Group Sev Research Articles

Effects of sevoflurane on inflammatory reaction in rats with vascular cognitive impairment

Objective To investigate the effects of sevoflurane on inflammatory reaction in rats with vascular cognitive impairment. Methods Forty-two adult female Wistar rats, weighting 200-250 g, were randomly divided into 3 groups: sham operation group(group S, n = 6), vascular cognitive impairment group (group VCI, n = 18) and sevoflurane group (group Sev, n = 18). Vaesular cognitive impairment was induced by permanent bilateral occlusion of both common carotid arteries. Group Sev received inhalation of sevnflurane (end-tidal concentration 1.8%) in oxygen 0.5 L/min for 12 h after both common carotid arteries were occluded. Learning ability and memory were assessed using Morris water maze test and shuttle box task 2 d after treatment in group S while 2, 14, 26 d after treatment in group VCI and Sev. The level of IL-1β and TNF-α in serum and brain tissue were determined by ELISA and the expression of IL-1β mRNA and TNF-α mRNA in brain tissue were determined by RT-PCR 2 d after treatment in group S while 12, 24, 36 d after treatment in group VCI and Sev. Results Compared with group S, the latency of study was significantly prolonged, the latency of memory, the number of times of passive avoidance response and active avoidance response were significantly decreased, the level of IL-1β and TNF-α in serum and brain tissue were significantly increased, the expression of IL-1β mRNA and TNF-α mRNA in brain tissue were significantly up-regulated in group VCI and Sev. Compared with group VCI, the latency of study was significantly shortened, the latency of memory, the number of times of passive avoidance response and active avoidance response were significantly increased, the level of IL-1β and TNF-α in serum and brain tissue were significantly decreased, the expression of IL-1β mRNA and TNF-α mRNA in brain tissue were significantly down-regulated in group Sev. Conclusion Sevoflurane can attenuate vascular cognitive impairment in rats by inhibiting inflammatory reaction. Key words: Anesthetics, inhalation; Cognition disorders; Inflammation

Inclusion of Sevoflurane in Cardioplegia Reduces Neutrophil Activity During Cardiopulmonary Bypass

The purpose of this study was to examine the effects of sevoflurane cardioplegia on neutrophil response and complement activation after cardiopulmonary bypass (CPB). A prospective, randomized clinical investigation. University-affiliated hospital; single institutional. Twenty-one male patients undergoing coronary bypass surgery using CPB. Eleven patients were randomly assigned to receive sevoflurane 2% as a part of the cardioplegic mixture (SEV). The control group (n = 10) received no sevoflurane in their cardioplegia (control). Myeloperoxidase activity (MPO) was assayed in coronary sinus blood as a surrogate for neutrophilic response at the termination of CPB. MPO activity in the coronary sinus blood was lower in the patients who received sevoflurane compared with controls. MPO activity was higher in patients with cardiac events at 4-year follow-up when compared with asymptomatic patients. IL-8, C4b, C3d, C5a, and CH50 were assessed in coronary sinus and peripheral blood at time of CPB initiation (T0) and upon the termination of CPB (T2). Peripheral blood sampling occurred at the sixth hour after T0 (T6). IL-8 levels were significantly inhibited in the SEV group when compared with controls at T2 and T6. CH50 (an index of global activation of complement system) decreased 30% at T2 and 52% at T6. The classic component of the complement pathway (C4b) was effectively inhibited in the SEV group, whereas the common pathway (C3d and C5a) was similar in both groups. The addition of sevoflurane to cardioplegia is associated with an inhibition of neutrophils after CPB. A major component of the neutrophil response appears to be IL-8 mediated, although the classic complement pathway is also inhibited by sevoflurane.

Effects of chronic heart failure in rats on the recovery of microvascular PO2 after contractions in muscles of opposing fibre type.

Chronic heart failure (CHF) impairs muscle O2 delivery (QO2) and, at a given O2 uptake (VO2), lowers microvascular O2 pressures (PmvO2: determined by the QO2-to-VO2 ratio), which may impair recovery of high-energy phosphates following exercise. Because CHF preferentially decreases QO2 to slow-twitch muscles, we hypothesized that recovery PmvO2 kinetics would be slowed to a greater extent in soleus (SOL: approximately 84% type I fibres) than in peroneal (PER: approximately 14% type I) muscles of CHF rats. PmvO2 dynamics were determined in SOL and PER muscles of control (CON: n= 6; left ventricular end-diastolic pressure, LVEDP: approximately 3 mmHg), moderate CHF (MOD: n= 7; LVEDP: approximately 11 mmHg) and severe CHF (SEV: n= 4; LVEDP: approximately 25 mmHg) following cessation of electrical stimulation (180 s; 1 Hz). In PER, neither the recovery PmvO2 values nor the mean response time (MRT; a weighted average of the time to 63% of the overall response) were altered by CHF (CON: 66.8 +/- 8.0, MOD: 72.4 +/- 11.8, SEV: 69.1 +/- 9.5 s). In marked contrast, SOL PmvO2, at recovery onset, was reduced significantly in the SEV group ( approximately 6 Torr) and PmvO2 MRT was slowed with increased severity of CHF (CON: 45.1 +/- 5.3, MOD: 63.2 +/- 9.4, SEV: 82.6 +/- 12.3 s; P < 0.05 CON vs. MOD and SEV). These data indicate that CHF slows PmvO2 recovery following contractions and lowers capillary O2 driving pressure in slow-twitch SOL, but not in fast-twitch PER muscle. These results may explain, in part, the slowed recovery kinetics (phosphocreatine and VO2) and pronounced fatigue following muscular work in CHF patients.

Recovery of Microvascular Po2 in Rats with Chronic Heart Failure

0181 Chronic heart failure (CHF) impairs muscle O2 delivery (Qo2) and thus reduces microvascular O2 pressures (Po2m: determined by the Qo2-to-O2 utilization ratio), which may impair the recovery of high-energy phosphates following exercise. PURPOSE: Because CHF preferentially impairs Qo2 to slow-twitch muscles (Musch & Terrell, Am. J. Physiol. 262: H411-419, 1992), we hypothesized that recovery Po2m kinetics would be slowed to a greater extent in soleus (SOL: ∼84% type I fibers) than peroneal (PER: ∼14% type I) muscles of CHF rats. METHODS:Po2m dynamics were determined in SOL and PER muscles of control (CON: n = 6; left ventricular enddiastolic pressure, LVEDP: 3±1 mmHg), moderate CHF (MOD: n = 7; LVEDP: 10±2 mmHg) and severe CHF (SEV: n = 4; LVEDP: 28±4 mmHg) CHF following cessation of electrical stimulation (180s; 1 Hz). RESULTS: In PER, neither the recovery Po2m values nor their recovery kinetics (mean response time, MRT; CON: 66.8±8.0, MOD: 72.4±11.8, SEV: 69.1±9.5s) were altered by CHF. In marked contrast, SOL Po2m was reduced significantly in the SEV group (∼6 Torr) and Po2m recovery kinetics were slowed progressively with increased severity of CHF (MRT, CON: 45.1±5.3, MOD: 63.2±9.4, SEV: 82.6±12.3s; P<0.05 CON vs SEV). CONCLUSION: These data indicate that CHF slows Po2m recovery and thus lowers capillary O2 driving pressure in slow-twitch SOL, but not fast-twitch PER muscle with SEV CHF. These results may explain, in part, the slowed recovery kinetics (phosphocreatine and Vo V2) and fatigue following muscular work in CHF patients. Supported by: NIH HL-50306, HL-67619, AG-19228

Recovery of Microvascular Po2 in Rats with Chronic Heart Failure

0181 Chronic heart failure (CHF) impairs muscle O2 delivery (Qo2) and thus reduces microvascular O2 pressures (Po2m: determined by the Qo2-to-O2 utilization ratio), which may impair the recovery of high-energy phosphates following exercise. PURPOSE: Because CHF preferentially impairs Qo2 to slow-twitch muscles (Musch & Terrell, Am. J. Physiol. 262: H411-419, 1992), we hypothesized that recovery Po2m kinetics would be slowed to a greater extent in soleus (SOL: ∼84% type I fibers) than peroneal (PER: ∼14% type I) muscles of CHF rats. METHODS:Po2m dynamics were determined in SOL and PER muscles of control (CON: n = 6; left ventricular enddiastolic pressure, LVEDP: 3±1 mmHg), moderate CHF (MOD: n = 7; LVEDP: 10±2 mmHg) and severe CHF (SEV: n = 4; LVEDP: 28±4 mmHg) CHF following cessation of electrical stimulation (180s; 1 Hz). RESULTS: In PER, neither the recovery Po2m values nor their recovery kinetics (mean response time, MRT; CON: 66.8±8.0, MOD: 72.4±11.8, SEV: 69.1±9.5s) were altered by CHF. In marked contrast, SOL Po2m was reduced significantly in the SEV group (∼6 Torr) and Po2m recovery kinetics were slowed progressively with increased severity of CHF (MRT, CON: 45.1±5.3, MOD: 63.2±9.4, SEV: 82.6±12.3s; P<0.05 CON vs SEV). CONCLUSION: These data indicate that CHF slows Po2m recovery and thus lowers capillary O2 driving pressure in slow-twitch SOL, but not fast-twitch PER muscle with SEV CHF. These results may explain, in part, the slowed recovery kinetics (phosphocreatine and Vo V2) and fatigue following muscular work in CHF patients. Supported by: NIH HL-50306, HL-67619, AG-19228

Rapid inhalation induction with 7% sevoflurane combined with intravenous midazolam

Study Objective: To identify an improved rapid inhalation induction (RII) technique by investigating hemodynamics and heart rate variability of induction with midazolam and RII with 7% sevoflurane in comparison with RII alone. Design: Prospective, randomized study. Setting: Operating room of a university hospitals. Patients: 40 patients scheduled for gastrectomy without complications. Interventions: In the sevoflurane (Sev) group, anesthesia was induced with tidal volume breathing of 7% sevoflurane with 50% nitrous oxide (N 2 O) in oxygen (O 2 ) for 3 minutes. In the midazolam-sevoflurane group (Mid-Sev) intravenous midazolam 0.1 mg/kg was given, followed by 7% sevoflurane with 50% N 2 O. In both groups, endotracheal intubation was facilitated with vecuronium 0.15 mg/kg, which was administered at loss of consciousness. Measurements: Blood pressure, heart rate, heart rate variability, time to loss of response to verbal command (sleep time), rate of body movement or cough during induction, and patient satisfaction were monitored. Main Results: Blood pressure and heart rate increased significantly in the Sev group but not in the Mid-Sev group. Heart rate was significantly higher in the Sev group at 1 minute after intubation. High-frequency component (cardiac parasympathetic activity) in heart rate variability increased before intubation, with a higher value seen in the Sev group than the Mid-Sev group. The ratio of low-frequency component to high-frequency componnt (cardiac sympathetic activity) did not change in either group. Sleep time did not differ between the two groups. The numbers of patients with body movement and cough, and patients who were not satisfied with the induction method were, respectively, four, three, and eight in the Sev group; and one, zero, and two in the Mid-Sev group. The last value was significantly higher in the Sev group (p = 0.0285). Conclusions: The addition of intravenous midazolam 0.1 mg/kg provides more stable hemodynamics, cardiac autonomic nervous system activity, and patient satisfaction in RII with 7% sevoflurane.

Effects of nicorandil on myocardial function and metabolism in the post-ischaemic reperfused heart with or without inhalation anaesthetics.

Nicorandil, which is an ATP-sensitive K channel opener, has been reported to protect the ischaemic myocardium. However, its interaction with inhalation anaesthetics on the ischaemic myocardium has not been well elucidated. So, we have investigated whether isoflurane or sevoflurane modify the effects of nicorandil on cardiac function and metabolism in the rat heart-lung preparation. Animals were allocated to 4 groups as follows: Control group, no drug; Nic group, nicorandil; Nic+Iso group, nicorandil and isoflurane; Nic+Sev group, nicorandil and sevoflurane. Seven minutes after the start of perfusion, nicorandil was administered and 10 min after the start of perfusion, the heart was rendered globally ischaemic for 10 min, and then the heart was reperfused for 10 min. LVdP/dt max in the Nic group was higher than those in the other groups. Right atrial pressure in the Nic+Iso and Nic+Sev groups was significantly higher than in the Control and Nic groups. Myocardial ATP in the Nic group was higher than in the other groups. DHBA levels in the perfusate in the Nic and Nic+Iso groups were lower than those in the Control and Nic+Sev groups, but those in the Nic+Sev group were higher than those in the other groups. Nicorandil improved post-ischaemic cardiac function and preserved high-energy phosphates. However, these beneficial effects of nicorandil were abolished by the combination with isoflurane or sevoflurane. In addition, sevoflurane increased hydroxyl radical formation in the post-ischaemic reperfused heart.