Effects of olprinone on hepatosplanchnic circulation and mitochondrial oxidation in a porcine model of endotoxemia

Purpose This study was performed in order to assess the effects of olprinone, a phosphodiesterase III inhibitor, on hepatic oxygen delivery (DO₂H), oxygen consumption (VO₂H), and mitochondrial oxidation in the liver of a porcine endotoxemia model. Methods Fourteen pigs received continuous infusion of endotoxin via the portal vein for 240 min. From t = 150 to t = 240 min, animals were randomly divided into two groups to receive saline (control [CONT]; n = 7), or olprinone (OLP; n = 7) via the central vein. Results In the OLP group, prior to olprinone treatment at 150 min, endotoxin induced significant decreases in the cardiac index (CI; from 120 ± 31 to 65 ± 13 ml·kg⁻¹·min⁻¹; P < 0.01) and DO₂H (from 3.58 ± 0.81 to 1.55 ± 0.49 ml·kg⁻¹·min⁻¹; P < 0.01), while VO₂H was maintained. After administration of olprinone (from t = 150 to t = 240 min), CI was unchanged, while DO₂H increased from 1.55 ± 0.49 to 1.93 ± 0.38 ml·kg⁻¹·min⁻¹ (P < 0.01) and VO₂H increased from 0.42 ± 0.28 to 0.69 ± 0.38 ml·kg⁻¹·min⁻¹ (P < 0.01). At t = 240 min, the oxidation level of cytochrome aa3 was significantly higher in the OLP group than in the CONT group (OLP, 66.2 ± 19.3% vs CONT, 26.4 ± 17.3%; P < 0.01). Conclusion Our data for this porcine endotoxemia model suggest that olprinone may have beneficial therapeutic effects in restoring not only systemic and hepatic circulation but also mitochondrial oxidation in the liver.     

Hemodynamic effects of KRN2391 (potassium channel opener) in halothane-anesthetized dogs

The cardiovascular responses to an infusion of KRN2391, a potassium channel opener, was studied in halothane-anesthetized dogs. Intravenous administration of KRN2391 at 1.0 and 5.0 μg·kg⁻¹·min⁻¹ for 60 min produced dose-dependent decreases in mean arterial pressure (MAP) and systemic vascular resistance (SVR) associated with dose-dependent increases in the cardiac index (CI) and stroke volume index (SVI) but was not accompanied by an increase in heart rate (HR). The maximum decrease in MAP during the infusion of KRN2391 at 1.0 and 5.0 μg·kg⁻¹·min⁻¹ was −13±7% (P<0.01) and −37±10% (P<0.01), respectively. The maximum reduction in SVR after 1.0 and 5.0 μg·kg⁻¹·min⁻¹ was −20±11% (P<0.01) and −60±16% (P<0.01), respectively. A KRN2391 infusion of 1.0 and 5.0 μg·kg⁻¹·min⁻¹ increased Cl a maximum of 11±13% (P<0.05) and 65±33% (P<0.01), respectively. KRN2391 1.0 μg·kg⁻¹·min⁻¹ showed a tendency to increase SVI but this change was not significant, KRN2391 5.0 μg·kg⁻¹·min⁻¹, however, produced a significant increase in SVI. The present results demonstrate that the decrease in MAP and the increases in CI and SVI caused by KRN2391 are due to a reduction in the afterload. Therefore, we conclude that these cardiovascular profiles of KRN2391 may be benificial in perioperative uses including the control of systemic blood pressure and the treatment of hypertension during halothane anesthesia in clinical practice.     

Effect of peak inspiratory flow on gas exchange, pulmonary mechanics, and lung histology in rabbits with injured lungs

Purpose The aim of this study was to evaluate, using a rabbit model, the little-known effect of different levels of peak inspiratory flow on acutely injured lungs. Methods Fourteen male rabbits (body weight, 2711 ± 146 g) were anesthetized and their lungs were injured by alveolar overstretch with mechanical ventilation until Pa_O2 was reduced below 300 mmHg. Injured animals were randomly assigned to: the P group—to receive pressure-regulated volume-control ventilation (PRVCV; n = 7); and the V group—to receive volume-control ventilation (VCV; n = 7). Other ventilator settings were: fraction of inspired oxygen (FI_O2), 1.0; tidal volume, 20 ml·kg⁻¹; positive end-expiratory pressure (PEEP) 5 cmH₂O; and respiratory rate, 20 min⁻¹. The animals were thus ventilated for 4 h. Throughout the protocol, ventilatory parameters and blood gas were measured every 30 min. After the protocol, the lung wet-to-dry ratio and histological lung injury score were evaluated in the excised lungs. Results Throughout the protocol, peak inspiratory flow and mean inspiratory flow values in the P group were significantly higher than those in the V group (26.7 ± 5.0 l·min⁻¹ vs 1.2 ± 0.2 l·min⁻¹, and 4.3 ± 0.3 l·min⁻¹ vs 1.1 ± 0.1 l·min⁻¹; P < 0.05). The wet-to-dry ratio in the P group was also significantly higher than that in the V group (7.7 ± 0.9 vs 6.3 ± 0.5; P < 0.05). More animals in the P group than in the V group had end-of-protocol Pa_O2/FI_O2 ratios below 200 mmHg (43% vs 0%; P = 0.06). Conclusion In rabbits with injured lungs, high peak inspiratory flow with high tidal volume (V_T) reduces the Pa_O2/FI_O2 ratio and increases the lung wet-to-dry ratio.     

Effect of low-dose infusion of prostaglandin E1 on vecuronium-induced neuromuscular blockade

The effect of low-dose (20 ng·kg⁻¹·min⁻¹) infusion of prostaglandin E₁ (PGE₁) on vecuronium-induced neuromuscular blockade was studied. The study population consisted of 24 elderly patients (65–75 years old) and 24 younger adult patients (25–56 years old). They were randomly assigned to the control and PGE₁ groups. The steady-state dose requirement (SSDR) of vecuronium was derived from ondemand infusion of the drug which produced a stable twitch height of 20% of its baseline reading, and recovery time after steady-state infusion was defined as the time for recovery from twitch height from 25% to 75%. The patients in the PGE₁ group received an infusion of PGE₁ 20 ng·kg⁻¹·min⁻¹, while those in the control group received an infusion of normal saline. The SSDR (23.2±9.1 and 34.2±5.9 μg·kg⁻¹. hr⁻¹, respectively;P=0.02) was significantly less and the recovery time (35.0±9.5 and 19.9±4.2 min, respectively;P=0.01) was significantly longer in the elderly than in the younger patients. However, low-dose infusion of PGE₁ significantly increased the SSDR (23.2±9.1 to 37.4±3.7 μg· kg⁻¹·hr⁻¹;P=0.01) and shortened the recovery time (35.0±9.5 to 23.5±4.0 min;P=0.02) in elderly patients. We concluded that low-dose infusion of PGE₁ is effective in preventing the prolonged action of vecuronium in elderly patients.     

Temporary Pancreatic Duct Occlusion by Ethibloc: Cause of Microcirculatory Shutdown, Acute Inflammation, and Pancreas Necrosis

Temporary obliteration of the pancreatic duct has been suggested to be beneficial in chronic pancreatitis, segmental pancreatic transplantation, and following Roux-Y pancreaticojejunostomy. Little is known, however, as to whether obliteration of the duct alters exocrine pancreatic physiology. Therefore we studied in male inbred Lewis rats the immediate effects of Ethibloc-induced duct obliteration (Ethibloc: Ethicon, Norderstedt, Germany) on pancreatic microcirculation, inflammation, and tissue injury (n= 8), and compared these effects with those caused by experimental pancreatitis (4% sodium taurocholate; n= 8). Animals receiving an intraductal infusion of saline served as controls (n= 8). Duct occlusion with Ethibloc resulted in a marked decrease (p < 0.05) in capillary red blood cell (RBC) velocity and functional capillary density (FCD) to 88 ± 39 μm/s (baseline 716 ± 40 μm/s) and 72 ± 33 cm⁻¹ (baseline 493 ± 21 cm⁻¹), respectively, which was even more pronounced when compared with that observed in experimental pancreatitis (333 ± 62 μm/s and 195 ± 44 cm⁻¹, respectively). In parallel, the manifestation of tissue damage was found to be more severe after Ethibloc; and chloracetate esterase staining showed a larger number of infiltrating leukocytes [555 ± 86/high power field (HPF) versus pancreatitis: 160 ± 12/HPF; p < 0.05). We conclude that intraductal application of Ethibloc induces significant microcirculatory failure and a marked inflammatory response, which are even more pronounced when compared with the changes observed with experimental pancreatitis. Based on these results and the fact that there is no direct proof for a benefit of temporary duct occlusion by Ethibloc, it is proposed that the procedure be reevaluated for its use in pancreatic surgery.     

Net Fluxes Over Working Thigh of Hormones,Growth Factors and Biomarkers of Bone Metabolism During Short Lasting Dynamic Exercise

The purpose of this study was to evaluate the responses of hormones, growth factors, and biomarkers involved in bone and muscle metabolism during exercise and in recovery. One leg knee-extension exercise and concomitant sampling from the artery and vein were performed. In 12 healthy individuals (6 men and 6 women; age 21–36 years) blood was drawn from the femoral artery and vein at rest, after 10 minutes warm-up, after 15 minutes work at 61% of peak one leg VO₂, and after 5 minutes work at peak one leg VO₂, as well as 5, 30, and 60 minutes in recovery. Blood flow in the femoral vein was measured using the thermodilution technique. Arteriovenous differences were measured over working thigh for growth hormone (GH), insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein 3 (IGF BP3), parathyroid hormone (PTH) and bone biomarkers, i.e., the carboxyterminal propeptide of type I procollagen (PICP), the carboxyterminal cross-linked telopeptide of type I collagen (ICTP), osteocalcin, and bone-specific alkaline phosphatase (b-ALP). There was an uptake of GH (3.1 ± 1.2 mU · min⁻¹, P < 0.001; mean ± SE) over thigh during exercise and a release of IGF-I at the end of exercise (60 ± 36 μg · min⁻¹; P < 0.01). PICP was also released after the maximal exercise (23 ± 12 μg · min⁻¹; P < 0.01) as well as ICTP (0.5 ± 0.3 μg · min⁻¹; P < 0.05) and b-ALP (0.2 ± 0.1 μkat · min⁻¹; P < 0.05). Osteocalcin, IGF BP3, and PTH revealed no clearcut pattern. In the present study, exercise induces endocrine changes which point to anabolic effects on muscle and bone tissue. Received: 12 February 1996 / Accepted: 6 June 1996     

Comparison of heart rate changes after neostigmine-atropine administration during recovery from propofol-N2O and isoflurane-2O anesthesia

Purpose. Propofol augments the reduction of heart rate (HR) in combination with cholinergic agents and attenuates the HR response to atropine. We examined whether propofol anesthesia was associated with an increased incidence and extent of bradycardia after neostigmine-atropine administration compared with the effects of isoflurane anesthesia. Methods. Thirty-six adult patients were randomly assigned to two groups (n = 18 each): the propofol group patients were anesthetized with propofol (5–10 mg·kg⁻¹·h⁻¹)-₂O-fentanyl, and the isoflurane group patients were anesthetized with isoflurane (0.5%–1.0%)-₂O-fentanyl. When surgery was completed, anesthetics were discontinued, and then a mixture of neostigmine 0.05 mg·kg⁻¹ and atropine 0.02 mg·kg⁻¹ was injected intravenously over 20 s. Blood pressure (BP) and HR were measured noninvasively at 1-min intervals for 10 min. Results. At the completion of the surgery, the average infusion rate of propofol was 6.2 ± 1.7 mg·kg⁻¹·h⁻¹, and the average inspired concentration of isoflurane was 0.73 ± 0.15%. Immediately before the neostigmine-atropine injections, HR and mean BP were similar in the two groups. The maximum increase in HR after the neostigmine-atropine injections was significantly less in the propofol group than in the isoflurane group (16 ± 9 and 34 ± 6 beats·min⁻¹, respectively, P < 0.01). The subsequent maximum decrease in HR was greater in the propofol group than in the isoflurane group (−9 ± 4 and −5 ± 4 beats·min⁻¹, respectively; P < 0.01). The incidence of bradycardia (HR < 50 beats·min⁻¹) after neostigmine-atropine injection was greater in the propofol group than in the isoflurane group (61% and 28%, respectively; P < 0.01). Conclusion. We conclude that propofol anesthesia attenuates the initial increases in HR, enhances the subsequent decreases in HR, and increases the incidence of bradycardia after neostigmine-atropine injections compared with the effects of isoflurane anesthesia. Received: May 21, 2001 / Accepted: August 29, 2001     

Effects of iso- and hypervolemic hemodilution on regional cerebral blood flow and oxygen delivery for patients with vasospasm after aneurysmal subarachnoid hemorrhage

Summary. Summary.   Background: Arterial vasospasm after subarachnoid hemorrhage may cause cerebral ischemia. Treatment with hemodilution, reducing blood viscosity, and hypervolemia, increasing cardiac performance and distending the vasospastic artery, are clinically established methods to improve blood flow through the vasospastic arterial bed.   Method: Eight patients with transcranial Doppler verified vasospasm after subarachnoid hemorrhage were investigated with global (two-dimensional ¹³³Xenon) and regional (three-dimensional ^{99 m}Tc-HMPAO) cerebral blood flow (CBF) measurements, before and after 1/iso- and 2/hypervolemic hemodilution. Hematocrit was reduced to 0.28 from 0.36. Hypervolemia was achieved by increasing blood volume by 1100 ml.   Findings: Isovolemic hemodilution increased global cerebral blood flow from 52.25±10.12 to 58.56±11.73 ml * 100 g⁻¹ * min⁻¹ (p<0.05), but after hypervolemic hemodilution CBF returned to 51.38±11.34 ml * 100 g⁻¹ * min⁻¹. Global cerebral delivery rate of oxygen (CDRO₂) decreased from 7.94±1.92 to 6.98±1.66 ml * 100 g⁻¹ * min⁻¹ (p<0.001) during isovolemic hemodilution and remained reduced, 6.77±1.60 ml * 100 g⁻¹ * min⁻¹ (p<0.001), after the hypervolemic hemodilution. As a test of the hemodilution effect on regional CDRO₂ an ischemic threshold was defined as the maximal amount of oxygen transported by a CBF of 10 ml * 100 g⁻¹ * min⁻¹ at a Hb 140 g/l which corresponds to a CDRO₂ of 1.83 ml * 100 g⁻¹ * min⁻¹. The brain volume with a CDRO₂ exceeding the ichemic threshold was 1300±236 ml before intervention. After isovolemic hemodilution the non-ischemic brain volume was reduced to 1206±341 (p<0,003). After hypervolemic hemodilution the non-ischemic brain volume remained reduced at 1228±347 ml (p<0.05).   Interpretation: The present study of controlled isovolemic hemodilution demonstrated increased global CBF, but there was a pronounced reduction in oxygen delivery capacity. Both CBF and CDRO₂ remained decreased during further hypervolemic hemodilution. We conclude that hemodilution to hematocrit 0.28 is not beneficial for patients with cerebral vasospasm after SAH. Published online July 18, 2002     

Normalization of Insulin Sensitivity in the Obese Patient after Stable Weight Reduction with Bilio-Pancreatic Diversion

Insulin resistance is a common feature in obese patients. To evaluate the modifications in insulin sensitivity after a bariatric operation such as Bilio-pancreatic diversion (BPD), three groups of subjects (14 normal controls (N); seven eX-obese patients (X) with at least 2 years at weight-stable conditions after BPD surgery; and eight morbidly obese patients (O)) were studied with intravenous (IVGTT) and oral (OGTT) glucose tolerance tests. The ratio of the area under the curve (AUC) for glucose over that of insulin was used as a measure of insulin sensitivity. All the following tests were conducted as Bonferroni-corrected pairwise t-tests, in case overall ANOVA was significant. No significant difference was found between N and X subjects, while obese patients showed a reduced AUCg/AUCi ratio with respect to the normal controls (O vs N: 0.01164 ± 0.00039 vs 0.02392 ± 0.0039, p < 0.05). IVGTT, AUCs: significant differences were found in each case: N vs X: 0.0591 ± 0.0075 vs 0.1402 ± 0.0399, p < 0.05; N vs O: 0.0591 ± 0.0075 vs 0.0223 ± 0.0031, p < 0.01; X vs O: 0.1402 ± 0.0399 vs 0.0223 ± 0.0031, p < 0.05. IVGTT-derived data were also analyzed using the minimal model of glucose kinetics; with this method, glucose effectiveness was significantly different between normal subject and obese subjects (0.0248 ± 0.00288 vs 0.00905 ± 0.00135 per min, p < 0.001). The insulin sensitivity index was not significantly different between normal and ex-obese subjects, while both of these groups were significantly different from obese patients (N vs O: 12.04 × 10⁻⁵ ± 2.61 × 10⁻⁵ vs 3.29 × 10⁻⁵ ± 0.61 × 10⁻⁵, p < 0.066; X vs O: 16.42 × 10⁻⁵ ± 4.23 × 10⁻⁵ vs 3.29 × 10⁻⁵ ± 0.61 × 10⁻⁵ per min per pM, p < 0.02). In conclusion, the present study indicates that, after a body weight reduction operation capable of almost re-establishing ideal body weight like BPD, obese individuals with a family history of obesity show a normalization of insulin response to glucose load.     

Effects of nicardipine-induced hypotension on cerebrovascular carbon dioxide reactivity in patients with diabetes mellitus under sevoflurane anesthesia

Purpose The purpose of this study was to examine the effects of nicardipine-induced hypotension on cerebrovascular CO₂ reactivity in patients with diabetes mellitus under sevoflurane anesthesia. Methods Nineteen diabetic patients, and 11 nondiabetic patients (serving as controls), undergoing elective orthopedic, cardiovascular, or thoracic surgery were included in the study. The diabetic patients were divided into three groups according to the antidiabetic therapy they were receiving, i.e., diet therapy (n = 6), oral antidiabetic drugs (n = 7), and insulin (n = 6). Anesthesia was maintained with 1.0 minimum alveolar concentration of sevoflurane. Absolute and relative cerebrovascular CO₂ reactivity was calculated using a 2.5-MHz pulsed transcranial Doppler (TCD) probe for the continuous measurement of mean blood flow velocity in the middle cerebral artery (Vmca). The cerebrovascular CO₂ reactivity was measured both at baseline and during hypotension by increasing the ventilatory frequency by 4 to 7 breaths·min⁻¹. Nicardipine was used to induce hypotension. Results We found that values for the Bispectral index (BSI), baseline mean blood pressure, endtidal CO₂ (Pet_{CO 2}), and Vmca were essentially identical in all patients, irrespective of the type of antidiabetic treatment being taken. Values for absolute and relative CO₂ reactivity in insulin-dependent patients, at both baseline blood pressure and during hypotension, were lower than those in patients in the antidiabetic drug, diet, and control groups (during hypotension, absolute CO₂ reactivity: diet group: 3.2 ± 0.9; oral antidiabetic drug group: 3.2 ± 0.7; insulin group: 1.5 ± 0.6; control group: 3.4 ± 0.8 cm·s⁻¹·mmHg⁻¹, [P < 0.05 insulin group vs the other groups]; relative CO₂ reactivity: diet group, 6.3 ± 1.0; oral antidiabetic drug group, 6.5 ± 0.8; insulin group, 3.5 ± 0.8; control group, 6.5 ± 0.7%·mmHg⁻¹, [P < 0.05 insulin group vs the other groups]. Conclusion We concluded that cerebrovascular CO₂ reactivity in insulin-dependent patients is impaired during nicardipine-induced hypotension under sevoflurane anesthesia.     

Effect of external high-frequency oscillation on severe cardiogenic pulmonary edema

Effective gas exchange can be maintained in animals without endotracheal intubation using external high-frequency oscillation (EHFO). The aim of this study was to evaluate the effect of EHFO in patients with respiratory failure due to severe cardiogenic pulmonary edema. Seven patients were ventilated with EHFO for 2h at 60 oscillations·min⁻¹, with a cuiras pressure of 36 cmH₂O (−26 to +10) and an inspiratory to expiratory ratio of 1:1, with EHFO. Blood gas values and hemodynamic parameters were measured. Significant increases were noted in cardiac index (2.3±0.5 to 2.5±0.5 l·m⁻²;P<0.05), stroke volume index (24±7 to 28±8 ml·m⁻²;P<0.05), and arterial O₂ pressure (Pao₂) (70±4 to 95±23 mmHg;P<0.01) without a change in pulmonary artery wedge pressure at 1 h after EHFO. The respiratory rate decreased from 28±3 to 22 ±3 breaths·min⁻¹ at 5 min after the termination of EHFO (P <0.01). Arterial CO₂ pressure (Paco₂) did not, however, decrease. Increased stroke volume without a change in pulmonary artery wedge pressure (preload) suggests either improved inotropic function of the left ventricle or reduced left ventricular afterload with EHFO. The use of EHFO may be effective not only for gas exchange but also for left ventricular function in patients with severe cardiogenic pulmonary edema.     

Landiolol has a less potent negative inotropic effect than esmolol in isolated rabbit hearts

Purpose  We compared the negative chronotropic and inotropic effects of landiolol and esmolol, two clinically available short-acting β1-blockers with high β1-selectivity, using whole isolated rabbit heart preparations. Methods  Tachycardia was induced by continuous perfusion of 10⁻⁷ M isoproterenol, and we used concentrations of landiolol or esmolol in ascending steps (1 · 10⁻⁶, 3 · 10⁻⁶, 1 · 10⁻⁵, 3 · 10⁻⁵, and 1 · 10⁻⁴ M). Heart rate (HR), left ventricular developed pressure (LVDP), the maximal rates of left ventricular force development (LVdP/dt_max), and myocardial oxygen consumption (MVO₂) were measured and compared. Results  Both landiolol and esmolol produced dosedependent decreases in HR, LVDP, LVdP/dt_max, and MVO₂. The HR lowering effects of the two agents were comparable. At concentrations of 3 · 10⁻⁵ and 1 · 10⁻⁴ M, esmolol produced more profound depression of LVDP (47 ± 26 and 12 ± 11 mmHg, respectively; mean ± SD) and reduction of LVdP/dt_max (650 ± 287 and 120 ± 103 mmHg·s⁻¹) than landiolol (68 ± 20 and 64 ± 20 mmHg, and 897 ± 236 and 852 ± 240 mmHg·s⁻¹, respectively). At the same concentrations, esmolol caused more profound reduction in MVO₂ (40 ± 11 and 35 ± 10 μl·min⁻¹ · g⁻¹) than landiolol (50 ± 8 and 48 ± 8 μl·min⁻¹ · g⁻¹), respectively. Conclusion  Our results indicate that in the isolated rabbit heart, landiolol and esmolol had equipotent negative chronotropic effects, however, landiolol had a less potent negative inotropic effect than esmolol.     

Intracisternal infusion of magnesium sulfate solution improved reduced cerebral blood flow induced by experimental subarachnoid hemorrhage in the rat

Magnesium has neuroprotective and antivasospastic properties in the presence of subarachnoid hemorrhage (SAH). The present study investigated the effect of intracisternal administration of magnesium on cerebral vasospasm in the experimental SAH rat model. The rat double-SAH model (0.2 mL autologous blood injected twice into the cisterna magna) was used. Normal saline (SAH group, N = 8) or 10 mmol/L magnesium sulfate in normal saline (SAH + MG group, N = 8) was infused into the cisterna magna at 1.5 μL/min for 30 min on day 5. Control rats without SAH also received intracisternal infusion of normal saline (control group, N = 6). Local cerebral blood flow (CBF) at 24 locations and the weighted average were quantitatively measured by the autoradiographic technique using [¹⁴C]iodoantipyrine during infusion. The weighted average CBF was significantly reduced (P < 0.01, Student’s t-test) in the SAH group (0.78 ± 0.16 mL g⁻¹ min⁻¹) compared to the control group (1.0 ± 0.15 mL g⁻¹ min⁻¹) and was significantly improved (P < 0.01, Student’s t-test) in the SAH + MG group (0.98 ± 0.18 mL g⁻¹ min⁻¹). Local CBF was significantly reduced (P < 0.05, unpaired t test) in 16 locations in the SAH group and significantly improved (P < 0.05, unpaired t test) in 12 locations in the SAH + MG group. Intracisternal infusion of magnesium sulfate significantly improved reduced CBF induced by experimental SAH in the rat.     

Evaluation of a new semi-continuous cardiac output system in the intensive care unit

Purpose  A new semi-continuous thermodilution cardiac output (CCO) system has been developed recently (Opti-Q™ and Q-vue™ Abbott critical care system). The aim of this study was to compare the accuracy and reproducibility of this new device with conventional ice-bolus thermodilution cardiac output (BCO). Methods  Fifteen critically ill patients who needed pulmonary artery catheterization were prospectively investigated. Eighty seven paired data using BCO and CCO methods were compared. Reproducibility was assessed from 90 BCO and 87 CCO determinations by calculation of the mean standard error (SEM) and according to Bland and Altman methodology. Results  The BCO and CCO ranged from 2.46 to 11.20 L·min⁻¹ and from 1.75 to 10.05 L·min⁻¹ respectively. Bias (mean difference between BCO and CCO) was null (0.002 L·min⁻¹,P = 0.98), precision (SD of the bias) was 0.74 L·min⁻¹ and the limits of agreement (mean difference ± 1.96 SD) ranged from -1.45 to 1.45 L·min⁻¹. The threshold to consider two cardiac outputs as different (3 × SEM) was equivalent for BCO and CCO (0.54 and 0.465 L·min⁻¹ respectively). According to the Bland and Altman method, reproducibility of CCO was greater than that of BCO: bias of repeated measurements of BCO and CCO were 0.15 L·min⁻¹ (P < 0.05) and 0.047 L·min⁻¹ (NS), respectively. Conclusion  Compared with BCO, this new device was accurate but cannot be considered as interchangeable regarding the limits of agreement. Reproducibility of CCO was superior to BCO.

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Résumé Objectifs  Récemment, un nouveau système de mesure semi-continue du débit cardiaque (CCO) a été commercialisé (Opti-™ and Q-vue Abbott critical care system). Le but de cette étude était d’évaluer les performances de ce nouveau système en comparaison à la thermodilution classique par injection de soluté froid (BCO). Méthodes  Quinze patients de réanimation, pour lesquels l’indication d’un cathétérisme droit était posée, ont été prospectivement évalués. Quatre vingt sept couples de mesures étaient comparés. La reproductibilité était estimée par le calcul de l’erreur standard moyenne (SEM) et selon la méthode de Bland et Altman sur 90 mesures pour le BCO et 87 pour le CCQ. Résultats  Les BCO et CCO s’étendaient respectivement de 2,46 à 11,20 L·min⁻¹ et 1,75 à 10,05 L·min⁻¹. Le biais (différence moyenne entre BCO et CCO) était nul (0,002 L·min⁻¹,P = 0,98), la précision (écart type du biais) était de 0,74 L·min⁻¹ et les limites d’agrément (biais ± 1,96 écart type) s’étendaient de -1,45 à 1,45 L·min⁻¹. Le seuil pour considérer deux débits cardiaques comme différents (3 × SEM) pour BCO et CCO était équivalent (0,54 et 0,465 L·min⁻¹ respectivement). Néanmoins selon la méthode de Bland et Altman, la reproductibilité du CCO était supérieure à celle du BCO: le biais de mesures répétées pour BCO et CCO était respectivement de 0,15 L·min⁻¹ (P < 0,05) et 0,047 L·min⁻¹ (NS). Conclusions  Comparé à la thermodilution classique ce nouveau système de mesure en continu du débit cardiaque est suffisant en pratique clinique mais ne peut être réellement considérer comme interchangeable. La reproductibilité du CCO est supérieure au BCO.

     

Effects of nicardipine and diltiazem on fractal features of short-term heart rate variability—application of coarse graining spectral analysis

Purpose. This study was designed to investigate the effects of nicardipine and diltiazem on the fractal features of short-term heart rate variability (HRV), using coarse graining spectral analysis (CGSA). Methods. Eighteen healthy volunteers participated in this study; they were divided into two groups according to the drug administered. Five-minute electrocardiogram and arterial pressure recordings were made during stepwise infusions of either nicardipine (0.4, 0.8, 1.6, and 3.2 μg·kg⁻¹·min⁻¹) or diltiazem (2, 4, 8, and 16 μg·kg⁻¹·min⁻¹) under rate-controlled breathing at 0.25 Hz. CGSA broke down the total power of the time series into harmonic (low frequency [0.0–0.15 Hz; LF] and high frequency [0.15–0.5 Hz; HF]) and nonharmonic (fractal) components. Cardiac sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) activity indicators were evaluated as the ratios LF/HF and HF/TP (total spectral power), respectively. Fractal components were evaluated as %fractal and the spectral exponent β of 1/f^β. Results. Compared with control measurements, the maximum dose of nicardipine infusion caused a significant decrease in systolic arterial pressure, a significant increase in the mean heart rate, and a significant increase in plasma norepinephrine level, findings that were associated with significant increases in %fractal and β values (54.2 ± 13.3 vs 75.6 ± 9.8, and 0.86 ± 0.22 vs 1.32 ± 0.46, respectively; P < 0.05). PNS and SNS indicators showed decreased and increased values, respectively. Diltiazem caused a reduction in arterial pressure; however, no other parameters, including the nonharmonic components of HRV, were affected by this drug. Conclusions. These findings strongly suggest that nicardipine suppresses vagal cardiac neural outflow and activate the SNS, an action which, subsequently, causes changes in the fractal features of HRV. Although diltiazem reduces arterial pressure, it preserves the basic neural balance of the autonomic nervous system in regard to heart rate control. Received: April 16, 2001 / Accepted: October 9, 2001     

Bone modeling in gallium nitrate-treated rats

Summary Gallium nitrate (GaN) reduces cancer-related hypercalcemia and inhibits bone resorptionin vitro. This study investigated the effects of chronic GaN administration on bone, kidney, and parathyroid gland activity of growing rats. Experimental animals received GaN (1.75 mg elemental gallium i.p. QOD×8, Ga⁺), and controls received the solvent (Ga⁻). In the bone of Ga⁺ rats the number of osteoclasts was increased (Ga⁺: 70.4±2.31 osteoclasts/mm²; Ga⁻: 46.5±1.61 osteoclasts/mm²,P<0.001), and apposition rate and osteoid width were unchanged. Ga was concentrated in bone (2.4 μmol/g cortical bone) and detected by electron microprobe on the surface of a few trabeculae. Alkaline (Alp) and acid (Acp) phosphatase activities were higher in Ga⁺ than in Ga⁻ calvaria (Ga⁺: Alp 223±23.4 U/mg prot, Ga⁻: Alp 145±13.3 U/mg prot,P<0.02; Ga⁺: Acp 69.5±4.7 U/mg prot, Ga⁻: 57.5±2.8 U/mg prot,P<0.05). Serum iPTH was increased (Ga⁺: 112.9±17.6 pg/ml, Ga⁻: 41.4±7.4 pg/ml,P<0.01), serum calcium was reduced (Ga⁺: 2.4±0.02 mmol/l, Ga⁻: 2.6±0.03 mmol/l,P<0.001); calciuria remained comparable to controls. Relative to the hypocalcemia this suggests renal loss of Ca. The calcemic response to hPTH 1-34 (i.v. 50 μ/kg) was decreased 2 hours after injection of the hormone (ΔCa: TPTX Ga⁺: 0.11±0.04 mmol/l, Ga⁻: 0.33 ±0.03 mmol/lP<0.01). In conclusion, Ga, at the dosage used, does not inhibit the activity of osteoblasts in rats and does not interfere with mineralization but increases the number of osteoclasts through stimulation of parathyroid gland activity, induced by a fall in serum calcium. The hypocalcemia seems to be related to skeletal resistance to PTH and to increased renal calcium loss.     

Comparison of renal function under deliberate hypotension during epidural plus light-enflurane anesthesia and during enflurane anesthesia

We compared the effects of deliberate hypotension induced with trimethaphan on renal function and renal tubular damage under combined epidural and light-enflurane anesthesia (epidural group) and enflurane anesthesia alone (enflurane group). The mean arterial blood pressure was maintained at 50–55 mm Hg for 2.5 h in both groups using continuous infusion of trimethaphan. The urine volume and free water clearance were significantly greater in the epidural group than in the enflurane group [1.8±1.8 (SD)vs 0.4±0.3 ml·kg⁻¹·h⁻¹ and 0.81±1.30vs −0.15±0.22 ml·min⁻¹, respectively] (P<0.05). The creatinine clearance and fractional sodium excretion rate did not differ significantly between the two groups. Urinary excretion of norepinephrine was significantly less in the epidural group than in the enflurane group (P<0.05); however, epinephrine excretion did not differ. Urinary excretion ofN-acetyl-β-d-glucosaminidase was significantly less in the epidural group than in the enflurane, group (4.2±2.5vs 12.2±4.6 U·g⁻¹ CR) (P<0.01). The plasma antidiuretic hormone concentration was significantly lower in the epidural group compared to the enflurene group (13±23vs 57±42 pg·ml⁻¹) (P<0.05). No significant difference in plasma atrial natriuretic peptide concentration was found between the groups. We conclude that renal function during trimethaphan-induced hypotension is better maintained under epidural plus light-enflurane anesthesia than under enflurane anesthesia alone.     

Comparison between in vivo and in vitro pharmacokinetics of succinylcholine in humans

Purpose. To compare the in vivo and in vitro pharma-cokinetics of succinylcholine (SCh) in humans. Methods. A bolus of SCh 1 mg·kg⁻¹ (n = 7) or 2 mg·kg⁻¹ (n = 11) was given to 18 patients anesthetized with thiopental. Arterial blood samples for determination of in vivo SCh concentrations were collected every 30 s for 5 min. Another 20-ml blood sample was obtained before induction of anes-thesia for determination of in vitro SCh. Concentrations of SCh were measured by high-performance liquid chromato-graphy. In vivo and in vitro concentrations of SCh vs time data were analyzed by the one-compartment model. Results. The respective in vivo and in vitro pharmacokinetic parameters (SCh 1 mg·kg⁻¹ vs SCh 2 mg·kg⁻¹) were as follows: Plasma clearance was 4.17 ± 2.37 and 1.85 ± 0.28 l·min⁻¹, P < 0.05, vs 2.91 ± 2.01 and 1.27 ± 0.43 l·min⁻¹, P < 0.05. Elimination half-life was 25.4 ± 10.6 and 47.4 ± 5.4 s, P < 0.002 vs 26.3 ± 10.0 and 75.2 ± 21.8 s, P < 0.00005. Conclusion. These results suggest that the rapid disap-pearance of SCh from the circulation is due to diffusion out of the blood vessels rather than to enzymatic hydrolysis. Received for publication on August 31, 1998; accepted on May 11, 1999     

Effect of linear polarized light radiation on impaired mitochondrial oxidative phosphorylation in skeletal muscle

Purpose. The aim of this study was to investigate the effect of linear polarized light radiation (LPLR) on mitochondrial oxidative phosphorylation impaired by hemorrhagic shock or Escherichia coli lipopolysaccharide (LPS) in skeletal muscle. Methods. We studied the effect of LPLR on mitochondrial function of skeletal muscle by using a model of mitochondria impaired by hemorrhage or LPS. The oxygen uptake in states 3 and 4, the respiratory control ratio (RCR), and the adenosine diphosphate-to-oxygen ratio (ADP/O) were measured with a Clark oxygen electrode. Results. Oxygen uptake in states 3 and 4, RCR, and ADP/O were significantly decreased by hemorrhage for 4 h and by LPS treatment for 12 h. Oxygen uptake in states 3 and 4 impaired by hemorrhage increased significantly from 40.1 ± 3.2 to 60.1 ± 5.4 nmol O₂·min⁻¹·mg protein⁻¹ after LPLR, and oxygen uptake in state 4 decreased significantly from 22.8 ± 2.4 to 17.7 ± 1.5 nmol O₂·min⁻¹·mg protein⁻¹ after LPLR. RCR and ADP/O were also significantly increased from 1.8 ± 0.3 and 0.9 ± 0.2 to 3.4 ± 0.3 and 1.5 ± 0.1, respectively, by LPLR. Oxygen uptake in states 3 and 4 impaired by LPS was improved from 46.6 ± 5.1 and 21.0 ± 1.9 to 53.8 ± 6.2 and 17.9 ± 2.3 nmol O₂·min⁻¹·mg protein⁻¹, respectively following LPLR. RCR and ADP/O were also elevated significantly from 2.2 ± 0.2 and 0.9 ± 0.2 to 3.0 ± 0.3 and 1.4 ± 0.2, respectively, after LPLR. Conclusion. LPLR improved mitochondrial oxidative phosphorylation of skeletal muscle impaired by hemorrhagic shock or E. coli LPS. Received: November 4, 1999/Accepted: April 24, 2000     

Continuous measurement of oxygen consumption using the reversed fick method

We developed a continuous oxygen consumption (Vo₂) measurement system employed the reversed Fick method, in which Vo₂ in computed from continuously measured sured arterial and mixed venous oxygen saturation assed by pulse oximetry and mixed venous oximetry, respectively, and cardiac output by the heat deprivation technique. This system was compared with the conventional intermittent reversed fick method in 7 patients during surgery and with indirect calorimetry in 4 intensive care unit (ICU) patients. The Vo₂ measured by the continuous reversed Fick method showed a high correlation with those simultaneously measured by the intermittent Fick method (r=0.97,P<0.01) and by indirect calorimetry (r=0.74,P<0.01). The 95% confidence limits (bias±2 SD) of the continuous reversed Fick method were −0.6±45 ml·min⁻¹ with the intermittent Fick method and −31±56 ml·min⁻¹ with indirect calorimetry. The continuous Fick method is in satisfactory agreement with the conventional methods for the measured of Vo₂ and potentially allows for convenient assessment of Vo₂ in critically ill patients. This study was supported in part by Grants-in-Aid for the Encouragement of Young Scientists 01771185 and 04857171 from the Ministry of Education, Science and Culture of Japan