• Journal of Chest Surgery
• /
• v.48 no.3
• /
• pp.164-173
• /
• 2015

Background: Hypertrophied myocardium is especially vulnerable to ischemic injury. This study aimed to compare the early and late clinical outcomes of three different methods of myocardial protection in patients with aortic stenosis. Methods: This retrospective study included 225 consecutive patients (mean age, 65{\pm}10 years; 123 males) with severe aortic stenosis who underwent aortic valve replacement. Patients were excluded if they had coronary artery disease, an ejection fraction <50%, more than mild aortic regurgitation, or endocarditis. The patients were divided into three groups: group A, which was treated with antegrade and retrograde cold blood cardioplegia; group B, which was treated with antegrade crystalloid cardioplegia using histidine-tryptophan-ketoglutarate (HTK) solution; and group C, treated with retrograde cold blood cardioplegia. Results: Group A contained 70 patients (31.1%), group B contained 74 patients (32.9%), and group C contained 81 patients (36%). The three groups showed significant differences with regard to the proportion of patients with a New York Heart Association functional classification ${\geq}III$ (p=0.035), N-terminal pro-brain natriuretic peptide levels (p=0.042), ejection fraction (p=0.035), left ventricular dimensions (p<0.001), left ventricular mass index (p<0.001), and right ventricular systolic pressure (p <0.001). Differences in cardiopulmonary bypass time (p=0.532) and aortic cross-clamp time (p=0.48) among the three groups were not statistically significant. During postoperative recovery, no significant differences were found regarding the use of inotropes (p=0.328), mechanical support (n=0), arrhythmias (atrial fibrillation, p=0.347; non-sustained ventricular tachycardia, p=0.1), and ventilator support time (p=0.162). No operative mortality occurred. Similarly, no significant differences were found in long-term outcomes. Conclusion: Although the three groups showed some significant differences with regard to patient characteristics, both antegrade crystalloid cardioplegia with HTK solution and retrograde cold blood cardioplegia led to early and late clinical results similar to those achieved with combined antegrade and retrograde cold blood cardioplegia.

• Journal of Oriental Physiology
• /
• v.14 no.2 s.20
• /
• pp.179-187
• /
• 1999

To investigate how Jagamchotang provent cellular injury by a certain starting point on reperfusion injury after ischemia in myocardial cell, conducted MTT assay, LM stydy and measured LDH secretion, heart rate and nitric oxide(NO), and got the following results. 1. Jagamchotang did not injure cells even in $20{\mu}g/ml$. 2. Jaganchotang repressed the toxicity of mitochondria and cell membrane in reperfusing after ischemia and repressed the contraction of promontory of myocardial cell and reduction of the number of cells. Also maintained regular heart rate and reduced the number of heart rate. 3. Synthesis of NO by Jagamchotang in ischemia increased 1.9 times than a control. 4. When reperfusing with sodium nitropruside (SNO), NO donor in ischemia repressed the toxicity of mitochondria as the case of reperfusing with Jagamchotang in ischemia. Therefore, putting these findings together, it. can be said the effect of Jagamchotang in ischemia will be closely related with generation of NO.

• Biomedical Science Letters
• /
• v.7 no.2
• /
• pp.91-98
• /
• 2001

The present study was prospectively designed to assess the clinical effect of leukocyte-depleted blood cardioplegic solution (BCS) on myocardium during cardiac surgery with cardiopulmonary bypass (CPB). 30 adult patients scheduled for elective cardiac surgery were divided into control group (n＝15), which infused routine BCS, and leukocyte-depleted (LD) group (n＝15), which infused leukocyte-depleted BCS. Total and differential leukocyte counts in BCS, malondialdehyde (MDA) and troponin-T (TnT) concentrations in coronary sinus blood, and cardiac index (CI) were measured at preoperative and postoperative period. The BCS in LD group had less total leukocyte counts with neutropenia than that in control group (P＜0.01). MDA (3.70$\pm$0.35 vs 5.90$\pm$0.57 $\mu$mol/L, p<0.05) and TnT (0.42$\pm$0.03 vs 0.60$\pm$0.09 ng/mL, p<0.05) were significantly low in LD group compared with control group, while LD group had higher CI (3.28$\pm$0.16 L/min/$m^2$, p<0.05) than control group (2.69$\pm$0.18 L/min/$m^2$). These results suggest that leukocyte-depleted blood cardioplegic solution has a better myocardial protective effect with less generations of oxygen free radicals and ischemia/reperfusion injury.

• The Korean Journal of Pharmacology
• /
• v.27 no.2
• /
• pp.109-118
• /
• 1991

The present study was conducted to assess the possible contribution of arachidonic acid to generation of reactive oxygen metabolites and myocardial damage in ischemic-reperfused heart. Langendorff preparations of isolated rat heart were made ischemic by hypoperfusion (0.5 ml/min) for 45 min, and then followed by normal oxygenated reperfusion (7 ml/min). The generation of superoxide anion was estimated by measuring the SOD-inhibitable ferricytochrome C reduction. The myocardial cellular damage was observed by measuring LDH released into the coronary effluent. Oxygenated reperfusion following a period of ischemia produced superoxide anion, which was inhibited by both indomethacin (60 nmole/ml) and ibuprofen $(30\;{\mu}g/ml)$. Sodium arachidonate $(10^{-7}-10^{-2}{\mu}g/ml)$ administered during the period of oxygenated reperfusion stimulated superoxide anion production dose-dependently. The rate of arachidonate-induced superoxide generation was markedly inhibited by indomethacin, a cyclooxygenase inhibitor; nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, and by eicosatetraynoic acid (ETYA), a substrate inhibitor of arachidonic acid metabolism. The release of LDH was increased by Na arachidonate and was inhibited by superoxide dismutase. The release of LDH induced by arachidonic acid was also inhibited by indomethacin, NDGA and ETYA. In conclusion, the present result suggests that arachidonic acid metabolism is involved in the production of reactive oxygen metabolite and plays a contributory role in the genesis of reperfusion injuy of myocardium.

• Journal of Chest Surgery
• /
• v.40 no.6 s.275
• /
• pp.399-406
• /
• 2007

Background: Ischemia-reperfusion injury related to unsuccessful myocardial protection affects postoperative ventricular function and mortality during open-heart surgery. We prospectively compared the effects of administration of histidine-tryptophan-ketoglutarate (HTK) solution and cold blood cardioplegia (CBC) on myocardial protection and clinical outcome in patients undergoing mitral valve surgery. Material and Method: Seventy patients with mitral regurgitation (MR) undergoing mitral valve surgery were randomly divided into the HTK group (n=31) and the CBC group (n=31 ): eight patients were excluded. Perioperative hemodynamics, cardiac medications, pacing, postoperative outcomes and complications were recorded during the hospital stay. All patients received follow-up for at least 6 months postoperatively for morbidity and mortality. Resuか: There were no significant differences in the hemodynamics between the groups during the study period, except for the mean pulmonary artery pressure (MPAP), PCWP and CVP that were lower in the HTK group at 15 min after weaning of CBP. There were no differences for inotropic support and pacing during the 12 hrs postoperatively between the groups. CK-MB values on day 1 and day 2 were $77{\pm}54$ and $41{\pm}23$ for the HTK group and $70{\pm}69$ and $44{\pm}34$ for the CBC group, respectively (p=NS). Postoperative clinical outcomes were similar in both groups for at least 6 months during the follow-up period. Conclusion: These results suggest that the use of HTK solution is as safe as cold blood cardioplegia in terms of myocardial protection.

• The Korean Journal of Physiology and Pharmacology
• /
• v.8 no.4
• /
• pp.207-211
• /
• 2004

The purpose of the present study was to evaluate the expression of cardiac marker protein in rabbit cardiac tissue that was exposed to ischemic preconditioning (IPC), or ischemiareperfusion injury (IR) using two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). We compared 2DE gels of control (uninjured) cardiac tissue with those of IPC and IR cardiac tissue. Expression of one protein was detected in IR heart tissue, however the protein was not detected in the samples of control and IPC tissue. To further characterize the detected protein molecule, the protein in the 2D gel was isolated and subjected to trypsin digestion, followed by MALDI-MS. The protein was identified as myoglobin, which was confirmed also by Western blot analysis. These results are consistent with previous studies of cardiac markers in ischemic hearts, indicating myoglobin as a suitable marker of myocardial injury. In addition, the present use of multiple techniques indicates that proteomic analysis is an appropriate means to identify cardiac markers in studies of IPC and IR.

• The Korean Journal of Physiology and Pharmacology
• /
• v.8 no.2
• /
• pp.95-100
• /
• 2004

Ischemic preconditioning (IPC) has been accepted as a heart protection phenomenon against ischemia and reperfusion (I/R) injury. The activation of ATP-sensitive potassium $(K_{ATP})$ channels and the release of myocardial nitric oxide (NO) induced by IPC were demonstrated as the triggers or mediators of IPC. A common action mechanism of NO is a direct or indirect increase in tissue cGMP content. Furthermore, cGMP has also been shown to contribute cardiac protective effect to reduce heart I/R-induced infarction. The present investigation tested the hypothesis that $K_{ATP}$ channels attenuate DNA strand breaks and oxidative damage in an in vitro model of I/R utilizing rat ventricular myocytes. We estimated DNA strand breaks and oxidative damage by mean of single cell gel electrophoresis with endonuclease III cutting sites (comet assay). In the I/R model, the level of DNA damage increased massively. Preconditioning with a single 5-min anoxia, diazoxide $(100\;{\mu}M)$, SNAP $(300\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP) $(100\;{\mu}M)$ followed by 15 min reoxygenation reduced DNA damage level against subsequent 30 min anoxia and 60 min reoxygenation. These protective effects were blocked by the concomitant presence of glibenclamide $(50\;{\mu}M)$, 5-hydroxydecanoate (5-HD) $(100\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-8-pCPT-cGMP) $(100\;{\mu}M)$. These results suggest that NO-cGMP-protein kinase G (PKG) pathway contributes to cardioprotective effect of $K_{ATP}$ channels in rat ventricular myocytes.

• Journal of Chest Surgery
• /
• v.13 no.4
• /
• pp.321-337
• /
• 1980

The increasing use of cardioplegic solution for the reduction of ischemic tissue injury requires that all cardiplegic solution be carefully assessed for any protective or damaging properties. This study describes functional, enzymatic and structural assessment of the efficiency of three cardioplegic solutions (Young & GIK, Bretschneider, and $K^{+}$ Albumin solution) in a Modified Isolated Rat Heart Model of cardiopulmonary bypass and ischemic arrest. Isolated rat heart were subjected to a 2-minute period of coronary infusion with a cold cardioplegic or a noncardioplegic solution immediately before and also at the midpoint of a 60-minute period of hypothermic ($10{\pm}1$. C) ischemic cardiac arrest. The results of this study were as follow: 1. Spontaneous heart beat after ischemic arrest occured 16 seconds later after Langendorff reperfusion in the Young & GIK group (n=6), and 40 second later in the Bretschneider group (n=6) and 6 minute later in the $K^{+}$ Albumin group (n=6), and 16 minute later in the control group (non-cardioplegia). A good recovery state of spontaneous heart beat was shown in the Young & GIK and Bretschneider groups. 2. The percentage of recorveries of heart function at 30 minute after postischemic working heart perfusion were : heart rate $91.6{\pm}3.1$% (P<0.01)m oeaj airtuc oressyre $83{\pm}3$% (P<0.01), coronary flow $70{\pm}8$% (P<0.05) and aortic flow flow rate $39{\pm}9.3$% (P<0.05) in the Young & GIK group. This percentage of recoveries of the Young & GIK group was significantly greater than the control group. In the Bretschneider group, the percentage of recoveries were : heart rate $87.8{\pm}7.5$%(P<0.05), peak aortic pressure $71{\pm}2.3$% (P<0.05) and aortic flow rate $33.2{\pm}6.6$%(P<0.05). hte percentage of recoveries were significantly greater than in the control group. In the $K^{+}$ Albumin group, recoveries of heart function were poor. 3. Total CPK leakage was $131.2{\pm}12.75$IU/30 min/gm. dry weight in the control group, $50.65{\pm}12.75$IU in the Young & GIK gruop, $69.40{\pm}32.21$Iu in Bretschneider group, and $103.65{\pm}15.47$IU in the $K^{+}$ Albumin group during the 30 minute postischemic Langendorff reperfusion. Total CPK leakage was significantly less (P<0.001) in the Young & GIK group, than in the control group. 4. Direct correlatin between percentage recovery of aortic flow rate and total amount of CPK leakage from Myocardium was noticed.(Correlation Coefficient r = 0.76, P<0.001). 5. Mild perivascular edema was the only finding of light microscopic study of myocardium after 60 minute ischemic arrest with cold cardioplegic solutions and hypothermla.

• Journal of Chest Surgery
• /
• v.30 no.2
• /
• pp.119-124
• /
• 1997

Using isolated rat heart preparations, we observed the protective effe ts of verapamil cardioplegia on ischemic myocardial injury. Isolated rat hearts were subjected to global ischemia at $25^{\circ}C$ Twenty four isolated Sprague Dawley rat hearts underwent 30 minutes of the retrograde nonworking perfusion with Krebs-Henseleit buffer solution followed by $25^{\circ}C$ cardioplegic solution (St. Thomas'Hospital Cardioplegic Solution) for 60 minutes. Before ischemic arrest, rat hearts were treated with cold cardioplegic solution in control group (n=12) and cold cardioplegic solution with verapamil (1 mg/L) in experimental group (n=12). After 60 minutes of ischemia, hemodynamic and biochemical parameters such as heart rate, left ventricular pressure (LVP), + dp/dt max, coronary flow and creatine phosphokinase (CPK) were measured before giving cardioplegia and 30 minutes after reperfusion. Verapamil group exhibited greater recovery of heart rate, LVP, +dpldt max, coronary flow and CPK than control group (p < 0.05).

• Journal of Chest Surgery
• /
• v.36 no.11
• /
• pp.828-833
• /
• 2003

Background: It has been reported that the recently developed intermittent antegrade warm blood cardioplegia (IAWBC) has better myocardial protective effects during coronary artery bypass surgery than cold blood cardioplegia or continuos retrograde cold blood cardioplegia. The aim of this study is to evaluate the safety and usefulness of IAWBC by comparing it retrospectively with intermittent retrograde cold blood cardioplegia (lRCBC). Material and Method: From April 2001 to Feb. 2003, fifty seven patients who underwent isolated coronary surgery were divided into two groups (IAWBC vs. IRCBC). The two group had similar demographic and angiographic characteristics. There were no statistical differences in age, sex, Canadian Cardiovascular Society Functional Classification for angina, ejection fraction, and number of grafts. Result: Aortic cross clamping time and total pump time in IAWBC (99$\pm$23 and vs. 126$\pm$32 min) were shorter than those of IRCBC (118$\pm$32 min. and 185$\pm$48 min.)(p<0.05). The reperfusion time (13$\pm$7 min) in IAWBC was shorter than that of IRCBC (62$\pm$109 min.)(p<0.05). CKMB at 12 hours and 24 hours (16$\pm$15 and 9$\pm$13) in IAWBC was lower than that of IRCBC (33$\pm$47 and 17$\pm$26)(p<0.05). The awakening time in IAWBC (2$\pm$1 hour) was shorter than that of IRCBC (4$\pm$3)(p<0.05). The number of spontaneous heart beat recovery in IAWBC (85%) was more than that of IRCBC (35%)(p<0.05). The cardiac index after discontinuing cardio-pulmonary bypass was significantly elevated in the IAWBC group. The prevalence of perioperative myocardial infarction in IAWBC (4%) was lower than that of IRCBC group (20%)(p<0.05). Conclusion: Intermittent antegrade warm blood cardioplegia is a safe, reliable, and effective technique for myocardial protection. It can also provide simpler and economic way than the retrograde cold cardioplegia by shortening of cardiopulmonary bypass time and avoiding retrograde cannulation for coronary sinus.