Miwako Shihara

In-hospital and one-year outcomes for patients undergoing percutaneous coronary intervention for acute myocardial infarction

Previous studies have identified risk factors for short- and long-term outcomes for patients undergoing percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). However, it remains unknown whether they can be generalized to current PCI practice for a broader cohort of patients. We analyzed the follow-up information (mortality and revascularization procedures) obtained from a nationwide Japanese registry during 1997 of a total of 2,211 patients with AMI who underwent PCI at 143 facilities. Demographic, clinical, angiographic, and procedural variables were submitted to statistical analysis to detect the risk factors of adverse outcomes. In-hospital and 1-year mortality rates were 7.1% and 10.9%, respectively. The most important risk factor for in-hospital death was attempted PCI of the left main (LM) coronary artery. Further independent risk factors for death were left ventricular (LV) dysfunction (ejection fraction </=40%), LM disease, older age, multivessel disease, cerebrovascular disease, and diabetes. The receiver-operating characteristics curve for the predicted probability of death was 0.88, indicating a good ability to discriminate high-risk patients. Independent risk factors for 1-year postdischarge mortality were LV dysfunction, older age, renal failure, multivessel disease, and diabetes. The incidence of the need for repeat PCI or bypass surgery was significantly higher in patients with multivessel and LM disease. PCI is a valuable treatment strategy for a broad spectrum of patients with AMI. However, the mortality for patients with LM disease and poor LV function is still high even using current practice standards.

Role of Endogenous Nitric Oxide in the Brain Stem on the Rapid AdaptatKion of Baroreflex

It has been shown that nitric oxide in the brain stem plays an important role in the control of sympathetic nerve activity. We examined the role of endogenous nitric oxide in the brain stem in the rapid central adaptation of baroreflex control of sympathetic nerve activity in anesthetized rabbits. Bilateral carotid sinuses were isolated, and a stepwise increase in pressure of 25 or 50 mm Hg for 50 to 60 seconds was applied to the carotid sinuses while the arterial pressure and renal sympathetic nerve activity were recorded. The renal sympathetic nerve activity was inhibited by the stepwise increase in carotid sinus pressure, but thereafter it gradually returned toward the baseline level despite the fact that carotid sinus pressure was kept constant. This procedure was performed after intracisternal injection of N(omega)-nitro-L-arginine methyl ester (L-NAME, 8 micromol), N(omega)-nitro-D-arginine methyl ester (D-NAME, 8 micromol), L-arginine (40 micromol), or the vehicle solution. The magnitude of the immediate and maximal inhibition of renal sympathetic nerve activity caused by a stepwise increase in carotid sinus pressure was similar between the vehicle and L-NAME treatment, but the rate of recovery of the renal sympathetic nerve activity after immediate inhibition was faster after L-NAME than after vehicle. L-Arginine reversed the effects of L-NAME. However, D-NAME or L-arginine alone had no such effects on the rate of recovery of the nerve activity. These results thus suggest that endogenous nitric oxide in the brain stem attenuates rapid adaptation of the arterial baroreflex control of the sympathetic nerve activity in rabbits.

Endothelin-1 increases the neuronal activity and augments the responses to glutamate in the NTS

The aims of this study were to determine 1) whether endothelin (ET)-1 affects the neuronal activity of the NTS neurons, 2) whether specific ET receptor antagonists affect the neuronal activity of the NTS neurons, and 3) whether ET-1 or ET receptor antagonists modulate the responses of the nucleus of the solitary tract (NTS) neurons to l-glutamate (Glu). The single-unit discharge was extracellularly recorded with a fine electrode from medulla brain slice preparations of rats. ET-1 and Glu were iontophoretically applied to the recorded neuron. Both ET-1 and Glu increased the neuronal activity. The ETA receptor antagonist BQ-123 attenuated the basal neuronal activity. ET-1 augmented the magnitude of the increases in the neuronal activity evoked by Glu, and these responses were antagonized by BQ-123. These studies suggest the following conclusions: 1) ET-1 increases the neuronal activity of the NTS neurons via ETA receptors, 2) endogenous ET plays a controlling role of the neuronal activity of NTS neurons, and 3) ET-1 augments the responses evoked by Glu, believed to be the neurotransmitter from the solitary tract, via ETA receptors. These results suggest that ET-1 facilitates synaptic transmission in the NTS.

Cholinergic systems in the nucleus of the solitary tract of rats

The pharmacological and physiological properties of excitatory amino acid and ACh systems in the nucleus of the solitary tract (NTS) were studied in slices of rat brain stem by extracellular and intracellular recordings from neurons activated by solitary tract (ST) stimulation. These neurons were characterized as having several long dendrites with multiple varicosities. Synaptic activation of the medial NTS (mNTS) neurons by ST stimulation was mediated by non- N-methyl-d-aspartate (NMDA) glutamate (Glu) receptors, because the excitation was blocked by 6-cyano-7-nitro-quinoxaline-2,3-dione but not by NMDA, nicotinic, or muscarinic antagonists. Identified mNTS neurons were excited by iontophoresis of both Glu and ACh. The most sensitive region of the cell was on the dendrites ∼100 μm from the cell body for both putative neurotransmitters. Nicotinic and/or muscarinic excitatory ACh responses were detected on the mNTS neurons. Our observations suggest that both types of ACh receptors may contribute to the attenuation of the baroreceptor reflex, but the functional correlation of this receptor profile remains to be determined.

Isoproterenol infusion provokes vasovagal response without upright tilt in a patient exhibiting syncopal episodes

SummaryWe report a case of a patient with vasovagal syncope, in whom isoproterenol infusion provoked vasovagal response without upright tilting. We subjected the patient, who had had two previous syncopal and several presyncopal episodes, to upright tilting with isoproterenol infusion. Before a control tilt was performed for 10min (80°), the patient was placed in the supine position for 5 min. The control tilt did not provoke a vasovagal response. With isoproterenol being infused at a dose of 1 µg/min, the sequence of positioning in the supine position for 5min and upright tilting for 10min was repeated. This dose of isoproterenol infusion did not provoke any vasovagal response in the patient, either in the supine or in the upright position. When the dose of isoproterenol infusion was then increased to 2 µg/min, the heart rate increased to 121/min, but then suddenly dropped to 74/min; systemic arterial pressure simultaneously fell from 148/80 to 108/80 mmHg. The patient complained of palpitation and anxiety, and showed profound cold sweating. The drop in the heart rate and the fall in blood pressure occurred when the patient was in the supine position, indicating that, unlike upright tilting with isoproterenol infusion, venous return was not decreased at the beginning of vasovagal response in this setting. This observation suggests that isoproterenol infusion, even without upright tilting, may provoke the vasovagal response in some patients.