Effect of the combination of alinidine and other anti-anginal drugs on heart rate and blood pressure in healthy volunteers.

1. Heart rate and blood pressure changes following the administration of alinidine 30 mg alone and in combination with atenolol 25 mg, nifedipine retard 20 mg and glyceryl trinitrate 500 micrograms were investigated in three groups of six healthy male volunteers. 2. Concomitant administration of alinidine and atenolol reduced (P less than 0.05) supine, standing and exercise heart rate when compared with alinidine alone. The maximum reduction in exercise heart rate was 116 +/- 2.4 beats min-1 for the combination vs 129.0 +/- 3.1 beats min-1 for alinidine alone. 3. Supine (3, 4, 8 h) and standing (2 h) systolic BP were also reduced (P less than 0.05) with the alinidine and atenolol combination compared with alinidine alone. Little change occurred in diastolic blood pressure. 4. Alinidine and nifedipine in combination reduced (P less than 0.05) the nifedipine induced increase in heart rate in the supine (2, 4 h) and standing (4 h) position and following exercise (2, 4 h). No further decreases in systolic and diastolic blood pressure occurred with the combination. 5. Alinidine administered 2 h before a glyceryl trinitrate challenge reduced (P less than 0.05) the glyceryl trinitrate induced increase in standing heart rate at all time intervals (1 to 6 min); the maximum reduction occurred at 3 min (105.0 +/- 4.3 (glyceryl trinitrate) vs 86.8 +/- 6.7 beats min-1 (combination]. Systolic blood pressure was further reduced at all time intervals with glyceryl trinitrate taken in the presence of alinidine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationships between heart rate and PR interval during physiological and pharmacological interventions.

The relationships between heart rates (HR) and corresponding PR intervals (PR) were studied in 12 healthy young subjects during rest, standing and graduated treadmill exercise to heart rates of 160 to 170 beats min-1 and during the infusion of isoprenaline to heart rates of 100 to 110 beats min-1. During exercise, PR diminished with increasing HR. Over the range of HR from 60 to 160 beats min-1 all 12 individual subjects exhibited negative linear correlations between HR and PR described by the equation: PR (ms) = -0.351 HR (beats min-1) + 176.7 for composite data. During isoprenaline infusion the PR interval also diminished with increasing heart rate. Over the range of HR from 60 to 110 beats min-1, 11 of the 12 subjects exhibited negative linear correlations between HR and PR described by the equation: PR (ms) = -0.582 HR (beats min-1) + 186.5 for composite data. The exercise model was used to study the indirect (or rate-dependent) effects and the direct actions on atrioventricular conduction of beta-adrenoceptor blocking drugs and calcium channel antagonists, alone and in combination, in three groups of healthy subjects. Control and placebo observations on HR and PR at rest, standing and during exercise in these additional subjects also exhibited individual inverse linear relationships between HR and PR. Following the administration of beta-adrenoceptor blockers, PR were prolonged more than expected at the HR observed. Rate-adjusted PR prolongation during exercise exceeded standing which exceeded resting, indicating greater beta-adrenoceptor blockade in atrioventricular nodal tissue than in sinoatrial nodal tissue at each level of activity.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of a week's beta-adrenoceptor antagonism on daytime heart-rates, subjective responses to exercise, and physical activity in normal subjects.

The effects on heart rate (HR) and physical activity of 1 week's treatment with three different beta-adrenoceptor antagonists (20 mg betaxolol (Lorex); 160 mg propranolol LA; or 100 mg atenolol daily) have been compared with placebo in a double-blind study of 12 normal men. On the fifth day of each treatment a body-borne tape-recorder was worn during waking hours for recording of ECG and footfall signals. Each record was calibrated in terms of the subject's response to laboratory ergometer exercise, and a computer analysis provided objective indices of physical activity. While on beta-adrenoceptor antagonists the subjects perceived standard exercise as significantly harder than on placebo and reported more side-effects (albeit mild and transient). Ambulatory monitoring of HR showed that subjects spent 13% of their waking day at heart rates below 50 beats min-1 while on propranolol, compared with 1% on placebo and 20% on atenolol and betaxolol. On these latter drugs, the group spent as much as 10% of their waking time with HR below 45 beats min-1. The lowest individual heart-rates recorded were below 35 beats min-1. Objective indices of physical activity, such as the duration of periods spent with heart rates above the HR found at 100 W in the ergometer test, showed no differences between the treatments. This negative finding was confirmed by pedometer step counts over the whole week.     

Indomethacin and cognitive function in healthy elderly volunteers.

1. The aim of this randomised, double-blind four way crossover study was to assess the interaction between the new calcium antagonist, lacidipine and atenolol, in patients with mild to moderate hypertension. 2. Sitting blood pressure at 4 h post-dosing with lacidipine (4 mg) and atenolol (100 mg) alone was significantly lower compared with placebo (137/89 +/- 3/3 mmHg; 142/89 +/- 5/3 mmHg; and 154/98 +/- 5/3 mmHg respectively; P < 0.001). Co-administration of both drugs produced a significant additive effect compared with atenolol and lacidipine alone (124/80 +/- 4/2 mmHg; P < 0.002). 3. Heart rate on treatment with lacidipine alone was significantly greater at 4 h compared with placebo (86 +/- 1 beats min-1 and 74 +/- 2 beats min-1 respectively; P < 0.001). When both drugs were used in combination, there was a significant decrease in pulse rate compared with lacidipine alone (58 +/- 1 beats min-1 and 86 +/- 1 beats min-1 respectively; P < 0.001). 4. Home blood pressure recordings confirmed the statistically significant reduction in blood pressure on co-dosing (120/82 +/- 10/2 mmHg) compared with lacidipine (140/92 +/- 5/3 mmHg) and atenolol (146/90 +/- 6/3 mmHg) given alone (P < 0.05). 5. Lacidipine alone produced a significant exercise tachycardia compared with atenolol alone and the atenolol/lacidipine combination (97 +/- 8 beats min-1; 65 +/- 4 beats min-1 and 75 +/- 7 beats min-1 respectively; P < 0.001). Exercise tolerance was not adversely affected by the co-administration of both lacidipine and atenolol.     

Autonomic components of the cardiovascular responses to an acoustic startle stimulus in rats

1 A loud acoustic stimulus was administered to rats prior to and after treatment with autonomic blockers in order to unravel the autonomic mechanisms of the blood pressure (BP) and heart rate (HR) responses to startle. 2 Six rats, implanted with a BP telemetric system, were used in a randomized crossover saline-controlled (saline vs. autonomic blocker) study with a washout period of 7 days between each active session. A first acoustic stimulus (110 dB, 0.7 s) was administered. An autonomic blocker i.e. atropine methylnitrate (15 mg. kg^?1), atenolol (15 mg. kg^?1) or prazosin HCl (1 mg. kg^?1), or physiological saline was administered i.p. 40 min prior to a second identical acoustic stimulus. 3 The average BP rise following the first stimulus was +25 mmHg and the average HR change was +17 bpm. The responses after autonomic blockades were affected as follows: atropine increased the HR rise (+45.1 ± 1.7 bpm), atenolol reversed the HR changes to a bradycardic response (?21.4 ± 9.1 bpm), after prazosin treatment the BP rise was reversed into a BP decrease (?11.3 ± 3.2 mmHg) and the HR increase was amplified (+76.0 ± 10.0 bpm). Finally, the delay for obtaining the maximal BP change was increased from 1.9 to 2.6 s following prazosin pretreatment. 4 These results indicate that the BP rise resulting from an acute loud noise depends on a vascular sympathetic activation (prevented with prazosin), which is partly blunted by vasodilation (revealed with prazosin). The evoked HR changes combine a sympathetic activation (fully expressed following atropine) and a vagal activation (unmasked with atenolol). Further experiments are necessary to document the vasodilatory component unmasked with prazosin.     

Effects of single doses of quinapril and atenolol on autonomic nervous function and exercise capacity in healthy volunteers

Summary The effects of single oral doses of the angiotensin converting enzyme (ACE) inhibitor quinapril (CI-906) 40 mg and the cardioselective -adrenoceptor blocker atenolol 100 mg on sympathetic and parasympathetic function and on exercise capacity have been studied in 8 healthy young men. The trial followed a double-blind, placebo controlled, randomized cross-over design, with at least one week between treatments.Blood pressure (BP) and heart rate (HR) at rest were slightly reduced by atenolol but were not affected by quinapril. Atenolol impaired the sympathetically mediated increases in HR and BP caused by standing, immersion of the hand into melting ice, the Valsalva manoeuvre and isometric forearm exercise. Quinapril did not influence those responses nor the vagally mediated bradycardia of the diving reflex. Atenolol, however, augmented the vagal bradycardia, presumably by sympathetic inhibition. In a dynamic bicycle ergometer test with a stepwise increasing work load, exercise performance was decreased by atenolol but not by quinapril. Inhibition of the renin-angiotensin system by quinapril was shown by a marked decrease in serum ACE activity and a several-fold increase in plasma renin activity (PRA). Atenolol produced a moderate reduction in PRA. Before or during exercise, plasma noradrenaline and adrenaline were not influenced by either drug.The results indicate that, unlike the atenolol-induced -adrenoceptor blockade, ACE inhibition by a single dose of quinapril had no clear effect on autonomic nervous function or exercise capacity.Preliminary results from this study were presented at the XX Congress of the Nordic Society of Military Medicine, Helsinki, 14–16 May, 1987, and were published in 1988 in Ann Milit Med Fenn, 63 (1–2)     

Investigation of the effects of physiological and vasodilation-induced autonomic activation on the QTc Interval in healthy male subjects

AIMS: Drug-induced prolongation of the QTc interval is an important marker for potential proarrhythmic action. Prolongation of the QTc interval results from alteration of the ionic currents that regulate cardiac repolarisation. Such effects may result from direct drug action or alternatively they could also occur indirectly by drug-induced modulation of autonomic tone, which is known to regulate cardiac repolarization. This study examined the effects of physiological and drug-induced autonomic activation on heart rate, QT and QTc intervals. METHODS: We studied 29 healthy male subjects aged 18-30 years. Electrocardiographs were recorded before and during autonomic activation induced by mental activation, standing, exercise and glyceryl trinitrate (GTN) (0.5 mg sublingual)-induced vasodilation in the presence and absence of beta-blockade (atenolol 100 mg daily for 4 days). QT intervals were measured manually by electronic callipers and corrected using the Fridericia formula. RESULTS: Heart rates were significantly increased during mental arithmetic, standing, exercise and GTN and this effect was significantly attenuated by atenolol, except for mental activation. QTc intervals were significantly reduced on standing and exercise and this was significantly attenuated by atenolol during exercise. In contrast, GTN increased QTc intervals (Delta = 5.7 ms, confidence interval +/- 3.2 ms, P < 0.005) and this was not attenuated by atenolol. CONCLUSIONS: Alteration in QTc intervals may result from physiological manoeuvres and vasodilation, interventions known to induce autonomic activation. We suggest that QTc prolongation due to GTN is indirectly mediated and unlikely to carry any proarrhythmic effect. Understanding whether drug-induced QTc prolongation is directly or indirectly mediated may be important to determine any potential proarrhythmic risk.     

Clinical studies with the potassium channel activator cromakalim in normotensive and hypertensive subjects.

Eight normotensive subjects received single and multiple doses of cromakalim (1 mg) and placebo in a randomised double-blind cross-over study to examine general tolerance to cromakalim and its effects on blood pressure (BP), heart rate (HR), and pressor responses to norepinephrine (NE) and angiotensin II (AII). In a second study, 10 hypertensive patients whose BP control was unsatisfactory with atenolol 50-100 mg received additional treatment with placebo followed by cromakalim 1 mg daily for 4 weeks. Assessments were made of BP, HR, apparent hepatic blood flow and renal blood flow (RBF), pulmonary function, and the pharmacokinetics of atenolol. Cromakalim was generally well tolerated in both normotensive and hypertensive subjects. In the normotensive group, cromakalim produced a reflex increase in HR without any detectable decrease in BP: average (placebo-subtracted) increases in HR at 4 h were 16 beats/min with subjects in an erect position after the single dose and 14 beats/min after 7 days. Cromakalim had no effect on pressor responses to NE and AII. Addition of cromakalim to atenolol was associated with modest further reductions in BP between 0.5 and 3 h after drug administration, with maximal reductions of 21/14 mm Hg (subjects in supine position) 2 h after the first dose. Cromakalim had no effect on apparent liver blood flow and RBF, pulmonary function, and the steady-state pharmacokinetics of atenolol. Single and multiple 1-mg doses of cromakalim are well tolerated but are associated with only modest vasodilator activity.     

Effects of fenoldopam, a specific dopamine receptor agonist, on blood pressure and left ventricular function in systemic hypertension.

1. The effects of fenoldopam, an orally active, specific dopamine-1 receptor agonist, were studied in eleven patients with essential hypertension, using intra-arterial blood pressure recording and equilibrium gated radionuclide angiography. 2. A single dose of fenoldopam 100 mg produced a fall in blood pressure (BP) starting after 20 min. The maximum BP reduction (23/25 mm Hg) occurred after 50 min and was accompanied by a heart rate (HR) increase of 10 beats min-1. The acute effects on BP lasted for 130 min. 3. After 8 weeks of fenoldopam 100 mg, twice daily, only a small, statistically insignificant, hypotensive effect was still apparent after each dose of drug. The duration of the effect was too short to be clinically useful. Tilt-testing produced a BP fall of 24/14 mm Hg and a HR increase of 17 beats min-1. Three patients experienced symptoms of postural hypotension during the study. 4. The drug attenuated the blood pressure rise produced by dynamic cycle exercise and isometric hand grip. 5. Acute administration of fenoldopam increased the left ventricular ejection fraction from 61% to 71% (P less than 0.005) and increased the peak filling rate from 2.52 to 3.86 end diastolic vol s-1 (P less than 0.002). After chronic fenoldopam administration, the left ventricular ejection fraction was 65% (P = NS) pre-dose, rising to 69% (P less than 0.02) post-dose and the peak filling rate was increased from 2.7 to 3.38 end diastolic vol s-1 (P less than 0.01) 60 min post-dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of digoxin on the heart in normal subjects: influence of isometric exercise and autonomic blockade: a noninvasive study.

1. Eight healthy subjects were studied before digoxin and after successive therapy periods of 1 week 0.125, 0.25 and 0.50 mg of digoxin. The mean serum concentrations (+/- s. d.) were 0.4 +/- 0.2, 0.6 +/- 0.3 and 1.4 +/- 0.5 nmol l-1, respectively. The effects of digitalis were studied by echocardiography and systolic time intervals at rest and after 3 min handgrip exercise. Effects of simultaneous autonomic blockade induced by atropine and propranolol were also examined. 2. Digoxin in increasing doses slowed the heart rate at rest; with the daily dose of 0.50 mg from 63 +/- 10 to 53 +/- 6 beats min-1, and fractional shortening rose from 28 +/- 6 to 33 +/- 3% (P less than 0.05 for both). Preload, afterload and cardiac output did not change. The electromechanic systolic time index (QS2I) decreased (P less than 0.001) and the observed alteration of QS2I was dose-related. 3. The influence of digoxin was similar during isometric exercise, except for unchanged fractional shortening. 4. During autonomic blockade digoxin slowed the intrinsic heart rate from 93 +/- 6 to 86 +/- 6 beats min-1 (0.25 mg) and to 83 +/- 6 beats min-1 (0.50 mg) (P less than 0.01 for both). QS2I was shortened (P less than 0.01). Echocardiographically determined ejection phase indices remained unchanged. 5. When handgrip stress was induced during autonomic blockade, digoxin evoked a clearcut increase in contractile function, resembling the effects of digoxin alone at rest. Thus, fractional shortening increased by 14% and QS2I decreased by 16 ms (P less than 0.01 for both). 6. We conclude that digoxin increases the contractility in normal heart without changes in loading conditions. The rise in inotropy at rest is obvious from both fractional shortening by echo and systolic time intervals. The same takes place during handgrip with autonomic blockade, when the heart lacks sympathetic support. The influence of long-term digoxin on heart rate is partly direct without autonomic mediation. The effect of digoxin is dose-dependent.     

Altered baroreflex control of heart rate in bradykinin B2-receptor knockout mice

Recently, we have shown that a knockout mouse strain lacking the bradykinin B2-receptor gene exhibits an accelerated heart rate (HR) under basal conditions, this alteration being associated with mildly elevated blood pressure (BP) levels and ultimately with the development of cardiomyopathy. The goal of the present study was to determine whether genetic disruption of the B2-receptor alters autonomic cardiovascular reflexes to acute or chronic changes in BP. The direct mean BP and HR levels of unrestrained B2 knockout mice (B2-/-) were higher than those of wild type (B2+/+) controls (131 +/- 2 vs. 105 +/- 2 mm Hg and 480 +/- 5 vs. 414 +/- 8 beats/min, P < 0.01 for both comparisons). The difference in HR observed between groups under basal conditions was nullified by the acute administration of propranolol and atropine as well as by hexamethonium; it was attenuated by long-term blockade of angiotensin AT1 receptors. In B2-/- mice, the presence of an alteration in baroreceptor regulation of HR was supported by a reduced gain in the HR responses to acute nitroprusside-induced hypotension or phenylephrine-induced hypertension (slope of the regression line: 0.82 +/- 0.07 vs. 5.58 +/- 0.08 beats/min per mmHg in B2+/+, P < 0.01), as well as by an exaggerated tachycardic response to chronic hypertension induced by clipping of the left renal artery (60 +/- 3 vs. 15 +/- 3 beats/min in B2+/+, P < 0.01). Our findings indicate that disruption of the bradykinin B2-receptor gene is associated with an impaired baroreflex control of HR. The combination of chronically elevated resting HR and impaired baroreflex control could contribute to the development of cardiomyopathy in these animals.     

Effects of atropine on left ventricular volumes and ejection and filling rates at rest and during exercise.

1. The influence of the parasympathetic nervous system on left ventricular function including ejection and filling rates was studied by radionuclide cardiography in eight healthy young men at rest and during upright exercise. 2. After parasympathetic blockade induced by atropine, the mean heart rate (HR) at upright rest increased from 67 to 114 beats min-1, cardiac output (CO) from 4.05 to 5.17 1 min-1 (both P less than 0.001), and the diastolic blood pressure by 13 mm Hg (P less than 0.01). 3. Stroke volume (SV), left ventricular end diastolic and end systolic volume all decreased significantly after atropine. The relative ejection time increased from 0.33 to 0.51 of the cardiac cycle length (P less than 0.001), and the appropriate ejection and filling rates increased by 13% (P less than 0.05) and 147% (P less than 0.001), respectively. Haemodynamic changes in the supine position were virtually the same. 4. During exercise atropine increased HR from 115 to 146 beats min-1 (P less than 0.001) and CO by 12% (P less than 0.05), whereas SV decreased by 12% (P less than 0.05) and the systolic blood pressure by 16 mm Hg (P less than 0.001). Changes in ejection and filling rate of the left ventricle were of the same nature as those found at rest. 5. Thus apart from its HR limiting properties, secondary effects of parasympathetic nervous tone are dilatation of the left ventricle and enhancement of ejection, effects that are counteracted by atropine.     

Pharmacodynamic without pharmacokinetic interaction between cicloprolol, a partial beta 1-adrenoceptor agonist, and digoxin in healthy subjects.

1. Cicloprolol is a partial beta 1-adrenoceptor agonist considered for the treatment of patients with coronary artery disease and impaired left ventricular function. In such patients, digoxin remains in widespread use. 2. We assessed the pharmacokinetic and pharmacodynamic interaction between oral cicloprolol 50 mg day-1 and oral digoxin 0.25 mg day-1 in 10 healthy male volunteers, using a double-blind, randomised protocol, during three 8 day periods. Digoxin was given alone during the first period to reach steady state; then digoxin was given with cicloprolol or placebo during the second and third periods, according to a cross-over design. 3. No significant adverse effects were observed. 4. The pharmacokinetics of digoxin were not different significantly at the end of the placebo-digoxin and cicloprolol-digoxin periods. 5. A significant increase in minimum heart rate and mean nocturnal heart rate, assessed by 24 h Holter recordings, was observed at the end of the cicloprolol-digoxin period as compared with the placebo-digoxin period (means +/- s.e. mean, 57.1 +/- 3.2 beats min-1 vs 52.2 +/- 3.1 beats min-1, P less than 0.01; and 65.6 +/- 3.8 beats min-1 vs 59.9 +/- 3.9 beats min-1, P less than 0.01, respectively). 6. A significant increase in left ventricular ejection fraction and shortening fraction, assessed by echocardiography, was noted at the end of the cicloprolol-digoxin period as compared with the placebo-digoxin period (means +/- s.e. mean, 66.4 +/- 1.4% vs 61.3 +/- 1.2%, P less than 0.05; and 37.0 +/- 1.1% vs 33.3 +/- 0.9%, P less than 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of atenolol, verapamil, and xamoterol on heart rate and exercise tolerance in digitalised patients with chronic atrial fibrillation

The aim of the study was to compare the effects of atenolol (50 mg b.i.d.), verapamil (80 mg b.i.d.), xamoterol (200 mg b.i.d.), and matching placebo on heart rate (HR) and exercise tolerance in digitalised patients with chronic atrial fibrillation. Each treatment was taken for 4 weeks, and digoxin was continued throughout the study. During treatment with placebo (digoxin alone), the mean postexercise heart rate was 164 beats/min, and four subjects had rates of greater than or equal to 170 beats/min. Atenolol, verapamil, and xamoterol achieved significantly better control of exercise-induced tachycardia, mean postexercise heart rates being reduced to 120, 131, and 130 beats/min, respectively (p less than 0.01 for each). However, minimum HRs less than or equal to 45 beats/min occurred during treatment with placebo, atenolol, and verapamil, whereas treatment with xamoterol was associated with a minimum heart rate of 56 beats/min. Treatment with atenolol was associated with a marked reduction in maximum treadmill walking distance (mean 356 m) as compared both with placebo (mean 421 m, p less than 0.01) and verapamil (mean 439 m, p less than 0.01). Xamoterol reduced maximum walking distances as compared with verapamil (402 vs. 439 m; p less than 0.05) but not placebo (402 vs. 421 m; NSS). Thus, atenolol, verapamil, and xamoterol achieved better control of exercise-induced tachycardia than digoxin, but atenolol clearly impaired exercise tolerance whereas verapamil did not. Xamoterol achieved more even control of ventricular response rates and prevented the resting bradycardias that occurred with the other treatments. However, walking distances were significantly lower than those noted during treatment with verapamil.     

Antianginal effects of atenolol and pindolol in patients with stable effort angina pectoris

A double blind, randomised crossover study with 20 patients was performed to compare the antianginal effects of atenolol 100 mg once daily and pindolol 5 mg thrice daily. After a placebo run-in period, 2 treatments were given for 2 wk each. The number of anginal attacks and the nitroglycerin (NTG) consumption were determined. During bicycle exercise testing, the systolic blood pressure (BP), heart rate (HR), double product and exercise tolerance were measured. Both drugs reduced the number of anginal attacks and NTG consumption relative to the placebo, with atenolol being more effective than pindolol. During exercise, both beta-blockers produced a slight increase in BP and HR compared to the placebo. HR attained with atenolol was lower than pindolol at the same workload. The total duration of exercise and the maximal tolerated workload were greater in atenolol than pindolol experiment. The special properties of beta-blockers, such as cardioselectivity or intrinsic sympathomimetic activity (ISA), may have clinical importance in the treatment of angina pectoris.     

应激状态下应用缓释维拉帕米及合用西拉普利的有益作用

目的 :探讨应激状态下缓释维拉帕米 (VerSR)及合用西拉普利 (Cil)的有益作用。方法 :5 4例原发性高血压病人 ,随机分为 3组 :VerSR组 19例(VerSR 2 4 0～ 36 0mg ,po ,qd) ,Cil组 14例 (Cil 2 .5～ 5mg ,po ,qd) ,VerSR +Cil组 2 1例 (VerSR 12 0～ 2 4 0mg ,po ,qd +Cil 2 .5～ 5mg ,po ,qd)。 (1)随访服药后 1,2和 4wk后坐位血压 (BP)及心率(HR) ;(2 )服药前及服药后 4wk做心算、冷压、握掌试验及运动激发试验 ,观察BP ,HR及血浆去甲肾上腺素 (NE) ,肾上腺素 (E) ,多巴胺 (DA)的变化。结果 :(1)VerSR组总有效率 93% ,Cil组总有效率77% ,VerSR +Cil组总有效率 10 0 % (P >0 .0 5 ) ;(2 )VerSR能明显降低心算试验后的BP(1.7± 0 .9/1.3± 0 .7)kPa(P <0 .0 1)、冷压试验后的BP(2 .5±1.4 /1.2± 0 .9)kPa(P <0 .0 1)及握掌试验后的收缩压 (SBP) (1.6± 1.4 )kPa(P <0 .0 1) ;Cil仅能降低握掌试验后的SBP ,(1.1± 1.4 )kPa(P <0 .0 5 ) ;VerSR +Cil则明显降低心算试验后的BP(3.0± 2 .9/2 .1± 1.1)kPa(P <0 .0 1)和HR(10± 9)次·min- 1(P <0 .0 1)、握掌试验后BP(1.8± 1.6 /1.8± 0 .9)kPa(P <0 .0 1)和HR(6± 7)次·min- 1(P <0 .0 5 )及冷压试验后的SBP(1.9± 1.8)kPa(P <0 .0 1)。Cil对运动激发试?     

Correlation between short-term heart rate variability indices and heart rate, blood pressure indices, pressor reactivity to isometric handgrip in healthy young male subjects

The purpose of the present study was to determine whether readily measured blood pressure (BP) indices and, responses to autonomic reflex tests could be used as surrogates of short-term heart rate variability (HRV), which is an established marker of autonomic regulation of SA node. Therefore, we examined the correlation between short-term HRV and heart rate (HR), BP indices viz. systolic pressure, diastolic pressure, pulse pressure (PP), and rate-pressure product (RPP), during supine rest and head-up tilt in 17 young healthy normotensive subjects, aged 19.8 +/- 1 yr (mean +/- SD). Three classic autonomic indices viz. Valsalva ratio, HR response to deep breathing and pressor response to isometric handgrip were also determined. We noted two interesting and statistically significant (P < 0.05 in both cases) correlations viz. i) a positive correlation (r = 0.6) between change in RPP during tilt and change in low frequency (LF) RR spectral power expressed in normalized units (LF nu) during tilt, and ii) a negative correlation (r = -0.6) between change in PP during isometric handgrip and LF nu during tilt. The possible physiologic significance of these and other correlations is discussed in this paper. In conclusion, the presence of a statistically significant correlation between RPP, PP and spectral measures of short-term HRV supports a simplistic approach to autonomic assessment, in that, easily measurable BP indices could be used as surrogates of HRV when it is not feasible to determine HRV indices directly. However, the same have to be tested in healthy subjects belonging to various age groups and in patients with conditions known to be associated with autonomic dysregulation.     

The comparative beta-adrenoceptor blocking effects of penbutolol,atenolol and sustained-release metoprolol in healthy volunteers

Summary The effects of penbutolol (40 mg), atenolol (100 mg) and sustained-release metoprolol (metoprolol SA) (200 mg) upon heart rate (HR) and blood pressure (BP) at rest and during bicycle ergometer exercise, have been compared in 12 healthy young men using a double-blind crossover design. Measurements of each drug's effect were made before and at 3, 10 and 24 h after a single dose, and again at 24 h after the last of seven consecutive daily doses. Resting HR and systolic BP were reduced to an equivalent extent by all three drugs. During the third minute of exercise, the effects of penbutolol and atenolol upon HR and systolic BP were consistently similar and greater than those of metoprolol SA.     

Heart rate and blood pressure responses of left-handers and right-handers to autonomic stressors

We hypothesized that cerebral dominance may contribute to differences in cardio-vascular responses of right-handers (RH) and left-handers (LH) to autonomic stressors. We tested this hypothesis by exposing 14 RH, and 14 LH males to category I tests in which the hand and cerebral cortex were involved in performing the test viz.--i) Cold pressor test (CPT), ii) Handgrip dynamometry (HGD) and; category II (no use of hand)--i) Orthostatic Tolerance Test (OTT), ii) Valsalva Manuever (VM), iii) Controlled Breathing Test for sinus arrhythmia (SA) in a random sequence, and measured their heart rate (HR/min) and blood pressure (MAP mmHg). All subjects had similar resting HR and MAP values, and responded to the category I interventions with increased HR and BP. The absolute HR values of LH and RH did not differ significantly during the interventions. However, the increase in HR from control induced by the CPT, and the HGD was greater for LH (P<0.05). Also, LH showed a greater decrease in HR and MAP in the recovery phase (P<0.05). The VAS scores for degree of discomfort during the CPT were similar for both the groups. During the OTT, the increase in HR was more in RH (P<0.05). The Valsalva ratios for LH and RH were similar. Our findings suggest that the autonomic control over the cardio-vascular system may be different in LH and RH, and that this imbalance could be attributable to a variation in cerebral dominance.     

Effects of dilevalol (R,R-labetalol) compared with nifedipine on heart rate, blood pressure and muscle blood flow at rest and on exercise in hypertensive patients.

1. Dilevalol (R,R-labetalol) is a non-selective beta-adrenoceptor antagonist with beta 2-adrenoceptor agonist activity. Its effects after 1 month's administration on heart rate, blood pressure and muscle blood flow were studied in a double-blind crossover comparison with nifedipine in 16 hypertensive patients. 2. Dilevalol and nifedipine were similarly effective in lowering systolic and diastolic blood pressure at rest, but dilevalol limited the rise in systolic blood pressure induced by exercise more than nifedipine (rise of 27 vs 53 mm Hg respectively, P < 0.01). 3. Dilevalol decreased resting heart rate compared with nifedipine (73 vs 92 beats min-1 respectively, P < 0.01). Dilevalol limited the exercise induced rise in heart rate more than nifedipine (36 vs 48 beats min-1 respectively, P < 0.01). 4. Muscle blood flow (measured by strain gauge plethysmography) was not affected by either dilevalol or nifedipine at rest. After exercise, dilevalol caused an increase in excess blood flow compared with placebo (10.8 vs 5.1 ml min-1 dl-1 respectively, P < 0.01). The difference between dilevalol and nifedipine did not reach statistical significance (10.8 vs 6.5 ml min-1 dl-1 respectively, P > 0.05). 5. On blood pressure and heart rate, dilevalol demonstrated beta-adrenoceptor blocker activity at rest and on exercise. On muscle blood flow, dilevalol appeared to have no effect at rest, but may have acted as a beta-adrenoceptor blocker rather than as a beta 2-adrenoceptor agonist during exercise.