Naomitsu Okubo

Xenon and nitrous oxide do not depress cardiac function in an isolated rat heart model

PurposeTo examine the inotropic and chronotropic effects of xenon (Xe) and nitrous oxide (N2O) compared with nitrogen (N2) on isolated rat hearts. The differences between Xe and N2O were also compared.MethodsThe effects of Xe, N2O and N2 on coronary perfusion pressure (CPP), heart rate, left ventricular developed pressure (LVDP) and double product (DP) were examined in isolated rat hearts perfused at constant flow ( 10 mL·min−1). Following stabilization and baseline measurement with 95% O2 (plus 5% CO2), the heart was exposed to buffer equilibrated with one of three test gases; 50% N2with 45% O2 (Group N2:n=9), 50% Xe with 45% O2 (Group Xe:n = 9), or 50% N2O with 45% O2 (Group N2O:n=9) for 30 min. Measurements were performed in the last minute of exposure to the test gases.ResultsGas exposure in all three groups decreased O2 delivery (- 50%), CPP (−11%), LVDP (−30%) and DP (−44%) compared with baseline values (P < 0.001). However, there were no differences among the groups.ConclusionOur data suggest that cardiac contractility was decreased by the effects of reduced O2 delivery, but both Xe and N2O did not cause further cardiac depressant effects compared to N2 in this experimental model.RésuméObjectifVérifier les effets inotropiques et chronotropiques du xénon (Xe) et du protoxyde d’azote (N2O) comparés à ceux de l’azote (N2) sur des cæurs de rats isolés. Comparer aussi les différences entre le Xe et le N2O.MéthodeLes effets du Xe, de N2O et de N2 sur la pression de perfusion coronarienne (PPC), la fréquence cardiaque (FC) la pression développée dans le ventricule gauche (PDVG) et le double produit (DP) ont été vérifiés dans des cæurs de rat isolés perfusés à débit constant (10 mL·min−1). Après la stabilisation et les mesures de base avec de l’O2 à 95% (plus du CO2 à 5%), le cæur a été exposé à un tampon équilibré avec l’un des trois gaz expérimentaux; N2 à 50% avec O2 à 45% (Groupe N2 : n = 9), Xeà 50% avec O2 à 45% (Groupe Xe:n = 9) ou N2O à 50% avec O2 à 45% (Groupe N2O : n = 9) pendant 30 min. Les mesures ont été faites pendant la derniére minute de l’exposition aux gaz testés.RésultatsDans les trois groupes, l’exposition aux gaz a réduit l’apport d’O2 (−50%), la PPC (−11%), la PDVG (−30%) et le DP (−44 %) par rapport aux mesures initiales (P < 0,001). II n’y a cependant pas eu de différence intergroupe.ConclusionNos données laissent croire que la contractilité cardiaque a été abaissée par les effets d’un apport réduit d’O2, mais que ni le Xe ni le N2O comparés au N2 n’ont causé de dépression cardiaque supplémentaire chez ce modèle expérimental.

Efficacy of Whole Bowel Irrigation Using Solutions with or without Adsorbent in the Removal of Paraquat in Dogs

1 The efficacy of whole bowel irrigation with a solution containing either polyethylene glycol (PEG) with electrolyte or an adsorbent (Kayexalate™) with a cathartic (sorbitol) was investigated in 18 dogs who had been given 250 mg kg -1 paraquat dichloride via a jejunal tube to eliminate the influence of gastric absorption. 2 Plasma paraquat concentrations 2 and 3 h after the initiation of bowel irrigation and at the end of the study (5 h later) were significantly lower in the bowel irrigation groups than in the control (no bowel irrigation) group. 3 The total body clearances of paraquat in the bowel irrigation groups were significantly greater than in the control group. 4 There were no significant differences between the two different irrigation solution groups in plasma paraquat concentration, the area under the plasma concentration time curve and the total body clearance. 5 In the PEG with electrolyte group, about 70% of the administered dose of paraquat was removed by means of bowel irrigation (n=4). 6 The adjunction of the adsorbent had no beneficial effects. 7 Haemodynamic changes associated with whole bowel irrigation were unremarkable except that right atrial and pulmonary arterial pressures were elevated in the latter part of the study.

Milrinone Versus Glucagon: Comparative Hemodynamic Effects in Canine Propranolol Poisoning

Glucagon has been reported to be one of the most effective treatments for severe beta-blocker poisoning. Recently, amrinone was suggested as an alternative therapeutic choice for beta-blocker poisoning. Milrinone, a derivative of amrinone, acts independently of beta-adrenoceptors and increases cyclic AMP. Therefore milrinone may also be effective in the treatment of beta-blocker poisoning. In the present study, we compared the effect of glucagon and milrinone in treating severe beta-blocker poisoning. Following the administration of 10 mg/kg propranolol i.v. over 10 min, heart rate, cardiac output, mean arterial pressure, stroke volume, and end tidal CO2 were depressed, while central venous pressure, and pulmonary capillary wedge pressure increased significantly (p < 0.05). Following the administration of saline (Group S, N = 3), glucagon 20 micrograms/kg (Group G, N = 5), and milrinone 300 micrograms/kg (Group M, N = 5), hemodynamic parameters were observed for 30 min. In group M, mean arterial pressure, cardiac output and stroke volume recovered to their baseline values, while central venous pressure and pulmonary capillary wedge pressure decreased. Although there were no significant differences between groups G and M, the heart rate, central venous pressure and pulmonary capillary wedge pressure, mean arterial pressure and stroke volume did not return to baseline values in group G. Milrinone administration produced a significant hemodynamic improvement without increasing the heart rate in the canine model of severe heart failure caused by propranolol. In the glucagon treatment group, central venous pressure and pulmonary capillary wedge pressure improved less than the milrinone group. Although more data are needed before a clinical recommendation, milrinone might be an effective drug to treat beta-blocker poisoning.

Combined Use of Glucagon and Milrinone May Not Be Preferable for Severe Propranolol Poisoning in the Canine Model

In a previous study of propranolol poisoning, glucagon and milrinone significantly increased cardiac output, but the improvement caused by glucagon was almost entirely due to the chronotropic effect. This study investigates the combined effect of glucagon, in a dose not inducing tachycardia, and milrinone on beta-blocker poisoning. Following the administration of 10 mg/kg propranolol IV over ten minutes, dogs (N = 20) were divided into four treatment groups, group S (saline), group G (glucagon 2.5 micrograms/kg), group M (milrinone 100 micrograms/kg), and group G + M (glucagon 2.5 micrograms/kg plus milrinone 100 micrograms/kg). Hemodynamic parameters were observed over the next thirty minutes. Heart rate, cardiac output, and mean arterial pressure were decreased in all groups after the administration of propranolol. Heart rate, mean arterial pressure, cardiac output, and stroke volume recovered to the baseline values in group G + M. However, heart rate in group G + M showed a significant increase versus the other three groups. In a canine model of severe propranolol poisoning, the combined effect of glucagon 2.5 micrograms/kg and milrinone 100 micrograms/kg brought about a significant hemodynamic improvement, but it was accompanied by an excessive increase of heart rate. Combined therapy of milrinone and glucagon may not be preferable therapy in beta-blocker poisoning in the canine model.

Arteriovenous differences in PCO2 and cardiac output during CPR in the dog

Using 14 mongrel dogs, we investigated the correlation between arteriovenous differences of PCO2 (AVD-CO2) and cardiac output (CO) during CPR. Ventricular fibrillation was induced by an electrical current and the respirator was stopped for 5 min. Cardiopulmonary resuscitation (CPR) was performed during the next 10 min and CO was measured with simultaneous arterial and venous blood gas analysis. CO was measured 26 times during CPR. The animals were divided into two groups according to the values of CO during CPR: low-CO group (CO < 0.3 l/min) and high-CO group (CO > or = 0.3 l/min). AVD-CO2 in the low CO group was 39.8 +/- 5.7 mmHg and that of the high group was 27.4 +/- 14.8 mmHg (mean +/- S.D., P < 0.05). In conclusion, AVD-CO2 showed an inverse result with the degree of CO during CPR.

End-tidal CO2 and plasma lactate level: a comparison of their use as parameters for evaluating successful CPR.

Serial changes of end-tidal CO2 (ETCO2) and plasma lactate levels during CPR have been described as useful to investigate or evaluate the results of CPR. However, there have been no reports comparing these parameters in the same model. By inducing cardiopulmonary arrest (2-7 min) in 28 Wistar rats, ETCO2 and serum lactate levels were studied after and just before CPR, respectively. In the survived group (N = 16), ETCO2 was maintained in high levels (20.1-16.3 mmHg), however in the non-survived group (N = 12), ETCO2 showed an abrupt decline (6.0-2.0 mmHg). The lactate levels before CPR in two groups were significantly higher than those of control levels, however there was no significant difference just before the CPR between the two groups. ETCO2 during CPR is a useful indicator for determining the successful application of CPR. However, serum lactate levels sampled just before the onset of CPR did not prove to be a useful indicator of successful CPR in rats.

Arteriovenous differences of blood alcohol concentrations after celiac plexus block

After a celiac plexus block with ethyl alcohol, patients sometimes complain of symptoms of alcohol intoxication. We studied the consecutive changes of arterial and venous blood alcohol concentrations in 11 patients and investigated whether an arteriovenous difference exists. We performed a celiac plexus block with 10 ml absolute ethyl alcohol. The sampling sites were radial artery and internal jugular vein. Blood samples were collected at 0, 5, 10, 15, 30, 60, 120, 240 and 480 minutes after the block. The maximum level was reached 15 minutes after injection in both arterial and venous blood, 29.9 ± 19.4 and 27.7 ± 21.8 mg/dl (means ± SD), respectively. Arteriovenous differences were observed 5 and 10 minutes after ethyl alcohol injection (p < 0.01). There was a significant negative correlation between the ratio of arteriovenous differences to venous sampling and the time elapsed after the block (r = 0.41, p < 0.01).

Plasma lidocaine, monoethylglycinexylidide, and glycinexylidide concentrations after epidural administration in geriatric patients.

Background and Objectives: The purpose of this study was to evaluate the effect of age on the pharmacokinetics of lidocaine after epidural administration. Methods: Two percent lidocaine with epinephrine (5 μg/mL) was administered in two different age groups: an adult group (age 42 ± 6 years, n = 10) and an elderly group (age 77 ± 4 years, n = 10). Concentrations of lidocaine and its active metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), were measured in plasma samples obtained after 15, 30, 45, 60, 90, 120, 150, and 180 minutes of administration using high‐performance liquid chromatography with ultraviolet detection. Results: No significant differences in plasma concentrations of lidocaine and its metabolites were observed between the two groups during the 3 hours of study. However, the elderly group showed significantly longer mean residence times (MRTs) and lower plasma clearance of lidocaine during the period compared with the adult group (P < .05). Plasma concentration ratios of MEGX/lidocaine were significantly lower in the elderly group after 2 hours of lidocaine administration (P < .05). Conclusions: The increase in plasma lidocaine concentration after epidural anesthesia in elderly patients was not as high as anticipated. However, the elderly patients showed longer MRTs, lower clearance, and lower ratios of MEGX/lidocaine than did the adult (middle‐age) patients.

Spinal anesthesia attenuates myocardial ischemia during coronary artery spasm induced by intraaortic methacholine in rats.

Coronary artery spasm is not rare in patients with coronary artery disease, but the influence of regional anesthesia on spasm‐induced myocardial ischemia is not known. We investigated the effects of spinal anesthesia on myocardial ischemia during coronary artery spasm in rats, and compared these with the effects of an alpha‐ and beta‐adrenergic antagonist, and an alpha‐adrenergic agonist.

Age-related decrease in toe-thumb temperature difference with lumbar epidural anaesthesia

With lumbar epidural anaesthesia, big toe skin temperature increases and is associated with a compensatory decrease of thumb temperature. The purpose of the present study was to examine whether thumb-big toe temperature differences were affected by age. Following the attachment of temperature probes at the digital pad of the right big toe and the right thumb, lumbar epidural anaesthesia at L2/3 was performed in 54 patients with 10 ml lidocaine 1.5%. Big toe and thumb skin temperatures were measured continuously and recorded every minute. Fifteen minutes after epidural injection, the toe temperature increased 6.3 ± 2.1° C (ΔF) from the control value, 29.4 ± 2.2° C, and the thumb temperature decreased −1.5 ± 1.0 ° C (ΔH) from the control value, 31.6 ± 2.8° C. Regression coefficient between ΔT15 (toe-thumb skin temperature 15 min after epidural injection) and age was: Y= −0.7X + 8.95 (r = 0.35, P < 0.01; Y = ΔT15, X = age). The ratio of ΔH to ΔF and age was expressed as: Y = 0.51X − 46.57 (r = 0.41, P < 0.01: Y = ΔH/ΔF, X = age). It is concluded that, in lumbar epidural anaesthesia, the decrease of the thumb skin temperature is reduced with aging.RésuméPendant l’anesthésie épidurale lombaire, le température du gros orteil augmente et est associée avec une baisse compensatoire de la température du pouce. Cette étude vise à évaluer si les différences de température orteil-pouce sont affectées par l’âge. Après la mise en place de la sonde de température sur la pulpe du gros orteil et du pouce droits, une épidurale lombaire à L2/3 est réalisé chez 54 patients avec 10 ml de lidocaïne 1,5%. Les températures cutanées du gros orteil et du pouce sont mesurée en continu et enregistrées à la minute. Quinze minutes après l’injection épidurale, la température du gros orteil augmente de 6,3 ± 2,1° C (ΔF) comparativement aux valeurs de contrôle, 29,4 ± 2,2° C, et la température du pouce diminue de −1,5 ± 1,0° C (ΔH) comparativement aux valeurs de contrôle, 31,6 ± 2,8° C. Le coefficient de régression entre ΔT15 (la température cutanée orteil-pouce 15 min après l’injection épidurale) et l’âge est: Y = −0,07X + 8,95 (r = 0,35, P < 0,01: Y = ΔT15, X = âge). La relation de ΔH à ΔF avec l’âge s’exprime ainsi: Y = 0,51X − 46,57 (r = 0,41, P < 0,01: Y = ΔH/ΔF, X = âge). On conclut que sous anesthésie épidurale que la baisse de la température cutanée du pouce diminue avec l’âge.