Real-World Experience of Angiotensin Receptor-Neprilysin Inhibition in Reduced Ejection Fraction Heart Failure Patients With Advanced Kidney Disease.

OBJECTIVE: To investigate the effectiveness and safety of angiotensin receptor-neprilysin inhibitors (ARNIs) in real-world patients with heart failure with reduced ejection fraction (HFrEF) and advanced chronic kidney disease (estimated glomerular filtration rate [eGFR] < 30 mL/min per 1.73 m2), which have been excluded from the landmark trials. PATIENTS AND METHODS: This study examined 3281 patients pooled from two multicenter HFrEF cohorts, and 661 patients with baseline eGFR less than 30 mL/min per 1.73 m2 were further analyzed (the Taiwan Society of Cardiology - Heart Failure with reduced Ejection Fraction (TSOC-HFrEF) registry: May 1, 2013 to October 31, 2014, and the Treatment with Angiotensin Receptor neprilysin inhibitor fOr Taiwan Heart Failure patients (TAROT-HF) study: March 1, 2017, to December 31, 2018). Propensity score matching was performed to adjust for confounders. At 1-year follow-up, all-cause mortality, total heart failure hospitalizations, renal function, and left ventricular ejection fraction (LVEF) were used as the endpoints. RESULTS: After propensity score matching, 510 patients (age, 69.8±13.9 years; male, 61.0%; mean LVEF, 29.8±7.3%; mean eGFR, 19.8±9.0 mL/min per 1.73 m2) were included in the final analysis, including 278 patients receiving ARNI treatment (ARNI group) and 232 patients not on ARNI treatment (non-ARNI group). Baseline characteristics were comparable between the two groups. At 1 year, eGFR and LVEF measurements were significantly higher in the ARNI group than in the non-ARNI group (25.0±17.1 mL/min per 1.73 m2 vs 21.4±17.5 mL/min per 1.73 m2; P=.04; and 40.1±12.9% vs. 33.1±10.8%, P<.001, respectively). The ARNI group had significantly lower risks of 1-year all-cause mortality (19.4 vs 30.9 per 100-person year; P=.02), and total HF rehospitalizations (70.0 vs 110.4 per 100-person year; P=.01) than non-ARNI users. CONCLUSION: Our results show the effectiveness of ARNIs in HFrEF patients with advanced chronic kidney disease in a real-world setting.

Differential Diagnosis of Thoracoacromial Artery Pseudoaneurysm from Shoulder Inflammatory Pseudotumor: A Case Report.

Diagnosing shoulder tumors is a challenge because the joint is very complex, and a static examination can misdiagnose some tumors. However, we found that a pseudoaneurysm provides a differential diagnosis of a tumor, and to that end, we present a case that mimics shoulder infection. The patient was an 80-year-old female who had a history of coronary artery disease and end-stage renal disease under regular hemodialysis and complained of right shoulder swelling and progression. A magnetic resonance imaging (MRI) scan revealed an abscess, inflammatory pseudotumor (IPT), and osteomyelitis of the humerus. Computed tomography (CT)-guided pigtail drainage was performed twice without significant improvement. An angiogram revealed a right shoulder pseudoaneurysm fed by the acromial branch of the thoracoacromial artery. After endovascular coiling, the patient was discharged and outpatient follow-up was arranged. If aspiration of the abscess leads to only mild improvement in shoulder swelling, further evaluation should be arranged. An angiogram examination is a good method for diagnosing and designing operations, and endovascular treatment is good for preventing injury to the muscle, tendon, nerve, or blood vessels.

Radial artery harvesting in coronary artery bypass grafting surgery-Endoscopic or open method? A meta-analysis.

We analyzed the clinical outcomes of open radial artery harvesting (OAH) and endoscopic radial artery harvesting (EAH) undergoing coronary artery bypass grafting (CABG). We designed this meta-analysis conducted using Pubmed, Medline, the Cochrane Library, and EMBASE. Articles with comparisons of OAH and EAH undergoing CABG were included. Primary outcomes included the wound infection rate, the wound complication rate, neurological complications of the forearm, in-hospital mortality, long-term survival, and the patency rate. The results of our study included six randomized controlled trials (RCTs), two non-randomized controlled trials (NRCTs) with matching, and 10 NRCTs. In total, 2919 patients were included in 18 studies, while 1187 (40.7%) and 1732 (59.3%) patients received EAH and OAH, respectively. EAH was associated with a lower incidence of wound infection (RR = 0.29, 95% confidence interval (CI) = 0.14 to 0.60, p = 0.03), and neurological complications over the harvesting site (RR = 0.41, 95% CI = 0.27 to 0.62, p < 0.0001). There was no significant difference in 30-day mortality, long-term survival (over one year), and the graft patency rate. According to our analysis, endoscopic radial artery harvesting can improve the outcome of the harvesting site, without affecting the mortality, long-term survival, and graft patency.

Using an incentive spirometer reduces pulmonary complications in patients with traumatic rib fractures: a randomized controlled trial.

BACKGROUND: An incentive spirometer (IS) is a mechanical device that promotes lung expansion. It is commonly used to prevent postoperative lung atelectasis and decrease pulmonary complications after cardiac, lung, or abdominal surgery. This study explored its effect on lung function and pulmonary complication rates in patients with rib fractures. METHODS: Between June 2014 and May 2017, 50 adult patients with traumatic rib fractures were prospectively investigated. Patients who were unconscious, had a history of chronic obstructive pulmonary disease or asthma, or an Injury Severity Score (ISS) ≥ 16 were excluded. Patients were randomly divided into a study group (n = 24), who underwent IS therapy, and a control group (n = 26). All patients received the same analgesic protocol. Chest X-rays and pulmonary function tests (PFTs) were performed on the 5th and 7th days after trauma. RESULTS: The groups were considered demographically homogeneous. The mean age was 55.2 years and 68% were male. Mean pretreatment ISSs and mean number of ribs fractured were not significantly different (8.23 vs. 8.08 and 4 vs. 4, respectively). Of 50 patients, 28 (56%) developed pulmonary complications, which were more prevalent in the control group (80.7% vs. 29.2%; p = 0.001). Altogether, 25 patients had delayed hemothorax, which was more prevalent in the control group (69.2% vs. 29.2%; p = 0.005). Two patients in the control group developed atelectasis, one patient developed pneumothorax, and five patients required thoracostomy. PFT results showed decreased forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) in the control group. Comparing pre- and posttreatment FVC and FEV1, the study group had significantly greater improvements (p < 0.001). CONCLUSIONS: In conclusion, the use of an IS reduced pulmonary complications and improved PFT results in patients with rib fractures. The IS is a cost-effective device for patients with rib fractures and its use has clinical benefits without harmful effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04006587. Registered on 3 July 2019.

High Systolic and Diastolic Blood Pressure Variability Is Correlated with the Occurrence of Peripheral Arterial Disease in the First Decade following a Diagnosis of Type 2 Diabetes Mellitus: A New Biomarker from Old Measurement.

Background. To assess whether the visit-to-visit variability in blood pressure (BP) is a risk factor of peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM) 10 years after diagnosis. Methods. The electronic medical records of 825 patients, who were diagnosed with type 2 diabetes mellitus (T2DM) during 2000-2002 and regularly followed for 10 years, were retrospectively reviewed. A total of 53,284 clinic visit records, including analysis of BP, BMI, serum glycohemoglobin, and lipid profile, were analyzed. Results. Patients were categorized into two groups according to their visit-to-visit variability in systolic and diastolic BP (SBP and DBP, resp.). The high-risk group included patients with high SBP and DBP visit-to-visit variability; this group had a 1.679-fold (95% CI: 1.141-2.472, P = 0.009) increased risk of PAD compared with patients in the low-risk group. Cox regression analysis also demonstrated that the age at which the patients were diagnosed with T2DM, smoking status, and mean creatinine level was significantly associated with increased risk of PAD with a hazard ration of 1.064 (95% CI: 1.043-1.084, P < 0.001), 1.803 (95% CI: 1.160-2.804, P = 0.009), and 1.208 (95% CI: 1.042-1.401, P = 0.012), respectively. Conclusions. High SBP and DBP visit-to-visit variability is correlated with PAD in the first decade following a diagnosis of T2DM.

A simple weighted scoring system to guide surgical decision-making in patients with parapneumonic pleural effusion.

BACKGROUND: The selection of ideal candidates for surgical intervention among patients with parapneumonic pleural effusion remains challenging. In this retrospective study, we sought to identify the main predictors of surgical treatment and devise a simple scoring system to guide surgical decision-making. METHOD: Between 2005 and 2014, we identified 276 patients with parapneumonic pleural effusion. Patients in the training set (n=201) were divided into two groups according to their treatment modality (non-surgery vs. surgery). Using multivariable logistic regression analysis, we devised a scoring system to guide surgical decision-making. The score was subsequently validated in an independent set of 75 patients. RESULTS: A white blood cell count >13,500/µL, pleuritic pain, loculations, and split pleura sign were identified as independent predictors of surgical treatment. A weighted score based on these factors was devised, as follows: white blood cell count >13,500/µL (one point), pleuritic pain (one point), loculations (two points), and split pleura sign (three points). A score >4 was associated with a surgical approach with a sensitivity of 93.4%, a specificity of 82.4%, and an area under curve (AUC) of 0.879 (95% confidence interval: 0.828-0.930). In the validation set, a sensitivity of 94.3% and a specificity of 79.6% were found (AUC=0.869). CONCLUSIONS: The proposed scoring system reliably identifies patients with parapneumonic pleural effusion who are candidates for surgery. Pending independent external validation, our score may inform the appropriate use of surgical interventions in this clinical setting.

Direct Revascularization With the Angiosome Concept for Lower Limb Ischemia: A Systematic Review and Meta-Analysis.

The angiosome concept provides practical information regarding the vascular anatomy of reconstructive and vascular surgery for the treatment of peripheral arterial occlusive disease and, particularly, critical lower limb ischemia.The aim of the study was to confirm the efficacy of direct revascularization with the angiosome concept (DR) for lower limb ischemia.Complementary manual searches were performed through the Pubmed, Cochrane Library, and EMBASE databases.We searched all randomized and nonrandomized studies (NRSs) comparing DR with indirect revascularization (IR) (without the angiosome concept) for lower limb ischemia. Only 9 nonrandomized controlled retrospective cohort studies were found and included. Trials published in any language were included.Primary endpoints were time to limb amputation and time to wound healing. Data extraction and trial quality assessment were performed by two authors independently. A third author was consulted for disagreements settlement and quality assurance.Five NRSs involving 779 lower limbs revealed that DR significantly improved the overall survival of limbs (hazard ratio [HR] 0.61; 95% confidence interval [CI] = 0.46-0.80; P < 0.001; I = 0%). In addition, DR significantly improved time to wound healing (HR 1.38; 95% CI = 1.13-1.69; P = 0.002; I = 0%, in 5 studies including 605 limbs).All included studies were retrospective comparative studies, and no consensus was obtained in describing wound conditions in the included studies.Our results suggested that treatment of lower limb ischemia using DR is more effective in salvaging limbs and healing wounds than IR is. Additional randomized controlled studies are necessary to confirm these results.

Carvedilol treatment after myocardial infarct decreases cardiomyocytic apoptosis in the peri-infarct zone during cardioplegia-induced cardiac arrest.

OBJECTIVE: In this study, experiments were designed to determine which parts and how carvedilol provided protection of the failed hearts under cardioplegia-induced hypoxia/reperfusion (H/R) insult. BACKGROUND: Carvedilol could improve the perioperative and postoperative prognosis of the heart failure patients. The mechanism of carvedilol in prevention of the occurrence of cardiomyocytic apoptosis and preservation of cardiac function had been rarely studied. METHODS: Fifty Sprague-Dawley rats treated with placebo or daily carvedilol after coronary artery ligation were divided into five groups (ligation only-group 2; ligation followed with cardioplegia-induced cardiac arrest-group 3; daily oral carvedilol treatment at 0.1, 1.0, or 10.0 mg/kg after ligation followed with cardioplegia-induced cardiac arrest-groups 4, 5, and 6), whereas another 10 animals received sham operation only (group 1), 30 days before ex vivo H/R injury. Failed hearts were harvested and received 1-h cardiac hypoxia with intermittent cold cardioplegia infusion and followed by 2-h reperfusion with warm oxygenated phosphate-buffered saline solution using a Langendorff apparatus. Perfusate was sampled at various time points. After H/R injury, the myocardium was carefully dissected into infarct, peri-infarct, and remote zones, which were used for further studies. In vitro H/R studies were carried on HL-1 cardiomyocytes to further explore the possible downstream pathways. RESULTS: Carvedilol could reduce the H/R-induced cardiomyocytic apoptosis and related proteins expression, especially in the peri-infarct zone, in a dose-dependent pattern. Carvedilol could also preserve cardiac contractility via modulation of the tumor necrosis factor α and interleukin 8 mRNA expression and reduction of Bcl-2 and cytochrome c protein production and decrease the occurrence of apoptosis ex vivo. In vitro experiments revealed that carvedilol exerted its antiapoptotic effect by way of phosphatidylinositol 3-kinase and MEK (mitogen-activated protein-kinase kinase), instead of protein kinase A, pathways. CONCLUSIONS: In the failed heart, pretreatment with carvedilol could preserve cardiac contractility during cardioplegia-induced myocardial H/R injury by lessening inflammation-related genes and expression of cytokines, decreasing apoptosis-related proteins production and diminishing the occurrence of cardiomyocytic apoptosis in the peri-infarct zone. The cardinal pathways of the antiapoptotic mechanism of carvedilol were PI3K- and MEK-related pathways.

MicroRNA-27a regulates cardiomyocytic apoptosis during cardioplegia-induced cardiac arrest by targeting interleukin 10-related pathways.

In this study, experiments were designed to determine whether microRNAs (miRNAs) play a role in the regulation or modulation of cardiomyocytic reactions under cardioplegia-induced cardiac arrest during cardiopulmonary bypass. MicroRNAs play powerful and unexpected roles in numerous cardiovascular diseases. MicroRNA-based therapeutics may provide a unique opportunity to translate this knowledge into the clinical setting. Sprague-Dawley rats (10 per group) were randomly divided into three groups: control, perfusion, and arrest groups. In the perfusion group, isolated hearts were perfused with oxygenated physiologic buffered solution for 3 h using a Langendorff apparatus. In the arrest group, cold crystalloid cardioplegia solution was used to induce and maintain cardiac arrest for 1 h; hearts were reperfused for 2 h with warm oxygenated phosphate-buffered saline solution. Cardiac miRNAs and protein expression patterns were detected using miRNA arrays and two-dimensional fluorescence difference gel electrophoresis followed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Of 103 different miRNAs and 222 different proteins expressed in the three groups, miRNA-27a was the one considered to be related to the regulation of cardiomyocyte apoptosis by targeting the interleukin 10 pathway. Transfection of H9c2 cardiomyocytes with pre-miRNA-27a, which significantly decreased the mRNA and protein levels of interleukin 10 and increased expression of nuclear factor κB and its downstream cytokines during hypoxia/reperfusion injury, could activate caspase 3 and apoptosis. Our study demonstrated the altered expression of miRNAs in cardiomyocytes during cardioplegia-induced cardiac arrest. The involvement of miRNAs in cardiomyocytic apoptosis adds another level of complexity to gene regulation, which could open up novel avenues for cardiac protection strategies during cardiac surgery.

Cardiomyocytic apoptosis limited by bradykinin via restoration of nitric oxide after cardioplegic arrest.

BACKGROUND: Our previous studies revealed that cardioplegia-induced cardiac arrest under cardiopulmonary bypass (CPB) decreased cardiomyocytic nitric oxide and increased apoptosis. We hypothesized that pretreatment with bradykinin (BK) would improve the profile of anti-apoptotic proteins and inhibit cardiomyocytic apoptosis. MATERIALS AND METHODS: New Zealand white rabbits received total CPB. Rabbits were weaned from CPB and reperfused for 4 h. Blood was sampled at various time points. Bradykinin and/or nitric oxide synthase (NOS) inhibitors or BK-receptor antagonists were infused systemically 30 min before beginning of CPB, and continued throughout the procedure. The ascending aorta was cross-clamped for 60 min while cold crystalloid cardioplegic solution was intermittently infused into the aortic root. The hearts were harvested and studied for evidence of apoptosis and ischemia/reperfusion induced inflammation-related cytokine production by cardiomyocytes. RESULTS: Our results revealed that bradykinin supplementation during cardioplegia could prevent I/R-induced inflammatory and apoptotic effects, which could be reversed with a NOS inhibitor. BK antagonists and NOS inhibitors worsened the inflammatory and apoptotic responses of cardiomyocytes, which could be reversed with an exogenous NO donor. CONCLUSIONS: Restoring the NO concentration after cardioplegia-induced cardiac arrest (CCA) under CPB with bradykinin could modulate (1) the nuclear translocation of NF-kappaB, (2) the plasma levels of inflammation-related cytokines, (3) the Bcl-2/Bax ratio, and (4) the occurrence of apoptosis. Exogenous bradykinin administration was associated with the myocardial apoptotic response by inhibition of NF-kappaB translocation, inflammatory cytokine production, Akt activation, and elevation of the Bcl-2/Bax ratio via a NO-mediated pathway.

Leriche's syndrome presenting as sciatica.

Sciatica is a common cause of lower back pain and claudication; the true etiology is often misunderstood. We report a case of a 53-year-old man who presented with sciatica. Clinically, there was evidence of aortoiliac obstruction with the absence of femoral pulses and a vascular index of 0.4 at the ankle. An aortogram revealed a very tight irregular stenosis of the aortic bifurcation and bilateral proximal common iliac arteries. After resection of diseased aorta, an aortoiliac graft was inserted. The symptoms subsided. This case highlights the importance of performing a complete vascular evaluation in patients diagnosed with sciatica.

Effects of dietary fish oil supplementation on cellular adhesion molecule expression and tissue myeloperoxidase activity in hypercholesterolemic mice with sepsis.

This study investigated the effects of fish oil on adhesion molecule expression and tissue myeloperoxidase (MPO) activity in hypercholesterolemic mice with sepsis. There were one control and two experimental groups in this study. The control group (C) was fed a regular chow diet for 7 weeks, while hypercholesterolemia in the experimental group was induced by feeding a high-fat diet (20%, w/w) with cholesterol (2%, w/w) for 4 weeks. Then the experimental group was divided into two subgroups with identical nutrient distributions except that one subgroup was fed soybean oil (SO), while part of the soybean oil was replaced by fish oil (FO) in the other one for 3 weeks. After feeding the diets for 7 weeks, sepsis was induced in all three groups by cecal and ligation and puncture (CLP), and mice were sacrificed at 0, 6 or 24 h after CLP, respectively. The results showed that the FO group had a higher intracellular interferon-gamma/interleukin-4 ratio and lower tumor necrosis factor-alpha and monocyte chemoattractant protein-1 concentrations in peritoneal lavage fluid at 6 h after CLP than those in the C and SO groups. Lymphocyte CD11a/CD18 expressions were higher at 0 and 6 h and neutrophil CD11b/CD18 were higher at 6 h in the SO group than in the FO and C groups. The SO group had higher plasma intercellular adhesion molecule (ICAM)-1 levels than C group at 0 and 6 h, whereas no difference in ICAM-1 concentrations were observed between the C and FO groups at 0 h after CLP. Hypercholesterolemia resulted in higher tissue MPO activities. There were no differences in MPO activities in various organs between the two experimental groups. These results suggest that hypercholesterolemic mice fed FO did not exhibit immunosuppression when complicated with sepsis. FO administration reduced adhesion molecule expressions and inflammatory-related mediators at the site of injury at an early but not a late stage of sepsis. However, compared with the SO group, the influences of FO on MPO activities in various organs were not obvious in hypercholesterolemic mice with sepsis.

Midterm outcomes of rheumatic mitral repair versus replacement.

Mitral repair is feasible for patients with degenerative or ischemic heart disease, however, the appropriateness of repair for rheumatic heart disease remains controversial. We compared our outcomes for primary isolated mitral repair versus replacement in an elderly population. From November 1997 to July 2005, mitral repair (group I) was performed in 33 patients while 59 underwent replacement (group II). Survival and risk factors were evaluated by Kaplan-Meier and Cox regression analysis. Mean age at operation for groups I and II was 49.7 +/- 13.2 versus 58.1 +/- 11.2 (P = 0.002). No statistically significant differences with regards to demographic parameters were observed except for there being fewer percutaneous transvenous mitral commissurotomy procedures and a lower severity of pulmonary hypertension in group I. Patients with a greater Wilkins score and more valvular calcification underwent replacement more often (P < 0.001). In-hospital mortality, ICU/hospital stay, and postoperative congestive heart failure functional class did not differ significantly. Major adverse cardiac events occurred in 13 and 19 patients, respectively (P = 0.50). There were 4 versus 6 late deaths (P = 0.74). Only two from group I underwent subsequent mitral reoperation. Kaplan-Meier overall survival and event-free survival at 5 years for groups I and II were 0.81 +/- 0.08 versus 0.81 +/- 0.06 (P = 0.90) and 0.52 +/- 0.10 versus 0.51 +/- 0.10 (P = 0.21), respectively. Old age, renal insufficiency, LVEF < 40%, and a history of stroke were poor predictors of patient survival. Compared with replacement, mitral repair for rheumatic heart disease was associated with a lower surgical mortality, higher repeat-surgery rate, and good survival. Rheumatic mitral valves should be repaired in select patients with appropriate valvular pathology.

Nitric oxide attenuates cardiomyocytic apoptosis via diminished mitochondrial complex I up-regulation from cardiac ischemia-reperfusion injury under cardiopulmonary bypass.

OBJECTIVE: This study tested the hypothesis that cardioplegic solution supplemented with a nitric oxide donor agent attenuates postischemic cardiomyocytic apoptosis by reduction of mitochondrial complex I up-regulation during global cardiac arrest under cardiopulmonary bypass. METHODS: Twenty-four anesthetized dogs supported by total vented bypass were divided evenly into 4 groups (n = 6) and subjected to 60 minutes of hypothermic ischemia followed by 4 degrees C multidose crystalloid cardioplegic solution infusion. Hearts received either standard crystalloid cardioplegic solution (control), crystalloid cardioplegic solution supplemented with 2 mmol/L L-arginine (L-Arg group), crystalloid cardioplegic solution supplemented with 400 micromol/L N(G)-monomethyl-L-arginine (L-NMMA group), or crystalloid cardioplegic solution supplemented with 100 micromol/L of NO donor compound (3-morpholinosydnonimine; SIN-1 group). After 60 minutes of cardioplegic arrest, the heart was reperfused for a total of 240 minutes after discontinuation of bypass. The occurrence of cardiomyocytic apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling and Western blot analysis of caspase-3. RESULTS: The occurrence of cardiomyocytic apoptosis was significantly reduced in SIN-1 and L-Arg groups compared with the control group. Mitochondrial complex I mRNA was up-regulated in the control group, and its expression was significantly higher in the L-NMMA group but significantly reduced in the SIN-1 and L-Arg groups. Western blot analysis of Bcl-2 and cytochrome c, an index of mitochondrial damage in postischemic myocardium, revealed a similar pattern. CONCLUSION: Nitric oxide-supplemented crystalloid cardioplegic solution diminished postischemic cardiomyocytic apoptosis after global cardiac arrest under cardiopulmonary bypass, possibly via prevention of mitochondrial complex I up-regulation.

Ischemic preconditioning or heat shock pretreatment ameliorates neuronal apoptosis following hypothermic circulatory arrest.

OBJECTIVE: Hypothermic circulatory arrest has been widely used in complex cardiac and aortic surgery. Stroke and/or neurologic injury can occur after prolonged hypothermic circulatory arrest, possibly due to apoptosis. Ischemic preconditioning has been widely used as a neuroprotective tool, but its application in neuronal injury under hypothermic circulatory arrest has never been studied. METHODS: Forty male New Zealand white rabbits were placed on closed-chest cardiopulmonary bypass, subjected to hypothermic circulatory arrest, and rewarmed to normothermia. Experimental groups were treated with heat shock or ischemic preconditioning before hypothermic circulatory arrest. Hippocampal CA1 neurons were analyzed histopathologically. Apoptosis was confirmed by TUNEL assay and Western blot analysis, and serum S-100beta levels, c-Fos and Bcl-2 antibodies, and caspase-3 and heat shock protein 70 levels were measured. RESULTS: After 2-hour hypothermic circulatory arrest and 4-hour reperfusion, apoptosis was observed in hippocampal CA1 neurons with elevation of serum S-100beta levels, which could be ameliorated by ischemic preconditioning or heat shock manipulations. TUNEL-positive nuclear expression of caspase-3 increased after hypothermic circulatory arrest (3.08% +/- 0.71%, P <.001) and was diminished with ischemic preconditioning (1.61% +/- 0.42%) and heat shock (1.72% +/- 0.38%) manipulations. Ischemic preconditioning or heat shock manipulations produced diverse patterns of heat shock protein 70, c-Fos, and Bcl-2 protein expression, suggesting that these manipulations provide neuroprotection via different pathways. CONCLUSIONS: Ischemic preconditioning and heat shock can attenuate hippocampal CA1 neuronal apoptosis after prolonged hypothermic circulatory arrest under cardiopulmonary bypass. The expression of heat shock protein 70 may not play a major role in the first window of ischemic preconditioning-induced neuroprotection.

Differential-display polymerase chain reaction identifies nicotinamide adenine dinucleotide-ubiquinone oxidoreductase as an ischemia/reperfusion-regulated gene in cardiomyocytes.

OBJECTIVE: Cardiac ischemia/reperfusion-induced oxidative damage often occurs in mitochondria. We identified differentially expressed genes in the canine heart after global cardiac ischemia/reperfusion injury was induced during cardiopulmonary bypass (CPB). METHODS: Differential-display polymerase chain reaction (ddPCR) was performed on cardiac tissue from canine hearts with or without global cardiac ischemia/reperfusion injury induced during CPB. Ischemia/reperfusion-associated mitochondrial injury was investigated at the protein level using various cardioplegic solutions and Western blot analysis. RESULTS: A mitochondrial protein nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase gene was identified on ddPCR. The NADH:ubiquinone oxidoreductase gene was up-regulated in canine hearts after 60 min of global cardiac ischemia/reperfusion injury during CPB. Western blot analysis revealed that, after manipulation with different cardioplegic solutions, increased Bcl-2 expression and decreased cytochrome c expression were associated with cardiomyocytic apoptosis. CONCLUSIONS: The NADH:ubiquinone oxidoreductase gene is up-regulated during global cardiac ischemia/reperfusion injury during CPB in canines. To our knowledge, involvement of this gene in global cardiac ischemia/reperfusion injury during CPB has not been described previously. The NADH:ubiquinone oxidoreductase gene may have a role in the regulation of molecular changes during the global cardiac ischemia/reperfusion injury during CPB, such as the up-regulation of Bcl-2, which might block release of cytochrome c from the mitochondria and prevent cardiomyocytic apoptosis.

Risk factors for descending aortic aneurysm formation in medium-term follow-up of patients with type A aortic dissection.

BACKGROUND: After surgery to repair a type A aortic dissection, most late complications and mortality result from descending aorta-related problems. This study was performed to determine the risk factors leading to descending aortic aneurysm formation and late mortality in patients undergoing the type A aortic dissection operation. METHODS: The medical records of patients who survived the operation for type A aortic dissection between 1984 and 1998 were reviewed. There were 144 patients (95 men and 49 women), ranging in age from 24 to 78 years (mean age, 52 years). Most patients were acutely ill, 15 patients were in shock, and 54 patients had cardiac tamponade at the time of the surgical procedure. One hundred thirty-seven patients had ascending aortic replacement only, and of the other 6 patients 2 had hemiarch and 4 had total arch replacement using the elephant trunk technique. The aortic valve was replaced in 23 patients, resuspended in 100, and untouched in 21. Twenty-four risk factors were evaluated in statistical analyses for the prediction of descending aortic aneurysm formation and 3-year mortality. Risk factors were investigated using univariate and multiple logistic regression and survival analyses. RESULTS: The 3-year, 5-year, and 8-year cumulative survival rates were 96.2%, 89.1%, and 80.0%, respectively. The 3-year, 5-year, and 8-year cumulative survival rates, free from descending aortic aneurysm formation or descending aorta operation, were 74.7%, 58.6%, and 43.0%, respectively. Multivariate analysis confirmed that patent false lumen and initial descending aortic diameter were statistically significant risk factors for descending aortic aneurysm formation. CONCLUSIONS: The medium-term survival rate of patients who received operations for type A aortic dissection was satisfactory, despite the high incidence of descending aortic aneurysm formation. The intimal entry site over the aortic arch that was resected during the first operation could decrease the patency rate of a false lumen over the descending aorta. In the absence of a patent false lumen over the descending aorta, the chance of descending aortic aneurysm formation or operation is lessened, and the late survival rate is increased.

Continuous tepid blood cardioplegia can preserve coronary endothelium and ameliorate the occurrence of cardiomyocyte apoptosis.

OBJECTIVE: In modern cardiac surgery, crystalloid or blood cardioplegic solutions have been used widely for myocardial protection; however, ischemia does occur during protection with intermittent infusion of cold crystalloid or blood cardioplegic solutions. The present study was designed to evaluate the effect of different cardioplegic methods on myocardial apoptosis and coronary endothelial injury after global ischemia, cardiopulmonary bypass (CPB), and reperfusion in anesthetized open-chest dogs. METHODS: The dogs were classified into five groups to identify the injury of myocardium and coronary endothelium: group 1, normothermic CPB without cardiac arrest; group 2, hypothermic CPB with continuous tepid blood cardioplegia, and with cardiac arrest; group 3, hypothermic CPB with intermittent cold blood cardioplegia, and with cardiac arrest; group 4, hypothermic CPB with intermittent cold crystalloid cardioplegia, and with cardiac arrest; and group 5, sham-operated control group. During CPB, cardiac arrest was achieved with different cardioplegia solutions for 60 min, followed by reperfusion for 4 h before the myocardium and coronary arteries were harvested. Coronary arteries were harvested immediately and analyzed by scanning electron microscopy. Cardiomyocytic apoptosis was detected using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling, Western blot, and DNA ladder methods. RESULTS: Regardless of the detection method used, significantly higher percentages of apoptotic cardiomyocytes were found in group 3 and group 4 than in other groups. Expression of caspase-3 correlated with increased apoptosis. Scanning electron microscopy revealed severe endothelial injury of coronary arteries in group 3 and group 4. CONCLUSION: These results point to an important explanation for the difference in cardiac recovery after hypothermic ischemia and arrest with various cardioplegic solutions.