Ethacizin: a new efficacious Soviet antiarrhythmic drug of the phenothiazine group

Ethacizin, a new Soviet antiarrhythmic agent of the phenothiazine group, was tested on 82 patients with ventricular rhythm disturbances. Antiarrhythmic effects of the drug were assessed by means of ambulatory ECG monitoring. The investigation protocol included acute drug testing with 50 mg, 100 mg, and 150 mg, and short-term maintenance therapy with 150 to 300 mg/24 hours of ethacizin (mean 183 +/- 46 mg/24 hours) for 3 to 14 days (mean 7 +/- 3 days). Ethacizin reduced the total number of ventricular premature beats (VPBs) from 17,263/24 hours (on placebo) to 3458/24 hours (p less than 0.001) and suppressed couplets and ventricular tachycardia (VT) runs by 90% in 94% and 96% of patients, respectively. Maximum blood plasma concentration of ethacizin was observed in 110 to 120 minutes and accounted for 300 to 447 ng/ml (mean 354 +/- 77 ng/ml), with a minimum therapeutic drug plasma concentration ranging from 29 to 101 ng/ml (mean 73 +/- 27 ng/ml). There was a significant increase in PQ and QRS intervals with ethacizin. Ethacizin was well tolerated. Thus ethacizin had high antiarrhythmic efficacy in patients with VPBs and no significant side effects.     

Correlation between the anti-arrhythmia effect of ethacizin and pharmacokinetic parameters in a model of rhythm adoption by the heart

Pharmacokinetics and pharmacodynamics of ethacizin were studied in a model of rhythm adoption by the heart, with the drug administered intravenously to anesthetized cats. A relation was demonstrated between blood ethacizin pattern and the drug's biphasic effect on the adoption of stimulation-imposed pace by the heart and ventricular fibrillation threshold. The estimated correlation coefficients, reflecting the relationship between the development of ethacizin anti-arrhythmic and antifibrillation effects and variation of its plasma levels between 10 and 120 min after the administration, were rather high (-0.85 and +0.93, respectively). Ethacizin shows anti-arrhythmic and antifibrillation activity when its plasma levels are between 2400 and 200 ng/ml.     

Effect of ethacizin (diethylamine analog of ethmozine) on the efferent activity of the sympathetic and parasympathetic nerves of the heart

This study examined the effects of the diethylamino analogue of ethmozin (ethacizin) (1 mg/kg, i.v.) on the spontaneous and reflex elicited efferent activity in thoracic cardiac sympathetic and parasympathetic nerves. Nitroglycerin and phenylephrine (4 and 8 micrograms/kg, i.v.) were administered to 15 anesthetized mongrel dogs while monitoring blood pressure and heart rate. In each dog, two cardiac nerves were isolated and efferent neurograms were simultaneously recorded and analyzed by microprocessor. Ethacizin significantly attenuated the spontaneous sympathetic efferent activity in both left and right, preganglionic (n-8) and postganglionic (n-14) sympathetic nerves to the heart. In contrast, reflex changes in sympathetic activity elicited by baroreceptor challenges, were not affected by ethacizin. Also, ethacizin did not significantly affect either spontaneous or baroreceptor reflex-induced parasympathetic efferent activities in 8 preganglionic nerves. Thus, this new phenothiazine derivative may exert part of its antiarrhythmic action through a reduction of the spontaneous sympathetic tonic discharges to the heart. The fact that ethacizin did neither reduce the reflex-induced changes in sympathetic or parasympathetic activities nor influence the tonic vagal discharges further suggests that the compound is not likely to interfere with reflexly mediated cardiovascular adaptive changes.     

Differential inotropic actions of ethmozine and ethacizin (diethylamine analog of ethmozine)

The direct inotropic actions of ethmozine and of its diethylamine analog, ethacizin, were studied in the presence of muscarinic and beta-adrenoreceptor blockade in 12 ferret right ventricular papillary muscles. In each muscle ethmozine caused a small but consistent and significant (p less than 0.05) increase in contractile performance, whereas ethacizin significantly (p less than 0.05) diminished contractility. Although both phenothiazines are fast channel blockers, it appears that the net positive inotropic action of ethmozine is due to its stimulatory effect on the slow inward current and that the negative inotropic action of ethacizin is largely due to its recently demonstrated decreases of the slow inward current.     

Electrophysiology of Ethacizin: Effects on Arrhythmias in the In Situ Heart and Transmembrane Action Potentials of Purkinje Fibers and Ventricular Muscle Cells

Therapeutic and Toxic Effects of Ethacizin. Ethacizin is a new antiarrhythmic drug that is a derivative of ethmozine. We confirmed the early findings that ethacizin reduces the arrhythmias that occur in dogs 24 hours after ligation of the left anterior descending coronary artery. However, we found that QRS duration and R-on-T beats were increased by ethacizin, and that sudden death occurred in one-third of the dogs. In control experiments, etbmozine (n = 6) and quinidine (n = 6) produced antiarrhythmic effects comparable to those of ethacizin, but sudden death did not occur. Studies then were carried out on canine cardiac tissues using standard microelectrode techniques. Ethacizin 300 ng/mL decreased dV/dt_max in Purkinje fibers and ventricular muscle. These decreases were rate dependent. Ethacizin decreased action potential plateau duration (APD-60 mV) in false tendon Purkinje fibers, and increased it in ventricular muscle. In spontaneously firing Purkinje fibers, ethacizin consistently decreased high-potential (normal) and low-potential (abnormal) automaticity to 14% and 12% of control, respectively. The effects of ethacizin on catecholamine-enhanced high-potential automaticity were more variable. Automaticity decreased in about half of the fibers, but did not change greatly in the remainder. The antiarrhythmic actions of ethacizin may result from reduction of impulse initiation or conduction in Purkinje fibers or myocardial cells. (J Cardiovasc Electrophysiol, Vol. 1, pp. 411–425, October 1990)     

Atherogenic properties of phenothiazine drugs manifesting in cultured cells of the human aortic intima]

The effects of phenothiazine drugs on the levels of cholesterol in smooth cells of the human aortic intima. Two antiarrhythmics (ethacizin and ethmozine) and two neuroleptics (trifluoperazine and chlorpromazine) were evaluated. The three agents ethacizin, trifluoperazine, and chlorpromazine given in concentrations of 10(-7) to 10(-5) M were ascertained to cause intracellular cholesterol accumulation, whereas ethmozine produced no effects on the intracellular levels of cholesterol. Ethacizin failed to cause cholesterol accumulation when the cells were incubated with ethacizin in the culture medium supplemented with lipid-deficient serum. Ethacizin in a concentration o 10(-5) M was shown to inhibit the synthesis of cholesterol esters and had no action on the intracellular synthesis of steroids.     

Pulmonary microvascular and alveolar epithelial permeability characteristics in N-nitroso-N-methylurethane-injected dogs

The subcutaneous injection of 5 to 6 mg/kg of body weight of N-nitroso-N-methylurethane (NNNMU) has been reported to cause acute alveolar injury in animals. To determine the permeability characteristics of the alveolar epithelium, we employed the in vivo saline-filled dog lung model and determined the time to 50 percent equilibration in minutes of a specific tracer in the blood and the lung model and determined the time to 50 percent equilibration in minutes of a specific tracer in the blood and the lung liquid (T 1/2) for endogenous serum albumin (MW 69,000 daltons, molecular radius 35 A) and exogenously administered 500,000 MW polydispersed dextrans (molecular radius 200 A). Compared to control animals, T1/2 decreased (permeability increased) in NNNMU-injected dogs from 3,500 +/- 100 to 682 +/- 160 minutes for albumin and from 20,000 +/- 250 to 2,790 +/- 750 minutes for 500,000 MW dextran (P less than 0.001). To determine the permeability characteristics of the pulmonary microvasculature, we employed the right lymph duct cannulation dog model and measured lymph flow/30 minutes, lymph albumin and dextran concentration, and lymph/plasma albumin and dextran ratios in control and NNNMU-injected dogs. Compared to control animals, lymph flow was significantly greater in NNNMU dogs, 2.07 +/- 1.1 vs .71 +/- .50 ml/30 minutes (P less than 0.01), respectively. We conclude that NNNMU injection increases permeability in both the alveolar epithelium and the pulmonary microvasculature.     

Mechanism of action and the effectiveness of ethacizin in patients with paroxysmal atrioventricular nodal reciprocal tachycardia

An electrophysiologic study of ethacizin's mechanisms of action was carried out in patients with paroxysmal atrioventricular nodal tachycardia. Tachycardia was controlled by 0.5 mg/kg ethacizin in all patients. No patients demonstrated induced tachycardia in the presence of the drug, and 55% developed a complete retrograde atrioventricular block. The assessment of the preventive effect of oral ethacizin administration showed that paroxysms of tachycardia could not be provoked by esophageal electrostimulation of the heart in 87% of the patients. In the same patients, stable antiarrhythmic effect was maintained by long-term treatment with this drug. The suppression of retrograde stimulus conduction along the quick path of the atrioventricular node is assumed to be the principal electrophysiological mechanism of ethacizin action. Ethacizin can be used to control or prevent paroxysms of atrioventricular nodal tachycardia.     

Influence of post haemodialysis sampling on Kt/V result

The recommended Kt/V is 1.2. Unfortunately there is no written policy for nurses on the procedure for taking blood urea nitrogen samples post haemodialysis. The aim of this study was to establish the Kt/V variability of haemodialysis patients depending on the method of collection of post-haemodialysis blood urea nitrogen. Twenty-two patients were analysed. A Kt/V was performed every 15 days during a period of 2 months. It was taken five times on each patient: 30 minutes before the end of a haemodialysis session (Kt/V30), at the end of haemodialysis (Kt/V1), after slowing flows (50 ml/min) for 2 minutes (Kt/V2) and after the blood circuit had been returned to the patient at 5 and 15 minutes respectively. (Kt/V5, Kt/V15). The Kt/V results were: Kt/V1 1.23 +/- 0.2 Vs Kt/V2 1.14 +/- 0.19 (p < 0.003); Kt/V5- 1.05 +/- 0.19 (p < 0.002 Vs Kt/V2); Kt/V15 1 +/- 0.16 (p < 0.05 Vs Kt/V5); Kt/V30 1.12 +/- 0.21 (pNS Vs Kt/V2). In conclusion, there was a large variability in the Kt/V depending on the method of collection of the blood urea nitrogen sample post-haemodialysis.     

Failure of intravenous N-acetylcysteine to reduce methemoglobin produced by sodium nitrite in human volunteers: A randomized controlled trial

STUDY OBJECTIVE: To determine whether intravenous N -acetylcysteine (NAC) produces a clinically significant decline in sodium nitrite-induced methemoglobinemia in human volunteers. METHODS: We conducted a randomized, control crossover trial with each subject serving as his own control. Methemoglobinemia was induced with intravenous sodium nitrite (4 mg/kg) administered over 10 minutes starting at time 0. At time 30 minutes, subjects were randomly assigned to treatment with intravenous NAC for 100 minutes (150 mg/kg over 1 hour followed by 14 mg/kg per hour for 40 minutes) or administration of an equal volume of 5% dextrose in water. Each subject received the alternative treatment after an interval of at least 1 week. Blood methemoglobin concentrations were measured by multiwavelength co-oximetry at time 0, 15, 30, 50, 70, 90, 110, and 130 minutes. Area under the methemoglobin concentration-time curve (AUC) between 30 and 130 minutes was compared between groups using a 2-tailed, paired t test. RESULTS: There were no statistically significant differences in the control and treatment groups with respect to baseline hemoglobin or methemoglobin concentrations, as well as nitrite-induced methemoglobin concentrations at the initiation of treatment (0.85+/-0.06 g/dL, 0.88+/-0.04 g/dL; mean+/-SEM; P =.31). Mean AUC for the control group (77.1+/-5.7 g x min/dL) was significantly lower than the mean AUC for the treatment group (84.5+/-4.7 g x min/dL); P =.01). CONCLUSION: Intravenous NAC failed to enhance methemoglobin reduction in this model.     

The effect of a time delay on the characteristics of the canine glucoregulatory system

In order to elucidate the effect of a relative time delay on glucose regulation, we performed experiments with differently timed infusions of insulin and glucose in a canine model. When portal insulin infusion (0.03 U/kg over 5 minutes) preceded portal glucose infusion (0.05 g/kg over 5 minutes) by 1 minute, glycemia increased to a maximum value of 104 +/- 4 mg/dL at 6 minutes, whereas insulinemia peaked at 3 minutes at a level of 130 +/- 4 microU/mL (baseline, 21 +/- 7 microU/mL). C-peptide levels increased from 200 +/- 50 to 270 +/- 30 pmol/L. Glycemia then decreased to a minimum level of 61 +/- 4 mg/dL, significantly lower (P less than .02) than the corresponding values in control experiments when insulin was infused alone. With a reversed timing sequence of infusions with glucose infusion preceding insulin infusion by 1 minute, glycemia increased similarly, but decreased to a minimum level of only 84 +/- 4 mg/dL, which was significantly higher (P less than .01) than in the above experiment. Insulinemia peaked similarly at 126 +/- 7 microU/mL, and C-peptide increased from 210 +/- 50 to 280 +/- 50 pmol/L. These experiments demonstrated an unexpected effect: adding glucose to an insulin infusion almost doubled the biological activity of the exogenous insulin as measured by its hypoglycemic action. They also indicated that small perturbations of glycemia and insulinemia in the portal circulation have a profound effect on metabolism, and that even short relative time delays in elevating either insulinemia or glycemia can cause significantly different metabolic outcomes.(ABSTRACT TRUNCATED AT 250 WORDS)     

慢性阻塞性肺疾病与支气管哮喘患者支气管舒张反应曲线的比较

目的 建立慢性阻塞性肺疾病(COPD)和支气管哮喘(以下简称哮喘)支气管舒张反应曲线,探讨COPD和哮喘大、小气道扩张的特点.方法 动态观测2004年5月至2005年8月中山大学附属第五医院收治的COPD和哮喘患者吸入福莫特罗前后肺通气功能的变化.结果 COPD患者吸入福莫特罗后,第1秒用力呼气量(FEV1)和用力肺活量(FVC)的支气管舒张反应曲线在15 min内升高,120 min后开始下降,1秒率(FEV1/FVC)支气管舒张反应曲线呈波浪样变化,呼出50%肺活量时最大呼气流量(FEF50)与最大呼气中段流量(FEF75/25)的支气管舒张反应曲线在30 min内升高后即开始下降;FEV1,FVC,FEF50随时间点变化的拟合二次曲线模型方程差异有显著性意义(P＜0.05).哮喘患者FEV1,FVC,FEV1/FVC,FEF50,FEF75和FEF75/25的支气管舒张反应曲线在15～30 min内升高明显,120 min后开始下降;FEV1,FEV1/FVC,FEF75/25随时间点变化的拟合二次曲线模型方程差异有显著性意义(P＜0.05).结论 COPD与哮喘患者大、小气道舒张具有不同的特点,支气管舒张反应曲线可以用来鉴别两者.     

Angiotensin II relaxations of bovine adrenal cortical arteries: role of angiotensin II metabolites and endothelial nitric oxide

Angiotensin (Ang) II regulates adrenal steroidogenesis and adrenal cortical arterial tone. Vascular metabolism could decrease Ang II concentrations and produce metabolites with vascular activity. Our goals were to study adrenal artery Ang II metabolism and to characterize metabolite vascular activity. Bovine adrenal cortical arteries were incubated with Ang II (100 nmol/L) for 10 and 30 minutes. Metabolites were analyzed by mass spectrometry. Ang (1-7), Ang III, and Ang IV concentrations were 146+/-21, 173+/-42 and 58+/-11 pg/mg at 10 minutes and 845+/-163, 70+/-14, and 31+/-3 pg/mg at 30 minutes, respectively. Concentration-related relaxations of U46619-preconstricted cortical arteries to Ang II (maximum relaxation=29+/-3%; EC(50)=3.4 pmol/L) were eliminated by endothelium removal and inhibited by the NO synthase inhibitor, nitro-L-arginine (30 micromol/L; maximum relaxation=14+/-7%). Ang II relaxations were enhanced by the angiotensin type-1 receptor antagonist losartan (1 micromol/L; maximum relaxation=41+/-3%; EC(50)=11 pmol/L). Losartan-enhanced Ang II relaxations were inhibited by nitro-L-arginine (maximum relaxation=18+/-5%) and the angiotensin type-2 receptor antagonist PD123319 (10 micromol/L; maximum relaxation=27+/-5%). Ang (1-7) and Ang III caused concentration-related relaxations with less potency (EC(50)=43 and 24 nmol/L, respectively) but similar efficacy (maximum relaxations=39+/-3% and 48+/-5%, respectively) as losartan-enhanced Ang II relaxations. Ang (1-7) relaxations were inhibited by nitro-L-arginine (maximum relaxation=16+/-4%) and the Ang (1-7) receptor antagonist 7(D)-Ala-Ang (1-7) (1 micromol/L; maximum relaxation=10+/-3%) and eliminated by endothelium removal. Thus, Ang II metabolism by adrenal cortical arteries to metabolites with decreased vascular activity represents an inactivation pathway possibly decreasing Ang II presentation to adrenal steroidogenic cells and limits Ang II vascular effects.     

Relative efficacy of phenytoin and phenobarbital for the prevention of theophylline-induced seizures in mice

We evaluated the efficacy of pretreatment with phenytoin and phenobarbital to prevent seizures in mice given convulsive doses of theophylline. The control LD50 for theophylline was determined in 48 mice by intraperitoneal injections of increasing doses without anticonvulsant treatment. Anticonvulsant effects were determined in 105 additional mice pretreated with either phenytoin 30 mg/kg (n = 35), phenobarbital 35 mg/kg (n = 30), or phenobarbital 60 mg/kg (n = 40) one hour before theophylline administration. The theophylline LD50 (95% confidence interval) was 239 mg/kg (range, 229 to 248 mg/kg) for controls, 204 mg/kg (range, 194 to 214 mg/kg) for phenytoin, 305 mg/kg (range, 288 to 323 mg/kg) for low-dose phenobarbital, and 319 mg/kg (range, 307 to 331 mg/kg) for high-dose phenobarbital. Each LD50 differed significantly from control (P less than .05). The phenobarbital groups were significantly different from phenytoin (P less than .05) but not from each other. Theophylline serum concentrations were not significantly different among groups after adjustment for different doses. The mean +/- SEM time to seizure in minutes after adjustment for theophylline dose was 23.5 +/- 4.0 minutes for controls, 5.7 +/- 7.5 minutes for phenytoin, 44.1 +/- 7.1 minutes for low-dose phenobarbital, and 63.7 +/- 6.5 minutes for high-dose phenobarbital.(ABSTRACT TRUNCATED AT 250 WORDS)     

Outcomes of transplantation from living renal donor

Living donors represent 30% of our kidneys for renal transplantation. Laparoscopic nephrectomy is the best surgical procedure to obtain them due to its clear advantages such as low morbidity, less blood supply and donor time in hospital. From March 2002 to August 2004 we performed 50 laparoscopic nephrectomies for renal transplantation. Kidneys were transplanted to recipients receiving tacrolimus 0.1 mg/kg/bid, mycophenolate mofetil 1 g/bid and prednisone 0.5-1 mg/kg/day p.o 48 hours before transplantation. Mean time for surgery was 170 minutes (120-260), warm ischaemia time 3.1 minutes (1.5-10) and cold ischaemia time 1.27 hours (0.85-4). Mean bleeding was 270 cc (100-900) and donor time in hospital 5.5 days (3-9). Four cases required conversion of the laparoscopic procedure to open surgery because of bleeding. 72 hours post-transplant mean plasmatic creatinine was 170 micromol/l. None of the patients suffered delayed graft function. 18% presented acute rejection. Survival of donor and recipient was 100% at 1 year and graft survival was 94% at 1 year (kidney losses were due to acute rejection, severe acute pancreatitis and surgical problem).     

The effects of lysophosphatidate on thyrotropin-mediated differentiated thyroid function in FRTL-5 thyroid cells.

Lysophosphatidate (LPA; 1-acyl-sn-glycero-3-phosphate) is a novel lipid mediator with diverse biological activity. The intracellular mechanisms that mediate the actions of LPA include activation of phospholipase C and protein kinase C (PKC), increases in intracellular Ca2+, inhibition of adenylyl cyclase, and activation of phospholipase D (PLD). We have shown that thyrotropin (TSH) mediated PLD activation involves both the cyclic adenosine monophosphate (cAMP) and PKC pathways. We determined the effects of LPA (10 or 50 microM; 30 minutes) on TSH- and forskolin-mediated cAMP production in FRTL-5 thyroid cells. Basal cAMP was unaffected by LPA. However, both 10 microM and 50 microM LPA inhibited TSH-mediated cAMP production by 66% and 64%, respectively (p < 0.01, ANOVA). A similar inhibition of forskolin-mediated cAMP production was observed following LPA (p < 0.01, ANOVA). After 30-minutes exposure to 50 microM LPA, TSH-mediated iodide uptake (IU) was unaffected. However, 50 microM LPA enhanced TSH-IU after 24-hour exposure by 23%+/-8% (p < 0.03, ANOVA) and inhibited TSH-IU following 72-hour exposure by 43%+/-10% (p < 0.02, ANOVA). There was no effect of LPA on basal IU. To determine whether PLD activation mediated the effects of LPA, PLD activity was examined in FRTL-5 thyroid cells 30 minutes after LPA exposure. While PLD was increased 3.5-fold compared to control values following 50 microM LPA (p < 0.05, ANOVA), no increase in PLD activation was seen following treatment with 10 microM LPA. Preliminary evidence revealed no effect of a protein kinase C inhibitor on LPA inhibition of cAMP generation. To examine the products of PLD activation, we measured the production of phosphatidate (PA) and diacylglycerol (DAG) in FRTL-5 thyroid cells following treatment with 50 microM LPA or 100 microU/mL TSH. Within 1 minute following LPA, a rapid spike of DAG production was observed (1.5- +/- 0.2-fold above basal, p < 0.05, ANOVA). No similar increases in PA or bisPA were demonstrated. However, TSH caused a steady increase in PA and DAG that reached a maximum after 30 minutes. In summary, the effects of LPA on differentiated thyroid function in FRTL-5 thyroid cells are complex. LPA inhibits TSH- and forskolin-mediated cAMP generation most likely via a direct inhibition of adenylyl cyclase, whereas its effects on TSH-IU involve other mechanisms, possibly including PLD activation.     

Prostaglandin E1 attenuates postischemic contractile dysfunction after brief coronary occlusion and reperfusion

We have previously demonstrated that administration of the prostacyclin analogue iloprost improved postischemic functional recovery in reversibly injured ischemic-reperfused myocardium. The present study investigated the effects of administering an endogenous vasodilator prostanoid, prostaglandin E1 (PGE1), in the stunned myocardium (15 minutes of coronary artery occlusion and 3 hours of reperfusion) of anesthetized dogs. The percentage of regional myocardial segment shortening (%SS) after administration of PGE1 by two routes, intravenously (1 microgram/kg/min) or intraatrially (0.1 microgram/kg/min), to avoid pulmonary metabolism, 15 minutes before and throughout the period of occlusion, was compared to %SS in a control group treated with saline solution. Nearly equivalent reductions in mean arterial pressure during occlusion compared to pretreatment control (PTC) values were produced by intravenous (33%) or intraatrial (25%) PGE1. There was no difference in transmural myocardial blood flow (radioactive microsphere technique) in the ischemic region between the PGE1-treated and control groups at any time. Although there were no differences in %SS in the nonischemic region between groups throughout the experiment, postischemic recovery of segment function in the ischemic-reperfused area was significantly improved (p less than 0.05) at all times during reperfusion by intravenous PGE1 (%SS of PTC: 30 minutes = 65 +/- 8; 3 hours = 58 +/- 7) or intraatrial PGE1 (%SS of PTC: 30 minutes = 57 +/- 12; 3 hours = 50 +/- 4) compared to the control group (%SS of PTC: 30 minutes = 25 +/- 13; 3 hours = 10 +/- 13). Thus treatment with PGE1 attenuates postischemic contractile dysfunction in the stunned myocardium.2+ both.     

Comparison of the effectiveness of various routes of insulin injection: insulin levels and glucose response in normal subjects.

The difference in absorption of insulin and its glucose lowering-effect after the administration of crystalline insulin by the intravenous, intramuscular, and subcutaneous routes was compared in 14 lean normal subjects. Insulin in a dose of 0.1 U/kg body weight was given by the three different routes. Blood was drawn from the opposite arm at regular intervals for the determination of insulin, glucose, glucagon, cortisol, and potassium. Intravenous insulin produced the highest pharmacological level of insulin in 2 minutes (2099 +/- 414 muU/ml) with marked hypoglycemia at 30 minutes (a 68% drop). Intravenous insulin injection produced an increase in plasma glucagon and cortisol reaching a 2-fold increase above the fasting level 30 minutes after the glucose nadir. An equivalent amount of intramuscular insulin produced a maximal increase in plasma insulin at 50 minutes (45 +/- 4 muU/ml) and caused a 35% drop in plasma glucose at 60 minutes, which effects were greater than those caused by subcutaneous injection (highest IRI = 36 +/- 3.5 muU/ml and 23% glucose drop at 180 minutes). No significant increase in glucagon or cortisol was noted with equivalent amounts of subcutaneous or intramuscular insulin injection. Our studies suggest that, in normal lean subjects, insulin injection by the intramuscular route provides a faster absorption of insulin with a concomitant greater drop in plasma glucose than does injection by the subcutaneous route.     

Acute hypertension selectively potentiates constrictor responses of large coronary arteries to serotonin by altering endothelial function in vivo

We tested the hypothesis that acute coronary artery hypertension may damage vascular endothelium and alter vasomotor responses to humoral agents. We examined effects of intracoronary infusion of the endothelium-dependent agent serotonin and two endothelium-independent agents, angiotensin II and methoxamine, on large coronary artery diameter in the blood perfused dog heart. Responses were examined before and 30 minutes after brief periods of coronary hypertension (200 mm Hg for 10 seconds to 15 minutes). In open-chest anesthetized dogs, the left anterior descending coronary artery was perfused at constant pressure. Coronary diameter (D) was measured with piezoelectric crystals. At a control perfusion pressure of 80 mm Hg, serotonin produced dose-dependent constriction of the large coronary artery (mean +/- SEM; delta D = -22 +/- 10 microns at 5 micrograms/min; -108 +/- 50 microns at 50 micrograms/min). Increasing perfusion pressure to 200 mm Hg increased flow 515 +/- 79% and coronary diameter 509 +/- 9 microns. After 15 minutes of hypertension, when coronary diameter had returned to baseline values, the constriction of the large artery to serotonin was potentiated (delta D = -89 +/- 33 microns at 5 micrograms/min; -207 +/- 45 microns at 50 micrograms/min; p less than 0.05). Hypertension for 1-5 minutes potentiated constrictor responses of large coronary arteries for at least 2 1/2 hours. Removal of endothelium prevented effects of hypertension on constrictor responses of large arteries to serotonin. Hypertension did not alter constrictor responses to angiotension II (1 and 2.5 micrograms/min) or methoxamine (50 and 100 micrograms/min) or the dilator response to acetylcholine (40 micrograms/min). Acute hypertension altered endothelial morphology. There were small endothelial craters following 10 seconds of hypertension, and disruption of endothelial junctions with leukocyte adherence following 1-15 minutes of hypertension. We conclude that acute hypertension alters constrictor responses of large coronary arteries to serotonin by impairing endothelial function and not by directly affecting vascular smooth muscle. These effects of acute hypertension on vascular reactivity are selective in that they do not involve non-endothelium-dependent agents or the endothelium-dependent agent, acetylcholine. The effect of hypertension also persists long after pressure is restored to normotensive levels.     

链霉蛋白酶与利多卡因胶浆联用提高超声内镜检查清晰度的研究

目的评价检查前联合使用链霉蛋白酶和利多卡因胶浆对缩短超声胃镜操作时间和改善内镜、超声图像方面的效果。方法将超声内镜受检者80例随机分为A、B组,每组40例。A组于检查前15min口服利多卡因胶浆10ml;B组于检查前30rain口服含10000单位链霉蛋白酶和1g碳酸氢钠的温开水50ml,并于检查前15min口服利多卡因胶浆10ml。记录总操作时间,并对超声胃镜下胃内黏液附着量及超声图像的清晰度进行评分。结果A组操作时间长于B组[（15．5±3．0）min比（12．3±2．3）min,P〈0．001],B组内镜和超声内镜图像视野清晰度均优于A组。结论链酶蛋白酶和利多卡因胶浆联用可有效去除胃内黏液艉高超声内镜检查成像质量。