Purpose: The authors examined whether fasudil, a Rho-kinase inhibitor, administered during reperfusion could protect the heart against myocardial infarction and, if so, whether phosphatidylinositol 3-kinase(PI3K), extracellular signal-regulated kinase(ERK1/2), and nitric oxide synthase(NOS) pathways would be involved in the mechanism. Methods: All rats underwent 30 min of coronary artery occlusion followed by 2 h of reperfusion. Rats received fasudil at the beginning of reperfusion, or at 30 min after reperfusion. In other groups, rats received fasudil after administration of wortmannin, a PI3K inhibitor, PD98059, an ERK1/2 inhibitor, or N(ω)-nitro-L-arginine methyl ester(L-NAME), a nonselective NOS inhibitor. Results: Fasudil at the beginning of reperfusion(22±9%), but not at 30 min(42±12%) after reperfusion reduced infarct size as compared to the control group(42±7%). The beneficial effect of fasudil was blocked by wortmannin(36±9%) or L-NAME(47±6%), but not PD98059(26±8%). Conclusions: Fasudil administered early reperfusion protects the heart against myocardial infarction in anesthetized rats, and that this beneficial effect is mediated through PI3K and NOS, but not ERK1/2 activation.
Tachycardia and hypertension due to surgical and tourniquet pain often occur suddenly during general anesthesia for total knee arthroplasty. We evaluated the dose-related effects of landiolol on an abrupt tachycardic response in this clinical setting, since this agent is able to suppress the cardiovascular responses associated with sympathetic stimulation. After approval by the local ethical committee and informed consent, 114 patients, aged 51-89 yr, undergoing total knee arthroplasty under general anesthesia were enrolled in this study. Following general anesthesia induction with fentanyl 1-2 μg/kg, propofol 1.5-2 mg/kg and 5% sevoflurane, a laryngeal mask airway was inserted, and anesthesia was maintained with 1% sevoflurane, droperidol 5 mg and 50% N2O in oxygen. Thereafter, supplemental fentanyl 0.5-1 μg/kg was injected repeatedly to keep the end-tidal CO2 tension of 30-45 mmHg, and spontaneous respiratory rate of 10-25 breaths/min. When a tachycardic response(defined as heart rate of more than 90 beats/min for more than 3 minutes) was observed, landiolol or normal saline(as a time control group) was randomly infused continuously at a rate of 40 or 80 μg/kg/min, or of 0.24 mL/kg/h, respectively, until the end of surgery or tourniquet deflation. Hemodynamic and respiratory variables were recorded at 1-5 minute intervals. Data were analyzed by analysis of variance or Student's t-test with Bonferroni's correction for comparisons among groups or within each group, with p<0.05 being significant. Tachycardic responses developed in 50 of 114 patients(44%) studied. There were no significant differences in demographic data among patients who received landiolol 40 μg/kg/min(n＝24), landiolol 80 μg/kg/min(n＝20), and saline(n＝6). Heart rate decreased at 1 minute after the start of landiolol infusion and remained below pre-administration values(p<0.05) in patients receiving landiolol 40 and 80 μg/kg/min, while heart rate unchanged in control patients. Mean blood pressure remained unchanged as compared with pre-infusion values in all groups. When compared with the control group, heart rate was lower 5 and 4 minutes after the start of landiolol infusion(p<0.05) in patients given landiolol of 40 and 80 μg/kg/min, respectively. These data show that landiolol infusion at a rate of 80 μg/kg/min provided more rapid suppression of an abrupt tachycardia in patients undergoing total knee arthroplasty under general anesthesia. The prompt treatment of tachycardia by landiolol seems appropriate, particularly for the older patients who are likely to have occult ischemic heart disease.
A 60-year old man developed paraplegia three hours after thoracic endovascular aortic repair under general anesthesia for distal aortic arch aneurysm. This delayed-onset paraplegia was suspected to be due to a steal effect on the spinal small end arteries. The symptom was successfully alleviated by rapid lumbar cerebrospinal fluid drainage.