Time course changes in insulin sensitivity during cardiac surgery: A retrospective study on intraoperative glycemic management using an artificial pancreas.

INTRODUCTION: Glycemic control is essential for improving the prognosis of cardiac surgery, although precise recommendations have not yet been established. Under a constant blood glucose level, the insulin infusion rate correlates with insulin resistance during glycemic control using an artificial pancreas (AP). We conducted this retrospective study to elucidate changes in intraoperative insulin sensitivity as a first step to creating glycemic control guidelines. METHODS: Fifty-five cardiac surgery patients at our hospital who underwent intraoperative glycemic control using an AP were enrolled. Twenty-three patients undergoing surgical procedures requiring cardiac arrest under hypothermic cardiopulmonary bypass (CPB) with minimum rectal temperatures lower than 32°C, 13 patients undergoing surgical procedures requiring cardiac arrest under hypothermic CPB with minimum rectal temperatures of 32°C, eight patients undergoing on-pump beating coronary artery bypass grafting and 11 patients undergoing off-pump coronary artery bypass were assigned to groups A, B, C and D, respectively. We analyzed the time course of changes in the data derived from glycemic control using the AP. RESULTS: Significant time course changes were observed in groups A and B, but not in groups C and D. Insulin resistance was induced after the start of hypothermic CPB in groups A and B, and the induced change was not resolved by the rewarming procedure, remaining sustained until the end of surgery. CONCLUSIONS: Hypothermia is the predominant factor of the induced insulin resistance during cardiac surgery. Thus, careful glycemic management during hypothermic CPB is important. Prospective clinical studies are required to confirm the findings of this study.

Successful airway management with combined use of a McGRATHTM MAC videolaryngoscope and fiberoptic bronchoscope in a patient with congenital tracheal stenosis diagnosed in adulthood.

BACKGROUND: Most patients with congenital tracheal stenosis (CTS) develop respiratory symptoms early in life. CTS remaining undiagnosed until adulthood is rare. CASE PRESENTATION: A 51-year-old female was scheduled for cardiovascular surgery. She had undergone laparoscopic surgery 3 years earlier and was found to have a difficult airway. Postoperatively, she was diagnosed with CTS. For the current cardiovascular surgery, combined use of a McGRATHTM MAC videolaryngoscope and fiberoptic bronchoscope allowed sufficient visualization of the glottis and trachea, resulting in successful intubation. CONCLUSIONS: CTS patients have a high probability of difficult intubation. Our experience suggests the efficacy of combined use of a videolaryngoscope and fiberoptic bronchoscope for airway management in CTS patients.

[Shivering associated with general anesthesia using remifentanil].

General anesthesia using remifentanil is accompanied with post-operative shivering at a high incidence. Post-operative shivering can be divided into thermoregulatory and non-thermoregulatory. Hypothermia causes thermoregulatory shivering. The interthreshold range is defined as the difference between the sweating threshold and the vasoconstriction threshold. Generally, the interthreshold range is shifted to higher temperatures immediately after surgery under general anesthesia. Thus, thermoregulatory shivering can be exaggerated in patients without hypothermia. The application of patient warming devices and the administration of non-steroidal anti-inflammatory drugs are considered as effective treatments for the prevention of thermoregulatory shivering. Remifentanil is an ultra-short acting agent. Pharmacological effects of remifentanil quickly disappear just after the discontinuing of remifentanil infusion, leading to a kind of opioid withdrawal syndrome resulting in non-thermoregulatory shivering. In addition, postoperative pain shifts the shivering threshold to higher temperatures, resulting in non-thermoregulatory shivering. Thus, opioid transition using fentanyl and/or morphine during anesthetic management is essential for the prevention of non-thermoregulatory shivering. It is also reported that magnesium, ketamine and pethidine have preventive effects on non-thermoregulatory shivering. The mechanism underlying post-operative shivering associated with general anesthesia using remifentanil is very complicated; therefore, we speculate that multimodal approach is required for its prevention.

[Anesthetic management of laparoscopic cholecystectomy for a patient with Churg-Strauss syndrome: a case report].

Churg-Strauss syndrome (CSS) is an uncommon disease characterized by bronchial asthma, eosinophilia and systemic vasculitis. Many patients with CSS are suffering from cardiovascular disorders, neurological disorders and/or renal disorders which are associated with systemic vasculitis. Cardiac diseases are considered as the main cause of the death in patients with CSS. Steroid administration is the standard pharmacological therapy for CSS. There are very few clinical reports concerning anesthetic management for the patients with CSS. We suppose that precise perioperative managements are required for the patients with CSS, including the appropriate control of bronchial asthma and the careful treatments of disorders in cardiovascular system, neurological system and/or kidney. In addition, we believe that the steroid cover should be considered during the perioperative period of the patients with CSS. Here, we describe an anesthetic management of a 28-year-old man with CSS undergoing laparoscopic cholecystectomy. General anesthesia was induced with midazolam and fentanyl. Rocuronium was administered to facilitate tracheal intubation. After tracheal intubation, anesthesia was maintained with sevoflurane and remifentanil. Prior to the surgery, 100 mg of hydrocortisone was administered for the steroid cover. The surgery was uneventful. The patient emerged from general anesthesia smoothly, and was extubated safely.

Histamine H4-receptors inhibit mast cell renin release in ischemia/reperfusion via protein kinase C ε-dependent aldehyde dehydrogenase type-2 activation.

Renin released by ischemia/reperfusion (I/R) from cardiac mast cells (MCs) activates a local renin-angiotensin system (RAS) causing arrhythmic dysfunction. Ischemic preconditioning (IPC) inhibits MC renin release and consequent activation of this local RAS. We postulated that MC histamine H4-receptors (H4Rs), being Gαi/o-coupled, might activate a protein kinase C isotype-ε (PKCε)-aldehyde dehydrogenase type-2 (ALDH2) cascade, ultimately eliminating MC-degranulating and renin-releasing effects of aldehydes formed in I/R and associated arrhythmias. We tested this hypothesis in ex vivo hearts, human mastocytoma cells, and bone marrow-derived MCs from wild-type and H4R knockout mice. We found that activation of MC H4Rs mimics the cardioprotective anti-RAS effects of IPC and that protection depends on the sequential activation of PKCε and ALDH2 in MCs, reducing aldehyde-induced MC degranulation and renin release and alleviating reperfusion arrhythmias. These cardioprotective effects are mimicked by selective H4R agonists and disappear when H4Rs are pharmacologically blocked or genetically deleted. Our results uncover a novel cardioprotective pathway in I/R, whereby activation of H4Rs on the MC membrane, possibly by MC-derived histamine, leads sequentially to PKCε and ALDH2 activation, reduction of toxic aldehyde-induced MC renin release, prevention of RAS activation, reduction of norepinephrine release, and ultimately to alleviation of reperfusion arrhythmias. This newly discovered protective pathway suggests that MC H4Rs may represent a new pharmacologic and therapeutic target for the direct alleviation of RAS-induced cardiac dysfunctions, including ischemic heart disease and congestive heart failure.

[Desflurane anesthesia without muscle relaxant for a patient with myasthenia gravis undergoing laparoscopic high anterior resection: a case report].

Myasthenia gravis (MG) is an autoimmune disease affecting neuromuscular junction, which is characterized by fluctuating muscle weakness and abnormal fatigability. The use of muscle relaxants is major concern in anesthetic management for patients with MG. Muscle relaxant is a practical tool to assure immobilization during surgery under general anesthesia Anesthetic management without muscle relaxants for patients with MG is challenging, because it is difficult to assure immobilization. However, pharmacological effects of muscle relaxants can be prolonged in patients with MG, resulting in the increased incidence of postoperative respiratory support. We, here, describe an anesthetic management of an 82-year-old man with MG undergoing laparoscopic surgery. Anesthesia was induced with propofol and remifentanil Desflurane was administered via a face mask, and the patient was manually ventilated for 10 min, and the trachea was intubated safely without muscle relaxants. Anesthesia was maintained with desflurane and remifentanil. We did not administer muscle relaxants to the patient during surgery. Throughout laparoscopic procedures, no movements of the patient were observed, and there were no problems concerning the laparoscopic view of the operation filed. The surgery was uneventful. The patient emerged from anesthesia smoothly, and was extubated safely. The postoperative course of the patient was also uneventful.

[A case of acute renal failure following compartment syndrome after the surgery for femoral neck fracture].

Compartment syndrome is known to develop after a prolonged surgery in the lithotomy position. We experienced acute renal failure following compartment syndrome after the surgery in hemilithotomy position. A 62-year-old man underwent a left hip fixation for femoral neck fracture. The surgical leg was placed into traction in a foot piece and the intact leg was placed in the hemilithotomy position. Because of the difficulty in repositioning and the trouble with fluoroscope, the surgery took over 5 hours. He suffered acute pain, swelling and spasm in his intact leg placed into hemilithotomy after the surgery. Creatine kinase, blood urea nitrogen and creatinine markedly increased and myoglobinuria was recognized. We diagnosed an acute renal failure following compartment syndrome and treated him in the ICU on close monitoring. In spite of the treatment with massive transfusion and diuretics, he needed hemodialysis twice and then his renal function improved. Prevention is most essential for compartment syndrome after a prolonged surgery in the lithotomy position. Risk factors should be recognized before surgery and appropriate action should be taken such as using Allen stirrups and avoiding hypotension, hypovolemia and the prolonged lithotomy position with exaggerated elevation of legs.

Aldehyde dehydrogenase type 2 activation by adenosine and histamine inhibits ischemic norepinephrine release in cardiac sympathetic neurons: mediation by protein kinase Cε.

During myocardial ischemia/reperfusion, lipid peroxidation leads to the formation of toxic aldehydes that contribute to ischemic dysfunction. Mitochondrial aldehyde dehydrogenase type 2 (ALDH2) alleviates ischemic heart damage and reperfusion arrhythmias via aldehyde detoxification. Because excessive norepinephrine release in the heart is a pivotal arrhythmogenic mechanism, we hypothesized that neuronal ALDH2 activation might diminish ischemic norepinephrine release. Incubation of cardiac sympathetic nerve endings with acetaldehyde, at concentrations achieved in myocardial ischemia, caused a concentration-dependent increase in norepinephrine release. A major increase in norepinephrine release also occurred when sympathetic nerve endings were incubated in hypoxic conditions. ALDH2 activation substantially reduced acetaldehyde- and hypoxia-induced norepinephrine release, an action prevented by inhibition of ALDH2 or protein kinase Cε (PKCε). Selective activation of G(i/o)-coupled adenosine A(1), A(3), or histamine H(3) receptors markedly inhibited both acetaldehyde- and hypoxia-induced norepinephrine release. These effects were also abolished by PKCε and/or ALDH2 inhibition. Moreover, A(1)-, A(3)-, or H(3)-receptor activation increased ALDH2 activity in a sympathetic neuron model (differentiated PC12 cells stably transfected with H(3) receptors). This action was prevented by the inhibition of PKCε and ALDH2. Our findings suggest the existence in sympathetic neurons of a protective pathway initiated by A(1)-, A(3)-, and H(3)-receptor activation by adenosine and histamine released in close proximity of these terminals. This pathway comprises the sequential activation of PKCε and ALDH2, culminating in aldehyde detoxification and inhibition of hypoxic norepinephrine release. Thus, pharmacological activation of PKCε and ALDH2 in cardiac sympathetic nerves may have significant protective effects by alleviating norepinephrine-induced life-threatening arrhythmias that characterize myocardial ischemia/reperfusion.

Aldehyde dehydrogenase activation prevents reperfusion arrhythmias by inhibiting local renin release from cardiac mast cells.

BACKGROUND: Renin released by ischemia/reperfusion from cardiac mast cells activates a local renin-angiotensin system (RAS). This exacerbates norepinephrine release and reperfusion arrhythmias (ventricular tachycardia and fibrillation), making RAS a new therapeutic target in myocardial ischemia. METHODS AND RESULTS: We investigated whether ischemic preconditioning (IPC) prevents cardiac RAS activation in guinea pig hearts ex vivo. When ischemia/reperfusion (20 minutes of ischemia/30 minutes of reperfusion) was preceded by IPC (two 5-minute ischemia/reperfusion cycles), renin and norepinephrine release and ventricular tachycardia and fibrillation duration were markedly decreased, a cardioprotective anti-RAS effect. Activation and blockade of adenosine A(2b)/A(3) receptors and activation and inhibition of protein kinase Cepsilon (PKCepsilon) mimicked and prevented, respectively, the anti-RAS effects of IPC. Moreover, activation of A(2b)/A(3) receptors or activation of PKCepsilon prevented degranulation and renin release elicited by peroxide in cultured mast cells (HMC-1). Activation and inhibition of mitochondrial aldehyde dehydrogenase type-2 (ALDH2) also mimicked and prevented, respectively, the cardioprotective anti-RAS effects of IPC. Furthermore, ALDH2 activation inhibited degranulation and renin release by reactive aldehydes in HMC-1. Notably, PKCepsilon and ALDH2 were both activated by A(2b)/A(3) receptor stimulation in HMC-1, and PKCepsilon inhibition prevented ALDH2 activation. CONCLUSIONS: The results uncover a signaling cascade initiated by A(2b)/A(3) receptors, which triggers PKCepsilon-mediated ALDH2 activation in cardiac mast cells, contributing to IPC-induced cardioprotection by preventing mast cell renin release and the dysfunctional consequences of local RAS activation. Thus, unlike classic IPC in which cardiac myocytes are the main target, cardiac mast cells are the critical site at which the cardioprotective anti-RAS effects of IPC develop.

Hypotensive and hypertensive effects of acetaldehyde on blood pressure in rats.

Intravenous injection of acetaldehyde produced hypotensive actions in pentobarbital-anaesthetised whole rats, but hypertensive actions in pithed rats. The hypotensive effects of acetaldehyde in whole rats were abolished by pre-treatment with yohimbine. In pithed rats, the hypertensive effects of acetaldehyde were significantly attenuated by prazosin and phentolamine, and in rats that had been pre-treated with reserpine. Our results suggest that the hypertensive actions of acetaldehyde in pithed rats are due to the release of catecholamines, which subsequently leads to vasoconstriction. In whole rats the hypotensive actions of acetaldehyde may be due to alpha2-adrenoceptor stimulation in the central nervous or peripheral system.