不同剂量右美托咪啶对冠心病患者气管插管血流动力学的影响

目的研究不同剂量右美托咪啶对冠心病患者气管插管血流动力学的影响。方法择期气管内插管全身麻醉行腹部外科手术冠心病患者75例,随机将其分成L组(右美托咪啶0.5μg/kg)、M组(右美托咪啶1.0μg/kg)、C组(咪唑安定对照组),每组25例。麻醉诱导前静脉泵注用生理盐水稀释成50 ml右旋美托咪啶,L组0.5μg/kg,M组1.0μg/kg,输注时间为20 min;C组全麻诱导时先静脉注射咪唑安定0.03～0.05 mg/kg。记录入室后基础值(T1)、全麻诱导前(T2)、插管前(T3),插管后即刻(T4),插管后3 min(T5)各时点的心率(HR)、有创血压值[收缩压(SBP)、舒张压(DBP)]、心电图(ECG)变化。结果与基础值相比较,输注右美托嘧啶后全麻诱导前L组、M组患者HR、SBP、DBP均下降(P<0.05),但两组之间差异无统计学意义(P>0.05)。气管插管前,三组患者的SBP、DBP、HR均降至最低(与基础值比较,P<0.05);三组间差异均无统计学意义(P>0.05)。气管插管前M组出现4例窦性心动过缓(<52次/min),3例低血压(SBP下降>40%);L组出现1例窦性心动过缓;C组出现1例低血压,2例窦性心动过速。气管插管后即刻三组患者血压、心率有不同程度上升;C组HR、SBP、DBP与插管前L组、M组相比明显上升(P<0.05)。L组、M组与插管前相比差异无统计学意义(P>0.05)。气管插管后3 min,C组血压、心率与气管插管后即刻比较有明显下降(P<0.05);与插管前相比仍明显升高(P<0.05)。L组、M组血压、心率与插管后即刻、插管前比较差异无统计学意义(P>0.05)。结论冠心病患者术前输注右美托咪啶可减少气管插管血流动力学变化;0.5μg/kg右美托咪啶可能更适合冠心病患者。     

Metoclopramide enhances labetalol-induced antihypertensive effect during handgrip in hypertensive patients

The effects of metoclopramide, labetalol, and metoclopramide plus labetalol treatments on baseline cardiovascular parameters and isometric handgrip-induced changes were evaluated in 11 hypertensive subjects. Although all treatments were effective in reducing resting systolic (SBP) and diastolic (DBP) blood pressures, the combination of metoclopramide and labetalol appeared to provide a greater decrease (changes in SBP/DBP: 15/11 mm Hg, P < 0.05; from 149 +/- 4/95 +/- 4 mm Hg to 134 +/- 5/84 +/- 3 mm Hg) than did labetalol alone (changes in SBP/DBP: 10/9 mm Hg, P < 0.05; from 149 +/- 4/95 +/- 4 to 139 +/- 4/86 +/- 3 mm Hg). At 2 minutes, handgrip increased blood pressure on placebo (changes in SBP/DBP: 34/7 mm Hg, P < 0. 001). In the presence of metoclopramide and metoclopramide plus labetalol, however, handgrip induced lesser increases in blood pressure (changes in SBP/DBP: 23/7 mm Hg, P < 0.01, and 18/4 mm Hg, P < 0.01, for metoclopramide and metoclopramide plus labetalol treatments). We conclude that (1) metoclopramide lowers blood pressure in hypertensive patients; (2) metoclopramide attenuates blood pressure response to isometric handgrip; and (3) both compounds, labetalol and metoclopramide, seem to have a pharmacologic interaction concerning blood pressure decrease. A clinical significance is suggested for the metoclopramide effect.     

Sympathetic predominance of cardiovascular regulation during mild orthostatic stress in adolescents with chronic fatigue

Haemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular control. This study was designed to explore the pathophysiology in adolescent CFS-patients by analysing RR-interval (RRI) variability and diastolic blood pressure (DBP) variability during mild orthostatic stress, using an algorithm which accounts for non-stationary biosignals. A total of 27 adolescents with CFS and 33 healthy control subjects having equal age- and sex distribution underwent 15 min of 20 degrees head-up tilt (HUT). The spectral power densities of RRI and DBP were computed in the low-frequency (LF) band (0.04-0.15 Hz) and the high-frequency (HF) band (0.15-0.4 Hz) using an adaptive autoregressive algorithm to obtain a time-varying spectrum. RMSSD, a time domain index of RRI variability, was also computed. At rest, all indices of variability were similar in the two groups. During tilt, CFS patients had a larger increase in the LF/HF ratio (P相似文献   

A twelve-week, multicenter, randomized, double-blind, parallel-group, noninferiority trial of the antihypertensive efficacy and tolerability of imidapril and candesartan in adult patients with mild to moderate essential hypertension: the Iberian Multicenter Imidapril Study on Hypertension (IMISH)

OBJECTIVE: The aim of this study was to evaluate the annhypertensive efficacy and tolerability of the angiotensin-converting enzyme inhibitor imidapril and the angiotensin II type 1 receptor antagonist candesartan in mild to moderate essential hypertension. METHODS: The trial was conducted at 8 centers across Portugal and Spain (the Iberian Multicenter Imidapril Study on Hypertension [IMISH] Study Group). Patients aged between 30 and 70 years with essential hypertension were eligible. Following a 2- to 4-week, single-blind, placebo run-in period, patients were randomly assigned to receive imidapril at doses of up to 20 mg/d, or candesartan at doses up to 16 mg/d, once daily in a double-blind, parallel-group design with a 12-week active-treatment period. To achieve the target systolic/diastolic blood pressure (SBP/DBP) of <140/<90 mm Hg, imidapril was titrated from 5 to 20 mg/d and candesartan was titrated from 4 to 16 mg/d. The main end point was the change from baseline in sitting blood pressure (BP) at trough. Secondary end points were response rate, evaluation of SBP and DBP throughout the study, and change of SBP and DBP in subgroup of patients with moderate hypertension, as well as incidence and severity of adverse events related to treatment reported throughout the study. RESULTS: The intent-to-treat analysis consisted of 122 patients (imidapril group, 60 patients; 32 men, 28 women; mean [SD] age, 54.7 [9.2] years; white race, 59 [99.2%], Hispanic race, 1 [0.8%]; mean [SD] weight, 80.1 [12.8] kg; candesartan group, 62 patients; 36 men, 26 women; mean [SD] age, 53.9 [9.9] years; white race, 62 [100%]; mean [SD] weight, 77.6 [14.1] kg). In the imidapril group, the mean (SD) SBP and DBP were, respectively, 155.7 (10.2) and 96.7 (4.7) mm Hg at baseline and 139.4 (11.9) and 86.9 (7.6) mm Hg at the end of the 12-week treatment period (visit 5); SBP had decreased significantly from baseline, by 10.5% (mean [SD] Delta, -16.3 [12.3] mm Hg [95% CI, -19.5 to -13.1; P < 0.001]) and DBP had decreased significantly, by 10.1% (mean [SD] A, -9.8 [7.8] mm Hg [95% CI, -11.8 to -7.8; P < 0.001]). In the candesartan group, the mean (SD) SBP and DBP values were, respectively, 158.4 [11.2] and 98.3 [4.1] mm Hg at baseline and 139.8 [12.5] and 87.6 7.5] mm Hg at 12 weeks, corresponding to decreases of 11.7% in SBP (mean [SD] A, -18.6 [12.8] mm Hg [95% CI, -21.9 to -15.4; P < 0.001]) and 10.9% in DBP (mean [SD] A, -10.7 [7.3] mm Hg [95% CI, -12.5 to -8.8; P < 0.001]). Response rates were 78.3% (47/60) with imidapril and 69.4% (43/62) with candesartan, and BP normalization (<140/<90 mm Hg) was achieved in 55.0% (33/60) of patients with imidapril and 45.2% (28/62) of patients with candesartan. The incidences of adverse events were similar between groups. Most (73.9%) adverse events were mild in intensity. A serious adverse event (severe anxiety) was reported in the candesartan group and led to study discontinuation. No cases of dry cough or hypotension were reported. CONCLUSIONS: The results of this study suggest that imidapril once daily at doses up to 20 mg and candesartan once daily at doses up to 16 mg were effective in this population of mildly to moderately hypertensive patients. Both treatments were well tolerated.     

Spectral analysis of heart rate variability and respiration during sleep in cocaine‐exposed neonates

This study’s objective was to examine the autonomic control of heart rate and respiration during the neonatal period in human infants with prenatal exposure to cocaine. Four‐hour daytime recordings of the electrocardiogram (ECG) were obtained from 15 cocaine‐exposed and 13 non‐exposed full‐term neonates at 2 weeks of age during quiet sleep (QS) and active sleep (AS). For each 1‐min epoch of sleep, the power spectrum of the R‐R intervals was computed from the ECG to obtain the total power (0–2 Hz), and spectral power in the high‐frequency (HFP, 0·3–2 Hz), mid‐frequency (MFP, 0·1–0·2 Hz), and low‐frequency (LFP, 0·03–0·1 Hz) bands. Respiration was also monitored and processed using similar spectral analysis procedures. Cocaine‐exposed neonates showed enhanced heart rate variability reflected by an increase in spectral power across all frequency bands. Spectral power in LFP and MFP was higher in cocaine‐exposed neonates during both sleep states, but only in HFP during QS. There were no respiratory patterning differences between the groups to account for these findings. The index of sympathovagal balance (LFP + MFP)/HFP, showed no differences between the groups. We conclude that infants exposed to cocaine in utero show differences in the modulation of heart rate reflecting an increase in both vagal and sympathetic influences.     

不同剂量艾司洛尔预防双腔支气管内插管时心血管反应的临床研究

目的观察不同剂量的艾司洛尔对预防双腔支气管内插管时心血管反应的临床效果及合适剂量。方法选择ASAⅠ～Ⅱ级开胸手术患者60例,随机分为三组,每组20人。A组：注射生理盐水10ml（对照组）,B组：静脉注射艾司洛尔0．5mg／kg,C组：静脉注射艾司洛尔1mg／kg,记录麻醉诱导前（基础值）、诱导后2min、插管后即刻、插管后2min、5min、10min的收缩压（SBP）、舒张压（DBP）、心率（HR）,计算各对应时点HR和收缩压（SBP）的乘积（RPP）。结果与基础值相比,诱导后2min三组SBP、DBP、HR和RPP均较基础值显著降低（P〈0．05）,B组降低的程度比A组更甚,但不及c组低;气管插管后即刻,A组、B组的SBP、DBP、HR和RPP显著升高（P〈0．05）,但B组增高的程度明显低于A组（P〈0．05）,而C组保持稳定;插管后2min、5min、10min三组SBP、DBP、HR和RPP随时间逐渐趋于基础值,但B、C组仍低于A组（P〈0．05）。结论应用0．5mg／kg和1mg／kg两种剂量的艾司洛尔均能有效抑制双腔支气管内插管引起的心血管反应,但1mg／kg艾司洛尔为合适剂量,且血流动力学稳定。     

Effects of telmisartan on renal excretory function in conscious dogs

The present study investigated the effects of telmisartan, a selective AT1 receptor antagonist, on renal function in dogs. Conscious female dogs were treated with (i) vehicle (controls) and three doses of telmisartan (0.03 mg/kg, 0.1 mg/kg and 0.3 mg/kg) administered intravenously; (ii) vehicle and three doses of telmisartan (0.3 mg/kg, 1.0 mg/kg and 3.0 mg/kg) administered orally; or (iii) 1.0 mg/kg per day telmisartan orally for 12 days. Eight dogs were used for each experiment. Each of the four treatments in (i) and (ii) was administered 7 days apart. During the 6 h after intravenous administration, urine volume was significantly higher in dogs treated with telmisartan 0.1 mg/kg (8.5 +/- 1.6 ml/kg) and 0.3 mg/kg (7.0 +/- 0.9 ml/kg) than controls (2.7 +/- 0.3 ml/kg; P < 0.05), and renal sodium excretion was increased significantly with telmisartan 0.03 mg/kg (803 +/- 124 micromol/kg), 0.1 mg/kg (1039 +/- 213 micromol/kg) and 0.3 mg/kg (966 +/- 161 micromol/kg) versus controls (159 +/- 21 micromol/kg; P < 0.05). Oral telmisartan at doses of 1.0 mg/kg and 3.0 mg/kg also produced significant increases in urine volume (7.2 +/- 1.1 ml/kg and 6.6 +/- 1.2 ml/kg, respectively) and renal sodium excretion (599 +/- 146 micromol/kg and 555 +/- 131 micromol/kg, respectively) compared with controls (2.8 +/- 0.5 ml/kg and 80 +/- 33 mciromol/kg; P < 0.05) over the 6-h post-dose period. Telmisartan at all intravenous doses and at 3.0 mg/kg orally increased the urinary excretion of chloride significantly over the 6-h post-dose period compared with vehicle alone. The excretion of potassium and creatinine were unchanged by any treatment. Telmisartan 1.0 mg/kg administered orally for 12 days produced similar results. In conclusion, acute intravenous or oral as well as subchronic oral administration of telmisartan to conscious dogs promotes diuresis and natriuresis without affecting potassium or creatinine excretion.     

Individual and joint association of alpha1A-adrenergic receptor Arg347Cys polymorphism and plasma irbesartan concentration with blood pressure therapeutic response in Chinese hypertensive subjects

BACKGROUND: Individual variability in the therapeutic response to an antihypertensive drug could have a genetic basis. We investigated whether the alpha1A-adrenergic receptor (alpha1A-AR) Arg347Cys polymorphism is associated with the blood pressure (BP) therapeutic response to irbesartan and whether the association could be altered by the plasma irbesartan level. METHODS: A total of 696 hypertensive subjects were treated with a daily oral dose of 150 mg irbesartan. Baseline BP was measured before the first dose. On the 28th day, after 27 consecutive days of treatment and an overnight fast, BPs and blood samples were obtained before the morning dose (0 hours) and 6 hours after the morning dose was taken. Plasma irbesartan concentrations were measured by use of HPLC-fluorescence. RESULTS: BP therapeutic response was defined as baseline BP minus BP on the 28th day of irbesartan treatment. Relative to noncarriers, alpha1A-AR Cys347 allelic carriers had a significantly greater diastolic blood pressure (DBP) response at 0 hours (mean +/- SD, 7.5 +/- 8.4 mm Hg versus 5.5 +/- 8.4 mm Hg; P = .016) and at 6 hours (16.2 +/- 9.1 mm Hg versus 14.2 +/- 8.9 mm Hg, P = .025). Although the pattern was similar to the DBP response, alpha(1A)-AR Cys347 allelic carriers had only a moderately increased systolic blood pressure (SBP) response at the 2 time points. When subjects were stratified into subgroups with high or low plasma irbesartan concentrations (with the median value used as the cutoff point), Cys347 allelic carriers in the high-concentration group, relative to noncarriers, had a more pronounced DBP response at 0 hours (adjusted beta [+/- SE], 3.0 +/- 1.0 mm Hg; P = .004) and at 6 hours (adjusted beta, 3.0 +/- 1.2 mm Hg; P = .014), and the same was true for the SBP response at 0 hours (adjusted beta, 5.6 +/- 2.1 mm Hg; P = .006) and at 6 hours (adjusted beta, 4.7 +/- 2.0 mm Hg; P = .021). In contrast, in the low-concentration group, there was no significant association between DBP or SBP responses and Arg347Cys genotypes at 0 hours and 6 hours. CONCLUSION: Our data suggest that the alpha1A-AR Arg347Cys polymorphism is associated with BP response (particularly DBP) to short-term irbesartan treatment. Our data also showed evidence of an interaction between the alpha1A-AR Arg347Cys polymorphism and the plasma level of irbesartan in relation to BP therapeutic response. The association of the Arg347Cys polymorphism with the BP therapeutic response was more pronounced in those patients with higher plasma concentrations of irbesartan.     

Coffee consumption and blood pressure: an Italian study

The relation between habitual coffee consumption and blood pressure was studied in 500 Italian subjects, males and females, aged 18-62 years. After allowing for sex, age and weight, the pressure levels showed a significant decrease with increasing coffee consumption. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were respectively 130.4 +/- 1.8 (SE) mmHg and 81.5 +/- 1.1 mmHg for non-coffee drinkers, 129.4 +/- 1.4 and 82.2 +/- 0.9 mmHg for 1 cup per day, 128.4 +/- 0.8 and 81.4 +/- 0.5 mmHg for 2-3 cups per day, 124.9 +/- 1.1 and 78.8 +/- 0.7 mmHg for 4-6 cups per day, and 124.1 +/- 2.5 and 78.7 +/- 1.6 mmHg for more than 6 cups of coffee daily (analysis of covariance: SBP F = 3.46, 4 df, P less than 0.01; DBP F = 3.46, 4 df, P less than 0.01). Even after correcting pressure levels for habitual alcohol intake and cigarette smoking, we observed a mean reduction in SBP and DBP of 0.80 mmHg and 0.48 mmHg respectively per cup per day.     

Blood pressure and heart rate effects following a single dose of bitter orange

BACKGROUND: The ingredients of numerous "ephedra-free" dietary supplements used for weight loss include bitter orange, which contains sympathomimetic alkaloids such as synephrine. Due to the similarity in chemical structure to ephedrine and the potential sympathomimetic effects of synephrine, it is hypothesized that bitter orange may increase blood pressure (BP) and heart rate (HR). OBJECTIVE: To determine the effects on BP and HR after a single dose of bitter orange in healthy adults. METHODS: In a prospective, randomized, double-blind, placebo-controlled, crossover study, 15 young, healthy, adult subjects received either a single dose of Nature's Way Bitter Orange--a 900 mg dietary supplement extract standardized to 6% synephrine--or matching placebo, with a one week washout period. Systolic BP (SBP), diastolic BP (DBP), and HR were measured at baseline and every hour for 6 hours after administration. RESULTS: SBP after bitter orange was significantly increased versus placebo at hours 1-5 (p < 0.0001); the peak difference was 7.3 +/- 4.6 mm Hg. Although the baseline DBP was higher than after administration of both placebo and bitter orange, DBP after bitter orange was significantly increased versus placebo at hours 4 and 5 (p < or = 0.02); the peak difference was 2.6 +/- 3.8 mm Hg. HR was significantly increased after bitter orange versus placebo for hours 2-5 (p < 0.01); the peak difference was 4.2 +/- 4.5 beats/min. CONCLUSIONS: SBP, DBP, and HR were higher for up to 5 hours after a single dose of bitter orange versus placebo in young, healthy adults.     

Comparison of glargine insulin versus rosiglitazone addition in poorly controlled type 2 diabetic patients on metformin plus sulfonylurea

OBJECTIVE: We sought to examine the mechanisms by which the addition of glargine insulin or rosiglitazone improves glycemic control in type 2 diabetic subjects poorly controlled on maximally effective doses of metformin plus sulfonylurea. RESEARCH DESIGN AND METHODS: Subjects (aged 47 +/- 11 years, BMI 31 +/- 5 kg/m(2), HbA(1c) [A1C] 9.4 +/- 1.3%) received bedtime glargine insulin (titrated based on the fasting plasma glucose [FPG], n = 10) or rosiglitazone (4 mg twice daily, n = 10). At baseline and after 4 months, A1C was measured and an oral glucose tolerance test and a 3-h euglycemic insulin (80 mU/m(2) per min) clamp with [3-(3)H]glucose were performed. RESULTS: A1C and FPG decreased similarly in the glargine insulin (9.1 +/- 0.4 to 7.6 +/- 0.3% and 212 +/- 14 to 139 +/- 5 mg/dl, respectively, both P < 0.0001) and rosiglitazone (9.4 +/- 0.3 to 7.6 +/- 0.4% and 223 +/- 14 to 160 +/- 19 mg/dl, respectively, both P < 0.005) groups. After 4 months, endogenous glucose production (EGP) declined similarly with glargine insulin (2.27 +/- 0.10 to 1.73 +/- 0.12 mg . kg(-1) . min(-1), P < 0.0001) and rosiglitazone (2.21 +/- 0.12 to 1.88 +/- 0.12 mg . kg(-1) . min(-1), P = 0.01). The hepatic insulin resistance index declined in the rosiglitazone group (32 +/- 3 to 21 +/- 1 mg . kg(-1) . min(-1) x microU/ml, P = 0.03 vs. baseline and P < 0.05 vs. glargine insulin) and did not change in the glargine group (22 +/- 5 to 20 +/- 3 mg . kg(-1) . min(-1) x microU/ml, P = NS). At 4 months, glargine insulin (3.6 +/- 0.5 to 4.2 +/- 0.4 mg . kg(-1) . min(-1), P < 0.01) and rosiglitazone (2.7 +/- 0.3 to 3.8 +/- 0.3 mg . kg(-1) . min(-1), P < 0.0005) increased R(d), but the increment was greater in the rosiglitazone group (P < 0.05). Diastolic blood pressure was reduced only by rosiglitazone (P < 0.01). CONCLUSIONS: Triple therapy with glargine insulin or rosiglitazone similarly reduced A1C, primarily by suppressing basal EGP (hepatic). Glargine insulin reduced basal EGP by increasing plasma insulin levels, while rosiglitazone decreased basal hepatic glucose production by improving hepatic insulin sensitivity.     

Cardiorespiratory effects of naloxone in children

BACKGROUND: Data on the cardiorespiratory changes and complications following administration of naloxone in children are limited. OBJECTIVE: To evaluate the cardiorespiratory changes and complications following naloxone treatment in children. METHODS: The maximal changes in respiratory rate (RR), heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure, and any complications within 1 and 2 hours following naloxone were tabulated. RESULTS: One hundred ninety-five children received naloxone over 3 years. The mean +/- SD age was 9.7 +/- 6 years. The total doses of naloxone ranged from 0.01 to 7 mg (0.001-0.5 mg/kg body weight), with a median dose of 0.1 mg. Group 1 patients consisted of 116 (60%) children who were postoperative and had been given naloxone by an anesthesiologist; group 2 patients consisted of 79 (40%) children who received naloxone in the emergency department or pediatric intensive care unit. Patients in group 1 were older: 10.6 +/- 5.3 versus 8.2 +/- 6.7 years (p < 0.006), but received significantly lower doses of naloxone (0.09 +/- 0.2 vs. 1.1 +/- 0.76 mg; p < 0.001). When the entire cohort was evaluated, a significant increase in RR (15 +/- 7 vs. 21 +/- 8 breaths/min; p < 0.001), HR (102 +/- 29 vs.107 +/- 29 beats/min; p < 0.001), SBP (109 +/- 17 vs. 115 +/- 15 mm Hg; p < 0.001), and DBP (56 +/- 10 vs. 60 +/- 13 mm Hg; p < 0.001) within 1 hour following naloxone was noted. When the 2 groups were compared, only the changes in RR were greater in group 2 patients (6.8 +/- 7.9 vs. 4.7 +/- 5 breaths/min; p < 0.001) following naloxone. Systolic hypertension occurred in 33 of 195 (16.9%) of all patients, while diastolic hypertension occurred in 13 (6.6%) of all patients after naloxone. Only the incidence of diastolic hypertension was higher in group 2 compared with group 1 patients following naloxone (16% vs. 2%; p < 0.001). Hypertension resolved spontaneously. One child developed pulmonary edema and required positive pressure ventilation for 22 hours. CONCLUSIONS: Moderate increases in RR, HR, and BP occur after naloxone administration to children, but development of more serious complications is rare.     

Cardiovascular and hormonal effects of subcutaneous administration of ghrelin,a novel growth hormone-releasing peptide,in healthy humans

Ghrelin is a novel GH (growth hormone)-releasing peptide isolated from the stomach. The cardiovascular and hormonal effects of the subcutaneous administration of ghrelin in humans remain unknown. Six healthy volunteers each received subcutaneous administration of three doses of ghrelin (1, 5 or 10 microg/kg) and placebo; the order of administration was randomized, and separate doses were given at least 24 h apart. The serum GH level dose-dependently increased from 0.5 +/- 0.4 to 3.6 +/- 2.1 ng/ml (1 microg/kg ghrelin; P=0.99 compared with baseline), 27.1 +/- 12.0 ng/ml (5 microg/kg; P<0.01 compared with baseline) and 45.4 +/- 12.8 ng/ml (10 microg/kg; P<0.01 compared with baseline) 30 min after ghrelin administration. Subcutaneous administration of ghrelin did not significantly alter circulating levels of corticotropin, cortisol, insulin-like growth factor-1, noradrenaline or adrenaline, although 10 microg/kg ghrelin slightly increased the prolactin level. No significant changes in heart rate or mean arterial pressure were observed. In contrast, the left ventricular ejection fraction, as assessed by echocardiography, increased dose-dependently from 63.5 +/- 0.6% to 65.1 +/- 0.9% (1 microg/kg ghrelin; P=0.97 compared with baseline), 69.6 +/- 1.3% (5 microg/kg; P<0.01 compared with baseline) and 71.5 +/- 0.9% (10 microg/kg; P<0.01 compared with baseline) 30 min after ghrelin administration. These haemodynamic and hormonal changes were still apparent 60 min after ghrelin injection. In conclusion, subcutaneous administration of ghrelin dose-dependently induced relatively specific GH release and enhanced cardiac performance in humans.     

Blood pressure control in patients with mild to moderate essential hypertension switched from nifedipine gastrointestinal therapeutic system (GITS) 30 mg to nifedipine GITS 20 mg

BACKGROUND: Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides sustained plasma nifedipine concentrations throughout the 24-hour dosing interval. OBJECTIVE: This study was undertaken to determine if adult patients with mild to moderate essential hypertension whose blood pressure had been controlled for > or = 3 months with nifedipine GITS 30 mg could be successfully switched to a 20-mg daily dose with continued antihypertensive efficacy. METHODS: This was a randomized, double-blind, parallel-group study. Patients entered a 1-week run-in period during which they continued to receive their usual antihypertensive medication, including nifedipine GITS 30 mg. After baseline assessment, patients entered a 6-week treatment period during which they were randomly assigned to receive nifedipine GITS 30 or 20 mg. Men and women were eligible to participate if they were > or = 55 years of age, had received a diagnosis of mild to moderate essential hypertension (sitting diastolic blood pressure [DBP] 95-114 mm Hg), and had exhibited good blood pressure control (sitting DBP < or = 90 mm Hg) while taking nifedipine GITS 30 mg once daily for > or = 3 months. Systolic blood pressure (SBP), DBP, and heart rate were recorded at baseline and after 1, 3, and 6 weeks of treatment. Adverse events were reported by patients. The responder rate was defined as the percentage of patients whose sitting DBP was < 95 mm Hg at the final study assessment. Results were based on the intent-to-treat analyses, which included data for all patients who received > or = 1 dose and had 1 postbaseline blood pressure assessment. Statistical significance was set at P < 0.05. RESULTS: Seventy-five patients entered the 1-week run-in period; 71 patients (94.7%) were randomized to treatment. Twenty-four patients received nifedipine GITS 30 mg for 43.0 +/- 3.3 days, and 47 patients received nifedipine GITS 20 mg for 42.5 +/- 6.7 days. Both groups exhibited a sustained decrease in blood pressure throughout the study; minor variations were not statistically significant. End-point SBP and DBP for the 30- and 20-mg groups were 135.5 +/- 9.8/81.7 +/- 5.4 mm Hg and 138.6 +/- 11.8/82.9 +/- 7.6 mm Hg, respectively. Changes from baseline in end-point SBP and DBP did not differ significantly between groups. At the end of treatment, goal DBP (< 95 mm Hg) was achieved by 24 of 24 patients (100%) receiving the 30-mg dose and 45 of 47 patients (95.7%) receiving the 20-mg dose. Blood pressure control (sitting DBP < 90 mm Hg) was achieved by 21 of 24 (87.5%) patients in the 30-mg group and 35 of 47 (74.5%) patients in the 20-mg group. The most commonly reported adverse event was headache; 2 patients discontinued the study because of adverse events. Overall, 9 of 24 patients (37.5%) in the 30-mg group and 14 of 47 patients (29.8%) in the 20-mg group experienced > or = 1 treatment-related adverse event. CONCLUSIONS: Patients whose mild to moderate essential hypertension is controlled with nifedipine GITS 30 mg once daily may be able to switch to 20 mg once daily with continued antihypertensive efficacy. In addition to safety and economic advantages, such a switch may be a reasonable alternative in patients with lower body weight or as an adjunct to existing antihypertensive therapy.     

Differential time effect profiles of amlodipine, as compared to valsartan, revealed by ambulatory blood pressure monitoring, self blood pressure measurements and dose omission protocol

Amlodipine and valsartan are once-daily antihypertensive agents. To date, no comparison between these agents given as monotherapies was reported. This study was aimed to evaluate the therapeutic coverage and safety of amlodipine and valsartan in mild-to-moderate hypertensive patients. Multicenter, double-blind, randomized, comparative study. After a 4-week placebo wash-out period, 246 outpatients with office diastolic blood pressure 95 < or = DBP < or =110 mmHg and systolic blood pressure (SBP) < 180 mmHg, in addition to a mean daytime SBP and/or DBP > 135/85 mmHg on 24-h ambulatory blood pressure monitoring (ABPM), were randomly allocated to once-daily amlodipine 5-10 mg or valsartan 40-80 mg, for 12 weeks. In a subgroup of patients, 48-h ABPM were performed at the end of the treatment period. Dose omission was simulated by a single-blind placebo dosing. The primary efficacy end-point was the 24-h trough office BP after 12 weeks of active therapy. The reductions in 24-h trough BP were more pronounced in amlodipine compared with valsartan group as well in office [SBP: -17.8 +/- 10.9 vs. -14.6 +/- 11.2, P = 0.025, DBP: -12.7 +/- 7.2 vs. -10.9 +/- 7.8 mmHg, P = 0.06) as in ambulatory BP (SBP/DBP: -13.0 +/- 13.7/-10.8 +/- 9.1 vs. -7.2 +/- 19.4/-4.9 +/- 13.4 mmHg, P < 0.05). Forty-eight hours after the last active dose, the slope of the morning BP surge (4-9 h) was less steep with amlodipine vs. valsartan [DBP (P < 0.04), SBP (n.s.)]. Ankle edema were more often reported in amlodipine group. These results suggest a superior BP lowering and a longer duration of action with amlodipine compared with valsartan.     

A randomized,double-blind,controlled, parallel-group comparison of perindopril and candesartan in hypertensive patients with type 2 diabetes mellitus

BACKGROUND: When choosing an antihypertensive drug for patients with hypertension and diabetes mellitus (DM), the metabolic side effects, possibility of improving some metabolic parameters, and need for adequate blood pressure control must all be considered. OBJECTIVE: The goal of this study was to compare the impacts of perindopril and candesartan on blood pressure, glucose metabolism, serum lipid profile, and metabolic parameters in patients with mild hypertension and type 2 DM during therapy and after a 1-month washout period. METHODS: Type 2 DM patients with mild hypertension and good glucose control who were not taking hypercholesterolemic drugs were enrolled. Perindopril 4 mg QD or candesartan 16 mg QD was administered for 12 months in this randomized, double-blind, controlled, parallel-group clinical trial. Fasting plasma glucose (FPG), fasting plasma insulin (FPI), glycosylated hemoglobin, homeostasis model assessment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, lipoprotein(a) (Lp[a]), plasminogen activator inhibitor 1 (PAI-1), homocysteine, body mass index (BMI), and albumin excretion rate (AER) were assessed. RESULTS: Ninety-six patients (49 women and 47 men; mean [SD] ages, 53 [10] years [perindopril] and 55 [9] years [candesartan]) were enrolled. Mean (SD) body weight, height, and BMI were 78.2 (9.4) kg, 1.69 (0.05) m, and 27.2 (2.0) kg/m(2) in the perindopril group and 77.5 (8.6) kg, 1.70 (0.06) m, and 26.8 (2.5) kg/m(2) in the candesartan group. A significant change occurred from baseline to month 12 during treatment with perindopril in SBP and DBP (both P < 0.01), FPG (P < 0.05), FPI (P < 0.05), TC (P < 0.05), LDL-C (P < 0.05), Lp(a) (P < 0.05), PAM (P < 0.05), and AER (P < 0.05). Significant changes from baseline to month 12 occurred with candesartan in SBP and DBP (both P < 0.01) and AER (P < 0.05). The HOMA index was significantly lower at month 12 in the perindopril group than in the candesartan group (P < 0.05). When we interrupted perindopril and candesartan therapy for a 1-month washout period, changes in SBP and DBP values were significant compared with month 12 in both groups (all P < 0.05). Changes in TC and LDL-C from month 12 to the end of washout were significant only in the perindopril group (both P < 0.05). CONCLUSIONS: Perindopril and candesartan both effectively lowered blood pressure in this group of patients with mild hypertension and type 2 DM. Perindopril showed an improvement on some metabolic parameters compared with candesartan. However, the inclusion/exclusion criteria could limit the ability to extrapolate the results to a general population.     

Association between human atrial natriuretic peptide Val7Met polymorphism and baseline blood pressure, plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in rural Chinese patients with essential hypertension

BACKGROUND: Individual variations in the pharmacokinetics and pharmacodynamics of antihypertensive drugs are influenced by genetic and environmental factors. The ANP gene, which encodes the precursor of atrial natriuretic peptide (ANP), is among the candidate genes for genetic susceptibility to hypertension. OBJECTIVE: This study examined the relationship between ANP Val7Met polymorphism (Single Nucleotide Polymorphism database ID: rs5063) and baseline blood pressure (BP), plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in rural Chinese patients with essential hypertension. METHODS: Patients with essential hypertension who had taken no antihypertensive medications within 4 weeks of study initiation received oral irbesartan 150 mg/d for 4 weeks. Genotyping was performed for all patients. BP was measured before dosing on the 1st and 28th days of treatment. Plasma irbesartan concentrations were measured using high-performance liquid chromatography with fluorescent detection. Antihypertensive efficacy was defined as attainment of a diastolic BP (DBP) <90 mm Hg (DBP analysis), a systolic BP (SBP) <140 mm Hg (SBP analysis), and a DBP <90 mm Hg and SBP <140 mm Hg (DBP and SBP analysis). RESULTS: The study included 756 patients, 621 with the Val/Val genotype and 135 with the Val/Met+Met/Met genotypes. There were no significant differences in age, body mass index, sex, education level, occupation, alcohol consumption, or smoking status between the 2 groups. Patients with the Val/Met+Met/Met genotypes had a significantly lower mean baseline DBP compared with those with the Val/Val genotype (adjusted regression coefficient [SE]: -2.5 [1.0] mm Hg; P = 0.012) and significantly lower mean steady-state plasma trough irbesartan concentrations (adjusted regression coefficient: -12.6 [4.1]; P = 0.002). No significant association was found between antihypertensive efficacy and Val7Met polymorphism in the overall population, but in an analysis by baseline DBP status, patients with the Val/Met+Met/Met genotype a baseline DBP > or =100 mm Hg had significantly smaller reductions in DBP (adjusted regression coefficient: -5.7 [1.4] mm Hg; P < 0.001) and SBP compared with those with the Val/Val genotype and a baseline DBP > or =100 mm Hg (adjusted regression coefficient: -9.8 [2.9] mm Hg; P < 0.001). CONCLUSION: The findings of this study suggest that in these rural Chinese patients with essential hypertension, ANP Val7Met polymorphism may be a genetic marker for baseline DBP, plasma irbesartan concentrations, and the antihypertensive efficacy of short-term irbesartan therapy.     

To reverse or not to reverse: an evaluation of reversal of mivacurium chloride in women undergoing outpatient gynecological procedures.

BACKGROUND: A double-blind, randomized study compared differences between patients administered edrophonium and those administered placebo after mivacurium infusion. Neuromuscular blockade was quantified using the ParaGraph 1800 nerve stimulator-monitor (Vital Signs, Totowa, NJ), which can deliver a train-of-four stimulus to the ulnar nerve and quantify the ratio of the fourth twitch to the first twitch. METHODS: With Investigational Review Board approval and informed consent, 30 healthy outpatient gynecological surgery patients ASA I or II, aged 21 to 37 years, were randomly assigned to treatment or placebo. In a double-blind manner, one group received edrophonium (1 mg/kg) and atropine (0.01 mg/kg) reversal (E/A) and the other group received placebo (P) to recover spontaneously from a mivacurium infusion. Anesthesia was induced and a rapid infusion of mivacurium chloride (0.2 mg/kg) was administered. An infusion of mivacurium chloride was then initiated at a rate of 6-7 microg/kg/min to maintain neuromuscular blockade. Group differences in recovery time (time between administration of the edrophonium or placebo and a 5-second head lift followed by tracheal extubation) were compared, as was time from tracheal extubation to discharge from the postanesthesia care unit (PACU). Nausea and vomiting were documented until the patient was discharged from the hospital; a 24-hour follow-up evaluation was completed by telephone. RESULTS: Each group contained 15 patients, and their demographics were similar. The mean recovery time for E/A was statistically shorter than for P (P, 9.7 +/- 4.8 minutes; E/A, 6.1 +/- 3.9 minutes; p = 0. 017). There were no statistically significant differences found in the incidence of nausea and vomiting (P, 4; E/A, 6) or in time to discharge from the PACU. CONCLUSION: Recovery from a mivacurium chloride infusion is shorter by 3.6 minutes (margin of error +/- 3.3 minutes) when reversal with edrophonium/atropine is used. There is no difference in time to discharge from PACU and no evidence of differences in nausea and vomiting.     

Isoproterenol induced cardiovascular hypersensitiviy in nonpheochromocytoma patients with paroxysmal hyperadrenergic symptoms

The objective of this study was to determine whether graded isoproterenol infusion test identifies a specific hypersensitivity response of the LV diastolic relaxation properties in nonpheochromocytoma patients with paroxysmal symptoms of hyperadrenergic surges. We hypothesized that patients with hyperadrenergic surges, not due to pheochromocytoma, have hypersensitivity of cardiac beta-adrenergic receptor responses to exogenous catecholamines, resulting in enhancement of LV relaxation. We assessed the physiological beta 1 and beta 2 receptor responsiveness to graded isoproterenol infusion (0.01, 0.02, 0.03 and 0.04 microgram/kg per min) in 32 patients presented with hyperadrenergic surges not due to pheochromocytoma. Two major observations were made. First, systemic hemodynamic evaluation using 99m Technetium first pass method revealed hyperkinetic state only in 21 patients (20 females and 1 male; aged 31 +/- 9 years); the other 11 patients were without hyperkinetic circulatory state (10 females and 1 male; aged 41 +/- 9 years). At baseline, plasma catecholamines were not significantly different between the two groups. The baseline corrected LV peak filling and ejection rates (cPFR and cPER) were significantly higher in hyperkinetic group (cPFR: 10 +/- 2 vs 8 +/- 2 x 10(-2) Hz/ms, P = 0.03; cPER: 11 +/- 2 vs 8 +/- 1 x 10(-2) Hz/ms, P = 0.002) and their baseline HR was faster (85 +/- 16 vs 70 +/- 9 beats/min, P = 0.006). Second, the cardiac and vascular responses to isoproterenol infusion were compared between these two groups. During the graded isoproterenol infusion, the response of HR, systolic, and diastolic BP were not significantly different between the two groups at all doses of isoproterenol, but cPFR and cPER had a more marked response to the lowest dose of 0.01 mg/kg per min in the hyperkinetic group. Thus, the graded isoproterenol infusion test can differentiate between two groups of nonpheochromocytoma patients presenting with paroxysmal symptoms of hyperadrenergic surges. Only patients with baseline hyperkinetic hemodynamic profile had accentuated cardiac hyperresponsiveness to a low dose of isoproterenol. We concluded that cPFR and cPER is a more sensitive index to assess the response to isoproterenol, because of metabolic determinants affecting the rate of change in LV volume.     

Comparison of the efficacy and tolerability of telmisartan 40 mg vs. enalapril 10 mg in the treatment of mild-to-moderate hypertension: a multicentre, double-blind study in Taiwanese patients

The purpose of this randomised, double-blind, double-dummy, parallel-group study was to evaluate the efficacy and tolerability of telmisartan 40 mg once daily vs. enalapril 10 mg once daily in 147 Taiwanese patients with mild-to-moderate essential hypertension (diastolic blood pressure [DBP] 90-109 mmHg). After 6 weeks' treatment, telmisartan produced a significantly greater reduction from baseline in the primary endpoint of trough seated DBP compared with enalapril 10 mg (11.7 vs. 8.7 mmHg, respectively; p = 0.02). Numerically greater reductions compared with baseline in seated systolic blood pressure (SBP), standing DBP, and standing SBP were achieved with telmisartan compared with enalapril. Also, numerically greater proportions of patients achieved blood pressure control (DBP/systolic blood pressure [SBP] <90/140 mmHg) and responded to treatment (reduction from baseline in trough seated DBP > or = 10 mmHg and/or post-treatment DBP <90 mmHg; reduction from baseline in trough seated SBP > or = 10 mmHg and/or post-treatment SBP <140 mmHg) with telmisartan 40 mg compared with enalapril 10 mg. Although both treatments were well tolerated, the incidence of cough was markedly lower with telmisartan 40 mg (8.5%) than with enalapril 10 mg (18.4%) in this population of Taiwanese hypertensive patients.