Association between socioeconomic and motherhood characteristics with receiving community-based treatment services among justice-involved young female drug users: a retrospective cohort study in Taiwan.

BACKGROUND: Drug-involved individuals who contact treatment services in Taiwan are mostly driven by criminal justice systems either as an alternative or adjunct to criminal sanctions for a drug offence. With a focus on justice-involved young female drug users, the present study examines the extent to which socioeconomic and motherhood characteristics are associated with receiving deferred prosecution, a scheme diverting drug offenders to community-based addiction treatment. METHODS: We identified a cohort of 5869 women under the age of 30 arrested for using Schedule II drugs (primarily amphetamine-like stimulants) from the 2011-2017 National Police Criminal Records in Taiwan. Information concerning socioeconomic characteristics, pregnancy and live birth history, and deferred prosecution was obtained through linkage with the 2006-2019 National Health Insurance, birth registration, and deferred prosecution datasets. Multinomial logistic regression was used to evaluate the association with stratification by recidivism status. RESULTS: Within six months of arrest, 21% of first-time offenders (n = 2645) received deferred prosecution and 23% received correction-based rehabilitation; the corresponding estimates for recidivists (n = 3224) were 6% and 15%, respectively. Among first-time offenders, low/unstable income was associated with lower odds of deferred prosecution (adjusted odds ratio [aOR] = 0.71; 95% CI: 0.58, 0.88). For recidivists, those with low/unstable income (aOR = 1.58) or unemployment (aOR = 1.58) had higher odds of correction-based rehabilitation; being pregnant at arrest was linked with reduced odds of deferred prosecution (aOR = 0.31, 95% CI: 0.13, 0.71) and correction-based rehabilitation (aOR = 0.50, 95% CI: 0.32, 0.77). CONCLUSIONS: For the young women arrested for drug offences, disadvantaged socioeconomic conditions were generally unfavored by the diversion to treatment in the community. Childbearing upon arrest may lower not only the odds of receiving medical treatment but also correctional intervention. The criminal prosecution policy and process should be informed by female drug offenders' need for treatment and recovery.

TIMP-1 in the prognosis of patients who underwent coronary artery bypass surgery: a 12-year follow-up study.

Introduction: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been linked to clinical outcomes in patients with coronary artery disease (CAD). However, the prognostic value of TIMP-1 in patients with CAD who underwent coronary artery bypass grafting (CABG) has not been elucidated. We aimed to investigate the correlations of TIMP-1 with high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the long-term prognosis of consecutive patients who underwent CABG. Methods: A total of 234 patients (age: 70.4 ± 10.5 years, 84.6% men) with CAD who underwent CABG were prospectively enrolled. Preoperative levels of MMPs, TIMP-1, hs-CRP, and NT-proBNP were recorded. Major adverse cardiovascular events (MACE) were defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. Results: During a median follow-up of 12.1 years, 120 deaths were recorded. The deceased were older, had more manifest acute coronary syndrome (ACS), a lower left ventricular ejection fraction (LVEF), and an estimated glomerular filtration rate (eGFR), but significantly higher MMP13, TIMP-1, hs-CRP, and NT-proBNP compared with the survivors. After adjusting for age, sex, manifest ACS, eGFR, LVEF, total cholesterol, and triglycerides, TIMP-1 (hazard ratio and 95% confidence intervals per SD: 1.506, 1.183-1.917), hs-CRP (1.349, 1.183-1.561), and NT-ProBNP (1.707, 1.326-2.199) were all independently associated with all-cause mortality. The mediation analysis revealed that the mortality risks of TIMP-1 were partially mediated by NT-proBNP (62.2%) and hs-CRP (25.3%). The associations of TIMP-1 with MACE were partially mediated by NT-proBNP (54.4%) but not hs-CRP. Conclusions: TIMP-1 was an independent predictor of long-term outcomes after CABG, with possible roles in subclinical inflammation and postoperative cardiac remodeling.

Vitamin C supplementation attenuates oxidative stress and improves erythrocyte deformability in cardiac surgery with cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) depletes endogenous Vitamin C and generates oxidative stress in cardiac surgery. This study aimed to clarify whether Vitamin C supplementation reduces oxidant production and improves erythrocyte deformability in cardiac surgery with CPB. In a randomized and controlled design, 30 eligible patients undergoing cardiac surgery with hypothermic CPB were equally assigned to the Vitamin C group and control group. Subjects of the Vitamin C group and control group received an intravenous infusion of Vitamin C 20 mg·kg-1 and a placebo during rewarming period of CPB, respectively. We measured the plasma level of reactive oxygen species (ROS) and phosphorylation levels of non-muscle myosin IIA (NMIIA) in erythrocyte membrane, as an index of erythrocyte deformability, before and after CPB. Vitamin C supplementation attenuated the surge in plasma ROS after CPB, mean 1.661 ± standard deviation 0.801 folds in the Vitamin C group and 2.743 ± 1.802 in the control group. The tyrosine phosphorylation level of NMIIA after CPB was upregulated in the Vitamin C group compared to the control group, 2.159 ± 0.887 folds and 1.384 ± 0.445 (P = 0.0237). In addition, the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and focal adhesion kinase (FAK) in erythrocytes was concurrently enhanced in the Vitamin C group after CPB. The phosphorylation level of endothelial nitric oxide synthase in erythrocytes was significantly increased in the Vitamin C group (1.734 ± 0.371 folds) compared to control group (1.102 ± 0.249; P = 0.0061). Patients receiving Vitamin C had lower intraoperative blood loss and higher systemic vascular resistance after CPB compared to controls. Vitamin C supplementation attenuates oxidative stress and improves erythrocyte deformability via VASP/FAK signaling pathway in erythrocytes during CPB.

Magnolol reduces myocardial injury induced by renal ischemia and reperfusion.

BACKGROUND: Magnolol is a component of the bark of Magnolia officinalis, which is a traditional herbal remedy used in China. In this study, we investigated whether magnolol can reduce myocardial injury induced by renal ischemia and reperfusion (I/R). METHODS: Renal I/R was elicited by a 60-minute occlusion of the bilateral renal arteries and a 24-hour reperfusion in Sprague-Dawley rats. Magnolol was administered intravenously 10 minutes before renal I/R to evaluate its effects on myocardial injury induced by renal I/R. RESULTS: Renal I/R significantly increased the serum levels of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and cardiac troponin I and caused myocardial damage. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei and caspase-3 activation was significantly increased in the myocardium, indicating increase of apoptosis. Echocardiography revealed left ventricular dysfunction, as evidenced by reduction of left ventricular ejection fraction and left ventricular fractional shortening. Furthermore, serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6 were significantly elevated, while the IL-10 level was suppressed. However, intravenously, pretreatment with magnolol at doses of 0.003 and 0.006 mg/kg 10 minutes before renal I/R significantly prevented the increases of CPK, LDH, and cardiac troponin I levels, as well as the histological damage and the apoptosis in the myocardium. Echocardiography showed significant improvement of left ventricular function. Furthermore, the increases in TNF-α, IL-1ß, and IL-6 and the decrease in IL-10 were significantly limited, while Bcl-2 was increased and Bax was decreased in the myocardium. Phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 was increased, while phosphorylation of p38 and c-Jun N-terminal kinase was reduced. CONCLUSION: Magnolol reduces myocardial injury induced by renal I/R. The underlying mechanisms for this effect might be related to modulation of the production of pro- and anti-inflammatory cytokines and the limiting of apoptosis.

High-dose nitroglycerin administered during rewarming preserves erythrocyte deformability in cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: We aimed to determine whether high-dose nitroglycerin, a nitric oxide donor, preserves erythrocyte deformability during cardiopulmonary bypass and examines the signaling pathway of nitric oxide in erythrocytes. METHODS: In a randomized and controlled fashion, forty-two patients undergoing cardiac surgery with hypothermic cardiopulmonary bypass were allocated to high-dose (N = 21) and low-dose groups (N = 21). During rewarming period, patients were given intravenous nitroglycerin with an infusion rate 5 and 1 µg·kg-1 ·min-1 in high-dose and low-dose groups, respectively. Tyrosine phosphorylation level of non-muscle myosin IIA in erythrocyte membrane was used as an index of erythrocyte deformability and analyzed using immunoblotting. RESULTS: Tyrosine phosphorylation of non-muscle myosin IIA was significantly enhanced after bypass in high-dose group (3.729 ± 1.700 folds, P = .011) but not low-dose group (1.545 ± 0.595 folds, P = .076). Phosphorylation of aquaporin 1, vasodilator-stimulated phosphoprotein, and focal adhesion kinase in erythrocyte membrane was also upregulated in high-dose group after bypass. Besides, plasma nitric oxide level was highly correlated with fold change of non-muscle myosin IIA phosphorylation (Pearson's correlation coefficient .871). CONCLUSIONS: High-dose nitroglycerin administered during cardiopulmonary bypass improves erythrocyte deformability through activating phosphorylation of aquaporin 1, vasodilator-stimulated phosphoprotein, and focal adhesion kinase in erythrocytes.

The effect of high-dose nitroglycerin on the cerebral saturation and renal function in cardiac surgery: A propensity score analysis.

BACKGROUND: The aim of the study was to evaluate the effects of high-dose nitroglycerine administered during cardiopulmonary bypass on the intraoperative cerebral saturation and postoperative serum creatinine concentration in cardiac surgery. METHODS: In a retrospective cohort study, a total of 239 patients undergoing cardiac surgery with cardiopulmonary bypass at a tertiary medical center were included. General anesthesia consisted of volatile anesthetic and either intravenous loading of high-dose nitroglycerin (infusion rate 10 to 20 mg·h with a total dose of ≥0.5 mg·kg) starting from rewarming of cardiopulmonary bypass throughout the end of the surgery (NTG group; N = 96) or without high-dose nitroglycerin (control group; N = 143). Data for intraoperative cerebral saturation and serum creatinine concentrations before and after cardiac surgery were collected. Propensity score method was used to adjust for potential confounders. RESULTS: Patients receiving high-dose nitroglycerin had significantly lower mean arterial pressure and hematocrit levels during and after cardiopulmonary bypass. The risk of intraoperative cerebral desaturation was left-sided 23.9% versus 38.5% (p = 0.023), right-sided 28.1% versus 35.7% in the NTG and control groups, respectively. The risk of new-onset stroke and postoperative dialysis was 2.1% versus 6.3% and 1.0% versus 3.5% in the NTG and control groups, respectively. CONCLUSION: An infusion of high-dose nitroglycerin initiating at rewarming of cardiopulmonary bypass and throughout the postbypass interval may induce hypotension and hemodilution in cardiac surgical patients. Cerebral saturation and renal function were well maintained without increasing the risk of stroke and renal replacement therapy after cardiac surgery with cardiopulmonary bypass.

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-1ß (IL-1ß), 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-1ß, 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.

Baicalein Attenuates Lung Injury Induced by Myocardial Ischemia and Reperfusion.

Baicalein is an active component of Scutellaria baicalensis Georgi, which has traditionally been used to treat cardiovascular diseases in China. In this study, we investigated if treatment with baicalein can attenuate the lung injury induced by myocardial ischemia and reperfusion (I/R). Myocardial I/R, induced by a 40-min occlusion of the left anterior descending coronary artery and a 3-h reperfusion, significantly increased histological damage and the wet-to-dry weight ratio of lungs in rats. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive nuclei and caspase-3 activation was significantly increased in the lungs. Serum and bronchoalveolar lavage fluid levels of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1[Formula: see text] (IL-1[Formula: see text]), and interleukin-6 (IL-6) were significantly elevated, as were TNF-[Formula: see text] levels in the lung. Intravenous administration with baicalein at doses of 3, 10, and 30[Formula: see text]mg/kg for ten minutes before myocardial I/R significantly reduced histological damage, the wet-to-dry weight ratio, and apoptosis in the lung. Baicalein also significantly inhibited the increase in levels of TNF-[Formula: see text], IL-1[Formula: see text], and IL-6. Moreover, baicalein increased Bcl-2 and decreased p53, Bax, and cytochrome [Formula: see text] in lungs. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/2), was increased, while the phosphorylation of the pro-apoptotic mitogen-activated protein kinases, including p38 and c-Jun N-terminal kinase (JNK), was decreased. In conclusion, treatment with baicalein attenuates the lung injury induced by myocardial I/R. The mechanisms might be related to the limiting of apoptosis, possibly via the inhibition of both the extrinsic and intrinsic pathways of apoptosis, including the inhibition of TNF-[Formula: see text] production and modulation of pro- and anti-apoptotic signaling elements.

Baicalein Reduces Liver Injury Induced by Myocardial Ischemia and Reperfusion.

Baicalein is a component of the root of Scutellaria baicalensis Georgi, which has traditionally been used to treat liver disease in China. In the present study, we investigated baicalein' ability to reduce the liver injury induced by myocardial ischemia and reperfusion (I/R). Myocardial I/R was induced in this experiment by a 40[Formula: see text]min occlusion of the left anterior descending coronary artery and a 3[Formula: see text]h reperfusion in rats. The induced myocardial I/R significantly increased the serum levels of aspartate transaminase (AST) and alanine transaminase (ALT), indicating the presence of liver injury. Hepatic apoptosis was significantly increased. The serum levels of tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text]), interleukin-1[Formula: see text] (IL-1[Formula: see text]), and interleukin-6 (IL-6) were significantly elevated, as was the TNF-[Formula: see text] level in the liver. Intravenous pretreatment with baicalein (3, 10, or 30[Formula: see text]mg/kg) 10[Formula: see text]min before myocardial I/R significantly reduced the serum level increase of AST and ALT, apoptosis in the liver, and the elevation of TNF-[Formula: see text], IL-1[Formula: see text], and IL-6 levels. Moreover, baicalein increased Bcl-2 and decreased Bax in the liver. Phosphorylation of the prosurvival kinases, including Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/2), was also increased. In conclusion, we found that baicalein can reduce the liver injury induced by myocardial I/R. The underlying mechanisms are likely related to the inhibition of the extrinsic and intrinsic apoptotic pathways, possibly via the inhibition of TNF-[Formula: see text] production, the modulation of Bcl-2 and Bax, and the activation of Akt and ERK1/2. Our findings may provide a rationale for the application of baicalein or traditional Chinese medicine containing large amounts of baicalein to prevent liver injury in acute myocardial infarction and cardiac surgery.

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.

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-α 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-α, modulation of expression of Bcl-2 and Bax, and activation of the prosurvival kinases.

Brief pressure overload of the left ventricle reduces myocardial infarct size via activation of protein kinase C.

BACKGROUND: We have previously reported that brief pressure overload of the left ventricle reduced myocardial infarct (MI) size. However, the role of protein kinase C (PKC) remains uncertain. In this study, we investigated whether pressure overload reduces MI size by activating PKC. METHODS: MI was induced by a 40-minute occlusion of the left anterior descending coronary artery and a 3-hour reperfusion in anesthetized Sprague-Dawley rats. MI size was determined using triphenyl tetrazolium chloride staining. Brief pressure overload was achieved by two 10-minute partial snarings of the ascending aorta, raising the systolic left ventricular pressure 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions and 10-minute reperfusions. Dimethyl sulfoxide (vehicle) or calphostin C (0.1 mg/kg, a specific inhibitor of PKC) was administered intravenously as pretreatment. RESULTS: The MI size, expressed as the percentage of the area at risk, was significantly reduced in the pressure overload group and the ischemic preconditioning group (19.0 ± 2.9% and 18.7 ± 3.0% vs. 26.1 ± 2.6% in the control group, where p < 0.001). Pretreatment with calphostin C significantly limited the protection by pressure overload and ischemic preconditioning (25.2 ± 2.4% and 25.0 ± 2.3%, where p < 0.001). Calphostin C itself did not significantly affect MI size (25.5 ± 2.4%). Additionally, the hemodynamics, area at risk, and mortality were not significantly different. CONCLUSION: Brief pressure overload of the left ventricle reduced MI size. Since calphostin C significantly limited the decrease of MI size, our results suggested that brief pressure overload reduces MI size via activation of PKC.

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.

Myocardial preconditioning reduces kidney injury and apoptosis induced by myocardial ischaemia and reperfusion.

OBJECTIVES: Acute kidney injury is a common and serious complication of cardiac surgery. Because its underlying mechanisms are unclear, there is no specific therapy to prevent or treat it. A regional transient ischaemia and reperfusion (I/R) may provide protection to distant tissue or organs, a phenomenon known as remote preconditioning. In this study, we investigated whether myocardial preconditioning (MPC) would reduce kidney injury and apoptosis induced by myocardial I/R, as well as the mechanisms involved. METHODS: Myocardial I/R was induced by a 40-min occlusion of the left anterior descending artery and a 3-h reperfusion in anaesthetized Sprague-Dawley rats. MPC was elicited by two 10-min coronary artery occlusions and two 10-min reperfusions. A sham group received the same surgical procedures without coronary artery occlusion and reperfusion. RESULTS: Compared with the sham group, myocardial I/R significantly increased the serum creatinine levels (1.15 ± 0.44 vs 0.54 ± 0.23 mg/dl, P < 0.05, mean ± standard deviation) and renal histological damage, indicating increased kidney injury. Kidney apoptosis was also significantly increased, as evidenced by the increase in the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labelling (TUNEL)-positive nuclei, clear DNA laddering and increased caspase-3 activation. Serum levels of tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) were significantly elevated, as were TNF-α levels in the kidneys. MPC significantly decreased myocardial infarct size (18.5 ± 3.1 vs 25.6 ± 2.1% of area at risk, P < 0.001). Additionally, MPC significantly reduced the serum creatinine level (0.65 ± 0.19 mg/dl, P < 0.05), renal histological damage and apoptosis. The increase in the serum levels of TNF-α, IL-1 and IL-6, and of TNF-α in the kidneys, was significantly inhibited. Western blot analysis found that MPC significantly increased Bcl-2 and decreased Bax in the kidneys. Phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 (ERK1/2) was significantly increased. Haemodynamics, area at risk and mortality did not differ significantly among the groups. CONCLUSIONS: MPC significantly reduces kidney injury and apoptosis induced by myocardial I/R. The underlying mechanisms might be related to inhibition of both the extrinsic and intrinsic pathways of apoptosis, possibly via inhibition of TNF-α production, modulation of Bcl-2 and Bax and activation of Akt and ERK1/2.

The role of adenosine in preconditioning by brief pressure overload in rats.

BACKGROUND/PURPOSE: Brief pressure overload of the left ventricle reduced myocardial infarct (MI) size in rabbits has been previously reported. Its effects in other species are not known. This study investigates effects of pressure overload and the role of adenosine in rats in this study. METHODS: MI was induced by 40-minute occlusion of the left anterior descending coronary artery followed by 3-hour reperfusion. MI size was determined by triphenyl tetrazolium chloride staining. Brief pressure overload was induced by two 10-minute episodes of partial snaring of the ascending aorta. Systolic left ventricular pressure was raised 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions. RESULTS: The MI size (mean ± standard deviation), expressed as percentage of area at risk, was significantly reduced in the pressure overload group as well as in the ischemic preconditioning group (17.4 ± 3.0% and 18.2 ± 1.5% vs. 26.6 ± 2.4% in the control group, p < 0.001). Pretreatment with 8-(p-sulfophenyl)-theophylline (SPT), an inhibitor of adenosine receptors, did not significantly limit the protection by pressure overload and ischemic preconditioning (18.3 ± 1.5% and 18.2 ± 2.0%, respectively, p < 0.001). SPT itself did not affect the extent of infarct (25.4 ± 2.0%). The hemodynamics, area at risk and mortality were not significantly different among all groups of animals. CONCLUSION: Brief pressure overload of the left ventricle preconditioned rat myocardium against infarction. Because SPT did not significantly alter MI size reduction, our results did not support a role of adenosine in preconditioning by pressure overload in rats.

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.

The association between heme oxygenase-1 gene promoter polymorphism and the outcomes of catheter ablation of atrial fibrillation.

A length polymorphism of GT repeats in the promoter region of the human heme oxygenase-1 (HO-1) gene modulates its gene transcription to protect against myocardial injury. The present study investigated the association between HO-1 promoter polymorphisms and the outcomes of catheter ablation of atrial fibrillation (AF). The allelic frequencies of GT repeats in the HO-1 gene promoter were screened in 205 random individuals who underwent catheter ablation for drug refractory AF.In the patients who received catheter ablation, those with AF recurrence had fewer GT repeats (53.4±7.1 vs. 56.1±6.5, p = 0.004), a lower incidence of hyperlipidemia, more non-paroxysmal AF, and a larger left atrial diameter. After conducting a multivariate logistic analysis, the number of GT repeats (Odds ratio: 0.94, 95% CI 0.90-0.99, p = 0.01) and the diameter of the left atrium (Odds ratio: 1.08, 95% CI 1.02-1.15, p = 0.01) remained independent predictors. The carriers of GT repeats, which were <29 in both alleles, were associated with a lower sinus maintenance rate after catheter ablation (38.5% vs. 60.1%, p = 0.003). The patients were divided into paroxysmal and non-paroxysmal AF groups; the number of GT repeats was associated with AF recurrence only in the patients with paroxysmal AF. The number of GT repeats, combined with LAD, was significant for predicting AF recurrence after catheter ablation (p = 0.01). The number of GT repeats was not found to be associated with differences in the left atrial diameter, the biatrial voltage, or the levels of bilirubin, ferritin, iron, C-reactive protein, or von-Willibrand factor. In conclusions, HO-1 gene promoter polymorphisms were associated with AF recurrence after catheter ablation.

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.

Influence of particle location on the number of charges per charged nanoparticle at the outlet of a needle charger.

This study has investigated numerically the influence of particle location on the number of charges per charged particle in the 10-40 nm size range at the outlet of a needle charger by simulating flow field, electric field, particle charging, and particle trajectory at various conditions. The results show that the total (i.e., diffusion + field charging) number of charges per particle increase with decreasing ratio values of radial location at the outlet of the charger due to the particle position close to the needle tip. It has also been shown that in the outlet region of the charger there is a critical radial location at which the number of charges per particle is a maximum; this critical radial location represents the point at which the charged particle trajectory becomes closest to the needle electrode. The maximum value of number of charges increases with increasing Reynolds number and slightly increases with decreasing applied voltage for particle diameter larger than 20 nm. The maximum number of charges per charged nanoparticle increases with increasing particle diameter. In addition, the minimum ratio value of radial particle location decreases with increasing Reynolds number for various particle diameters.