Cardioprotective effect and mechanism of action of landiolol on the ischemic reperfused heart.

PURPOSE: The authors examined the cardioprotective effect of landiolol, an ultra short-acting, highly selective beta1-blocker, and its role in cardiac work, antioxidative effect, and sarcoplasmic reticulum (SR) function in hearts subjected to ischemia-reperfusion. METHODS: Isolated guinea pig hearts were subjected to ischemia-reperfusion by stopping the perfusion for 45 min and reperfusing. Before the ischemia, hearts were treated with landiolol (20, 100, or 500 microM) for 15 min (LAN group). In another set of experiments, before ischemia, hearts were washed out for 15 min after treatment with landiolol (WO group). In other hearts, the tissue concentration of malondialdehyde was measured after reperfusion. We also examined the phosphorylation of phospholamban at Ser(16) and Thr(17)residues to evaluate the SR function. RESULTS: After 90 min of reperfusion, left ventricular pressure (LVP) was restored significantly in the LAN-500 microM group regardless of heart rate. However, the improvement in recovery in LVP disappeared in the WO group. The tissue malondialdehyde levels were decreased in the LAN group compared with those in the control group. In the control group, the phosphorylation of phospholamban at Ser(16) and Thr(17) residues was markedly increased after reperfusion. Landiolol at 500 microM suppressed the increase of phosphorylation at Ser(16) residues. CONCLUSION: The present study demonstrated that landiolol had a lipid peroxidation-reducing effect and suppressed the increase in phospholamban phosphorylation at the Ser(16) residue in hearts subjected to ischemia-reperfusion. These findings indicate that landiolol may have an anti-ischemic effect, via an antioxidant effect and/or via preserving SR function during the ischemic period.

Effects of ulinastatin on pulmonary artery pressure during abdominal aortic aneurysmectomy.

STUDY OBJECTIVE: Abdominal aortic aneurysmectomy (AAAectomy) results in a general ischemia-reperfusion syndrome accompanied by an acute rise in pulmonary artery pressure (PAP). We examined whether ulinastatin, a urinary trypsin inhibitor, prevents ischemia-reperfusion injury and increase in PAP after aortic unclamping (XU) during AAAectomy. DESIGN: Prospective study. SETTING: Public, university-affiliated hospital. PATIENTS: Sixteen patients (11 males and 5 females) scheduled for AAAectomy. INTERVENTIONS AND MEASUREMENTS: The patients received 300000 IU of ulinastatin intravenously before XU (n = 8) or no additional treatment (n = 8) (control). Heart rate, central venous pressure, PAP, pulmonary arterial wedge pressure, arterial pressure, mixed venous oxygen saturation (Sv(O2)), and cardiac output were monitored. Arterial and mixed venous blood samples were analyzed for pH, Pa(CO2), Pa(O2), hemoglobin, and oxygen saturation, and the physiological shunt function (Qs/Qt) were calculated. Plasma concentrations of malondialdehyde, myeloperoxidase, granulocyte elastase, alpha1-antitrypsine, and thromboxane B2 and the stable hydrolysis products of thromboxane A2 were measured. Measurements were conducted before aortic crossclamping (XC) (baseline) and at 10, 30, and 60 minutes after XU. MAIN RESULTS: A significant increase in PAP was observed 10 minutes after XU in the control group but not in the ulinastatin group. At 60 minutes after XU, Qs/Qt values had increased in the control group but had decreased in the ulinastatin group. There were no significant changes in malondialdehyde, thromboxane B2, granulocyte elastase, and alpha1-antitrypsine levels after XU in either group. A significant decrease in the plasma level of myeloperoxidase after XU was found in both groups. CONCLUSIONS: The present study demonstrated that ulinastatin prevents increase in PAP and shunting after XU during AAAectomy.

[In vitro evaluation of lubrication properties of a suction catheter].

BACKGROUND: Lubrication is an important factor for passage of a suction catheter through a tracheal tube. This study was carried out to evaluate the effects of lubricants on resistance against removal of a suction catheter from a tracheal tube in an experimental setting. METHODS: A tracheal tube (I.D. of 7.5mm) was inserted into a mannequin, and the resistance against removal of a suction catheter from the tube was measured. RESULTS: Lubrication was improved by using a lubricant (lidocaine jelly or KY jelly), but there was no difference between the effects of the two lubricants. The use of water as lubricant markedly decreased lubrication. Differences in lubrication depending on the type of tracheal tube used, probably due to differences in coating, were also found. CONCLUSIONS: The use of water as a lubricant is not recommended for tracheal suction.

A comparison of the failure times of pulse oximeters during blood pressure cuff-induced hypoperfusion in volunteers.

Important information may not be obtained if the pulse oximetry signal is lost during inflation of a cuff for blood pressure measurement, particularly in patients with hemodynamic instability. In the present study, we compared the failure times of pulse oximeters during cuff-induced hypoperfusion in volunteers. A pulse oximeter sensor was attached to the index finger, and a blood pressure cuff was attached to the same arm of each volunteer. MasimoSET Radical (Masimo), Nellcor N-395 (N-395), Nellcor N-20PA, and Nellcor D-25 were tested. To evaluate the failure time of each pulse oximeter, time to peak of cuff pressure, time to loss of signal, time to recovery of signal, and failure interval were measured. All measurements were performed three times for each pulse oximeter and were averaged. There were no differences in hemodynamic measurements among the groups. Time to loss of signal was longer in Masimo than the other pulse oximeters. Masimo and N-395 showed significantly shorter times to recovery of signal than those of the other two pulse oximeters. Failure interval was in the order of Masimo << N-395 < Nellcor D-25 = Nellcor N-20PA. Masimo did not lose a signal as rapidly as the other oximeters studied. Masimo was similar in performance to the N-395 at providing useful data sooner than conventional technology after a loss of the signal. These observations suggest that data will be more available with fewer false-positive alarms when using the Masimo oximeter followed by the N-395 when compared with conventional oximeters.

Differential pressor response to intravenous ephedrine during recovery from deliberate hypotension.

STUDY OBJECTIVE: To determine whether nitroglycerin or trimethaphan alters pressor response to intravenous (i.v.) ephedrine. DESIGN: Prospective, randomized study. SETTING: Operating room of a university hospital. PATIENTS: 60 ASA physical status I female patients scheduled for mastectomy. INTERVENTIONS: Patients were assigned to one of six groups (n = 10 in each). Group 1: nitroglycerin + normal saline (NS) i.v., Group 2: nitroglycerin + ephedrine 0.1 mg/kg i.v., Group 3: nitroglycerin + ephedrine 0.15 mg/kg i.v., Group 4: trimethaphan + NS i.v., Group 5: trimethaphan + ephedrine 0.1 mg/kg i.v., and Group 6: trimethaphan + ephedrine 0.15 mg/kg i.v. MEASUREMENTS: Hemodynamic responses to ephedrine following withdrawal of vasodilators were observed for 15 minutes. MAIN RESULTS: Ephedrine increased heart rate and mean blood pressure. After ephedrine 0.1 mg/kg i.v., the maximum pressor response in the trimethaphan group was approximately twofold that of the nitroglycerin group (p = 0.038). CONCLUSIONS: Ephedrine restored BP more easily in those patients who had received trimethaphan compared with those who had received nitroglycerin for deliberate hypotension.

Landiolol, esmolol and propranolol protect from ischemia/reperfusion injury in isolated guinea pig hearts.

PURPOSE: Beta blockers are thought to exert beneficial effects on the ischemic heart. The authors examined the effects of landiolol (ONO 1101), a highly selective beta1 antagonist, propranolol, a nonspecific beta blocker, and esmolol, a selective beta1 antagonist, on postischemic contractile recovery. Drugs were given prophylactically. METHODS: Ischemia-reperfusion in isolated guinea pig hearts was induced by stopping the perfusion for 45 min and reperfusing for 60 min. Hearts (n = 7 in each group) were treated with or without propranolol (1 or 10 microM), esmolol (5 or 50 microM), or landiolol (20, 100 or 500 microM) ten minutes before inducing ischemia. RESULTS: At the end of reperfusion, left ventricular pressure (LVP) recovered to 64 +/- 3% of the baseline value in the control group. With 1 and 10 microM propranolol, LVP recovered to 90 +/- 5% and 100 +/- 6% of the baseline value at 60 min after reperfusion, respectively. Fifty microM but not 5 microM of esmolol resulted in restoration of LVP to 97 +/- 17% of the pre-ischemic value at 60 min after reperfusion. In hearts pretreated with 100 and 500 microM landiolol, LVP was restored to 109 +/- 5% and 104 +/- 5% of the baseline value, respectively. Landiolol 100 microM did not depress LVP in the pre-ischemic period. CONCLUSIONS: The present study shows that landiolol, an ultra-short-acting cardioselective beta1 blocker, has cardioprotective effects on ischemia-reperfusion injury in isolated guinea pig hearts. All three beta blockers were equally protective but the intermediate dosage of landiolol preserved LVP during the pre-ischemic period.

Differential effects of propofol and sevoflurane on heart rate variability.

BACKGROUND: Propofol is reported to reduce both sympathetic and parasympathetic tone; however, it is not clear whether the changes in heart rate variability are associated with depth of anesthesia. The purposes of the present study were (1) to evaluate the changes in heart rate variability at different depths of hypnosis and (2) to compare the effects of propofol on heart rate variability with that of sevoflurane. METHODS: Thirty patients were randomly allocated into the propofol or sevoflurane for induction of anesthesia. The depth of hypnosis was monitored by the Bispectral Index (BIS). Spectral analysis of heart rate variability using a maximum-entropy method resulted in a characteristic power spectrum with two main regions, a high frequency (HF) and a low frequency (LF). Hemodynamics, entropy, LF, HF, and LF/HF were monitored when the patients were awake and after induction of anesthesia. RESULTS: Both propofol and sevoflurane decreased blood pressure in a BIS-dependent manner, whereas heart rate showed no significant changes during the study period. In the propofol group, entropy and HF decreased with a reduction in the BIS value. Although LF decreased after induction of anesthesia, propofol caused no further decrease in LF in spite of a reduction in the BIS value. In the sevoflurane group, LF decreased with a reduction in the BIS value. Entropy and HF decreased after induction of anesthesia (BIS at 80); however, no further decreases were observed in spite of a reduction in the BIS value. CONCLUSIONS: Induction of anesthesia with propofol decreased blood pressure, entropy, and HF in a BIS-dependent manner, indicating that propofol reduces cardiac parasympathetic tone depending on the depth of hypnosis. Conversely, sevoflurane did not show the BIS-dependent decreases in heart rate, blood pressure, HF, and entropy, indicating that sevoflurane has little or no effect on cardiac parasympathetic tone.