Role of nocturnal arterial hypotension in optic nerve head ischemic disorders

OBJECTIVE: To investigate the role of nocturnal arterial hypotension, intraocular pressure (IOP) and heart rate in optic nerve head (ONH) ischemic disorders, and the effects of systemic factors and topical beta-blocker eye-drops on nocturnal arterial hypotension and heart rate. METHODS: We investigated prospectively, by 24-hour ambulatory blood pressure (BP) monitoring and diurnal curve of the IOP, 275 white patients with anterior ischemic optic neuropathy (AION - 114), normal tension glaucoma (NTG - 131) and primary open angle glaucoma (POAG - 30). RESULTS: Hourly average BP data analyses showed a significantly greater drop in mean diastolic BP (p < 0.009) at night in NTG than AION. Cases with visual field deterioration had significantly (p = 0.05) lower minimum nighttime diastolic BP. Arterial hypertensives on oral hypotensive therapy showed a significantly lower mean nighttime systolic BP (p = 0.006) and larger mean percentage drop in systolic (p < 0.0001), diastolic (p = 0.0009) and mean (p < 0.0001) BPs. Normotensives and hypertensives without therapy had no such difference. IOP showed no significant correlation with visual field deterioration in any of these conditions. Patients using beta-blocker eyedrops, compared with those not using them, had greater percentage drop in diastolic BP (p = 0.028), lower minimum nighttime diastolic BP (p = 0.072) and lower minimum nighttime heart rate (p = 0.002). CONCLUSIONS: Findings of our study suggest that nocturnal hypotension, by reducing the ONH blood flow below a crucial level during sleep in a vulnerable ONH, may play a role in the pathogenesis of AION and glaucomatous optic neuropathy (GON) and progression of visual loss in them. Thus, nocturnal hypotension may be the final insult in a multifactorial situation.     

Mortality of aerospace workers exposed to trichloroethylene

We assessed the differential effects of a chronotherapeutic agent (controlled-onset extended release [COER] verapamil), administered at bedtime versus a conventional, homeostatic therapy (nifedipine gastrointestinal therapeutic system [GITS]) taken in the morning, on early morning and 24-hour blood pressure (BP), heart rate (HR), and the HR x systolic BP product. The study was a multicenter (n = 51), randomized, double-blind prospective clinical trial with a 10-week treatment period. Dose titration was performed by study investigators based on systolic and diastolic BP values at the doctor's office. Ambulatory BP monitoring was performed at placebo baseline, after 4 weeks of stable double-blind therapy, and at end of the study. Twenty-four-hour BP profiles were studied in 557 hypertensive patients. Changes in BP, HR, slope of the rate of rise of BP and HR, and the HR-systolic BP product during the 4 hours from 1 hour before to 3 hours after awakening were evaluated. The study was powered to show equivalence between the 2 regimens, predefined as a difference between treatment groups in mean change from baseline in early morning BP of +/- 5 mm Hg systolic and +/- 3 mm Hg diastolic. Changes in the early morning BP fell within the definition of equivalence for the 2 treatment strategies (-12.0/-8.2 mm Hg for COER-verapamil and -13.9/-7.3 mm Hg for nifedipine GITS). Changes in both the early morning HR and rate-pressure product were significantly greater following COER-verapamil therapy versus nifedipine GITS (HR, -3.8 beats/minute vs +2.6 beats/minute, p < 0.001 and HR-systolic BP product, -1,437 beats/min x mm Hg vs -703 beats/min x mm Hg, respectively, p < 0.001). Changes in ambulatory BP demonstrated clinically similar reductions for the awake period, but nifedipine GITS lowered systolic BP to a greater extent than COER-verapamil during sleep (-11.0 vs -5.8 mm Hg, p < 0.001). COER-verapamil and nifedipine GITS had equivalent effects (+/- 5/3 mm Hg) on early morning BP. In addition, both extended-release calcium antagonists effectively lowered 24-hour BP. However, COER-verapamil had greater effects than nifedipine GITS on early morning hemodynamics (HR, HR-systolic BP product, rate of rise of BP and HR) and lesser effects during sleep due to its intrinsic pharmacologic properties and chronotherapeutic delivery system.     

Autonomic nervous system dysfunction in elderly hypertensive patients with abnormal diurnal blood pressure variation: relation to silent cerebrovascular disease

To investigate the relationships among diurnal blood pressure (BP) variations and autonomic nervous system dysfunction, we assessed heart rate variability (HRV) using power spectral analysis of the 24-hour RR interval in 51 asymptomatic elderly hypertensive patients with various patterns of nocturnal BP fall. The extreme-dippers with marked nocturnal BP fall (n=16) had lower asleep low-frequency power (LF)/high-frequency power (HF) ratios (a relative index of sympathetic nervous system activity), while the nondippers without nocturnal BP fall (n=18) had lower awake LF/HF ratios and asleep/awake ratio for HF (an index of parasympathetic nervous activity), when compared with dippers with appropriate nocturnal BP fall (n=17). The incidence of multiple lacunar infarction detected by brain magnetic resonance imaging was 56% in the extreme-dippers and 38% in the nondippers, and both were markedly higher than that (6.3%) in the dippers (both P<.01). There was no significant relationship between the BP level and any HRV parameter for either the daytime or nighttime period. The asleep/awake ratio for systolic BP was significantly correlated with the asleep/awake ratio for HF (r= -.363, P<.01) and with the asleep/awake ratio for the LF/HF ratio (r=.540, P<.001), regardless of whether multiple lacunar infarction was present. In conclusion, the autonomic nervous system activity is not related to high BP level per se, rather its diurnal variation is more important as a determinant of the diurnal BP patterns, regardless of the presence or absence of cerebrovascular disease.     

Relation between nocturnal decline in blood pressure and mortality. The Ohasama Study

To investigate the relation between nocturnal decline in blood pressure and mortality, we obtained ambulatory blood pressures in 1542 residents aged 40 years or over of a rural Japanese community. Subjects were followed-up for a mean of 5.1 years and were then subdivided into four groups according to the percent decline in nocturnal blood pressure: 1) extreme dippers: percent decline in nocturnal blood pressure > or = 20% of the daytime blood pressure; 2) dippers: decline of > or = 10% but < 20%; 3) nondippers: decline of > or = 0% but < 10%; and 4) inverted dippers: no decline. The relationship between the decline in nocturnal blood pressure and mortality was examined by the Cox proportional hazards regression model adjusted for age, sex, smoking status, previous history of cardiovascular disease, and the use of antihypertensive medication. The mortality risk was highest in inverted dippers, followed by nondippers. There was no difference in mortality between extreme dippers and dippers. This relationship was observed for both treated and untreated subjects, was more pronounced for cardiovascular than for noncardiovascular mortality, and did not change after the data were adjusted for 24-h, daytime, and nighttime blood pressure levels.     

Effects of benazepril on stress testing blood pressure in essential hypertension

The effects of different doses of the angiotensin-converting enzyme inhibitor benazepril on cardiovascular response to a set of standardized laboratory tasks were analyzed. Eighteen patients (15 men and 3 women) with mild-to-moderate essential hypertension were randomly allocated to receive 10 or 20 mg of benazepril, or placebo, each administered once daily for 2 weeks, according to a double-blind, 3-period design. At the end of each treatment period, patients were examined at resting baseline and while performing mental arithmetic, handgrip and cycle ergometry tests. In comparison with placebo, the average reductions in resting systolic blood pressure (BP) were 8.7 mm Hg (95% confidence intervals [CI] -15.2 to -2.1) with 10 mg of benazepril, and 7.8 mm Hg (95% CI -14.4 to -1.3) with 20 mg; the corresponding reductions in resting diastolic BP were 5.1 mm Hg (95% CI -8.7 to -1.4) and 6.8 mm Hg (95% CI -10.4 to -3.1) (all p < 0.05). During mental arithmetic, the reductions in systolic BP were 10.4 mm Hg (95% CI -17.4 to -3.4) with 10 mg of benazepril, and 13.8 mm Hg (95% CI -20.8 to -6.8) with 20 mg; diastolic BP was reduced by 4.5 mm Hg (95% CI -8.5 to -0.5) and 8.3 mm Hg (95% CI -13.2 to -4.3), respectively (all p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ethnic differences in the hypertensive heart and 24-hour blood pressure profile

Black hypertensive persons have been observed to have a greater degree of left ventricular hypertrophy than white hypertensives. However, previous studies have matched groups for blood pressure (BP) measured in the clinic, and it has been demonstrated that black hypertensives have an attenuated nocturnal BP dip. Clinic BPs may thus underestimate mean 24-hour BP in this group. To investigate whether the differences in left ventricular hypertrophy can be accounted for by the greater mean 24-hour BP in black hypertensives, 92 previously untreated hypertensives were studied with 24-hour ambulatory BP monitoring and echocardiography. The 46 black hypertensives (24 men and 22 women) were matched with the 46 white hypertensives for age, gender, and mean 24-hour BP. Despite similar mean 24-hour BPs (blacks, 142/93 mm Hg; whites, 145/92 mm Hg; P=.53/.66), the black group had a smaller mean nocturnal dip than the white group (blacks, 8/8 mm Hg; whites, 16/13 mm Hg; P<.01). In addition, mean left ventricular mass index (LVMI) was greater (blacks, 130 g/m2; whites, 107 g/m2; P<.001). Mean 24-hour systolic BP was significantly related to LVMI in both groups (blacks, r=.45, P<.01; whites, r=.56, P<.01). However, systolic BP dip correlated inversely with LVMI only in the black group (blacks, r=-.30, P<.04; whites, r=.05, P=.76). In a multiple regression model, LVMI was independently related to both mean daytime BP and mean nocturnal BP dip in black subjects but only to mean daytime BP in white subjects. In conclusion, the increased left ventricular hypertrophy observed in black hypertensives compared with white hypertensives is not accounted for by differences in mean 24-hour BP. However, LVMI in black hypertensives appears to be more dependent on nocturnal BP than that in white hypertensives; this, coupled with the attenuated BP dip in black hypertensives, suggests that the BP profile rather than 24-hour BP may be important in determining the differences in left ventricular hypertrophy.     

Ambulatory blood pressure, nocturnal blood pressure reduction and plasma catecholamines

OBJECTIVE AND DESIGN: Controversial data have been reported on plasma catecholamines in hypertensives. Aims of this study were to find whether 24-hour ambulatory blood pressure was correlated with circulating catecholamines and to investigate whether nocturnal blood pressure reduction was associated with baseline plasma catecholamines. Samples for catecholamine determination were obtained in 34 consecutive male subjects after a 30-minute rest and before ambulatory blood pressure monitoring. RESULTS: Hypertensive patients (n = 22; 24-hour blood pressure: 145 +/- 14/94 +/- 6 mm Hg) showed similar norepinephrine and epinephrine levels when compared with normotensives (n = 12; 24-hour blood pressure: 124 +/- 6/81 +/- 6 mm Hg), and higher dopamine values (hypertensives: 64.6 +/- 58; normotensives: 26.2 +/- 31 pg/ml; p < 0.05). A positive correlation was observed between dopamine and diastolic nocturnal blood pressure (p < 0.05) while a negative correlation was found between dopamine and nocturnal diastolic blood pressure reduction (p < 0.025). No significant relationship was observed between both norepinephrine and epinephrine, and 24-hour blood pressures. CONCLUSIONS: Since previous reports have documented malfunctioning of dopaminergic system in hypertension, the higher levels of circulating plasma dopamine found in hypertensive patients in the present study may account for a peripheral compensatory increase. The correlation between dopamine and nocturnal blood pressure fall seems to indicate that the impairment of dopaminergic system may influence the 24-hour blood pressure profile, affecting the nocturnal blood pressure reduction.     

Use of dynamic two-dimensional transesophageal echocardiography for renal cell carcinoma with cavoatrial tumor thrombus

Previous investigations involving continuous blood pressure (BP) monitoring have shown an important alteration of the 24-hour BP profile in patients with obstructive sleep apnea syndrome (OSAS). We investigated the impact of REM sleep on the 24-hour BP cycle in 16 severe OSAS male patients (mean respiratory disturbance index = 66 +/- 16 events/hour of sleep), with hypertension (mean BP 162 +/- 21/105 +/- 11 mmHg World Health Organization (WHO) protocol). Two successive nights of polysomnography were performed, and arterial BP was monitored continuously during the second 24-hour period after brachial artery cannulation. During the daytime, subjects were kept awake and supine. At 3 p.m. BP was continuously monitored during quiet supine wakefulness for 20 minutes. Systolic, diastolic and mean BP and heart rate (HR) were analyzed and tabulated in mean values of 5 minute segments. Sleep/wake information were correlated with cardiovascular variables. Each uninterrupted REM sleep period was identified and comparison between the period of quiet supine wakefulness and REM sleep HR and BP values was performed. 8 OSAS patients presented a normal drop of the mean arterial BP during the nocturnal REM sleep periods compared to quiet supine wakefulness (mean value = -10.8 +/- 7.3 mmHg) ("dippers") while the other 8 subjects ("REM sleep non dippers"), revealed an elevated mean arterial BP during REM sleep (mean value = 18.9 +/- 10.9 mm Hg). The absence of the normal circadian BP dip seen during the nocturnal sleep period is considered as an indication of vascular risk. The REM sleep non dipping may play a role in this risk.     

Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients

Several studies have shown that n-3 polyunsaturated fatty acids (n-3 PUFA) are able to lower blood pressure (BP) in humans, but large doses of fish oils have been often used. Moreover, most of the studies available in the literature were not able to evaluate the specific effects of n-3 PUFA because they employed fish oils which contain, together with n-3 PUFA, many other different components. The aim of this preliminary study was to evaluate if medium-term supplementation with a moderate dose of highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl esters is able to reduce BP in mild hypertensive patients. Sixteen mild essential hypertensive (diastolic BP: 95-104 mm Hg), non-diabetic, normolipidemic male outpatients and 16 normotensive male controls were recruited to participate in the study. Both hypertensive and control subjects were randomly assigned to receive either EPA and DHA ethyl esters (2.04 g EPA and 1.4 g DHA) as active treatment or olive oil (4 g/day) as a placebo for a period of 4 months. These subjects were followed up with 24-hour ambulatory BP monitoring and blood chemistry analyses at 2 and 4 months of treatment and 2 months after its discontinuation. The intake of n-3 PUFA was checked by red blood cell (RBC) phosphatidylcholine (PC) fatty acid composition. The effect of n-3 PUFA on BP in the active group was maximum after 2 months. Both systolic (-6 mm Hg, p<0.05) and diastolic (-5 mm Hg, p<0.05) BP significantly decreased during the n-3 PUFA ethyl ester supplementation. No further effect was observed at 4 months with a return to baseline values during the recovery period. These data indicate that 4 g/day of highly purified EPA + DHA ethyl esters are able to favorably affect BP in mild hypertensives.     

Epidemiology of extrapulmonary tuberculosis among persons with AIDS in the United States

We compared the antihypertensive efficacy of once-daily amlodipine (AM) versus nitrendipine (NTR) by 24-h ambulatory blood pressure monitoring (24-h ABPM) in 32 patients with mild to moderate essential hypertension (EH). After a 2-week single-blind, placebo run-in period, patients were randomized in a double-blind, parallel fashion: 14 received AM 5 mg and 18 NTR 10 mg. After 2 weeks, dose was adjusted if necessary (AM 10 mg or NTR 20 mg) and continued for another 6-week period. At the end of the placebo period and during the last week of treatment, patients underwent 24-h ABPM. Initial office BP mean values were similar in both groups (169.8 +/- 14/102.5 +/- 6 vs. 167.1 +/- 14/98.7 +/- 5 mm Hg, respectively, p = NS). A comparable decrease in office mean values of systolic BP (SBP, -22.3 +/- 13 vs. -19.1 +/- 16 mm Hg) and diastolic BP (DBP, -12.0 +/- 5 vs. -8.1 +/- 8 mm Hg) was observed. Nevertheless, 24-h ABPM mean values differed significantly between patients treated with AM or NTR with regard to 24-h SBP (120.0 +/- 10 vs. 132.5 +/- 1 mm Hg, p = 0.01). Moreover, the average decrease in 24-h SBP (-19.3 +/- 6 vs. -5.2 +/- 11 mm Hg, p = 0.0036) and 24-h DBP (-10.7 +/- 4 vs. -3.7 +/- 6 mm Hg, p = 0.0047) was higher in the AM group, with no changes in 24-h heart rate (HR). At equivalent once-daily dosage, AM was more effective than NTR in decreasing BP assessed by 24-h ABPM.     

Impact of ambulatory blood pressure on left ventricular diastolic dysfunction in uncomplicated arterial systemic hypertension

To determine the relations of 24-hour blood pressure (BP) and its different phases with left ventricular (LV) diastolic filling, 125 subjects (mean age 46 years) not taking cardiac drugs were studied by Doppler echocardiography and ambulatory BP recording. Subjects (excluding those with coronary artery or valvular heart disease, heart failure, or diabetes) were classified into 2 groups according to the level of Doppler-derived ratio of peak early to atrial velocity (E/A ratio): 59 had E/A >1 (normal diastole), 62 had E/A <1 (impaired diastole), and 4 had E/A = 1. Patients with E/A <1 were older and had higher LV mass indexed for height, average 24-hour BP, average nighttime BP, and lower day-night BP decrease, whereas average daytime BP did not differ significantly between the 2 groups. Negative correlations of E/A were found with age, heart rate, office, average 24-hour and average nighttime systolic and diastolic BP, and LV mass index. In a multivariate model that included potentially confounding factors, only age (standardized beta coefficient = -0.52, p<0.00001), nighttime BP (beta = -0.28, p<0.0001), and heart rate (beta = -0.22, p<0.001) were independent predictors of E/A in the pooled population. In conclusion, LV diastolic function is more closely related to ambulatory, rather than to clinic, BP measurements, and high average nocturnal diastolic BP is a powerful marker of LV filling impairment.     

Multiple injuries in peacetime and wartime estimate of severity of injury by the Injury Severity Score and Polytraumaschlüssel

The aim of this study was to evaluate the efficacy and tolerability of valsartan, a new angiotensin II receptor antagonist, versus atenolol in the treatment of severe primary hypertension. A total of 103 adult out-patients were randomised to receive either valsartan 160 mg or atenolol 100 mg once daily for 6 weeks. If necessary, additional blood pressure (BP) control could be provided as add-on therapy. Both valsartan and atenolol decreased mean sitting diastolic BP (DBP) and mean sitting systolic BP (SBP): least squares mean change from baseline in DBP; valsartan, -20.0 mm Hg; atenolol, -20.4 mm Hg: in SBP; valsartan, -30.0 mm Hg; atenolol, -25.5 mm Hg. There was no statistically significant difference between the treatment groups. Add-on hydrochlorothiazide (HCTZ) 25 mg was required by 97.2% of patients receiving atenolol and 83.6% of patients receiving valsartan; additional verapamil SR 240 mg was also required by 58.3% of patients receiving atenolol and 64.2% receiving valsartan. Valsartan was well tolerated, with a comparable incidence of treatment-related adverse experiences in both groups. In conclusion valsartan 160 mg is as well tolerated and effective as atenolol 100 mg in lowering BP in severely hypertensive patients.     

Low dosages of felodipine ER once daily as monotherapy in elderly hypertensive patients: effect on ambulatory blood pressure and quality of life

OBJECTIVE: To establish the efficacy of 24-h ambulatory and casual blood pressure (BP) reduction, and the tolerability of once daily felodipine extended release (ER) 2.5 mg and felodipine ER 5 mg as monotherapy. DESIGN: Randomised, double-blind placebo controlled 6 weeks parallel study. SETTING: From 15 general practices centres (with 19 GPs) in the region of the University of Maastricht, The Netherlands. SUBJECTS: A total of 129 subjects aged 50-80 years with primary hypertension were screened; 27 men and 61 women with a casual diastolic BP of 100-115 mm Hg and/or a systolic BP of less than 200 mm Hg entered the study. MAIN OUTCOME MEASURES: Casual and 24-h ambulatory BP and a subjective symptom assessment (SSA) questionnaire after 6 weeks of therapy. RESULTS: After correlation for placebo response the mean casual systolic/diastolic BP (SBP/DBP) reduction was 10/5 mm Hg (NS) and 12/10 mm Hg (P < 0.05) for felodipine ER 2.5 and 5 mg, respectively. By using 24-h ambulatory BP measurements these reduction were 6/4 mm Hg (NS) and 13/8 mm Hg (P < 0.05), respectively. No significant difference for SBP and DBP was found during the night time between felodipine 2.5 and placebo (-1/0). Felodipine ER 5 mg lowered the BP load significantly during both daytime and night time but felodipine ER 2.5 mg only for DBP during the daytime. There was a significant difference for the number of responders between placebo (28%) vs felodipine ER 2.5 mg (55%) and ER 5.0 mg (59%). Both felodipine dosages and placebo were comparable in (a low) number of adverse events and results of the SSA. CONCLUSIONS: During daytime felodipine ER 2.5 mg and 5 mg are effective in BP lowering in elderly hypertensive patients. However, only felodipine ER mg is effective in reducing BP during night time (22.00-7.00). Only felodipine ER 5 mg has a significant reducing effect on BP load during day and night time. Both felodipine ER 2.5 and ER 5.0 have a significant effect on the responder rate. It appeared from this study that compared to placebo, and in contrast with felodipine ER 5 mg, the ER form of felodipine 2.5 mg has no BP lowering effect during night time in elderly patients. To assess the effectivity during night time of felodipine ER 2.5 mg in an individual patient it is recommendable to measure the BP at the end of the dose interval.     

Indomethacin does not attenuate the hypotensive effect of trandolapril

This is a randomised, double-blind, placebo-controlled, four-way crossover study to determine if indomethacin attenuates the hypotensive effect of trandolapril. Twenty-three hypertensive patients (diastolic blood pressure (DBP) 95-115) requiring NSAID were recruited. Seventeen completed the study. Three week treatment periods: trandolapril 2 mg od and indomethacin 25 mg tds, trandolapril 2 mg and placebo, indomethacin and placebo, placebo and placebo. Clinic and ambulatory BP after 3 weeks of each treatment. Study had 85% power to detect a 5 mm Hg difference in BP (s.d. 7 mm Hg). End of treatment clinic BPs were: 152.9/98 mm Hg (95% CI 147.2, 158.6/95.8, 101.4) with placebo and placebo; 150.4/94.9 mm Hg (95% CI 144.7, 156.1/92.1, 97.7) with trandolapril and indomethacin; 148.2/96.5 mm Hg (95% CI 142.5, 153.9/93.7, 99.3) with trandolapril and placebo; and 156.6/97.4 mm Hg (95% CI 150.9, 162.3/94.6, 100.2) with indomethacin and placebo. There were no significant interactions between trandolapril and indomethacin for clinic systolic BP (SBP) (P = 0.79) or clinic DBP (P = 0.87). When trandolapril treatments (placebo or with indomethacin) were compared to treatments without trandolapril (placebo or indomethacin), trandolapril lowered clinic SBP by 5.4 mm Hg (P = 0.047) and DBP by 2.3 mm Hg (P = 0.08). Mean ambulatory BP was: 140.6/88.2 mm Hg (trandolapril and placebo); 142.8/89.7 mm Hg (trandolapril and indomethacin); 149.6/95.0 mm Hg, (indomethacin and placebo); 147.7/94.0 mm Hg (placebo and placebo). Compared with placebo, trandolapril and placebo lowered BP by 6.5/7.5 mm Hg (P < 0.001, SBP; P < 0.001, DBP). Compared with indomethacin, trandolapril and indomethacin lowered BP by 5.0/5.5 mm Hg (P = 0.001, SBP; P < 0.001, DBP). In the present study trandolapril 2 mg lowered clinic SBP and ambulatory BP, but indomethacin did not attenuate this. Indomethacin had no significant effect on either clinic or ambulatory BP. The antihypertensive effects of trandolapril in this study were modest. Patient selection factors may have contributed to the observed responses, but it seems unlikely from these data that a clinically important drug interaction has occurred.     

The cardiovascular and subjective effects of thyrotropin releasing hormone (TRH) and a stable analogue, dimethyl proline-TRH, in healthy volunteers

1. The cardiovascular effects of TRH 0.5 mg and 1 mg and a stable TRH analogue, dimethylproline-TRH (RX77368) 1 mg, infused intravenously over 1 min were assessed in healthy volunteers in two randomised, double-blind, placebo controlled crossover studies. 2. Both doses of TRH produced significant but transient increases in blood pressure (peak delta systolic: 0.5 mg = 9.2 mm Hg, 1.0 mg = 5.2 mm Hg; peak delta diastolic: 0.5 mg = 6.4 mm Hg, 1.0 mg = 5.4 mm Hg). 3. Beat-to-beat Finapres monitoring demonstrated a rapid onset of effects of RX77368 1 mg, with significant blood pressure effects by 45-60 s from the start of the infusion (delta systolic BP: 14.2 mm Hg, delta diastolic BP: 15.8 mm Hg and delta heart rate: 8.9 mm Hg at 60 s). 4. The pressor effects of RX77368 1 mg recorded by Dinamap (peak delta systolic: 14.3 mm Hg; peak delta diastolic: 11.8 mm Hg) were sustained, with diastolic pressure still elevated (delta diastolic: 8.2 mm Hg) at 60 min. Heart rate was more transiently elevated (peak delta heart rate: 9.0 beats min-1) during the first 6 min post infusion. 5. Mild apprehension was reported for the first 6 min after RX77368 1 mg, whereas paraesthesiae were noted after TRH. Otherwise both drugs were similar in the type (flushing, nausea, acid taste, urethral sensations) and duration of subjective effects.     

Effect on verapamil on ventricular function: studies in denervated human heart

Verapamil has complex influences on ventricular function owing to its direct myocardial effects, vasodilation, and reflex activation of the sympathetic nervous system. To investigate the direct myocardial effects of verapamil in humans independent of reflex sympathetic stimulation, we administered the drug to 13 recent heart transplant recipients with denervated ventricles. Hemodynamics and radionuclide angiograms were recorded at baseline, with altered loading conditions, and after intravenous (i.v.) verapamil (median dose 4 mg). Left ventricular (LV) systolic and diastolic function was analyzed by systolic pressure-volume relations (SPVR) and peak filling rate (PFR), respectively. Verapamil caused a decrease in blood pressure (BP) and heart rate (HR) with increases in right atrial pressure (RAP 6 +/- 3-8 +/- 3, p < 0.01) and pulmonary artery wedge pressure (PAWP, 9 +/- 3-11 +/- 3 mm Hg, p < 0.01) pressures. LV ejection fraction (EF) decreased (69 +/- 7-66 +/- 8%, p < 0.02) in association with an increase in LV end-systolic counts (3.45 +/- 1.27 to 4.72 +/- 1.78 kcts, p < 0.001). In 11 of 13 patients, the SPV point after verapamil administration was decreased from the line established during altered loading conditions. PFR (4.05 +/- 0.81 to 4.11 +/- 0.76 EDV/s) was unchanged. In the denervated ventricle, verapamil has negative chronotropic and inotropic effects with minimal effects on PFR.     

Comparative accuracy of three automated techniques in the noninvasive estimation of central blood pressure in men

Automated devices have regularly replaced manual sphygmomanometry for the determination of blood pressure not only in homes and clinics, but also in emergency and critical care settings. Few studies exist that correctly assess the accuracy of these devices, and even fewer that specifically compare commercially available units that rely on different physiologic events for measurement. Six hundred pressure measurements were obtained from 120 subjects using 1 of 3 randomly selected blood pressure monitors. In addition, central arterial pressure measurements were obtained simultaneously and directly from the ascending aorta of each subject. Overall, these devices tended to overestimate diastolic (+2.5 mm Hg, p < 0.0001) and mean (+3.8 mm Hg, p < 0.0001) pressures, but not systolic (+0.7 mm Hg, p = NS) pressure. Compared with the other 2 devices, device I, relying on oscillometric detection, demonstrated a significantly smaller mean absolute error for diastolic pressure (4.9 +/- 3.0 vs 7.0 +/- 4.8 and 6.2 +/- 5.3 mm Hg, p < 0.0001) and mean pressure (4.0 +/- 3.2 vs 7.8 +/- 5.9 and 8.6 +/- 7.5 mm Hg, p < 0.0001), and a trend toward smaller error with systolic pressure (6.8 +/- 6.5 vs 7.3 +/- 6.8 and 8.0 +/-5.6 mm Hg, p = 0.19). Clinically significant (+/-10 mm Hg) errors were common with each device (24.8% overall), but serious (+/-20 mm Hg) errors were unusual (3.2%) and did not occur at all with device I during diastolic and mean pressure measurement. All of the devices tested could be expected to perform satisfactorily in most clinical settings provided that an average error of 4.0 to 8.6 mm Hg is tolerable. This level of accuracy typically extended throughout the range of pressures anticipated in most noncritical clinical situations. As implemented in the devices tested, noninvasive measurement by oscillometry with stepped deflation is more accurate than automated auscultation.     

Diet and exercise intervention have favourable effects on blood pressure in mild hypertensives: the Oslo Diet and Exercise Study (ODES)

The purpose of this study was to investigate the effect of 1-year diet intervention, exercise intervention and both combined on blood pressure (BP) in normotensives and mild hypertensives. Two hundred and nineteen sedentary middle aged men and women with slightly deranged coronary heart disease (CHD) risk factors were randomised to a control, a diet, an exercise and a diet + exercise group. Based on baseline diastolic BP, participants were divided into tertiles, giving baseline average BP of 141.4/96.7 in tertile 1, 130.7/87.6 in tertile 2 and 121.9/79.0 in tertile 3. The 1-year net-difference in BP between the intervention groups and the control group decreased across the tertiles; in tertile 1 being -11.2/-6.7 (p < 0.05), -11.3/-6.7 (p < 0.05 for systolic BP only) and -7.0/-5.1 (NS) in the combined, diet and exercise group respectively. Triglycerides, HDL cholesterol, and insulin variables were significantly and favourably changed, the changes being most marked in the combined group. The results show that diet and diet + exercise are about equally effective in reducing BP, and the effects may be dependent on the baseline level. Within the upper tertile of baseline BP, the decline in BP in the combined intervention and the diet group are almost comparable to those obtained with drug treatment. In addition, other important CHD risk factors were all changed in a beneficial direction.     

Nocturnal blood pressure elevation in patients with type 1 diabetes receiving intensive insulin therapy compared with that in patients receiving conventional insulin therapy

Studies have shown that type 1 diabetic patients may suffer from nocturnal elevation in blood pressure and that this elevation may be related to hyperinsulinemia. In this study we tested the hypothesis that tight type 1 diabetes control, which is usually accompanied by hyperinsulinemia and subclinical nocturnal hypoglycemia, may result in a higher rise in nocturnal blood pressure compared with conventional type 1 diabetes control. Eighteen patients treated with intensive insulin therapy (multiple daily injections; IIT) were compared with 18 patients treated with conventional insulin regimens (twice daily injections of regular and intermediate acting insulin; CIT). Both groups were matched for age, sex, duration of diabetes, body weight, body mass index, baseline daytime blood pressure, and microalbuminuria levels. Hemoglobin A1c was lower in the IIT group compared with that in the CIT group (8.1 +/- 1.2% vs. 11.0 +/- 3.2%; P < 0.01). The amount of insulin/body weight (units per kg) was higher in the IIT group than that in the CIT group (1.0 +/- 0.2 vs. 0.7 +/- 0.2 U/kg; P < 0.05). In all patients, a 24-h ambulatory blood pressure was recorded. The nocturnal diastolic blood pressure was higher in the IIT group (66 +/- 9 mm Hg) than in the CIT group (55 +/- 4 mm Hg; P < 0.01). The nocturnal decline in both systolic and diastolic blood pressure was lower in the IIT group (7 +/- 5 and 6 +/- 4 mm Hg, respectively) compared with that in the CIT group (13 +/- 6 and 16 +/- 6 mm Hg, respectively; P < 0.01). The nocturnal heart rate was higher in IIT group than in the CIT group (81 +/- 12 vs. 67 +/- 9/min; P < 0.05). These findings show that the intensive insulin therapy regimen may have a more deleterious effect than the conventional insulin therapy regimen on the nocturnal blood pressure of patients with type 1 diabetes.     

Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin

Fatigue is an important symptom of a disturbed circadian rhythm. To date, no studies of circadian rhythms in patients with chronic fatigue syndrome (CFS) have been published. The objectives of the study were to study rhythms of heart rate and systolic and diastolic blood pressure in patients with chronic fatigue syndrome compared with age-matched normotensive controls and to study the effects of melatonin and inopamil on such rhythms. Ambulatory blood pressure (ABP) measurements (Space Lab, Inc, validated) of 18 patients with CFS were made according to the 1987 U.S. Center for Disease Control Criteria, and measurements of 12 age-matched normotensive controls were used in a cosinor analysis of the two groups. The effects of melatonin and inopamil on ABP were studied subsequently in four patients in an 8-week open-label evaluation. One patient was hypertensive (diastolic blood pressure > 90 mm Hg at least once every 4 hours), and was, therefore, excluded. The data of the remaining 17 patients (15 women, 2 men) revealed a significant 12-hour rhythm in heart rate and 24-hour rhythm in systolic and diastolic blood pressure with 95% confidence intervals not significantly different from sinusoidal patterns. Although these rhythms were synchronous with the control group rhythms, their amplitudes were not and showed, respectively, 2.8, 2.8, and 9.0 times the size of the control group rhythms (p < 0.001, p < 0.001, and p < 0.0001, respectively). Systolic blood pressures in the patients with CFS were consistently below 100 mm Hg during the nighttime. In a subsequent pilot study of four patients from the study population treated with melatonin 4 mg daily and inopamil 200 mg daily for 4 weeks, inopamil reduced nighttime hypotension (p < 0.05), whereas melatonin increased nighttime hypotension (p < 0.02). Patients with CFS have increased amplitudes of circadian rhythms and systolic blood pressures consistently below 100 mm Hg during the nighttime. Positive inotropic compounds may be beneficial in such patients, but melatonin may not be.