Lack of Association of Clinical Factors (SAMe-TT2R2) with CYP2C9/VKORC1 Genotype and Anticoagulation Control Quality / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Advantages of new oral anticoagulations may be greater in atrial fibrillation (AF) patients of poor anticoagulation control with warfarin. The SAMe-TT2R2 scoring system, based on clinical variables, was recently developed to aid in identifying these patients. In this study, we investigated the association of this clinical composite score with genetic factors related warfarin dosing and the quality of anticoagulation control. METHODS: Clinical and genetic data were collected from 380 consecutive Korean patients with AF (CHA2DS2-VASc score, 3.5+/-1.8) who were followed for an average of 4 years. We evaluated factors associated with time in therapeutic range (TTR, INR 2-3), including the CYP2C9 and VKORC1 genotypes and the SAMe-TT2R2 score (Sex female, Age two co-morbidities], Treatment [interacting drugs, e.g., amiodarone], Tobacco use within 2 years [doubled], and Race non-white [doubled]). RESULTS: The average SAMe-TT2R2 score was 3.4+/-0.9, range 2-7; and 153 patients (40.2%) had SAMe-TT2R2 scores > or =4. Time in specific INR ranges varied depending on the VKORC1 genotype but not with the CYP2C9 genotype or the SAMe-TT2R2 score. TTR was higher in patients with the VKORC1 1173C>T than in VKORC1 TT (61.7+/-16% vs. 56.7+/-17.4%, P=0.031). Multivariate testing showed that VKORC1 genotype but not the SAMe-TT2R2 score was significantly associated with labile INRs. There was no correlation between the SAMe-TT2R2 scores and pharmacogenetic data. CONCLUSIONS: A genetic factor, but none of the common clinical and demographic factors, as combined in the SAMe-TT2R2 score, was associated with the quality of anticoagulation control in Korean patients with AF.

A Case of Vertebral Osteomyelitis With Epidural Abscess Caused by Mycobacterium intracellulare in a Rheumatoid Arthritis Patient

Mycobacterium avium complex (MAC) is the most common pathogen in nontuberculous mycobacterial lung diseases, but vertebral osteomyelitis caused by MAC is rare. We experienced a case of vertebral osteomyelitis with epidural abscess in a rheumatoid arthritis patient who received immunosuppressive agents. Initial assessment was tuberculous vertebral osteomyelitis, and then treated with antituberculous drugs. Fifty-six days later, Mycobacterium intracellulare was identified from abscess culture and drugs were altered to clarithromycin, rifabutin, and ethambutol. After 3 months of M. intracellulare treatment, the radiological findings showed increases of epidural abscess. According to the suseptibility, the patient received intravenous amikacin for four weeks, and then, oral ciprofloxacin in addition to clarithromycin, rifabutin, and ethambutol. The patient is being treated with the medication for 13 months and currently showing slow improvements.

A Case of Thyroid Papillary Carcinoma With Pulmonary Tumor Embolism

The tumor embolism is defined as tumor cells within the vascular system such as pulmonary artery that is not contiguous with the other metastatic foci. The incidence of tumor embolism varies widely ranging from 3% to 26% among several studies; whereas lung cancer, prostate cancer, colorectal cancer, breast cancer, pancreas cancer are associated with high risks for tumor embolism. However thyroid cancer is rarely associated with tumor embolism. Among the rare cases, tumor embolism was reported as being mostly of follicular carcinoma or undifferentiated carcinoma, but few of papillary carcinoma. We report an unusual presentation that pulmonary tumor embolism from thyroid papillary carcinoma was diagnosed with positron emission tomography/computed tomography (CT) and chest CT.

Hypothyroidism With Acute Renal Failure and Heart Failure

Here we report a 65-year-old male patient initially presented with dyspnea and chest discomfort. This patient was finally diagnosed with severe hypothyroidism accompanied by heart failure, pericardial effusion and acute renal failure. We suspected that heart failure, pericardial effusion and acute kidney injury were induced by severe hypothyroidism. Thus, we began thyroid hormone replacement therapy. After the therapy, the patient's dyspnea and chest discomfort were improved. Hypothyroidism has many complications, such as myxedema, dyslipidemia, and depression. In contrast, heart failure, pericardial effusion, and acute kidney injury are very rare complications of hypothyroidism. Only a few cases of heart failure or renal failure combined with hypothyroidism have been reported. Our case suggests that severe hypothyroidism can lead to multiorgan failure, such as heart failure as well as renal failure. Moreover, congestive heart failure induced by severe hypothyroidism can be reversed by thyroid hormone replacement therapy.

Polyuria with the Concurrent manifestation of Central Diabetes Insipidus (CDI) & Type 2 Diabetes Mellitus (DM)

We report a rare case of the concurrent manifestation of central diabetes insipidus (CDI) and type 2 diabetes mellitus (DM). A 56 year-old man was diagnosed as a type 2 DM on the basis of hyperglycemia with polyuria and polydipsia at a local clinic two months ago and started an oral hypoglycemic medication, but resulted in no symptomatic improvement at all. Upon admission to the university hospital, the patient's initial fasting blood sugar level was 140 mg/dL, and he showed polydipsic and polyuric conditions more than 8 L urine/day. Despite the hyperglycemia controlled with metformin and diet, his symptoms persisted. Further investigations including water deprivation test confirmed the coexisting CDI of unknown origin, and the patient's symptoms including an intense thirst were markedly improved by desmopressin nasal spray (10 microg/day). The possibility of a common origin of CDI and type 2 DM is raised in a review of the few relevant adult cases in the literature.

A Case of Adenocarcinoma of the Transverse Colon with Humoral Hypercalcemia of Malignancy

Hypercalcemia is a common electrolyte imbalance in patients with malignancy. Approximately 80% of hypercalcemia is associated with humoral hypercalcemia of malignancy (HHM), but occurs rarely in colorectal carcinomas. A 72-year-old man was admitted with abdominal pain and bowel habit change. Colonoscopy showed a malignant tumor in the transverse colon. Laboratory data showed an elevated serum calcium level (11.6 mg/dL) and elevated parathyroid hormone-related peptide level (12.2 pmol/L). Histology showed poorly differentiated adenocarcinoma. We infused intravenous normal saline, furosemide and pamidronate. The serum calcium level was subsequently normalized. However, the patient died from cancer progression 10 days later. With a review of the relevant literature, we report a case of adenocarcinoma of the transverse colon with HHM.

A Case of Bilateral Thalamic Glioma Presenting with Personality Change

No abstract available.

Relationship between Satisfaction of Volunteering and Meaning in Life of the Elderly: based on Hospital Voluntary Activity

No abstract available.

Effects of Oxygen Free Radical on Action Potential in Mouse Atrial Myocardium

BACKGROUND AND OBJECTIVES: Reactive oxygen species are known to be produced when atrial fibrillation develops. This study was performed to investigate the effects of hydrogen peroxide (H2O2) on the action potential parameters of the mouse atrium. SUBJECTS AND METHODS: Mouse (ICR) atrial fibers were excised and immersed in cold bicarbonate-containing Tyrode's solution. The preparations were then perfused with oxygenated (95% O2, 5% CO2) Tyrode's solution and driven by an electrical stimuli 1 ms in duration at a frequency of 1 Hz. The transmembrane potentials were recorded at 0, 2.5, 5, 10, 20 and 30 minute, and compared between groups I (control), II (H2O2 0.1 mM), III (H2O2 0.5 mM) and IV (H2O2 1 mM). RESULTS: In group I, the maximal diastolic potential (MDP), action potential amplitude (APA), maximal slope at phase 0 depolarization (Vmax), action potential duration until 50% and 90% of repolarization (APD50, APD90) were unchanged with increasing time. In group II, the MDP and APA were unchanged, but the Vmax was decreased, and the APD50 and APD90 prolonged. In group III, the MDP was increased and the Vmax decreased; the APD50 and APD90 were prolonged, but the APA unchanged. In group IV, the MDP was increased, the Vmax and APA decreased And the APD50 and APD90 prolonged. After-depolarization was observed in 40% (8/20) and 54.5% (12/22) of groups III and IV, respectively, and asystole occurred in 18.2% (4/22) of group IV. CONCLUSION: Hydrogen peroxide changed the action potential parameters in both time and dose dependent manner, and also elicited after-depolarization at higher concentrations. These results suggest reactive oxygen species are involved in the electrical remodeling and arrhythmogenesis in atrial myocardium.

A Case of Isolated Iridoplegia in Herpes Zoster Ophthalmicus

No abstract available.

Influence of Vasoactive Substances on the Regulation of Cardiac ATP-Sensitive Potassium Channel Activity

BACKGROUND AND OBJECTIVES: It has been known that various vasoactive agents are involved in the regulation of cardiac function through the modification of the K+ channel activities, including the ATP-sensitive K+ channel (KATP). We examined the effects of several vasoactive agents on the cardiac KATP currents in isolated cardiac myocytes. MATERIALS AND METHODS: Ventricular myocytes were isolated from the hearts of ICR mice by enzymatic digestion. The channel currents were recorded by the excised inside-out and cell-attached patch clamp configurations. RESULTS: In the excised inside-out patches, bradykinin (BRK; 1-10 micrometer) and prostaglandin I2 (PGI; 10-50 micrometer) did not affect the channel activities, whereas the vasodilators increased the attenuated channel activities in the presence of 100 micrometer ATP. BRK and PGI in parallel shifted the dose-response curves of ATP (1-1,000 micrometer), and this inhibited the KATP currents to the right. Endothelin (ET-1; 0.1-1 nM) and leukotriene D4 (LTD; 3-10 micrometer) decreased the channel activities immediately after making the inside-out patches. However, the vasoconstrictors did not affect the attenuated channel activities by ATP. In the cell-attached patches, both BRK and PGI increased the channel activities and these effects were markedly attenuated by glibenclamide (50 micrometer). ET-1 and LTD did not affect the baseline channel activities in the cell-attached patches, but they markedly attenuated the dinitrophenol-induced activities. CONCLUSION: It was inferred that certain vasoactive substances are involved in the regulation of cardiac KATP channel activities, and that bradykinin and PGI2 enhance the channel activities, and ET-1 and LTD4 inhibit the channel activities.

Effects of Phenylephrine on the Excitability of Medial Vestibular Nuclear Neurons in Rats

Coeruleo-vestibular pathway which connects locus coeruleus and vestibular nuclei is noradrenergic. This study was designed to elucidate the effects of phenylephrine on the spontaneous activity of acutely isolated medial vestibular nuclear neurons of rat by whole-cell patch-clamp technique. Sprague-Dawley rats, aged 14 to 16 days, were used. After enzymatic digestion, dissociated medial vestibular neurons were transferred to a recording chamber mounted on an inverted microscope, and spontaneous action potentials were recorded by standard patch-clamp techniques. In current-clamp mode, the frequency of spontaneous action potential of medial vestibular nuclear neurons was decreased by phenylephrine (n=15). Phenylephrine increased the amplitude of afterhyperpolarization without changes in the resting membrane potential and spike width. In voltage-clamp mode, the whole potassium currents of the medial vestibular nuclear neurons were increased by phenylephrine (n=12). These experimental results suggest that alpha-receptor mediates the inhibitory effects on the neuronal activity of the medial vestibular nuclear neuron.

Excitatory Effects of 5-Hydroxytryptamine on the Resting Activity of Medial Vestibular Nuclear Neurons in the Rat / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: This study was aimed to investigate the effects of 5-Hydroxytryptamine (5-HT) on the spontaneous activity of medial vestibular nuclear neurons of the rat. MATERIALS AND METHOD: Sprague-Dawley rats aged 14 to 16 days were anesthetized with ether and decapitated. After enzymatic digestion, the brainstem portion of medial vestibular nuclear neuron was obtained by micropunching. The dissociated neurons were transferred into a recording chamber mounted on an inverted microscope and spontaneous action potentials were recorded by standard patch-clamp techniques. RESULTS: The response of medial vestibular nuclear neurons to 5-HT applied in the recording chamber was not uniform. The spontaneous action potentials were increased in 10 cells, decreased in 3 cells and not altered in 2 of 15 cells. The spike width of the neurons was not affected by 5-HT. The spike frequency and resting membrane potential of these cells were increased by 5-HT. The depth of afterhyperpolarization was decreased by 5-HT. CONCLUSION: These results suggest 5-HT increases spontaneous firing of the medial vestibular nuclear neurons by altering the afterhyperpolarization.

Effects of Oxygen Free Radicals on KATP Channel Activity in Mouse Cardiac Myocytes

BACKGROUND AND OBJECTIVE: Oxygen-derived free radicals (OFRs), produced as myocardium is reperfused after ischemic injury, contribute to reversible and irreversible cellular injury. KATP channels, activated by ischemia, have been reported to participate in the arrhythmogenic response to acute myocardial ischemia. Therefore, we examined the effects of OFRs on the regulation of KATP channel activity. MATERIALS AND METHODS: Isolated mice (ICR) hearts were perfused with Tyrode's solution on a Langendorff apparatus. Single ventricular myocytes were isolated using enzymatic digestion with collagenase and protease. Single channel currents in the inside-out patch mode were recorded. OFRs were applied by mixing hypoxanthine and xanthine oxidase. The currents were recorded in the patch membrane at a holding potential of -60 mV. RESULTS: OFRs generated by 0.1 U/mL xanthine oxidase and 0.5 mM hypoxanthine had no effects on the activities of KATP channels before and after treatment with 200 micrometer ATP. OFRs generated with 0.2 U/mL xanthine oxidase and 1.0 mM hypoxanthine reactivated the channel activities which had been attenuated by 100 micrometer ATP. In the presence of 100 U/mL superoxide dismutase and 122 U/mL catalase, which are OFRs scavengers, OFRs did not affect the KATP channels activities. CONCLUSION: OFRs generated by the reaction of hypoxanthine and xanthine oxidase increased the KATP channel activities in the inside-out patch.

Effects of Endothelium-derived Relaxing Factors on the Regulation of ATP-sensitive Potassium Channel Activity in Cardiac Myocytes

BACKGROUND AND OBJECTIVES: Effects of the three major endothelium-derived relaxing factors (EDRFs), namely nitric oxide (NO), prostacyclin (PGI2), and 11, 12-epoxyeicosatrienoic acid (EET) on the ATP-sensitive potassium channel (K ATP channel) activity were examined in isolated cardiac ventricular myocytes. MATERIALS AND METHODS: K ATP channel activities were measured in the enzymatically (collagenase) isolated single mouse ventricular myocytes using excised inside-out, cell-attached, and perforated whole-cell patch clamp techniques. RESULTS: In inside-out patches, NO donors, SNP and spermine NONOate, did not affect the K ATP channel activity. In the presence of both ATP and ADP in the bath solution, the NO donors attenuated the activity of the K ATP channel. In cell-attached patches, the NO donors potentiated pinacidil-induced K ATP channel activity. In perforated whole-cell patch configuration, the NO donors decreased the K ATP current induced by PCO 400, a K ATP channel opener. PGI2 did not affect the K ATP channel activity in excised insideout patch. However, in the pres-ence of ATP in the internal solution, PGI2 increased the channel activity in a dose-dependent manner. In cell-attached patches, PGI2 did not only affect the channel activity itself, but also the dinitrophenol-induced K ATP channel activity. 11, 12-EET had no effect on K ATP channel activities.CONCLUSION: These results indicate that some of the endothelium-derived relaxing factors (nitric oxide and prostacyclin) are involved in the regulation of ATP-sensitive potassium channel activities in mouse ventricular myocytes; and the regulation type was com-plicated, activation or inhibition, depending on the cellular environment.

Influences of Free Fatty Acids on Transmembrane Action Potential and ATP-sensitive Potassium Channel Activity in Rat Myocardium

BACKGROUND: To evaluate the role of free fatty acids on the ischemic myocardium, influences of various free fatty acids upon transmembrane action potential and ATP-sensitive K+(KATP) channel activity were examined in the ventricular myocardium and single cardiac myocytes. METHODS: KATP channel activities were measured in the enzymatically (collagenase) isolated single rat ventricular cardiac myocytes by the method of the excised inside-out and the cell-attached patch clamp, and transmembrane action potentials were recorded using the conventional 3M-KCl microelectode techniques in the rat ventricular myocardium. RESULTS: Free fatty acids [FFAs; arachidonic acid (AA), linoleic acid (LA) and lysophosphatidylcholine (LPC)] reduced the KATP channel activity in a dose-dependent manner in the inside-out patch, and 50%-inhibition concentrations (IC50) were 88 +/- 11.2, 49 +/- 12.5, and 188 +/- 17.4 M respectively. Both frequency of channel opening and the mean open-burst duration were markedly decreased, but the amplitude of single channel currents were not changed by the FFAs. AA (50 micrometer) and LPC (50 micrometer) did not affect the dinitrophenol (DNP, 50 micrometer)-induced KATP channel activity, whereas LA (50 micrometer) had a tendency to reduce the activity. The channel inhibition effects by 10 micrometer AA in the inside-out patch were significantly augmented by diclofenac (10 micrometer), but was not changed by nordihydroguaiaretic acid. FFAs never stimulated KATP channel activity, even in the inside-out patch where KATP channel activity reduced in the presence of internal ATP (100 micrometer). Time for 90% repolarization (APD90) significantly increased during superfusion of the FFAs, to 22 (50 micrometer AA), 24 (50 micrometer LA), and 18 (50 micrometer LPC) % from those of the contol at the time of 10 min superfusion, but the other action potential characteristics were not changed by the FFAs. AA (10 micrometer) attenuated cromakalim (10 micrometer)-induced APD90 shortening effects. CONCLUSION: It was inferred that FFAs inhibit the KATP channel activity directly by themselves and/or indirectly by their metabolites in the rat ventricular cardiomyocytes, and therefore, duration of action potential lengthens to be a burden over the ischemic myocardium accounting for the injury of myocardium at the late stage of ischemia.

Influence of Ischemic-Simulation on the Action Potential Characteristics in Rat Atrial Fibers

BACKGROUND: To investigate the mechanisms of myocardial ischemia induced changes of electrophysiological properties, influences of various ischemic-simulated Tyrode's solutions on the changes of action potential characteristics were examined. METHOD: Action potential characteristics were measured during superfusion with various ischemic-simulated solutions (modified physiologic salt solution: MPSS) by the method of conventional microelectrode technique in rat atrial fibers. RESULTS: Hypoxic-, hyperkalemic-, and mixed-MPSS decreased 'maximum diastolic potential' (MDP) and 'action potential amplitude' (APA), however, no significant changes of MDP and APA were observed by acidic- and glucose-free-MPSS. 'Maximum velocity of phase 0 depolarization' (dV/dt(max)) and 'time for 90% repolarization' (APD90) significantly decreased during hypoxic- and mixed-MPSS superfusion, and hyperkalemic-MPSS also decreased the dV/dt(max) and APD90. However, no significant changes in dV/dt(max) and APD90 were observed by acidic- and glucose-free-MPSS. The decreasing effects of dV/dt(max) and APD90 by the MPSSes were attenuated when the MPSSes were replaced with normal Tyrode's solution. DPCPX (2x10(-6)M), a purinergic antagonist, inhibited the decreasing effects of APD90 at 5, 10, and 20 min superfusion of the mixed-MPSS, and glibenclamide (10(-6)M), a K(ATP) channel blocker, inhibited those at 10 and 20 min superfusion of the mixed-MPSS. Diclofenac (10(-6)M), a cyclooxygenase inhibitor inhibited only those at 20 min superfusion of the mixed-MPSS. CONCLUSION: The primary factors for changing the electrophysiological characteristics during ischemic insults could be hypoxia and high-extracellular K+, and the mechanisms of the electrophysiological changes are inferred that adenosine through purinoceptors is involved initially, and followed by K(ATP) channel and prostanoids.

Effect of prostaglandins D2, E2 and I2 on the regulation of KATP channel activity in rat cardiac myocytes

Contribution of prostaglandins D2, E2 and I2 (PGD2, PGE2 and PGI2) on the regulation of ATP-sensitive K+ channel (KATP channel) was investigated in isolated single rat ventricular cardiac myocytes using the patch clamp technique. PGD2, PGE2 and PGI2 did not affect KATP channel activity in the inside-out patch, but increased channel activity in a dose-dependent manner when the channel activities were attenuated by the administration of 100 muM ATP to the internal solution in the inside-out patch. Channel activations by the prostaglandins were abolished by 50 muM glibenclamide, a KATP channel blocker. Dose-response curves of relative channel activity against the ATP concentrations of internal solution in the inside-out patch were shifted to the right in the presence of those three prostaglandins. The rank order of the channel stimulatory potencies (as IC50 for ATP) calculated from the dose-response curves were PGI2 < PGD2 < PGE2. Conductance of the channel was not changed by those three prostaglandins. In conclusion, we suggest that prostaglandins D2, E2 and I2 are involved in the regulation of KATP channel activity in certain circumstances, and that those three prostaglandins may cause myocardial relaxation by opening KATP channels, thus protecting the heart from ischema.

Protective Action of Purinergic and Cholinergic Agonists on the Ischemic Myocardium in the Rat

BACKGROUND: Purinergic and cholinergic agonists elicit negative-inotropic and chronotropic effects, anticip-ating their protective action from the damage of overloaded myocardium. However, the actions of the agents during the ischemic insults are not yet clearly informed. The aim of this study was to investigate the role of the purinergic and cholinergic agonists on the simulated ischemic myocardium of the rat atrial fiber preparations. METHOD: Various action potential parameters (maximum diastolic potential MDP;action potential amplitude APA;velocity of phase 0 depolarization dV/dtmax;action potential duration APD90) were measured and compared in electrically paced, normal (NPSS) and modified physiological salt solution (MPSS) superfused rat atrial fibers in vitro, using conventional 3M-KCl microelectrode technique. Ischemia-simulated modified physiologic solutions were prepared by changing the solution's composition. RESULTS: Hypoxic-and/or hyperkalemic-MPSS decreased all the action potential (AP) variables. However, no significant changes of the AP variables were developed by the acidic-or glucose-free MPSS. Adenosine (Ado) and cyclopentyladenosine (CPA) only decreased the APD90 in a dose-dependent manner. Acetylcholine (Ach) and carbachol (Cch) hyperpolarized the MDP, increased the dV/dtmax with certain doses, and decreased the APD90 dose-depen-dently. The potency for APD90-decrease was greater in order, CPA>Cch>Ach>Ado. Ado and CPA did not affect the hypoxic, hypokalemic MPSS-induced dV/dtmax-decrease. On the other hand, Ach and Cch sig-nificantly inhibited the dV/dtmax-decrease by the hypoxic hypokalemic-MPSS. Ado, CPA, Ach and Cch sig-nificantly augmented the hypoxic, hypokalemic MPSS-induced APD90-decrease. The inhibition by the Ach and Cch on the MPSS-induced dV/dtmax-decrease was not affected by DPCPX, but atropine significantly attenuated the inhibition by the cholinergic agonists. DPCPX inhibited the augmentation by the Ado and CPA on the MPSS induced APD90-decrease, and atropine inhibited the effect of the cholinergic agonists. CONCLUSION: Both purinergic and cholinergic agonists not only shorten the AP duration by themselves but also enhance the AP-shortening effect elicited by the ischemia, and therefore, it is inferred that both agonists prevent further tissue damage from the ischemic insults.

Influence of the central benzodiazepinergic system on peripheral cardiovascular regulation

Diazepam is known to have cardiovascular depressive effects through a combined action on benzodiazepinergic receptor and the GABA receptor-chloride ion channel complex. Moreover, it is known that barbiturates also have some cardiovascular regulatory effects mediated by the central GABAergic system. Therefore, this study was undertaken to delineate the regulatory actions and interactions of these systems by measuring the responses of the cardiovascular system and renal nerve activity to muscimol, diazepam and pentobarbital, administered intracerebroventricularly in rabbits. When muscimol (0.03~-0.3 microgram/kg), diazepam (10~100 microgram/kg) and pentobarbital (1-10 microgram/kg) were injected into the lateral ventricle of the rabbit brain, there were similar dose-dependent decreases in blood pressure (BP) and renal nerve activity (RNA). The relative potency of the three drugs in decreasing BP and RNA was muscimol > pentobarbital >diazepam. Muscimol and pentobarbital also decreased the heart rate in a dose-dependent manner; however, diazepam produced a trivial, dose-independent decrease in heart rate. Diazepam (30 microgram/kg) pentobarbital (3 microgram/kg) did not. Bicuculline (0.5 microgram/kg), a GABAergic receptor blocker, significantly augmented the effect of muscimol (0.1 microgram/kg) in decreasing blood pressure and renal nerve activity, but of pentobarbital in decreasing BP and RNA, either alone or with muscimol. We inferred that the central benzodiazepinergic and barbiturate systems help regulate peripheral cardiovascular function by modulating the GABAergic system, which adjusts the output of the vasomotor center and hence controls peripheral sympathetic tone. Benzodiazepines more readily modulate the GABAergic system than barbiturates.