, bronchial and lung inflammation, and kidney disease. Cordyceps pruinosa (Clavicipitaceae; Hypocreales; Ascomycotina) has received special attention for medicinal purpose due to its various physiological activites. The nucleoside derivative N6-(2-hydroxyethyl) adenosine (HEA) isolated from it showed a $Ca^{2+}$ antagonistic effect and negative inotropic response. The artificial production of fruiting body of C. pruinosa has not been tried successfully yet by using living silkworm substrate. To develop techniques for the production of C. pruinosa stromata on a large scale, the infection of Bombyx mori with C. pruinosa and the growth characteristics of stroma of C. pruinosa were investigated. Also, studied about biological activities of fruiting body formed on silkworm. Infection rate of the silkworm pupae with C. pruinosa was the highest in injection inoculation. The formation of the fruiting body of C. pruinosa was quite good in the room controlled at $21{\sim}25^{\circ}C$, over 91% of relative humidity and over 1500 lx. Glucose concentration was high in the fruiting bodies of the silkworm pupae infected with C. pruinosa on a dry weight basis. The most abundant amino acid in the fruiting bodies was arginine and phenylalanine. The fruiting bodies of silkworm pupae infected with C. pruinosa was rich in oleic acid. The high amount of citric acid was found in the fruiting bodies of silkworm pupae infected with C. pruinosa.