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.     

Acute effects of ketanserin on left ventricular function, metabolism and coronary blood flow

An acute intravenous bolus of 10 mg ketanserin (a specific 5-HT antagonist) caused an abrupt fall in left ventricular systolic pressure of 17 +/- 9.2 mm Hg (P less than 0.025) in ten patients undergoing cardiac catheterisation for chest pains. A fall in pulmonary artery diastolic pressure of 2.1 +/- 0.74 mm Hg (P less than 0.02) was also observed. No changes in resting heart rate occurred and the response to pacing was largely unmodified by ketanserin, except for a reduction in pulmonary vascular resistance (3.70 +/- 1.27 units to 2.97 +/- 1.44 units, P less than 0.05), at the fastest rate (136 +/- 3 beats/min). At the highest pacing rate coronary sinus blood flow fell (83 +/- 12 ml 100 g-1 min-1 to 68 +/- 8 ml 100 g-1 min-1, P less than 0.05), as did myocardial oxygen consumption (18 +/- 2 ml-1 min to 14 +/- 1 ml min-1, P less than 0.05) after the drug. No changes in the parameters of left ventricular contractile function could be attributed to ketanserin, save for a modest increase in the ejection fraction (48 +/- 6% to 57 +/- 6%, P less than 0.05) in seven patients. There were no alterations in myocardial metabolism of lactate, pyruvate, hydroxybutyrate, glycerol nor free fatty acids after ketanserin. The findings are consistent with a peripheral site of action of this drug and its blood pressure lowering effect in the subjects suggest a non-specific hypotensive action rather than an anti-hypertensive effect.     

Studies with fenoldopam, a dopamine receptor DA1 agonist, in essential hypertension.

A series of studies were undertaken to assess the effect of oral fenoldopam, a specific DA1 dopamine receptor agonist on blood pressure and renal function in patients with mild essential hypertension. Six patients with essential hypertension were entered into a dose-ranging study and received either placebo, 25, 50 or 100 mg fenoldopam. A significant, dose-related reduction in diastolic blood pressure, and increase in heart rate was demonstrated (both P less than 0.05), maximal at 45 min to 1 h. Fenoldopam increased plasma renin activity. In a double-blind study, seven patients received a single dose of fenoldopam 100 mg or placebo. Fenoldopam produced a significant fall in systolic (P less than 0.05) and diastolic (P less than 0.01) blood pressure and renal vascular resistance (P less than 0.01). Urine flow rate (P less than 0.05), sodium excretion (P less than 0.01), plasma renin activity (P less than 0.05) and plasma aldosterone (P less than 0.05) increased. Five patients underwent measurement of the above parameters following a single dose of fenoldopam 100 mg with a repeat of these measurements after they had taken fenoldopam 100 mg four times daily for 1 month. The acute response of blood pressure to the single dose appeared unchanged but tachyphylaxis was evident in the responses of heart rate, plasma renin activity and plasma aldosterone.     

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.     

Influence of metoprolol and cilazapril on blood pressure and on sleep apnea activity.

Up to 50% of hypertensive men are subject to sleep apnea (SA). With a prevalence in men of up to 10%, SA is a common illness and hypertension (HT) one of its early symptoms. It is important to have available a drug treatment that will effectively control blood pressure (BP) without exacerbating symptoms of SA. Twelve patients with SA and HT were investigated in a double-blind, comparative trial. Patients were randomly allocated to either metoprolol (M) 100 mg daily or cilazapril (C) 2.5 mg daily. Polysomnographic measurements under standardized conditions including intraarterial BP monitoring were taken on two consecutive nights each before and after the 1-week treatment. Values in the M group were (mean +/- 95% CI) systolic BP 161 +/- 2.1 vs. 148 +/- 2.2 mm Hg (p less than 0.01); diastolic BP 98 +/- 1.8 vs. 93 +/- 1.8 mm Hg (p less than 0.01); and HR 73 +/- 1.2 vs 65 +/- 1.1 beats/min (p less than 0.01). Corresponding figures for the C group were systolic BP 140 +/- 2.1 vs. 127 +/- 2.1 mm Hg (p less than 0.01); diastolic BP 95 +/- 1.7 vs. 78 +/- 1.7 mm Hg (p less than 0.01); and HR 82 +/- 1.1 vs. 79 +/- 1.2 beats/min (p less than 0.01). Whereas C reduced both BP and HR in all sleep phases, M produced no changes during REM sleep. SA activity was 45 (range 15-91) vs. 34 (range 2-57) apneas per hour of sleep in the M group and 54 (range 21-84) vs. 40 (range 8-72) apneas per hour in the C group (p less than 0.01). There were no changes in total sleep time or in the proportions of non-REM to REM sleep. Both M and C reduce nocturnal BP in SA patients, but the effect of C is seen in all sleep phases. C has a more favorable effect on the disturbed nocturnal blood pressure of SA patients.     

Contribution of the vagus to the haemodynamic responses following intravenous boluses of isoprenaline.

1 Eight healthy subjects (six male, two female, aged 18-21 years) received graded intravenous bolus injections of isoprenaline sulphate. Heart rate and intra-arterial blood pressure were continuously monitored PRE- and POST-atropine (0.04 mg/kg). 2 PRE-atropine, an increase in heart rate of 25 beats/min was produced by 2.15 +/- 0.53 micrograms of isoprenaline and was associated with a fall in mean, systolic and diastolic pressures (18.9 +/- 2.8, 17.7 +/- 3.4 and 20.4 +/- 2.3 mm Hg respectively). 3 POST-atropine, the heart rate dose response curve was shifted to the right so that the dose of isoprenaline which increased heart rate 25 beats/min PRE-atropine, produced a significantly smaller heart rate rise of 20.3 +/- 1.7 beats/min (P less than 0.001). This was associated with a shift of the blood pressure dose-response curves to the left, and larger falls in mean, systolic and diastolic pressures (30.9 +/- 2.8, 31.8 +/- 3.3, 30.1 +/- 3.3 mm Hg respectively; P less than 0.01). 4 It is concluded that there is a significant contribution from a reflex withdrawal of cardiac vagal tone, to the tachycardia produced by a bolus of isoprenaline.     

The effect of felodipine on forearm haemodynamics and the myogenic response of the forearm resistance vessels in normal man.

The effect of felodipine 10 mg oral solution or placebo on peripheral haemodynamics and the response of the forearm resistance vessels to venous occlusion was studied in seven normotensive individuals. Felodipine produced a significant fall in diastolic blood pressure (DBP max = -15 mm Hg), a rise in heart rate (heart rate max = +15 beats min-1) (both P less than 0.01), and an overall fall in calculated forearm vascular resistance (calculated forearm vascular resistance max = -19.6 units, P less than 0.001). Felodipine had no significant effect on the vasodilator response, but limited the vasoconstrictor response following venous occlusion. These observations suggest that felodipine is a potent vasodilator and interferes with the myogenic response of vascular smooth muscle of the forearm resistance vessels.     

Atenolol and chlorthalidone in combination for hypertension.

1 The hypotensive effect of single daily dosing with atenolol 100 mg and chlorthalidone 25 mg given alone or in combination has been assessed in a double-blind, crossover, placebo controlled trial in fifteen hypertensive patients. 2 Average lying blood pressures were: Placebo 155.4/103.9 mm Hg, atenolol 134.6/85.8 mm Hg, chlorthalidone 139.5/90.1 mm Hg, combination 127.7/82.5 mm Hg. 3 The effect of the combination therapy in reducing lying diastolic pressure compared with placebo (a fall of 21.4 mm Hg) was significantly less than the 31.9 mm Hg fall predicted from the sum of the individual effects (P = 0.01). 4 Observations on blood pressure at rest and under mental, isometric and bicycle ergometer stress were made pre-dose and post-dose for a 12 h period at the end of the last treatment period. 5 Lying blood pressure declined from the zero hour (pre-dose) reading on all treatments to a low at 15.00--18.00 h and then rose again. 6 The rise in systolic blood pressure after isometric exercise and mental stress was of a similar magnitude with all four treatment regimes. 7 Atenolol, alone and in combination with chlorthalidone, reduced the blood pressure and the pulse rate increase on exercise 2 h post-dose when compared with readings 24 h post-dose. 8 Once daily dosing with a combination of atenolol and chlorthalidone produced a fall in supine blood pressure over a 24 h period but the effect on exercise induced changes was not uniform over this period.     

The effects of rilmenidine and atenolol on mental stress, dynamic exercise and autonomic function in mild to moderate hypertension.

1. The effects of 4 week treatment with rilmenidine or atenolol on tests of mental stress, dynamic exercise, autonomic function and psychometric tests were evaluated in a randomized, double-blind, placebo-controlled, cross-over study. 2. After a 4 week placebo run-in, 12 patients with essential hypertension (blood pressure [BP] 160/95 +/- 15/7 mmHg) received rilmenidine 1-2 mg day-1, and atenolol 50-100 mg day-1, each for 4 weeks, with a 4 week placebo wash-out between drug treatments. 3. Both agents produced a comparable reduction in supine and erect BP. During the mental arithmetic test, BP and heart rate (HR) responses were similar for rilmenidine and atenolol. 4. During bicycle exercise, the increase in HR was significantly greater after rilmenidine (+50 vs 41 beats min-1, P = 0.04). During recovery, the areas under the curve for diastolic BP (46,450 vs 51,400 mmHg s, P = 0.02) and HR (49,445 vs 63,597 beats min-1 s, P = 0.001) were significantly less with atenolol than rilmenidine. 5. Neither rilmenidine nor atenolol affected mental performance as judged by arithmetic and psychomotor tests. Physiological responses to autonomic function tests (deep breathing, facial immersion, isometric handgrip and cold pressor) were preserved with both drugs. The standing to lying ratio was higher on atenolol (P = 0.01) and Valsalva ratio was higher on rilmenidine (P = 0.03). 6. In conclusion, rilmenidine and atenolol exerted comparable antihypertensive effects both at rest and during mental and dynamic stress. Atenolol attenuated HR responses to dynamic exercise and the Valsalva manoeuvre; rilmenidine did not interfere with the physiological responses of BP and HR during autonomic function tests.     

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)     

Comparative effects of angiotensin II on Doppler parameters of left and right heart systolic and diastolic blood flow.

1. The purpose of the study was to investigate the effects of angiotensin II on Doppler parameters of right ventricular systolic and diastolic blood flow, and to compare these with effects on the left heart, in normal subjects. 2. Pulsed-wave Doppler measurements were made in eight normal volunteers: after a 30 min control i.v. infusion of dextrose, after 30 min stepwise infusions of angiotensin II (2, 4 and 6 ng kg-1 min-1), and finally 30 min after stopping the 6 ng kg-1 min-1 dose of angiotensin II. Aortic (Ao) and pulmonary (Po) systolic ejection parameters, as well as mitral (Mi) and tricuspid (Tc) diastolic filling parameters were measured. 3. Ao and Po maximal velocity were both significantly reduced by angiotensin II, whereas there were significant opposite effects on Ao (reduced) and Po (increased) mean acceleration. There was a dose-related fall in Po acceleration time with angiotensin II, whilst Ao acceleration time remained unchanged. 4. Mi and Tc early diastolic filling velocities were not significantly altered by angiotensin II compared with baseline, although there was a significant rebound increase in both Mi and Tc early filling after cessation of angiotensin II infusion. Mi and Tc pressure half-times were not significantly changed. 5. In conclusion, angiotensin II produced changes in Po ejection parameters consistent with a pressor response in the pulmonary vascular bed. Neither right nor left ventricular diastolic filling were directly affected by angiotensin II. The differential effects of angiotensin II on Po and Ao ejection parameters might be due to inherent differences in basal pulmonary and systemic vascular tone.     

Multicenter evaluation of the hemodynamic effects of bisoprolol in patients with mild to moderate hypertension

Twenty-six patients with mild-to-moderate essential hypertension participated in a 6-week outpatient, multicenter, randomized, double-blind, placebo-controlled two-way crossover study to assess the hemodynamic effects of bisoprolol (20 mg QD) at steady state. Hemodynamic assessments included sitting blood pressure, heart rate, and left-ventricular ejection fraction by radionuclide ventriculography after 7 days of bisoprolol or placebo at trough (24 h post-dose) and peak (3 h post-dose) values. The group adjusted mean ejection fraction was not significantly different in patients receiving bisoprolol compared with the placebo group at either peak or trough measurements; in fact, means in patients taking bisoprolol were slightly higher than in the placebo group. No symptomatic hypotension was documented. Blood pressure, measured 24 hours after dosing, was significantly lower in those receiving bisoprolol when compared with the placebo group, by 7.7 mm Hg and 9 mm Hg for diastolic and systolic blood pressure, respectively. Similarly, mean values of heart rate were 10 beats/min lower in the bisoprolol patients than in the placebo group. Only headache and insomnia occurred as adverse events. Bisoprolol (20 mg QD) effectively lowered blood pressure over a 24-hour period without significantly reducing ejection fraction or causing adverse clinical or biochemical events.     

甲磺酸罗哌卡因致荨麻疹

1例42岁女性患者行右侧甲状腺次全切除术,术前心率80次/min,血压130/80 mm Hg(1 mm Hg=0.133 kPa)。采用利罗合剂(2%利多卡因10 ml+0.894%甲磺酸罗哌卡因10 ml)行双侧颈神经丛阻滞麻醉。10 min后患者胸部出现荨麻疹,心率110次/min,血压155/110 mm Hg,随后腹部与下肢均出现荨麻疹,心率125次/min,血压160/100 mm Hg。即刻给予吸氧,静脉注射地塞米松10 mg,5 min后荨麻疹有所减退。又肌内注射苯海拉明20 mg,5 min后心率95次/min,血压140/90 mm Hg,荨麻疹完全消失。     

Propranolol disposition in patients with hepatosplenic schistosomiasis

Eight Sudanese patients with hepatosplenic schistosomiasis and seven Sudanese controls were administered a single oral dose of long acting (LA), propranolol 160 mg; blood propranolol levels were measured at regular intervals for 12 h using g.l.c. In patients with hepatosplenic schistosomiasis, propranolol blood concentrations were greater (P less than 0.05) at all time intervals, Cmax 63.5 (29-143) ng ml-1 (median and range) than controls Cmax 23 (12-37) ng ml-1. Median AUC0-12 was also greater (P less than 0.05) (533 and 218 ng ml-1 h respectively), tmax were not significantly different. In patients and controls prior to treatment, standing heart rate (77.5 (60-110), 72 (68-74) beats min-1) systolic (120 (105-150), 110 (100-120) mm Hg) and diastolic blood pressure (75 (60-90), 70 (60-80) mm Hg) were not significantly different. However following propranolol administration a reduction (P less than 0.05) occurred in both systolic (median 20 mm Hg) and diastolic (median 12.5 mm Hg) blood pressure in the patients compared with controls. Heart rate was reduced by a median of 10 beats min-1 in both groups. These observations indicate that propranolol bioavailability in patients with hepatosplenic schistosomiasis is increased possibly due to reduced presystemic extraction.     

Antihypertensive monotherapy and cardiovascular responses to an acoustic startle stimulus

To determine contribution of the autonomic nervous system to cardiovascular reactivity to noise, acoustic startle stimulus (110 dB, 1-20 kHz, 0.150 s) was administered to 35 subjects (19 women, 16 men) with mild essential hypertension. Among these patients, 10 were unmedicated and 25 were receiving long-term monotherapy (10 were taking 100 mg atenolol, 5 were taking 10 mg prazosin, and 10 were taking 50 mg losartan daily). Polygraphic recordings were obtained in supine position. Blood pressure (BP) and heart rate (HR) levels were stable until the noise was administered. In the unmedicated group BP and HR were elevated during the first 10 s. BP returned to resting levels after this period. The calculated hemodynamic indexes showed a biphasic change in total peripheral resistance (TPR), with an overall vasoconstriction associated with the BP rise phase, preceding a delayed vasodilation. The lowest HR changes were observed in the beta-blocker group with increases of 6 beats/min and 3 beats/min after the first and second noise stimulations, compared with 10 beats/min and 5 beats/min in the unmedicated group. Prazosin significantly reduced the BP rises to 7 mm Hg and 6 mm Hg for systolic BP and diastolic BP after the first stimulation compared with 22 mm Hg and 17 mm Hg in the untreated group (p < 0.01). The second stimulation after prazosin determined -5 mm Hg and 1 mm Hg changes for systolic BP and diastolic BP respectively, compared to rises of 13 mmHg for systolic BP and 10 mmHg for diastolic BP in the untreated group (p < 0.01). The hemodynamic percentage changes resulting from the first stimulation indicated prazosin markedly reduced the noise-induced rise in TPR (p < 0.05). No effect of beta-blocker was detectable using percentage changes. The rises in BP were amplified in the losartan-treated subjects compared with the other groups. Because of a low resting TPR in this group, the percentage changes in TPR resulting from noise were amplified in the subjects treated with the AT1 receptor antagonist. In conclusion the acoustic startle stimulus appeared as a simple and reliable procedure for inducing transient increases due to a rise in TPR. Cardiovascular responses differed according to the antihypertensive monotherapy, with a limited effect of noise in the prazosin-treated group.     

Sustained-release diltiazem: duration of antihypertensive effect

The antihypertensive activity of a sustained-release preparation of diltiazem (given each 12 hours) was assessed in 96 patients with supine diastolic blood pressure (BP) between 95 and 110 mm Hg in a multicenter, randomized, double-blind, placebo run-in, parallel-group trial comparing optimally titrated doses of diltiazem and placebo. The aim was to assess the onset of action as well as the extent and variability of BP control of this formulation during the 12-hour interval. Diltiazem was titrated from 120 mg bid to 180 mg bid as necessary to lower BP. At baseline, on the first day of titration, and at the end of 8 weeks, BP was evaluated at 0, 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours after dosing. The onset of action was within 2 hours, and the effect was maintained throughout the 12-hour period. Mean BP for the diltiazem group at baseline was 154/101 mm Hg. At week 8, BP was 148/93 mm Hg at hour "0" (P less than .02 and P = .0001 for systolic and diastolic BP vs. placebo), 139/84 mm Hg at the nadir at hour 5 (P = .0001), and 149/91 mm Hg at the end of the 12-hour period (P less than .02 and P = .0001 for systolic and diastolic BP). Diltiazem was significantly more effective than placebo (P = .0001) with 50% of patients controlled to a diastolic pressure of less than 90 mm Hg at 7 of the 10 evaluation points, including the evaluation point of 12 hours post-dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Controlled trial of ketanserin in hypertension.

We have completed a double-blind parallel group comparison of the 5-HT2 receptor antagonist ketanserin with placebo in 22 hypertensive patients. Ketanserin (20-40 mg twice daily) lowered sitting blood pressure more than placebo by 6.9 mm Hg systolic (NS), 13.1 mm Hg diastolic (P less than 0.05) and by 11.4 mm Hg mean arterial pressure (P less than 0.02). The fall in standing blood pressure was similar and we observed no first dose hypotensive effect. Ketanserin lowered the sitting heart rate by 11.1 beats/min (P less than 0.01). The drug was well tolerated.     

Method specificity of the auscultatory estimates of the inodilatory reduction of diastolic blood pressure based on Korotkoff IV and V criteria.

1. Non-invasive measurements of blood pressure (BP) are method-specific estimates of actual blood pressure. The agreement of the auscultatory Korokoff V ('disappearance' of sound, kv) and Korokoff IV ('sound muffling' kiv) cut-off points in measuring diastolic blood pressure (DBP) was evaluated in healthy subjects in the presence of various controlled inodilatory interventions. 2. Eating (n = 8), 10 min i.v. infusion of 1 microgram min-1 isoprenaline and adrenaline (n = 12), p.o. administration of 40 mg of the PDE-III inhibitors isomazole and meribendan (n = 18) and p.o. administration of 1200 mg celiprolol (n = 15) caused evident chrono-inodilatory responses: average HR increases of 7, 19, 10, 17, 17 and 8 beats min-1, estimated CO increases of 1.6, 4.5, 2.3, 1.9, 2.6 and 1.8 1 min-1 and average shortening of QS2c of 18, 41, 8, 37, 42 and 9 ms for food, isoprenaline, adrenaline, isomazole, meribendan and celiprolol, respectively. 3. In general, there was good agreement between DBPkV and DBPkIV measurements before the administration of the inodilatory treatments (bias DBPkV-DBPkIV: 1-2 mm Hg) but the extent of inodilatory DBP reduction (-8, -6, -10, -2, -7 and -8 mm Hg according to DBPkIV for food, isoprenaline, adrenaline, isomazole, meribendan and celiprolol, respectively) was substantially overestimated when based on Korotkoff-V rather than -IV (bias DBPkV-DBPkIV in estimating the inodilatory effect on DBP: -8, -12, 1, -13, -12 and -7 mm Hg for food, isoprenaline, adrenaline, isomazole, meribendan and celiprolol, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative haemodynamic effects of intravenous lignocaine, disopyramide and flecainide in uncomplicated acute myocardial infarction.

A prospective study evaluated the comparative haemodynamic effects of three Class I antiarrhythmics (lignocaine Class 1B, disopyramide Class 1A and flecainide Class 1C) in 30 patients with uncomplicated acute myocardial infarction. Three groups, each of 10 patients, were allocated to lignocaine (Group I) 1.5 mg kg-1 i.v. loading dose over 10 min followed by infusion at 3 mg kg-1 h-1, disopyramide (Group II) or flecainide (Group III), both administered as a 1.0 mg kg-1 i.v. loading bolus over 10 min followed by a 1.6 mg kg-1 h-1 infusion for 120 min. The plasma levels of each drug were in the described therapeutic range. Lignocaine decreased cardiac index (-0.3 l min-1 m-2 (9%); P less than 0.05) and stroke volume index (-5 ml m-2 (11%); P less than 0.01). Systemic blood pressure, heart rate and systemic vascular resistance index were unchanged. There was a small increase (+3 mm Hg (30%); P less than 0.01) in pulmonary artery occluded pressure (PAOP). Both disopyramide and flecainide increased systemic blood pressure; the maximum increases for mean blood pressure were +10 mm Hg (11%) and +4 mm Hg (4%) respectively. Both drugs reduced cardiac index (-0.5 l min-1 m-2 (16%): -0.4 l min-1 m-2 (11%)) and stroke volume index (-11 ml m-2 (25%): -5 ml m-2 (11%)). There were increases in heart rate (+13: +5 beats min-1) pulmonary artery occluded pressure (+2: +3 mm Hg) and systemic vascular resistance index (+696: +275 dyn s cm-5 m2).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of intravenous prenalterol on ventricular performance, as assessed by radionuclide ventriculography, in patients with ischaemic heart disease.

1 We have observed the effects of intravenous prenalterol (1 mg and 2 mg) on ventricular performance, assessed by radionuclide ventriculography, in nine patients with ischaemic heart disease with varying degrees of impairment of ventricular performance. In seven of these patients the effects of prenalterol were compared with those of isoprenaline infused at 1 microgram/min. 2 Prenalterol caused no significant increase in heart rate, but systolic blood pressure increased by 26% (P less than 0.002). In contrast, isoprenaline caused heart rate to increase by 22% (P less than 0.02) and diastolic blood pressure to fall by 9% (P less than 0.01). 3 Left ventricular ejection fraction (LVEF) increased with both drugs, but the increase was greater with isoprenaline, as was the fall in the ratio mean ejection time: left ventricular ejection time, which is an index of improved ventricular performance. 4 Because of the increased heart rate and stroke volume produced by isoprenaline, cardiac output increased 45% above control values (P less than 0.001), but the increase in cardiac output after prenalterol did not reach statistical significance. 5 In three patients with very poor ventricular function (LVEF less than 0.30) prenalterol had little effect on ejection fraction, and caused increased regional ventricular dyskinesia. 6 The increase in systolic blood pressure, and therefore cardiac afterload brought about by prenalterol may limit ventricular response. The response might be enhanced by the addition of vasodilator therapy.