Protocatechuic aldehyde protects cardiomycoytes against ischemic injury

Rescuing cells from stress damage emerges a potential therapeutic strategy to combat myocardial infarction. Protocatechuic aldehyde (PCA) is a major phenolic acid in Chinese herb Danshen (

Research progresses on pyruvate dehydrogenase kinases / 基础医学与临床

Pyruvate dehydrogenase kinases(PDKs 1-4) can regulate the activity of mitochondrial pyruvate dehydrogenase complex(PDC) to catalyse the oxidative decarboxylation of pyruvate,and then to link glycolysis to the tricarboxylic acid cycle and ATP production.In this review,we summarize up-to-date information of mechanisms regulating PDKs and the function of PDKs inhibitors in lowering blood glucose level,alleviate damage during heart ischemia and also triggering apoptosis in cancer cells.PDKs will be a possible pharmacological targets in diabetes,heart ischemia and cancer therapy.

Myocardial Viability: Comparison of Free-Breathing Navigator-echo-gated Three-Dimensional Inversion-Recovery Gradient-Echo MR and Standard Multiple Breath-Hold Two-Dimensional Inversion-Recovery Gradient-Echo MR

PURPOSE: To compare a free-breathing, navigator-echo-gated, three-dimensional, inversion-recovery, gradient-echo, MR pulse sequence (3D-MRI) with standard, multiple breath-hold, two-dimensional, inversion-recovery, gradient-echo MR (2D-MRI) for the evaluation of delayed hyperenhancement of nonviable myocardium in patients with chronic ischemic heart disease. MATERIALS AND METHODS: Ten patients with chronic ischemic heart disease were enrolled in this study. MRI was performed on a 1.5-T system. 3D-MRI was obtained in the short axis plane at 10 minutes after the administration of Gd-DTPA (0.2 mmol/kg, 4 cc/sec). Prospective gating of the acquisition based on the navigator echo was applied. 2D-MRI was performed immediately after finishing 3D-MRI. The area of total and hyperenhanced myocardium measured on both image sets was compared with paired Student t-test and Bland-Altman method. By using a 60-segment model, the transmural extent and segmental width of the hyperenhanced area were recorded by 3-scale grading method. The agreement between the two sequences was evaluated with kappa statistics. We also evaluated the agreement of hyperenhancement among the three portions (apical, middle and basal portion) of the left ventricle with kappa statistics. RESULTS: The two sequences showed good agreement for the measured area of total and hyperenhanced myocardium on paired t-test (p=0.11 and p=0.34, respectively). No systematic bias was shown on Bland-Altman analysis. Good agreement was found for the segmental width (Kappa=0.674) and transmural extent (Kappa=0.615) of hyperenhancement on the segmented analysis. However, the agreement of the transmural extent of hyperenhancement in the apical segments was relatively poor compared with that in the middle or basal portions. CONCLUSION: This study showed good agreement between 3D-MRI and 2D-MRI in evaluation of non-viable myocardium. Therefore, 3D-MRI may be useful in the assessment of myocardial viability in patients with dyspnea and children because it allows free-breathing during the examination.

MR Imaging of Ischemic Heart Disease

MRI has achieved many technical advances in the spatial resolution, temporal resolution, contrast resolution, signal-to-noise ratio, and postprocessing technique. At one session of examination within a tolerable time, MRI can provide integrated information on coronary artery stenosis, systolic dysfunction, myocardial perfusion, and myocardial viability. Delayed enhancement study after contrast administration is highly reproducible and offers unique vision for myocardial viability in the patients with myocardial infarction. Cardiac MRI is very cost-effective and may be one-stop solution for the evaluation of ischemic heart disease.

Coronary Artery Calcium Score using Electron Beam Tomography in the Patients with Acute Obstructive Coronary Arterial Disease : Comparative Study with Asymptomatic High-Risk Group of Atherosclerosis and Chronic Obstructive Coronary Arterial Disease Group

PURPOSE: To compare, through enalysis of the coronary artery calcium (CAC) score and the risk factors for atherosclerosis, the characteristics of acute coronary syndrone between an asymptomatic high-risk group of atherosclerosis patients and a chronic coronary arterial obstructive disease(CAOD) group. MATERIALS AND METHODS: The CAC scores of an asymptomatic high-risk group of atherosclerosis patients (group I, n=284), a chronic CAOD group (group II, n=39) and an acute coronary syndrome group (group III, n=21) were measured by electron beam tomography. Forty-seven patients with CAOD from groups II and III underwent coronary angiography, and we scrutinized age, sex, and risk factors including diabetes mellitus, hypertension, obesity, smoking, hypercholesterolemia and low high-density lipoproteinemia. The numbers of stenotic coronary arterial branches and degree of stenosis revealed by coronary angiography were also recorded. We determined the differences between the three groups in terms of CAC score and the risk factors, the relationship between CAC score and risk factors, and the characteristic features of each type of CAOD group. RESULTS: The mean CAC score of group III (135.1) was not statistically different from that of group I (135.7) or group II (365.8). Among patients aged below 50, the mean CAC score of group III (127.4) was significantly higher than that of group I (6.2), (p=0.006). The mean CAC score at the sixth decade was also significantly different between group I (81.5) and group II (266.9). The mean age of group III (54.2 years) was significantly lower than that of group I (58.1 years) (p=0.047) and of group II (60.1) (p=0.022). There was significant correlation between the number of stenotic coronary arterial branches and log(CAC+1) (p<.01). The square root of the CAC score and the maximal degree of stenosis was also well correlated (p<.01). There was no difference in the mean number of risk factors among the three groups, though the incidence of smoking in group III was significantly higher than in groups I and II. Multiple regression analysis showed that the CAC score was related to age, diabetes mellitus and hypertension in group I, diabetes mellitus only in group II, but no particular factor in group III. CONCLUSION: The CAC score of the acute coronary syndrome group tended to be lower than that of the chronic CAOD group. It appears to be difficult to predict acute coronary syndrome on the basis of CAC alone. Compared with the asymptomatic high-risk group of atherosclerosis patients, the acute coronary syndrome group, whose members are younger and have a higher incidence of smoking, has a relatively high CAC score.

The Effects of Isovolemic Hemodilution on Hemodynamic Changes in Myocardial Ischemia-Induced Dogs / 대한마취과학회지

BACKGROUND: Anesthesiologists often encounter patients who have acute, massive blood loss and severe hemodilution as the result of fluid therapy in the operating room. It is known that patients with normal heart function survive at hemoglobin 4 6 g/dl. Recently, the incidence of elderly patients with ischemic heart disease have been increasing progressively but studies about critical hematocrit level in patients with ischemic heart disease are rare. This study, therefore, was designed to evaluate the hemodynamic response of isovolemic hemodilution in myocardial ischemia-induced dogs. METHODS: In 12 anesthetized dogs, a Swan-Ganz catheter and left ventricle catheter were inserted and hemodynamic parameters were measured as control values. Myocardial ischemia was induced with a left anterior descending (LAD) coronary artery ligation. Thereafter, isovolemic hemodilutions were done several times to set the hematocrit levels of 36%, 31%, 26%, 21%, 16%, and 11%. Records and samples for hemodynamic parameters were obtained after LAD ligation and at each hematocrit level. RESULTS: There were significant decreases in diastolic blood pressures in hematocrits 21%, 16%, 11%, in mean arterial pressures in hematocrits 16%, 11% and in systolic blood pressure in hematocrit 11% (P < 0.05). Oxygen delivery progressively decreased in hematocrits 36%, 31%, 26%, 21%, 16% and 11% (P < 0.05). Oxygen extraction ratios progressively increased and were statistically significant in hematocrits 21%, 16% and 11% (P < 0.05). Arterial blood gases showed metabolic acidosis in hematocrits 16% and 11%. There was decreased PCO2 in hematocrit 11% (P < 0.05). Mixed venous blood oxy-hemoglobin saturation decreased in hematocrit 16% and 11% (P < 0.05). Other variables were not significant. CONCLUSIONS: Blood pressure decreased at hematocrit 16% so it is necessary to maintain a hematocrit level above 21% at least in cardiac depressed dogs.

Effects of Intracoronary Calcium Chloride and Epinephrine on Coronary Blood Flow, Oxidative Metabolism, and Mechanical Function in Canine Normal and Stunned Myocardium / 대한마취과학회지

BACKGROUND: The effects of calcium chloride (CaCl2) on regional mechanical function, coronary blood flow (CBF) and myocardial oxygen consumption (MVO2) were examined in normal and stunned myocardium in an open-chest canine model. The effects were compared with those of epinephrine. METHODS: Thirty-one dogs were acutely instrumented under enflurane anesthesia to measure aortic and left ventricular pressure, pulmonary and left anterior descending (LAD) coronary flow, and subendocardial segment length the in LAD region. CaCl2 (0.1, 0.25, 0.5, 0.75 mg/ml of LAD flow, n = 16) or epinephrine (4, 10, 20, 30 ng/ml of LAD flow, n = 15) was directly infused into the LAD before (normal) and after 15 min of its occlusion and reperfusion (stunned). Simultaneous measurements of arterial and coronary venous contents of oxygen and lactate were made to calculate oxygen (EO2) and lactate (Elac) extraction ratio during CaCl2 or epinephrine infusion. RESULTS: Both CaCl2 and epinephrine infusions in normal myocardium resulted in dose-dependent increases in mechanical functions and MVO2. These changes were accompanied by parallel increases in CBF, resulting in no changes of EO2 with CaCl2, while CBF increased more than MVO2 with epinephrine, resulting in a decrease in EO2. After ischemia and reperfusion, mechanical functions and Elac were significantly depressed, but similar mechanical responses to both agents with resultant unaltered EO2 were observed. Elac was decreased further during epinephrine, while it remained unaltered during CaCl2 infusion in stunned myocardium. CONCLUSIONS: CaCl2, similar to epinephrine, exerts positive inotropic and lusitropic effects in normal and stunned myocardium in dogs. In addition, CaCl2 has no direct effect on coronary vascular tone in either normal or stunned myocardium, while epinephrine causes direct vasodilation in normal but not in stunned myocardium.

Effect of Propofol on Regional Myocardial Function and Metabolism in the Canine Stunned Myocardium / 대한마취과학회지

BACKGROUND: A brief period of coronary artery occlusion followed by reperfusion is known to produce prolonged period of ventricular dysfunction without necrosis (myocardial stunning). The present study was aimed to investigate the effects of propofol on regional myocardial functions and metabolism in postischemic stunned myocardium in an open-chest canine model. METHODS: Twenty-two dogs were acutely instrumented under halothane anesthesia to measure aortic and left ventricular pressure, pulmonary, left anterior descending (LAD) and circumflex (LCX) coronary artery flow, and subendocardial segment length in both the regions supplied by LAD and LCX. All animals were then subjected to a 15 min of LAD occlusion and subsequent reperfusion. In the expermental group (n=12), after 30 min of reperfusion halothane was replaced by a bolus of 5 mg.kg 1 of propofol followed by a continuous infusion for 30 min at 0.2 (baseline), 0.3, 0.4, and 0.5 mg.kg 1.min 1, whereas halothane was maintained without propofol infusion throughout the reperfusion period in the control group (n=10). Percent segment shortening (%SS) and the preload recruitable stroke work slope (Mw), as an index of regional myocardial contractility, and peak lengthening rate (dL/dtmax) and percent post-systolic shortening (%PSS), as an index of regional diastolic function, were evaluated. Metabolic data were determined from simultaneous arterial and coronary venous measurements of oxygen and lactate. RESULTS: Significant and dose-dependent decreases in both %SS (8.8 +/- 1.7 at 0.2 to 6.5 +/-1.6% at the 0.5 mg.kg 1.min 1 infusion) and Mw (1.45 +/- 0.15 at 0.2 to 0.87 +/- 0.07 erg.cm 3.104 at the 0.5 mg.kg 1.min 1) in the LAD region were observed. Concomitant decrease in dL/dtmax (52.4 +/- 3.9 at 0.2 to 40.2 +/- 3.6 mm.sec 1 at the 0.5 mg.kg 1.min 1 infusion) in the LAD region was also observed. In contrast, %SS, Mw, and dL/dtmax in the LCX region as well as %PSS in both regions remained unchanged throughout the infusion period. Propofol infusion was accompanied by progressive Although propofol produced progressive decreases in coronary blood flow and myocardial oxygen consumption in both regions, its administration was not associated with any changes in oxygen and lactate extraction ratios. CONCLUSION: The results indicate that propofol produces a greater depression on both regional systolic and diastolic functions in stunned myocardium than those in normal myocardium. However, propofol does not impair myocardial aerobic metabolism in both stunned and normal myocardium.

Effects of Intracoronary Propofol on Functional Recovery of Stunned Myocardium and Coronary Endothelium in Dogs / 대한마취과학회지

BACKGROUND: Oxygen-derived free radicals are known to contribute to tissue injury during myocardial ischemia and reperfusion. Recent in vitro studies have shown that propofol has potent antioxidant properties. The present study was aimed to investigate the effects of propofol on recovery of mechanical and coronary endothelial function in a myocardial stunning model. METHODS: Thirty-five dogs were acutely instrumented under halothane anesthesia to measure aortic and left ventricular pressure, pulmonary and left anterior descending coronary artery (LAD) flow, and subendocardial segment length. After completion of the surgery, halothane was replaced by fentanyl- midazolam. Animals were then subjected to 15 min of LAD occlusion and 3 hrs of reperfusion under either intracoronary (i.c.) propofol (5 microgram/mL, n=11; 20 microgramg/mL LAD flow, n=12) or vehicle (saline, n=12) for 1 hr beginning 30 min before LAD occlusion. Percent segment shortening (%SS) and the slope of the preload recruitable stroke work (Mw), as an index of regional myocardial contractility, and peak lengthening rate (dL/dtmax) and percent post-systolic shortening (%PSS), as an index of regional diastolic function, were evaluated. Coronary endothelial function was assessed by examining LAD flow response to i.c. acetylcholine (ACh, 1 microgram over I min) and i.c. sodium nitroprusside (SNP, 20 microgram over I min). The myocardial content of malondialdehyde (MDA) from LAD area was measured to evaluate lipid peroxidation. RESULTS: Despite equally severe ischemic dysfunction during LAD occlusion, recovery of %SS was significantly improved during reperfusion by either dose of propofol compared to controls. However, Mw recovered to the baseline within 60 min of reperfusion in all three groups. In addition, propofol-treated dogs showed better recovery of both indices of regional diastolic function (dL/dtmax and %PSS) as compared to controls. Ischemia-reperfusion similarly attenuated the increases in the LAD flow by ACh in all the groups, whereas it had no significant effect on these increases in LAD flow by SNP. The increase in MDA induced by ischemia and reperfusion was significantly suppressed by either dose of propofol. CONCLUSIONS: The results indicate that propofol attenuates mechanical but not coronary endothelial dysfunction in postischemic, reperfused myocardium in an open-chest canine model. The protective action of propofol against mechanical dysfunction is probably due to its effect to reduce lipid peroxidation.

Effects of Acute Myocardial Ischemia on Regional Function of the Remote Nonischemic Myocardium in Dogs / 대한마취과학회지

INTRODUCTION: During an acute myocardial ischemia, maintenance of overall ventricular function may depend on remote nonischemic myocardium. Whereas fentanyl has minimal hemodynamic effects, volatile anesthetics, including halothane and isoflurane cause negative inotropic and lusitropic effects in normal myocardium. This investigation examined the effects of volatile anesthetics in comparision with fentanyl on compensatory responses to brief left anterior descending coronary artery (LAD) occlusion in remote normal myocardium (left circumflex coronary artery (LCX) supply) in an open-chest canine model. METHODS: Thirty-six mongrel dogs, acutely instrumented for measurement of pressure (left ventricle (LV) and aorta), flows (pulmonary trunk and LCX) and dimensions in ischemic and non-ischemic myocardium, were subjected to a 10-min LAD occlusion during fentanyl (n=10), halothane (n=13), or isoflurane (n=13) anesthesia. Regional contractile function was assessed using percent systolic shortening (%SS) and the preload recruitable stroke work slope (Mw). Diastolic function was evaluated using a regional time constant for intramyocardial pressure decline of LV (IMPtau), peak lengthening rate (dL/dtmax) and a regional chamber stiffness constant (Kp). RESULTS: Acute LAD occlusion caused immediate deterioration of anterior wall function similarly without changes in cardiac index, mean arterial pressure and dP/dtmax in all three groups. LV end-diastolic pressure (LVEDP), LVPtau, and heart rate increased and dP/dtmin decreased to the same extent with regional myocardial ischemia in all groups. During fentanyl anesthesia, acute myocardial ischemia was associated with an increase in %SS (26%) and Mw (48%) in LCX area without changes in IMPtau and dL/dtmax. With halothane or isoflurane anesthesia, %SS, Mw and IMPtau showed similar changes as those in fentanyl in response to LAD occlusion. However, dL/dtmax was increased (47 and 45% in the halothane and isoflurane groups, respectively) and Kp was increased (34 and 33% in the halothane and isoflurane groups, respectively) less compared to fentanyl (78%). Enhanced function in LCX zone was associated with a comparable increase (21~28% from baseline) in LCX flow in all groups. CONCLUSION: Enhanced regional contractility following acute coronary occlusion in nonischemic myocardium during fentanyl anesthesia is well-preserved with volatile anesthetics in an open-chest canine model. In addition, diastolic functions are also enhanced rather than depressed during anesthesia with volatile anesthetics. Halothane and isoflurane, however, do not differ in the compensatory responses to acute regional ischemia.

Protective effect of iscbemic preconditioning on pre-injured heart in rats / 中国介入心脏病学杂志

On the model of isoprenaline (ISO)-perinjured rat heart, the protctive effect of ischemic preconditioning (IPC) on ischemia reperfusion (I/R) damage was observed.It was found that compared with alone I/R group,IPC ameliorated I/R-induced reduced reduction of coronary blood flow (CBF) (8. 8 + 0. 6 vs 6. 6 + 0. 4mL/min,P

Effect of Exercise Intensity on Cardiac Calcitonin Gene-Related Peptide in Rats / 中国运动医学杂志

To study the effect of exercise on cardiac calcitonin gene-related peptide (CGRP) using immunnohistochemistry and the technique of computer image analysis, the expression and mechanism of cardiac CGRP on the animal model trained with different exercise intensities were investigated. The result showed that long-term low intensity of exercise was not able to induce obvious change in cardiac CGRP. After long-term moderate intensity of exercise, the expression of cardiac CGRP increased so as to improve blood supply and protect myocardium. Long-term high intensity of exercise decreased expression of cardiac CGRP and weakened the protection of myocardium which could be a chief cause of myocardial ischemia.