Takahiro Moriyama

The effect of amino-acid infusion during off-pump coronary arterial bypass surgery on thermogenic and hormonal regulation

PurposeAmino-acid (AA) infusions promote thermogenesis and prevent perioperative hypothermia, but the mechanism of action is unknown. We sought to verify the hypothesis that AA infusions stimulate the release of metabolic hormones during surgery and increase energy expenditure, resulting in thermogenesis.MethodsTwenty-four patients were randomly assigned to receive AA (4 kJ·kg−1·h−1) or saline, which was infused for 2 h during off-pump coronary artery bypass surgery (OPCABS). Arterial adrenaline, thyroid hormone, insulin, and leptin levels were determined at five defined times during surgery. Oxygen consumption was measured 3 h after the start of infusion.ResultsAA infusion maintained the body core temperature during OPCABS. This effect was accompanied by an increase in oxygen consumption, which depended on increased heart rate. AA infusion prominently stimulated the secretion of insulin and leptin; the insulin level increased rapidly within 2 h after the start of infusion, whereas leptin levels increased gradually over a 6-h period after the start of infusion.ConclusionAA infusion significantly increased body core temperature and oxygen consumption during surgery. Given the release of insulin and leptin in response to AA infusion, it is likely that these hormonal signaling pathways may, in part, have contributed to the thermogenic response that occurred during the surgery.

Atrial natriuretic peptide attenuation of renal ischemia–reperfusion injury after major surgery

BACKGROUND Ischemia-reperfusion (I/R) injury is one of the most important pathologic processes causing acute kidney injury. Human atrial natriuretic peptide (hANP) has various effects, including renal protection. The purpose of the present work was to study the effects of intrarenal angiotensin II (Ang II) and investigate the potential of hANP to prevent kidney injury. MATERIALS AND METHODS Male Sprague-Dawley rats were divided into three groups as follows: (1) sham; (2) I/R (30 min of bilateral renal ischemia followed by 6 h reperfusion); and (3) I/R + hANP (I/R injury + continuous intravenous infusion of hANP at 0.025 μg/kg/min). After 6 h of reperfusion, both renal and plasma Ang II concentrations were measured. Urinary angiotensinogen and neutrophil gelatinase-associated lipocalin were measured before ischemia and 2, 4, and 6 h after reperfusion. To evaluate the renal-protective effects of hANP, serum creatinine was determined 6 and 24 h after reperfusion. In addition, mitochondrial oxygen consumption in kidney cortex was measured in the presence of Ang II and hANP. RESULTS Renal Ang II concentrations were 24.5 ± 3.9 and 14.2 ± 3.4 pg/mg renal weight in the I/R and I/R + hANP groups, respectively. Urinary angiotensinogen and neutrophil gelatinase-associated lipocalin excretions were elevated after I/R injury. Treatment with hANP significantly attenuated this effect after 4 and 6 h. Oxygen consumption in renal mitochondria increased with the addition of Ang II, which was also attenuated by hANP. CONCLUSIONS Production of intrarenal Ang II was attenuated by hANP, indicating a potential to diminish renal I/R injury.

Relationship between Redox Behavior of Brain Cytochrome Oxidase and Neurological Prognosis

Currently, no on-line method of assessing cerebral oxygenation is sufficiently accurate to be clinically helpful. In an attempt to find a good predictor of postoperative cerebral outcome, we retrospectively studied the relationship between the redox behavior of cytochrome oxidase (cyt. ox.) during an operation and the neurological prognosis in 83 patients who underwent thoracic aortic surgery. Our data revealed three patterns of change in the redox behavior of cyt. ox. during the operation; the actual pattern exhibited by a given patient showed a highly significant correlation with the neurological prognosis (p < 0.0001). We conclude that the redox behavior of cyt. ox. during an operation is likely to be a good predictor of postoperative cerebral outcome, which implies that brain tissue oxygen sufficiency can be evaluated by near-infrared measurement of cytochrome oxidase (except for that in local regions far from the monitoring site).

Effects of a Novel Benzodiazepine Derivative, JM-1232(-), on Human Gastroepiploic Artery In Vitro

OBJECTIVE To investigate the effects of JM-1232(-) on norepinephrine (10(-6) mol/L)- and high K(+) (40 mmol/L)-induced contractions in isolated human gastroepiploic arteries (GEA), and to compare them with the effects of midazolam and propofol. In addition, to investigate whether the benzodiazepine-receptor antagonist, flumazenil, or μ-opioid-receptor antagonist, naloxone, influenced the vascular effects of JM-1232(-). DESIGN An in vitro experimental study. SETTING University laboratory. PARTICIPANTS GEA segments were used from 69 patients undergoing coronary artery bypass graft surgery. MEASUREMENTS AND MAIN RESULTS JM-1232(-) produced dose-dependent relaxation effects in the rings. Although these effects of JM-1232(-) were greater than those of midazolam and propofol at high concentrations (10(-5)-10(-4) mol/L), there were no significantly different relaxation effects at the clinical concentrations of 3 × 10(-6) mol/L JM-1232(-), 3 × 10(-6) mol/L midazolam, and 1 × 10(-5) mol/L propofol. In addition, all these effects were independent of the presence of a functional endothelium. Vasorelaxation induced by JM-1232(-) on norepinephrine-preconstricted GEA was inhibited by flumazenil, but not by naloxone. CONCLUSIONS These results indicate that JM-1232(-) dose-dependently relaxes smooth muscle in human GEA, this effect being independent of the endothelium. Within the ranges of plasma concentrations achieved in clinical practice, JM-1232(-) had similar vasorelaxation effects to midazolam and propofol. JM-1232(-)-induced vasorelaxation was inhibited by flumazenil, indicating that JM-1232(-)-induced vasorelaxation occurred via peripheral benzodiazepine receptor activation in the GEA.

Re-evaluation of the reliability of cytochrome oxidase--signal study of cardiopulmonary bypass.

The monitoring of brain oxygen status using near-infrared spectroscopy (NIRS) has recently been applied to clinical practice in the field of cardiovascular surgery. Published studies have indicated that NIRS could be used as a continuous and noninvasive way of observing changes in the cerebral oxygenation state during hypoxia and ischemia, since changes occur in optical properties under these conditions. However, the interpretation of NIRS data, especially the cytochrome oxidase (cyt. ox.) signal, remains controversial. A possible source of error that might interfere with the accurate measurement of the redox state of cyt. ox. derives from an overlapping of the absorption spectra for hemoglobin and cyt. ox. in the near-infrared region, with the absorption coefficient for hemoglobin being an order of magnitude greater than that for cyt. ox.. Recently, it was reported that the cyt. ox. signal measured by near-infrared spectroscopy (NIRS) is highly contaminated with the hemoglobin signal [1]. However, the cyt. ox. signal measured by NIRS would be expected to be strongly dependent on the algorithm employed. We have developed a new approach to the measurement of the redox state of cyt. ox. in the brain involving the use of a new algorithm [2], which has already been employed in clinical medicine [3, 4]. Therefore, in this paper we looked for evidence of cross-talk between the cytochrome and hemoglobin (Hb) signals when our new algorithm was used under cardiopulmonary bypass (CPB) in a dog model. Furthermore, we retrospectively studied the relationship between data obtained concerning the redox behavior of cyt. ox. during surgery (again using our new algorithm) and neurological prognosis in 105 patients.

Effects of L-Carnitine on Propofol-Induced Inhibition of Free Fatty Acid Metabolism in Fasted Rats and in Vitro

Background: Propofol inhibits fatty acid oxidation and induces mitochondrial deficiency, a possible mechanism involved in propofol infusion syndrome. This study investigated how propofol influences fatty acid, glucose, and amino acid metabolism, as well as whether L-carnitine may improve suppression of free fatty acid metabolism. Methods: Male Sprague-Dawley rats, fasted for 16 hours, were allocated to the following two groups: (Group P; continuous intravenous administration of 10 mg/kg/h propofol; n = 8) and (Group P + C; intravenous administration of 50 mg/kg and then 50 mg/kg/h L-carnitine continuously; n = 8). Concentrations of glucose, free fatty acid (FFA), amino acids, in-sulin, and β-hydroxybutyric acid were measured at the start and then one, two, and three hours after propofol administration. Intrahepatic triglyceride levels were measured at the end of experiments. In vitro experiments comprised measurement of oxygen consumption in human hepatocytes (Hepg2) and investigating dependency on palmitic acid, glucose, and glutamine as fuel during propofol administration, with or without L-carnitine. Results: FFA increased in Group P and gradually decreased in Group P + C. There were significant differences between the two groups (Group P; 331.2 ± 64.5 μM vs. Group P + C; 199 ± 73.6 μM). Glucose decreased in both groups (Group P; 53.8 ±16.6 mg/dL vs. Group P + C; 88 ± 11.3 mg/dL). Amino acid concentrations were higher in Group P + C after experiments; alanine and glutamine increased significantly. β-hydroxybutyric acid increased significantly in Group P + C, and intrahepatic triglyceride decreased in Group P + C. Dependency on fatty acid metabolism significantly decreased with propofol only; addition of L-carnitine prevented these effects. Conclusions: Propofol impaired mitochondrial fatty acid metabolism, which was compensated mainly by a switch to glucose metabolism and partially by amino acid metabolism. Addition of L-carnitine may improve this imbalance of energy metabolism.