Anesthetic management of a giant paraganglioma resection: a case report.

BACKGROUND: Patients with pheochromocytomas are often diagnosed with acute myocardial infarction (AMI) due to initial symptoms of palpitations and chest tightness. We describe a case of AMI syndrome where a giant paraganglioma was unexpectedly identified. The anesthetic management of the paraganglioma resection was challenging and complex. CASE PRESENTATION: A 66-year-old woman was admitted to the emergency department for complaints of palpitations, chest tightness and vomiting. A laboratory test revealed that troponin I and N-terminal pro-brain natriuretic peptide levels were dramatically increased. Emergency percutaneous coronary angiography (CAG) showed normal coronary arteries. In addition, the serum levels of free catecholamines were increased, and computed tomography and magnetic resonance imaging revealed a heterogenous mass lesion in the right retroperitoneal. All of this ultimately confirmed the diagnosis of pheochromocytoma. After three weeks of careful preoperative preparation by a multidisciplinary team, and an anesthesiologist team develops detailed perianesthesia management strategies to maintain hemodynamics and blood glucose stability and regulate acid-base balance, pheochromocytoma resection was performed successfully. About 2 weeks later, the patient was discharged healthy. A postoperative pathology test confirmed paraganglioma. CONCLUSIONS: To our knowledge, giant pheochromocytoma resection is a complex challenge for the anesthesiologists, this clinical case may supply a thoughtful experience for anesthetic management in the resection of giant pheochromocytomas. Adequate preoperative evaluation and prudent perianesthesia management by anesthesiologists are important guarantees for patients to obtain a good prognosis and discharge healthily.

Osthole-Mediated Inhibition of Neurotoxicity Induced by Ropivacaine via Amplification of the Cyclic Adenosine Monophosphate Signaling Pathway.

Background: Ropivacaine is widely used for clinical anesthesia and postoperative analgesia. However, the neurotoxicity induced by ropivacaine in a concentration- and duration-dependent manner, and it is difficult to prevent neurotoxicity. Osthole inhibits phosphodiesterase-4 activity by binding to its catalytic site to prevent cAMP hydrolysis. The aim of this present study is to explore the precise molecular mechanism of osthole-mediated inhibition of neurotoxicity induced by ropivacaine. Methods: SH-SY5Y cell viability and apoptosis were measured in different concentration and duration. Protein concentration was determined in each signaling pathway. The molecular mechanism of osthole-mediated inhibition of ropivacaine-caused neurotoxicity was evaluated. Results: The study demonstrated that osthole inhibits SH-SY5Y cells neurotoxicity in a duration- and concentration-dependent manner. Moreover, ropivacaine significantly increased the expression of caspase-3 by promoting the phosphorylation of p38. Osthole-induced upregulation of cAMP activated cAMP-dependent signaling pathway, sequentially leading to elevated cyclic nucleotide response element-binding protein levels, which inhibits P38-dependent signaling and decreases apoptosis of SH-SY5Y. Conclusions: This study display the evidence confirmed the molecular mechanism by which osthole amplification of cAMP-dependent signaling pathway, and overexpression of cyclic nucleotide response element-binding protein inhibits P38-dependent signaling and decreases ropivacaine-induced SH-SY5Y apoptosis.

Determination of the Median Effective Dose of Dexmedetomidine for the Prevention of Emergence Agitation in Geriatric Patients Undergoing Major Open Surgery With General Anesthesia: A Prospective, Double-Blinded, Dose-Response Trial.

Dexmedetomidine can effectively decrease the incidences of emergence agitation (EA) in adult patients, but there are major side effects related to increased dose of dexmedetomidine. The purpose of this study was to determine the median effective dose of dexmedetomidine in the prevention of EA among geriatric patients undergoing major open surgery with general anesthesia. A total of 50 geriatric patients were enrolled in this study. Dexmedetomidine 0.5 µg·kg-1·h-1 continuous intravenous infusion was administered to the first patient. The next dose was increased or decreased by .05 depending on the response of the previous patient, according to the Dixon up-and-down method. An "effective" or "ineffective" response was determined based on the Riker sedation-agitation score (RSAS), we defined "effective" as RSAS<5, and "ineffective" as RSAS≥5. The ED50 of dexmedetomidine in prevention of EA was .30 µg·kg-1·h-1 (95% CI, .27-.33) and the predicted ED95 was .42 µg·kg-1·h-1 (95% CI, .38-.51). The incidence of bradycardia was significantly increased in the group without EA compared to the group with EA (57.1% vs 13.6%, P = .002). The ED50 of dexmedetomidine in prevention of EA was .30 µg·kg-1·h-1 (95% CI, .27-.33) and the predicted ED95 was .42 µg·kg-1·h-1 (95% CI, .38-.51). Bradycardia was the main complication.

Determination of the median effective dose (ED50) of bupivacaine and ropivacaine unilateral spinal anesthesia : Prospective, double blinded, randomized dose-response trial.

BACKGROUND: Unilateral spinal anesthesia (USpA) has been reported to potentiate spinal anaesthesia and is used in geriatric patients. The purpose of this study was to determine the median effective dose (ED50) of 0.5% hypobaric bupivacaine and 0.5% hypobaric ropivacaine USpA for geriatric patients (age ≥ 70 years) undergoing elective hip replacement surgery. METHODS: A total of 60 geriatric patients (age ≥ 70 years) undergoing elective hip replacement surgery were enrolled in this study. The patients were randomized into 2 groups to receive either intrathecal 0.5% hypobaric bupivacaine USpA (group B) or 0.5% hypobaric ropivacaine USpA (group R). Effective anesthesia was defined as a T10 sensory blockade level maintained for more than 60 min, and a Bromage score of 3 on the operation side within 10 min after injection with no additional epidural anesthetic required during surgery. The ED50 of 0.5% hypobaric bupivacaine and 0.5% hypobaric ropivacaine was calculated using the Dixon and Massey formula. RESULTS: No significant differences were found between the two groups in terms of demographic data. The ED50 of 0.5% hypobaric bupivacaine USpA was 4.66 mg (95% confidence interval CI 4.69-4.63 mg) mg and that of 0.5% hypobaric ropivacaine USpA was 6.43 mg (95% CI 6.47-6.39 mg) for geriatric patients undergoing hip replacement surgery. CONCLUSION: We find the ED50 were lower, and the ED50 of 0.5% hypobaric bupivacaine and ropivacaine was 4.66 mg (95% CI 4.69-4.63 mg) and 6.43 mg (95% CI 6.47-6.39 mg), respectively, for USpA in geriatric patients (age ≥ 70 years) undergoing elective hip replacement surgery.

Adenovirus-mediated expression of hypoxia-inducible factor 1α double mutant converts neonatal cardiac fibroblasts into (cardio)myocyte phenotype.

Adenovirus-mediated expression of hypoxia-inducible factor 1α double mutant (pAd-HIF-1α-Ala564-Ala803) can be effectively transfected into bone marrow stem cells (MSCs) in the MSCs and cardiomyocytes co-culture system at normoxia to regulate the expression of downstream target genes of hypoxia-inducible factor 1α (HIF-1α), which in turn can promote MSC differentiation into cardiomyocytes. Fibroblasts share common characteristics with MSCs such as the morphology, phenotype and differentiation potential. Therefore, we further studied whether the pAd-HIF-1α-Ala564-Ala803 also can convert neonatal rat cardiac fibroblasts (NCFs) into (cardio)myocyte phenotype via regulating the downstream target genes of HIF-1α at normoxia. The immunostaining analysis showed that NCFs treated with pAd-HIF-1α-Ala564-Ala803 exhibited higher protein expression levels of smooth muscle α-actin (SMA, myocyte marker) and cardiac troponin T (cTnT, cardiomyocyte marker), compared with phosphate-buffered saline and pAd-LacZ treatments. The reverse transcription-polymerase chain reaction results showed that NCFs transfected with pAd-HIF-1α-Ala564-Ala803 augmented messenger RNA (mRNA) expression of transforming growth factor-ß1 (TGF-ß1), Smad4, NKx2.5, GATA4, myocardin, SMA and cTnT. The effects of HIF-1α-Ala564-Ala803 on NCFs were attenuated by pre-transfection of TGF-ß1 or myocardin small interference RNAs. Adult CFs transfected with pAd-HIF-1α-Ala564-Ala803 showed a lower protein expression of SMA but not cTnT without any change in the mRNA expression level of NKx2.5, myocardin. Therefore, NCFs but not adult CFs possess a similar differentiation potential to MSCs as evidenced by the fact that pAd-HIF-1α-Ala564-Ala803 can convert NCFs into (cardio)myocyte phenotype via regulating its downstream target genes.

Adenovirus-mediated hypoxia-inducible factor 1alpha double-mutant promotes differentiation of bone marrow stem cells to cardiomyocytes.

The hypoxia-inducible factor 1alpha (HIF-1alpha) regulates transcriptional genes involved in cell proliferation, survival, and differentiation. Under normoxia, HIF-1alpha has a short half-life (t((1/2)) approximately 5 min) and low transcriptional activity. An HIF-1alpha mutant, produced by substitution of alanine (Ala) for proline (Pro) at position 564 and asparagine (Asp) at position 803, can prevent HIF-1alpha hydroxylation and results in a highly active form of HIF-1alpha (HIF-1alpha-Ala564-Ala803). We hypothesized that adenovirus (Ad)-mediated transfer of the active form of HIF-1alpha (pAd-HIF-1alpha-Ala564-Ala803) could effectively occur in bone marrow stem cells (MSCs) and promote MSC differentiation under normoxia. PCR-based site-specific mutagenesis was used to construct the Ad vector expressing HIF-1alpha-Ala564-Ala803. RT-PCR and immunostaining were used to study whether pAd-HIF-1alpha-Ala564-Ala803 affected MSC differentiation to cardiomyocyte (CMC). pAd-HIF-1alpha-Ala564-Ala803 exhibited higher transcriptional activity and stable HIF-1alpha protein expression. Under normoxia, an MSC-CMC co-culture treated with pAd-HIF1a-Ala564-Ala803 augmented TGF-beta(1), Smad4, NKx2.5, and GATA4 expression. Higher expression of cTnT and alpha-actinin was observed by immunostaining in MSCs, compared with the control and contrast groups. Adenovirus-mediated hypoxia-inducible factor 1alpha double-mutant, pAd-HIF-1alpha-Ala564-Ala803, can stably express HIF-1alpha and promote its downstream genes and MSC differentiation to CMC in the MSC-CMC co-culture system under normoxia.

Bone marrow derived stromal cells modified by adenovirus-mediated HIF-1alpha double mutant protect cardiac myocytes against CoCl2-induced apoptosis.

Bone marrow derived stromal cells (MSCs) can prevent the apoptosis of ischemic cardiomyocytes (CMCs). This anti-apoptosis activity may be related to an activation of the HIF-1alpha signal pathway in MSCs. Therefore, we investigated protective effects of an adenovirus (Ad)-mediated active form of HIF-1alpha (HIF-1alpha-Ala564-Ala803) modified MSCs on CMCs against CoCl(2)-induced apoptosis. At normoxia, pAd-HIF1alpha-Ala564-Ala803 exhibited a stable HIF-1alpha protein expression in MSCs. Compared with the single CMC culture, the TGF-beta1 level and the Bcl-2 expression were significantly increased, concomitant with a reduced expression of caspase-3, the LDH release and TUNEL-positive CMCs in CMC and MSC, beta-galactosidase (LacZ)-MSC or HIF-1alpha-Ala564-Ala803-MSC coculture exposed to CoCl(2). Furthermore, these effects were more prominent in CMC and HIF-1alpha-Ala564-Ala803-MSC coculture than in CMC and MSC or LacZ-MSC coculture exposed to CoCl(2). Pre-transfection of TGF-beta1-small interfering RNA (siRNA) effectively inhibited the TGF-beta1 level, resulting in a dramatic reduction in the Bcl-2 expression as well as an increased level of apoptosis in CMC and HIF-1alpha-Ala564-Ala803-MSC coculture exposure to CoCl(2), whereas pre-transfection of green fluorescent protein (GFP)-siRNA had no such effects. These data suggest that HIF1alpha-Ala564-Ala803 modified MSCs have better protective effects of CMCs against the CoCl(2)-induced apoptosis and these protective effects are at least partly TGF-beta1-mediated.