Biomedical subjects

F Ichinose

Publications and source records attributed to F Ichinose.

27 records · Page 2Linked to original sources

PubMed1998

Pulmonary vasodilation by nitric oxide gas and prodrug aerosols in acute pulmonary hypertension.

Sodium 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA/NO; Et2N-[N(O)NO]Na) is a compound that spontaneously generates nitric oxide (NO). Because of its short half-life (2.1 min), we hypothesized that inhaling DEA/NO aerosol would selectively dilate the pulmonary circulation without decreasing systemic arterial pressure. We compared the pulmonary selectivity of this new NO donor with two other reference drugs: inhaled NO and inhaled sodium nitroprusside (SNP). In seven awake sheep with pulmonary hypertension induced by the infusion of U-46619, we compared the hemodynamic effects of DEA/NO with those of incremental doses of inhaled NO gas. In seven additional awake sheep, we examined the hemodynamic effects of incremental doses of inhaled nitroprusside (i.e., SNP). Inhaled NO gas selectively dilated the pulmonary vasculature. Inhaled DEA/NO produced nonselective vasodilation; both systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were reduced. Inhaled SNP selectively dilated the pulmonary circulation at low concentrations (< or = 10(-2)M), inducing a decrease of PVR of up to 42% without any significant decrease of SVR(-5%), but nonselectively dilated the systemic circulation at larger doses (> 10(-2)M). In conclusion, despite its short half-life, DEA/NO is not a selective pulmonary vasodilator compared with inhaled NO. Inhaled SNP appears to be selective to the pulmonary circulation at low doses but not at higher levels.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1997

Echocardiographic evaluation of global left ventricular function during high thoracic epidural anesthesia.

OBJECTIVES: To assess the effects of high thoracic epidural anesthesia on left ventricular (LV) diastolic filling and systolic function in patients without heart disease. DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: 24 ASA physical status I and II patients scheduled for elective noncardiac surgery. INTERVENTIONS: Patients received high thoracic (HTE; n = 12) or low thoracic (LTE; n = 12) epidural anesthesia. MEASUREMENT AND MAIN RESULTS: Left ventricular diastolic filling was noninvasively determined by precordial echocardiography using a pulsed Doppler technique and with a newly developed acoustic quantification (AQ) method that automatically detects endocardial borders and measures cavity area. All measurements were performed in awake premedicated patients. In the HTE group, the extent of sensory blockade of T1-T5, at the least, was induced with 2% lidocaine 5 ml. During HTE, systolic blood pressure (119 +/- 16 vs. 108 +/- 14 mmHg, p < 0.01), heart rate (73 +/- 9.8 vs. 63 +/- 6.8 beats/min, p < 0.01), cardiac output (CO; 4.5 +/- 1.1 vs. 3.8 +/- 1.2 L/min, p < 0.05), and fractional area change (50 +/- 11 vs. 37 +/- 11%, p < 0.01) decreased significantly, whereas end diastolic area (9.4 +/- 1.4 vs. 10.3 +/- 1.1 cm2, p < 0.01) and end systolic area (4.8 +/- 1.3 vs. 6.0 +/- 1.1 cm2, p < 0.05) showed a significant increase. As a result, stroke volume was kept constant (63 +/- 14 vs. 60 +/- 19 ml). Pulsed Doppler derived indices such as peak velocity during the early filling (E) and the atrial contraction (A) phases, peak early to atrial velocity ratio (E/A), and acceleration time remained unchanged. AQ derived peak dA/dt during the early diastolic (D1) and the atrial contraction phases (D2) and D1/D2 also remained unchanged. In contrast, in the LTE group, no significant differences were noted in all systolic and diastolic indices obtained by pulsed Doppler and AQ method. CONCLUSIONS: High thoracic epidural anesthesia causes a decrease in CO without changing LV ejection and diastolic filling performance in healthy subjects.

Adult↗

PubMed1997

Emergence times from xenon anaesthesia are independent of the duration of anaesthesia.

Xenon (MAC = 71%) has an extremely low blood:gas partition coefficient (0.14). Therefore, we predicted that the rate of emergence from xenon anaesthesia would not be affected greatly by duration of anaesthesia. We studied 54 ASA I-II patients undergoing lower abdominal surgery who received equal MAC anaesthesia with 60% xenon, 60% nitrous oxide with 0.5% isoflurane or 60% nitrous oxide with 0.7% sevoflurane (n = 18 per group), each supplemented with extradural mepivacaine anaesthesia. Duration of anaesthesia was 58-380 min. At the end of operation, all inhalation anaesthetics were discontinued and patients were allowed to wake up while breathing oxygen spontaneously. A blinded investigator recorded the time until patients opened their eyes on command (T1), were judged ready for tracheal extubation (T2), could correctly state their name, date of birth and name of the hospital (T3), and could count backwards from 10 to 1 in less than 15 s (T4). Emergence times after xenon and nitrous oxide-sevoflurane anaesthesia did not correlate with duration of anaesthesia, whereas those from nitrous oxide-isoflurane had positive correlations. Mean emergence times from xenon anaesthesia were: T1, 3.3 (SD 1.0) min; T2, 3.6 (1.0) min; T3, 5.0 (1.1) min; and T4, 6.2 (1.7) min. These values were approximately 50% of those after nitrous oxide-sevoflurane anaesthesia (T1, 5.6 (1.4) min; T4, 10.5 (2.0) min). We conclude that xenon provided fast emergence from anaesthesia, regardless of the duration of anaesthesia.

Adult↗

PubMed1997

Xenon provides faster emergence from anesthesia than does nitrous oxide-sevoflurane or nitrous oxide-isoflurane.

BACKGROUND: Xenon, an inert gas with anesthetic properties (minimum alveolar concentration [MAC] = 71%), has an extremely low blood:gas partition coefficient (0.14). Therefore, we predicted that xenon would provide more rapid emergence from anesthesia than does N2O+isoflurane or N2O+sevoflurane of equivalent MAC. METHODS: Thirty American Society of Anesthsiologists class I or II patients undergoing total abdominal hysterectomy were randomly assigned to receive 60% xenon, 60% N2O + 0.5% isoflurane, or 60% N2O + 0.70% sevoflurane (all concentrations are end-tidal: n = 10 per group). After placement of an epidural catheter, anesthesia was induced with standardized doses of midazolam, thiopental, and fentanyl. Thirty minutes later, xenon, N2O+isoflurane, or N2O+sevoflurane was started as previously assigned. These regimens were supplemented with epidural anesthesia with mepivacaine so that the mean arterial pressure and heart rate were controlled within 20% of the preoperative values. At the end of operation lasting approximately 2 h, all inhalational anesthetics were discontinued, and the patients were allowed to awaken while breathing spontaneously on an 8 l/min inflow of oxygen. A blinded investigator recorded the time until the patient opened her eyes on command (T1), was judged ready for extubation (T2), could correctly state her name, her date of birth, and the name of the hospital (T3), and could count backward from 10 to 1 in less than 15 s (T4). RESULTS: Emergence times from xenon anesthesia were: T1, 3.4 +/- 0.9 min; T2, 3.6 +/- 1 min; T3, 5.2 +/- 1.4 min; and T4, 6.0 +/- 1.6 min (mean +/- SD). These were one half to one third of those from N2O+sevoflurane (T1, 6.0 +/- 1.7 min; T4, 10.5 +/- 2.5 min) or N2O+isoflurane (T1, 7.0 +/- 1.9 min; T4, 14.3 +/- 2.8 min) anesthesia. The three groups did not differ in terms of patient demographics, the duration of anesthesia, the amount of epidural mepivacaine administered, or the postoperative pain rating. No patient could recalls intraoperative events. CONCLUSIONS: Emergence from xenon anesthesia is two or three times faster than that from equal-MAC N2O+isoflurane or N2O+sevoflurane anesthesia.

Adult↗

PubMed1997

Pulmonary vasoconstriction and hypertension in mice with targeted disruption of the endothelial nitric oxide synthase (NOS 3) gene.

NO, synthesized in endothelial cells by endothelial NO synthase (NOS 3), is believed to be an important endogenous pulmonary vasodilator substance that contributes to the normal low pulmonary vascular resistance. To selectively investigate the role of NOS 3 in the pulmonary circulation, mice with targeted disruption of the NOS 3 gene were studied. Pulmonary hemodynamics were studied by measuring pulmonary artery pressure, left ventricular end-diastolic pressure, and lower thoracic aortic flow by using a novel open-chest technique. Transient partial occlusion of the inferior vena cava was used to assess the pulmonary artery pressure-flow relationship. Tension developed by isolated pulmonary artery segments after acetylcholine stimulation was measured in vitro. The histological appearance of NOS 3-deficient and wild-type murine lungs was compared. NOS 3-deficient mice (n = 27), when compared with wild-type mice (n = 32), had pulmonary hypertension (pulmonary artery pressure, 19.0 +/- 0.8 versus 16.4 +/- 0.6 mm Hg [mean +/- SE]; P < .05) that was due to an increased total pulmonary resistance (62 +/- 6 versus 33 +/- 2 mm Hg.min.g.mL-1; P < .001). In vitro, acetylcholine induced vasodilation in the main pulmonary arteries of wild-type but not NOS 3-deficient mice. The morphology of the lungs of NOS 3-deficient mice did not differ from that of wild-type mice. We conclude that NOS 3 is a key enzyme responsible for providing basal pulmonary NO release. Congenital NOS 3 deficiency produces mild pulmonary hypertension in mice.

Acetylcholine↗

PubMed1996

Effects of nitroglycerin infusion on segmental wall motion abnormalities after anesthetic induction.

OBJECTIVES: To assess the effect of intravenous nitroglycerin (NTG) on segmental wall motion abnormalities (SWMAs) and global ventricular function after anesthetic induction in patients undergoing coronary artery bypass grafting (CABG). DESIGN: Prospective study. SETTING: University hospital. PARTICIPANTS: Twenty patients scheduled for elective CABG. INTERVENTIONS: Patients demonstrating SWMAs in at least two myocardial segments after induction received intravenous NTG at 2 micrograms/kg/min. MEASUREMENT AND MAIN RESULTS: Transesophageal echocardiography (TEE) was performed before and after the NTG infusion for analysis of segmental wall motion abnormalities. Mean arterial pressure (MAP), central venous pressure, and pulmonary capillary wedge pressure decreased significantly after NTG infusion, whereas cardiac index and heart rate remained unchanged. End-diastolic area and end-systolic area decreased, and consequently fractional area change increased significantly. Two of 20 patients (10%) showed electrocardiogram evidence of ischemia after induction. After NTG infusion, 15 of 20 patients (75%) showed an increase in a wall motion score more than two points. In these 15 patients with NTG-responsive wall motion abnormalities, the mean ratio of peak early diastolic filling velocity (E) to peak late diastolic filling velocity (A) increased from 0.89 +/- 0.20 to 1.04 +/- 0.25 (p < 0.01) after NTG infusion despite a decrease in filling pressure. Systolic wall thickening improved in segments with poor preoperative function from a pre-NTG value (mean +/- SD) of -1.0% +/- 7.4% to a post-NTG value of 31.4% +/- 24.9% (p < 0.01). CONCLUSIONS: Intravenous NTG improved postinduction SWMAs in 75% of patients with known coronary artery disease. TEE-guided NTG infusion after induction may provide an optimal baseline echocardiogram for monitoring intraoperative myocardial ischemia by improving the reversible portion of postinduction SWMAs.

Aged↗

PubMed1995

Effects of targeted neuronal nitric oxide synthase gene disruption and nitroG-L-arginine methylester on the threshold for isoflurane anesthesia.

BACKGROUND: Considerable evidence suggests that nitric oxide plays a role in synaptic transmission in the central and peripheral nervous system. Nonselective inhibition of nitric oxide synthase by nitroG-L-arginine methylester (L-NAME) reduces the minimum alveolar concentration of halothane anesthesia. The effects of selective neuronal nitric oxide synthase inhibition on the anesthetic requirements in mice congenitally deficient in neuronal nitric oxide synthase (knockout mice) were examined. METHODS: Isoflurane minimum alveolar concentration and righting reflex ED50 (RRED50) were determined in knockout and wild-type mice. Subsequently, the effects of intraperitoneal L-NAME on minimum alveolar concentration and RRED50 of knockout and wild-type mice were examined. In a separate experiment, the effects of week-long administration of L-NAME were examined in wild-type mice. Isoflurane minimum alveolar concentration and RRED50 were measured on the 8th day and were repeated after an acute intraperitoneal dose of L-NAME. RESULTS: Targeted disruption of the neuronal nitric oxide synthase gene did not modify isoflurane minimum alveolar concentration and RRED50 of knockout mice. Acute intraperitoneal L-NAME decreased the minimum alveolar concentration and RRED50 of wild-type but did not alter those values in knockout mice. The wild-type mice, when given L-NAME for a week, showed a minimum alveolar concentration and RRED50 identical to that of untreated wild-type mice. CONCLUSIONS: Although acute nonselective inhibition of nitric oxide synthase reduces the anesthetic requirements of wild-type mice, a chronic congenital deficiency of neuronal nitric oxide synthase or a week of L-NAME treatment of wild-type mice does not produce a state of greater sensitivity to the effects of isoflurane anesthesia.

Amino Acid Oxidoreductases↗

PubMed1995

Prolonged pulmonary vasodilator action of inhaled nitric oxide by Zaprinast in awake lambs.

Inhaled nitric oxide (NO) has been shown to selectively dilate the pulmonary vasculature. Zaprinast, an inhibitor of guanosine 3',5'-cyclic monophosphate-specific phosphodiesterase, augments smooth muscle relaxation induced by endothelium-dependent vasodilators. The present study was designed to determine whether intravenous administration of Zaprinast potentiates the vasodilating effects or prolongs the duration of action of intermittent NO inhalation. Eight awake lambs with U-46619-induced pulmonary hypertension breathed three concentrations of NO (5, 10, and 20 ppm) in a random order before and during an intravenous Zaprinast infusion (0.1 mg.kg-1.min-1). Inhaled NO decreased pulmonary arterial pressure (PAP) in a dose-dependent fashion, with mean PAP reduction at 5, 10, and 20 ppm NO inhalation of 6 +/- 1, 7 +/- 1, and 9 +/- 1 (SE) mmHg, respectively. Although the Zaprinast infusion did not change the magnitude of mean PAP reduction, it caused a statistically significant reduction of pulmonary vascular resistance and prolonged the duration of action of inhaled NO (half-times of vasodilator response to 5, 10, and 20 ppm NO inhalation: 1.9 +/- 0.1, 2.1 +/- 0.2, and 2.1 +/- 0.2 min, respectively; half-times of NO inhalation with Zaprinast: 9.7 +/- 1.7, 11.5 +/- 2.2, and 12.3 +/- 2.0, respectively). Plasma concentrations as well as the transpulmonary differences of guanosine 3',5'-cyclic monophosphate were increased by the Zaprinast infusion during NO inhalation. A stable level of pulmonary vasodilation was demonstrated in four additional lambs by combining intermittent NO breathing with an intravenous infusion of Zaprinast.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1994

Exhaled nitric oxide as a marker for organic nitrate tolerance.

BACKGROUND: This study was designed to demonstrate the development of biochemical tolerance to organic nitrates by measuring levels of exhaled gaseous nitric oxide (NO) in lambs given intravenous (IV) nitroglycerin or sodium nitroprusside. METHODS AND RESULTS: IV injections of nitroglycerin or sodium nitroprusside produced dose-dependent and sustained increases in the exhaled levels of nitric oxide measured by chemiluminescence in awake lambs with tracheostomies. After a 6-hour IV infusion of 25 micrograms.kg-1.min-1 nitroglycerin, peak exhaled NO levels were significantly reduced (-53.6 +/- 4.9%, mean +/- SEM, P < .001) and systemic hypotensive responses were attenuated (-52.6 +/- 5.9%, P < .001) after an IV challenge of nitroglycerin but not sodium nitroprusside. After a subsequent 12-hour nitroglycerin-free period, there was complete recovery of NO excretion in exhaled breath and a return to baseline of systemic hypotensive changes on administration of IV nitroglycerin boluses. For IV sodium nitroprusside challenges, pulmonary NO excretion and systemic hypotensive responses remained constant throughout the study. Challenges with IV nitroglycerin but not sodium nitroprusside during a 12-hour nitroglycerin-free period resulted in delayed biochemical recovery with various exhaled NO levels and systemic hypotensive responses to challenges with IV nitroglycerin. CONCLUSIONS: Measurements of exhaled NO provide in vivo, noninvasive evidence for the development of biochemical tolerance to nitroglycerin. There was reduced NO release into exhaled gas from the pulmonary vasculature concomitant with evidence of tolerance to nitroglycerin vasodilation in the systemic circulation.

Animals↗