Cheng-Hsiung Huang

Brief Pressure Overload Preconditions Rabbit Myocardium Independent of Adenosine Receptor Activation

BACKGROUND We previously reported brief pressure overload of the left ventricle reduced myocardial infarct size. The role of adenosine receptors was investigated in this study. METHODS Pressure overload was achieved by two 10-minute partial snaring of the ascending aorta. Systolic left ventricular pressure was raised 50% above baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions. Ten minutes after different pretreatments, 60-minute occlusion of the left anterior descending coronary artery followed by 3-hour reperfusion was done to induce infarction. The area at risk and myocardial infarct size were determined by Evans blue dye injection and triphenyltetrazolium chloride staining. RESULTS Myocardial infarct size (mean ± standard deviation), expressed as percentage of area at risk, was significantly reduced in the pressure overload group (19.3 ± 2.5 %, p < 0.001) and in the ischemic preconditioning group (18.3 ± 1.8 %, p < 0.001) versus the control group (27.3 ± 3.3 %). Pretreatment with 8-(p-sulfophenyl)-theophylline, an adenosine receptor antagonist, limited the protection by ischemic preconditioning (26.8 ± 3.7%), but not that by pressure overload (19.2 ± 2.5%, p < 0.001). The 8-(p-sulfophenyl)-theophylline did not significantly affect the extent of infarct (26.4 ± 5.4%). The hemodynamics prior to treatment, area at risk, and mortality were not significantly different among all groups of animals. CONCLUSIONS Brief pressure overload of the left ventricle preconditioned rabbit myocardium against infarction. Because 8-(p-sulfophenyl)-theophylline had no significant effect on this response, the results are consistent with the hypothesis that the underlying mechanism does not depend on activation of adenosine receptors.

Ischemic preconditioning activates prosurvival kinases and reduces myocardial apoptosis.

Background Ischemic preconditioning has been reported to protect the myocardium against ischemia and reperfusion injury. The underlying mechanisms have been extensively investigated but are not fully elucidated. In this study, we investigated the role of apoptosis in ischemic preconditioning protection and the signal pathways involved. Methods Myocardial ischemia and reperfusion were induced in anesthetized male Sprague–Dawley rats by a 40‐minute occlusion and a 3‐hour reperfusion of the left anterior descending coronary artery. Ischemic preconditioning was elicited by two 10‐minute coronary artery occlusions and two 10‐minute reperfusions. Results The myocardial infarct size, expressed as the percentage of area at risk, was significantly decreased in the ischemic preconditioning group (16.8 ± 2.0% and 27.9 ± 2.7% in the ischemia and reperfusion groups, respectively, p < 0.001). Additionally, ischemic preconditioning significantly reduced apoptosis, as evidenced by the decrease in the terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling‐positive nuclei, DNA laddering, and caspase‐3 activation. Western blot analysis revealed that ischemic preconditioning significantly reduced myocardial tumor necrosis factor‐&agr; levels. Bcl‐2 was increased, whereas Bax was decreased in the myocardium. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal‐regulated kinases 1 and 2, was significantly increased. Hemodynamics, area at risk, and mortality did not differ significantly among the groups. Conclusion Ischemic preconditioning reduces apoptosis induced by myocardial ischemia and reperfusion. The underlying mechanisms might be related to inhibition of both the extrinsic and the intrinsic apoptotic pathway via inhibition of production of tumor necrosis factor‐&agr;, modulation of expression of Bcl‐2 and Bax, and activation of the prosurvival kinases.

Subclavian Artery Thrombosis Associated With Acute ST-Segment Elevation Myocardial Infarction

Presentation of acute ST segment elevation myocardial infarction in the setting of acute subclavian artery thrombosis in a patient who underwent coronary artery bypass grafting with a left internal mammary artery graft, which is not believed to have been previously described. We report a 75-year-old woman with presentations of dizziness, nausea, left-arm numbness, and a cold left hand, who later had chest pain develop. Acute ST segment elevation myocardial infarction was diagnosed, and both a computed tomography and an angiography disclosed a thrombus extending from the proximal portion of the left subclavian artery to the orifice of the left internal mammary artery. The patient was free from the previously listed symptoms after undergoing emergent thrombectomy, with complete extraction of the long thrombus from the subclavian artery. Unfortunately, she died of pneumonia and septic shock 1 1/2 months later.

Baicalein, a Component of Scutellaria baicalensis, Attenuates Kidney Injury Induced by Myocardial Ischemia and Reperfusion.

Acute kidney injury is a common and severe complication of acute myocardial infarction and cardiac surgery. It results in increased mortality, morbidity, and duration of hospitalization. Baicalein is a component of the root of Scutellaria baicalensis, which has traditionally been used to treat cardiovascular and liver diseases in Asia. In this study, we investigated whether baicalein can attenuate kidney injury induced by myocardial ischemia and reperfusion in rats. Myocardial ischemia and reperfusion, induced by a 40-minute occlusion and a 3-hour reperfusion of the left anterior descending coronary artery, significantly increased blood urea nitrogen and creatinine levels in addition to causing histological changes in the kidneys. Kidney apoptosis was also significantly increased. Furthermore, myocardial ischemia and reperfusion significantly increased the serum levels of tumor necrosis factor-α, interleukin-1, and interleukin-6 as well as the tumor necrosis factor-α levels in the kidneys. Intravenous pretreatment with baicalein (in doses of 3, 10, or 30 mg/kg), however, significantly reduced the increases in the creatinine level, renal histological damage, and apoptosis induced by myocardial ischemia and reperfusion. In addition, the increases in the serum levels of tumor necrosis factor-α, interleukin-1, and interleukin-6, and of tumor necrosis factor-α in the kidneys were significantly reduced. Western blot analysis revealed that baicalein significantly increased Bcl-2 and reduced Bax in the kidneys. The phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 was also significantly increased. In conclusion, baicalein significantly attenuates kidney injury induced by myocardial ischemia and reperfusion. The underlying mechanisms might be related to the inhibition of apoptosis, possibly through the reduction of tumor necrosis factor-α production, the modulation of Bcl-2 and Bax, and the activation of Akt and extracellular signal-regulated kinases 1 and 2.

Brief left ventricular pressure overload reduces myocardial apoptosis

BACKGROUND Both apoptosis and necrosis contribute to cell death after myocardial ischemia and reperfusion. We previously reported that brief left ventricular pressure overload (LVPO) decreased myocardial infarct (MI) size. In this study, we investigated whether brief pressure overload reduces apoptosis and the mechanisms involved. MATERIALS AND METHODS MI was induced by a 40-min occlusion of the left anterior descending coronary artery and 3-h reperfusion in male anesthetized Sprague-Dawley rats. Brief LVPO was achieved by two 10-min partial snarings of the ascending aorta, raising the systolic left ventricular pressure 50% above the baseline value. Ischemic preconditioning was elicited by two 10-min coronary artery occlusions and 10-min reperfusions. RESULTS Brief LVPO and ischemic preconditioning significantly decreased MI size (P < 0.001). Brief pressure overload significantly reduced myocardial apoptosis, as evidenced by the decrease in the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei (P < 0.001), little or no DNA laddering, and reduced caspase-3 activation (P < 0.01). Moreover, brief pressure overload significantly increased Bcl-2 (P < 0.001) and decreased Bax (P < 0.001) and p53 (P < 0.01). Akt phosphorylation was significantly increased by brief pressure overload (P < 0.001), whereas c-Jun N-terminal kinase phosphorylation was significantly decreased (P < 0.001). Hemodynamics, area at risk, and mortality did not differ significantly among groups. CONCLUSIONS Brief left LVPO significantly reduces myocardial apoptosis. The underlying mechanisms might be related to modulation of Bcl-2 and Bax, inhibition of p53, increased Akt phosphorylation, and suppressed c-Jun N-terminal kinase phosphorylation.

Preconditioning threshold of brief pressure overload of the left ventricle.

Background: We previously reported that pressure overload of the left ventricle reduced myocardial infarct (MI) size in rabbits. The threshold of pressure overload was investigated in this study. Methods: Pressure overload of the left ventricle was induced by partial snare of the ascending aorta in anesthetized, open‐chest rabbits. Systolic left ventricular pressure (SLVP) was elevated 50% or 30% above baseline value by varying the degree of partial snaring. Different duration of pressure overload, including 10 minutes, 5 minutes, 3 minutes, or 2 minutes, was applied to determine the threshold of protective effects. Ischemic preconditioning was elicited by two 10‐minute coronary artery occlusions and reperfusions. Ten minutes after different pretreatment, 1 hour occlusion of the left anterior descending coronary artery followed by 3 hours reperfusion was done to induce MI. The size of area at risk and MI were determined by blue dye injection and triphenyl tetrazolium chloride staining after experiments. Results: Pressure overload increase of SLVP 50% above baseline value for 10 minutes, 5 minutes, and 3 minutes significantly reduced MI size (18.5 ± 3.6%, 21.4 ± 1.9% and 21.6 ± 1.7%, respectively, vs. 26.6 ± 1.0% in the control group, mean ± standard deviation, p < 0.01). A 30% increase of SLVP by pressure overload for 10 minutes, 5 minutes and 3 minutes also significantly decreased MI size (20.5 ± 2.5%, 21.6 ± 2.3%, and 21.5 ± 2.3%, p < 0.01). Ischemic preconditioning significantly decreased MI size (19.9 ± 2.8%, p < 0.001). Pressure overload to elevate SLVP 50% or 30% above baseline value for 2 minutes did not significantly alter MI size (25.0 ± 2.3% and 26.0 ± 1.7%, p = 0.122 and p = 0.457). Two episodes of 2 minutes pressure overload did not significantly decrease MI size (25.0 ± 2.2% and 25.5 ± 2.2%, p = 0.118 and p = 0.281). The hemodynamics, area at risk, and mortality were not significantly different among all groups of animals. Conclusion: Pressure overload to raise SLVP either 50% or 30% above baseline value reduced MI size. A minimum duration of 3 minutes was necessary to induce the protective effects.

Less invasive cardiac surgery via partial sternotomy

Background: Less invasive cardiac surgery is widely adopted nowadays. Upper or lower partial sternotomy is an approach for less invasive cardiac surgery. We report results of less invasive cardiac surgery via partial sternotomy. Methods: From August 1, 2009 to September 30, 2010, 35 patients underwent cardiac surgery via upper or lower partial sternotomy. The preoperative characteristics, operative variables, mortality, and morbidity were reviewed retrospectively. Results: Thirty‐five patients underwent cardiac surgery via partial sternotomy during the study period. Eleven patients (31%) were female. The mean age was 66 ± 11 years (range 38 to 88). Seven patients underwent aortic valve replacement via upper partial sternotomy. Simultaneous mitral valve replacement was done in one patient. Lower partial sternotomy was done in 28 patients. Sixteen patients received mitral valve replacement. Three patients underwent mitral valve repair. Concomitant tricuspid valve repair was done in eight patients. Two patients received aortic valve replacement. One patient had replacement of aortic and mitral valve replacement. One patient had repair of tricuspid valve. Two patients received LIMA anastomosis to the LAD. Two patients underwent emergent repair of the right ventricle. One patient had resection of myxoma in the left atrium. Direct cannulation of the aorta and right atrium was used for cardiopulmonary bypass in 15 patients (48%). Both antegrade and retrograde administration of cardioplegia solution was used routinely for myocardial protection. There was no mortality. Two patients developed respiratory failure. One patient suffered unstable sternum. One patient required conversion to full sternotomy. No patient suffered mediastinitis or groin wound infection. Conclusion: Upper or lower partial sternotomy provides adequate exposure for various kind of cardiac surgery. Conventional cardiopulmonary bypass and cardioplegia solution administration can be used. The immediate preliminary outcome was acceptable.

White-centered Retinal Hemorrhage in Ocular Ischemic Syndrome Resolved After Carotid Artery Stenting

Ocular ischemic syndrome (OIS) is characterized by ocular symptoms and signs that are secondary to severe carotid artery obstruction. We report a 69-year-old man who suffered from progressively blurred vision in both eyes. Fundus examination showed scattered areas of retinal hemorrhage, some with a white center, in both eyes. Fluorescence angiography revealed multiple microaneurysm-like hyperfluorescent spots over the retina mimicking diabetic retinopathy. Carotid Doppler ultrasonography revealed 90-95% stenosis of bilateral internal carotid arteries, and OIS was diagnosed. Thus, bilateral internal carotid artery stenting was performed. After treatment, the patients visual acuity recovered within 1 month and the areas of white-centered retinal hemorrhage completely resolved within 6 months.

Magnolol Reduces Renal Ischemia and Reperfusion Injury via Inhibition of Apoptosis

Magnolol, a constituent of the bark of Magnolia officinalis, has been reported to decrease myocardial stunning and infarct size. In this study, we investigated whether magnolol can reduce renal ischemia and reperfusion (I/R) injury. Renal I/R, induced by a 60-min occlusion of bilateral renal arteries and a 24-h reperfusion, significantly increased blood urea nitrogen (BUN) and creatinine levels, and caused histological damage to the kidneys of rats. Apoptosis, as evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and caspase-3 activation, was significantly increased in the kidneys. Furthermore, serum levels of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were significantly elevated, while the interleukin-10 (IL-10) level was suppressed. However, intravenous pretreatment with magnolol at doses of 0.003[Formula: see text]mg/kg and 0.006[Formula: see text]mg/kg 10[Formula: see text]min before renal I/R significantly limited the increases of BUN, creatinine, the histological damage, and apoptosis in the kidneys. The increases in TNF-[Formula: see text], IL-1β, and IL-6, and the decrease in IL-10 were also significantly inhibited. Additionally, magnolol increased Bcl-2 and decreased Bax in the kidneys. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/2), was elevated, while phosphorylation of the pro-apoptotic mitogen-activated protein kinases, including p38 and c-Jun N-terminal kinase (JNK), was suppressed. In conclusion, magnolol reduces renal I/R injury. The underlying mechanisms for this effect might be related to the prevention of apoptosis, possibly via the inhibition of both extrinsic and intrinsic apoptotic pathways, including the reduction of TNF-[Formula: see text] production and the modulation of pro- and anti-apoptotic signaling elements.

Coronary Artery Bypass Grafting in Patients with Left Ventricular Dysfunction

Background: Coronary artery bypass grafting surgery (CABG) remains a challenge for patients with coronary artery disease and left ventricular (LV) dysfunction. The aim of this study was to evaluate the result of CABG in patients with LV dysfunction. Methods: Medical records of 1,847 patients who underwent primary, isolated CABG at Taipei Veterans General Hospital from January 1, 1991 to December 31, 2002, were reviewed. The mortality rate associated with clinical and operative variables was compared between patients with LV ejection fraction (LVEF) = 35% and patients with LVEF < 35%. Results: Patients with LVEF < 35% had more episodes of myocardial infarction (57.5% vs 28.9%, p < 0.001) and history of congestive heart failure (18.1% vs 3.2%, p < 0.001), higher New York Heart Association (NYHA) class, and higher angina class. Longer cardiopulmonary bypass time (147 ± 44 minutes vs 137 ± 40 minutes, p < 0 .001) but fewer left internal mammary artery (LIMA) grafts (46.8% vs 65.7%, p < 0.001) were used in patients with LVEF < 35%. Patients with LVEF < 35% had significantly higher hospital mortality (6.6% vs 2.2%, p < 0.001), higher major morbidity (23.3% vs 16.1%, p < 0.01), and longer hospital stay (25 ± 23 days vs 21 ± 16 days, p < 0.01). Conclusion: Although patients with LV dysfunction had higher mortality and morbidity, CABG could be done in these high‐risk patients with acceptable results.