Nitric oxide sensitivity in pulmonary artery and airway smooth muscle: a possible role for cGMP responsiveness

We aimed to assess intrinsic smooth muscle mechanisms contributing to greater nitric oxide (NO) responsiveness in pulmonary vascular vs. airway smooth muscle. Porcine pulmonary artery smooth muscle (PASM) and tracheal smooth muscle (TSM) strips were used in concentration-response studies to the NO donor (Z)-1-[N-2-aminoethyl-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO). PASM consistently exhibited greater relaxation at a given DETA-NO concentration (NO responsiveness) than TSM NO responsiveness, with DETA-NO log EC50 being −6.55 ± 0.11 and −5.37 ± 0.13 for PASM and TSM, respectively (P < 0.01). We determined relationships between tissue cGMP concentration ([cGMP]i) and relaxation using the particulate guanylyl cyclase agonist atrial natriuretic peptide. Atrial natriuretic peptide resulted in nearly complete relaxation, with no detectable increase in [cGMP]i in PASM and only 20% relaxation (10-fold increase in [cGMP]i) in TSM, indicating that TSM is less cGMP responsive than PASM. Total cGMP-dependent protein kinase I (cGKI) mRNA expression was greater in PASM than in TSM (2.23 ± 0.36 vs. 0.93 ± 0.31 amol mRNA/μg total RNA, respectively; P < 0.01), but total cGKI protein expression was not significantly different (0.56 ± 0.07 and 0.49 ± 0.04 ng cGKI/μg protein, respectively). The phosphotransferase assay for the soluble fraction of tissue homogenates demonstrated no difference in the cGMP EC50 between PASM and TSM. The maximal phosphotransferase activity indexed to the amount of total cGKI in the homogenate differed significantly between PASM and TSM (1.61 ± 0.15 and 1.04 ± pmol·min−1·ng cGKI−1, respectively; P < 0.05), suggesting that cGKI may be regulated differently in the two tissues. A novel intrinsic smooth muscle mechanism accounting for greater NO responsiveness in PASM vs. TSM is thus greater cGMP responsiveness from increased cGKI-specific activity in PASM.ope

Cardiovascular effects of oral tri-iodothyronine in patients undergoing valvular cardiac surgery

BACKGROUND: Cardiopulmonary bypass produces a state of functional hypothyroidism characterized by low levels of circulating tri-iodothyronine (T3). Theoretically, supplementing T3 should result in improved hemodynamics as well as patients' outcome. The aim of the present study was to determine whether pretreatment with single oral T3 could prevent serum T3 reduction, and improve hemodynamics and clinical outcome. METHODS: Forty-seven patients undergoing valvular heart surgery were included in the study. Patients were randomly assigned into two groups (T = T group; C = control group) the day before surgery and received single oral T3 40 microg or placebo before operation. Blood samples were collected for determination of serum levels of total T3, T4 and TSH before administration of oral T3 or placebo (baseline), 1, 6 and 18 hour after weaning of cardiopulmonary bypass. Hemodynamic parameters and medication were recorded during the intraoperative period and throughout the first 24 h after arrival at the intensive care unit. RESULTS: T3 levels were significantly higher in the T group 1 hr after weaning of cardiopulmonary bypass. T3 levels in the T group were all maintained within the normal range throughout the study period, whereas it was decreased to below normal level in the C group at 18 hr after weaning of cardiopulmonary bypass. In the T group, vasoactive agent requirements were reduced during and after cardiopulmonary bypass. CONCLUSIONS: Pretreatment with single oral T3 prevented the reduction in T3 level after valvular heart surgery, with subsequent reduction in vasoactive agent requirementope

Management of a patient with atheromatous aortic arch diagnosed by a intraoperative transophageal echocardiography during coronary artery bypass grafting

Protruding atheromas of the aorta have been identified as one of the sources of a systemic emboli and a major cause of stroke following cardiac surgery. We report a case of surgical modification in a 58-year-old man with an atheromatous aortic arch detected by an intraoperative transesophageal echocardiography (TEE) during coronary artery bypass grafting (CABG). After induction of anesthesia, protruding atheromatous plaques with a mobile element in the aortic arch were identified by a TEE that was not noticed by a preoperative angiography and transthoracic echocardiograpy. Based on the TEE finding, the surgical technique was modified to CABG combined with an aortic atherectomy under deep hypothermic circulatory arrest. The atheromatous areas correlated well with the TEE finding and the patient recovered from anesthesia and surgery without neurologic deficit. Therefore, an intraoperative TEE examination is considered as a safe and reliable technique to identify atherosclerotic disease of the thoracic aorta in patients undergoing CABG and to minimize unexpected neurologic complications after CABG.ope

The Comparision of Nicardipine and Sodium Nitroprusside on Postoperative Hypertension after Coronary Artery Bypass Graft Surgery

Background: Hypertension following coronary artery bypass graft surgery (CABG) occurs frequently. Pharmacologic therapy of postoperative hypertension has often been treated with sodium nitroprusside (SNP). Nicardipine which is a dihydropyridine calcium-channel blocker, has little or no direct negative effects on cardiac contractility. Thus, we have compared the effects on hemodynamics between nicardipine and SNP after a CABG. Methods: After a CABG, when systolic blood pressure (SBP) was elevated above 140 ㎜Hg, patients were randomized to receive either nicardipine (N-group, n = 26) or SNP (S-group, n = 21) at an initial rate of 2㎍/㎏/min until the SBP was lowered to 120-130 mmHg (target blood pressure, TBP) for 10 minutes. If the TBP was not achieved, the infusion rates of both drugs were increased by 1㎍/㎏/min every 10 minutes. If SBP was lowered below 100 ㎜Hg, phenylephrine was infused. Hemodynamic measurements were obtained just before (T1) and at 10 min (T2), 60 min (T3) and 24 h (T4) after the infusin of nicardipine or SNP. Infusion time, total doses, creatine phosphokinase (CK)-MB, plasma catecholamine and the use of phenylephrine were compared between groups. Results: The SBP and systemic vascular resistance were significantly decreased in both groups. The cardiac index and stroke volume index were significantly increased at T3 in both groups but they were significantly increased only in the N-group at T2. The infusion time and the total doses of both drugs were significantly less in the N-group than the S-group. There were no significant differences in CK-MB, plasma catecholamine and the use of phenylephrine between groups. Conclusions: It has been suggested that the infusion of nicardipine is as effective as the infusion of SNP for the control of postoperative hypertension and the increase of cardiac output after a CABG. However, immediately after the drug infusion, nicardipine was superior to SNP in maintaining left ventricular performance.ope

Anesthetic Management for Off-Pump Coronary Artery Bypass Graft Surgery

Off-pump coronary artery bypass graft surgery (OPCAB) may be of benefit overall for the patient and surgical techniques for OPCAB have been developed markedly. The development of surgical techniques without severe hemodynamic instability allows surgeons to access to all coronary arteries. Hemodynamic instability due to the displacement and restraining of the heart and transient ischemia during anastomoses are major problems associated with OPCAB. The maintenance of stable hamodynamic and minimization of cardiac dysfunction during anastomosis should be stressed in the anesthesia for OPCAB. The baseline anesthetic methods and monitoring for OPCAB are the same as for conventional coronary artery bypass graft surgery (CABG). The temperature management is a significant problem and appropriate provision is needed for defibrillation and pacing during anastomosis because rhythm problems are not uncommon. Prevention and treatment of hypotension, low cardiac output, and dysrhythmia is a major focus of anesthetic management. Volume loading and Trendelenberg position is helpful maintaining cardiac output and perfusion pressure. If hemodynamic deterioration occurs, quickly progress to potent vasopressors/ inotropic agents. Treatment of myocardial ischemia must be guided by the patient's overall hemodynamic status. Therapies to consider include titrated beta-adrenergic blockers, increasing blood pressure to improve collateral flow, treating the spasm of native coronaries or arterial conduits, reversing Trendelenberg to reduce left ventricular filling and wall stress and shunting. Close observation for surgical field and open communication with surgeon is essential to predict the patients most likely to need above modalities and bearing similarities with anesthesia for CABG in mind will help the anesthesiologist to be more comfortable with anesthesia for OPCAB.ope

Redesigning an anesthesiology resident training program to improve practical procedure competency

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NO responsiveness in pulmonary artery and airway smooth muscle: the role of cGMP regulation

The purpose of this study was to assess intrinsic smooth muscle mechanisms contributing to greater nitric oxide (NO) responsiveness in pulmonary vascular vs. airway smooth muscle. Canine pulmonary artery smooth muscle (PASM) and tracheal smooth muscle (TSM) strips were used to perform concentration response studies to an NO donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO). PASM exhibited a greater NO responsiveness whether PASM and TSM were contracted with receptor agonists, phenylephrine and acetylcholine, respectively, or with KCl. The >10-fold difference in NO sensitivity in PASM was observed with both submaximal and maximal contractions. This difference in NO responsiveness was not due to differences in endothelial or epithelial barriers, since these were removed, nor was it due to the presence of cGMP-independent NO-mediated relaxation in either tissue. At equal concentrations of NO, the intracellular cGMP concentration ([cGMP]i) was also greater in PASM than in TSM. Phosphodiesterase (PDE) inhibition using isobutylmethylxanthine indicated that the greater [cGMP]i in PASM was not due to greater PDE activity in TSM. Expression of soluble guanylate cyclase (sGC) subunit mRNA (2 ± 0.2 and 1.3 ± 0.2 attomol/μg total RNA, respectively) and protein (47.4 ± 2 and 27.8 ± 3.9 ng/mg soluble homogenate protein, respectively) was greater in PASM than in TSM. sGCα1 and sGCβ1 mRNA expression was equal in PASM but was significantly different in TSM, suggesting independent regulation of their expression. An intrinsic smooth muscle mechanism accounting for greater NO responsiveness in PASM vs. TSM is greater sGC activity.ope

Effect of 6% Hydroxyethyl Starch 130/0.4 as a Priming Solution on Coagulation and Inflammation Following Complex Heart Surgery

PURPOSE: Prolonged duration of cardiopulmonary bypass aggravates the degree of inflammation and coagulopathy. We investigated the influence of 6% hydroxyethyl starch (HES) 130/0.4 on coagulation and inflammation compared with albumin when used for both cardiopulmonary bypass priming and perioperative fluid therapy in patients undergoing complex valvular heart surgery. MATERIALS AND METHODS: Fifty four patients were randomly allocated into albumin-HES, albumin-nonHES, and HES-HES groups. The cardiopulmonary bypass circuit was primed with 5% albumin in the albumin-HES and albumin-nonHES group, and with HES in the HES-HES group. As perioperative fluid, only plasmalyte was used in the albumin-nonHES group whereas HES was used up to 20 mL/kg in the albumin-HES and albumin-HES group. Serial assessments of coagulation profiles using the rotational thromboelastometry and inflammatory markers (tissue necrosis factor-α, interleukin-6, and interleukin-8) were performed. RESULTS: Patients' characteristics and the duration of cardiopulmonary bypass (albumin-HES; 137±34 min, HES-HES; 136±47 min, albumin-nonHES; 132±39 min) were all similar among the groups. Postoperative coagulation profiles demonstrated sporadic increases in clot formation time and coagulation time, without any differences in the actual amount of perioperative bleeding and transfusion requirements among the groups. Also, inflammatory markers showed significant activation after cardiopulmonary bypass without any differences among the groups. CONCLUSION: Even in the presence of prolonged duration of cardiopulmonary bypass, HES seemed to yield similar influence on the ensuing coagulopathy and inflammatory response when used for priming and perioperative fluid therapy following complex valvular heart surgery compared with conventional fluid regimen including albumin and plasmalyte.ope

Effects of Preinduction Atropine on the Hemody namic Response to Induction with Fentanyl and Vecuronium for Coronary Artery Bypass Grafting

Background: Induction of anesthesia with a high dose of fentanyl and vecuronium decreases the heart rate and blood pressure. This study was designed to evaluate the effect of preinduction atropine on these hemodynamic changes in patients undergoing coronary artery bypass graft surgery (CABG). Methods: Forty-one patients who underwent CABG were randomly divided into two groups. After insertion of a radial artery cannula and a Swan-Ganz catheter, normal saline 1 ml (control group, n = 20) or atropine 0.5 mg (atropine group, n = 21) was injected intravenously 1 min before the induction of anesthesia. Anesthesia was induced with a first dose of fentanyl (5-8μg/ kg) and vecuronium (0.12 mg/kg) and a second dose of fentanyl (5-10μg/kg). The patient was then intubated. Hemodynamic variables were measured before the induction of anesthesia, 1 min after the administration of each drug during the induction of anesthesia and 5, 10, and 30 min after the intubation. Results: There was no significant differences between the two groups in terms of demographic data except that the number of patients with diabetes mellitus was greater in the control group than in the atropine group. The number of patients treated for hypotension or bradycardia during the induction of anesthesia was greater in the control group than in the atropine group, but this was not statistically significant. Heart rates significantly decreased in the control group but were maintained in the atropine group without any significant tachycardia. Blood pressure significantly decreased in both groups. Conclusions: Intravenous injection of atropine before anesthetic induction in patients undergoing CABG attenuates the decrease in heart rate resulting from anesthetic induction with high dose fentanyl and vecuronium. However, it didn't prevent the decrease in blood pressure nor did it reduce the incidence of treatment for hypotension.ope

Effects of intraoperative inspired oxygen fraction (FiO2 0.3 vs 0.8) on patients undergoing off-pump coronary artery bypass grafting: the CARROT multicenter, cluster-randomized trial

BACKGROUND: To maintain adequate oxygenation is of utmost importance in intraoperative care. However, clinical evidence supporting specific oxygen levels in distinct surgical settings is lacking. This study aimed to compare the effects of 30% and 80% oxygen in off-pump coronary artery bypass grafting (OPCAB). METHODS: This multicenter trial was conducted in three tertiary hospitals from August 2019 to August 2021. Patients undergoing OPCAB were cluster-randomized to receive either 30% or 80% oxygen intraoperatively, based on the month when the surgery was performed. The primary endpoint was the length of hospital stay. Intraoperative hemodynamic data were also compared. RESULTS: A total of 414 patients were cluster-randomized. Length of hospital stay was not different in the 30% oxygen group compared to the 80% oxygen group (median, 7.0 days vs 7.0 days; the sub-distribution hazard ratio, 0.98; 95% confidence interval [CI] 0.83-1.16; P = 0.808). The incidence of postoperative acute kidney injury was significantly higher in the 30% oxygen group than in the 80% oxygen group (30.7% vs 19.4%; odds ratio, 1.94; 95% CI 1.18-3.17; P = 0.036). Intraoperative time-weighted average mixed venous oxygen saturation was significantly higher in the 80% oxygen group (74% vs 64%; P < 0.001). The 80% oxygen group also had a significantly greater intraoperative time-weighted average cerebral regional oxygen saturation than the 30% oxygen group (56% vs 52%; P = 0.002). CONCLUSIONS: In patients undergoing OPCAB, intraoperative administration of 80% oxygen did not decrease the length of hospital stay, compared to 30% oxygen, but may reduce postoperative acute kidney injury. Moreover, compared to 30% oxygen, intraoperative use of 80% oxygen improved oxygen delivery in patients undergoing OPCAB. Trial registration ClinicalTrials.gov (NCT03945565; April 8, 2019). © 2023. The Author(s).ope