L G Howes

Atrial Fibrillation After Coronary Artery Bypass Grafting Is Associated With Sympathetic Activation

BACKGROUNDnWe prospectively investigated the role of sympathetic activation in the etiology of atrial fibrillation following coronary artery bypass grafting.nnnMETHODSnContinuous ambulatory monitoring was performed for 80 hours in 131 patients after coronary artery bypass grafting. Right atrial plasma norepinephrine levels were assessed preoperatively and every 4 hours for 48 hours postoperatively.nnnRESULTSnOf the 131 patients, 50% (65) had development of atrial fibrillation and 36% (47) required treatment. Onset of atrial fibrillation was preceded by a significant increase in sinus rate and atrial ectopic activity. On multivariate logistic regression, elevated mean postoperative norepinephrine levels (5.78 +/- 2.83 versus 3.57 +/- 1.31 nmol/L; p < 0.0001), increased age (68.9 +/- 5.7 versus 63.8 +/- 8.7 years; p = 0.02), and decreased postoperative magnesium levels (0.79 +/- 0.09 versus 0.83 +/- 0.10 mmol/L; p = 0.02) were independently associated with the occurrence of atrial fibrillation.nnnCONCLUSIONSnElevated norepinephrine levels suggest that sympathetic activation may be important in the pathogenesis of atrial fibrillation after coronary artery bypass grafting, and this underlines the importance of beta-adrenoceptor blockade as prophylaxis.

Effects of pravastatin on cardiovascular reactivity to norepinephrine and angiotensin II in patients with hypercholesterolemia and systemic hypertension.

This study was conducted to examine the effects of short-term cholesterol reduction on cardiovascular reactivity in mildly hypertensive patients. Seven male and 7 female patients, aged 34 to 68 years, received pravastatin (40 mg/day) or matched placebo for 3 weeks in a randomized, double-blind, crossover study. Cardiovascular reactivity was assessed by measurement of blood pressure (BP) responses to incremental infusions of angiotensin II and norepinephrine, by cold pressor testing and isometric exercise. Compared with placebo, pravastatin caused significant reductions in plasma total and low-density lipoprotein cholesterol levels, which averaged 20% and 31%, respectively (both p < 0.0001), and in diastolic BP responses (expressed as the infusion rate required to raise BP by 20 mm Hg) to both angiotensin II (7.3 +/- 3.0 vs 9.7 +/- 4.7 ng/kg/min, p = 0.05) and norepinephrine (0.15 +/- 0.13 vs 0.38 +/- 0.33 micrograms/kg/min, p = 0.03). Systolic BP responses were similar with both treatments. Body weight, resting BP, and maximal BP responses to physical stressors were similar with each treatment.

Age Related Changes of Catecholamines and Their Metabolites in Central Nervous System Regions of Spontaneously Hypertensive (SHR) and Normotensive Wistar-Kyoto (Wky) Rats:

Adrenaline (A), dopamine (DA), noradrenaline (NA) the NA metabolite 3,4-dihydroxyphenylethylene-glycol (DHPG) and the DA metabolite 3,4 dihydroxyphenylacetic acid (DOPAC) were assayed in brain regions of male and female WKY and SHR at 6, 14, 28 and 36-40 weeks. Age related differences in catecholamine levels between the two strains were only seen with NA measurements. DOPAC levels were elevated in the striatum of SHR compared to WKY rats at all ages studied which might reflect the known hyperactivity of SHR strain. In the SHR NA but not DHPG levels in several regions, DA and DOPAC levels in midbrain and DA levels in lower brainstem were elevated at 6 weeks of age. These changes may represent a generalized alteration in central catecholamine metabolism in SHR during the early development of hypertension or merely reflect strain differences. It is emphasised that further genetic studies of F2 backcross rats are required to establish an aetiological association between these differences in catechol levels and differences in blood pressure between SHR and WKY rats.

A study of the alpha-1 adrenoceptor blocker prazosin in the prophylactic management of autonomic dysreflexia in high spinal cord injury patients

The ability of the alpha-1 adrenoceptor antagonist, prazosin, to reduce the severity and duration of episodes of autonomic dysreflexia was studied in cervical and high thoracic spinal cord injury patients with documented episodes of autonomic dysreflexia. Sixteen patients participated in a double blind parallel group study comparing prazosin 3 mg b.d. with placebo given for 2 weeks. Both groups were matched for age, sex and baseline severity of autonomic dysreflexia episodes. Prazosin was well tolerated and did not produce a significant lowering of resting blood pressure. Compared to baseline measurements, patients allocated to prazosin therapy were found to have fewer severe episodes of autonomic dysreflexia and during these episodes to have significant reductions in average rise in systolic and diastolic blood pressure, symptom duration and requirement for acute antihypertensive medication. The severity of headache during individual autonomic dysreflexia episodes was also diminished with prazosin therapy. No symptom parameter was significantly altered by placebo therapy. It is concluded that prazosin is superior to placebo in the prophylactic management of autonomic dysreflexia and that these findings are consistent with suggestions that alpha-1 adrenoceptors play an important role in the pathogenesis of this syndrome.

Short Term Effects of Pravastatin on Blood Pressure in Hypercholesterolaemic Hypertensive Patients

In this study, which was primarily designed to determine the lipid-lowering efficacy of pravastatin in the setting of background antihypertensive therapy with ACE inhibitors and calcium antagonists, we took the opportunity to examine whether pravastatin interacts with antihypertensive therapy to produce additional falls in blood pressure. This may help clarify the mechanism of action of pravastatins rapid beneficial effects on cardiovascular morbidity. We treated 25 hypertensive hypercholesterolaemic patients with 12 weeks of either pravastatin or placebo in this double blind, placebo controlled parallel group study. Placebo treatment did not alter plasma lipids, whereas 12 weeks treatment with pravastatin reduced total cholesterol by 27% (from 7.1 +/- 0.27 to 5.2 +/- 0.18, p < 0.001 compared with placebo) and low density lipoprotein cholesterol by 35% (from 4.9 +/- 0.36 to 3.2 +/- 0.17, p < 0.001). There were no changes in systolic or diastolic blood pressure either following 12 weeks treatment or 3 weeks withdrawal of pravastatin. Thus, pravastatin remains efficacious as a lipid lowering agent in the presence of antihypertensive therapy but does not enhance the blood pressure lowering action of these drugs. Therefore it is unlikely that blood pressure reduction is the mechanism by which pravastatin mediates its reported short term effects on cardiovascular morbidity.

COMPARISON OF THE PHARMACOKINETICS AND PHARMACODYNAMICS OF PERINDOPRIL, CILAZAPRIL AND ENALAPRIL

1. The pharmacokinetic and pharmacodynamic responses to enalapril, perindopril and cilazapril have been studied in essential hypertensives (2, 4 and 8 mg perindopril and 2.5 mg cilazapril, single dose and steady state) and normotensive volunteers (10 mg enalapril, single dose).

Effects of Dietary Lipid Modification on Adrenoceptor-Mediated Cardiovascular Responsiveness and Baroreflex Sensitivity in Normotensive Subjects

To examine the effects of short-term dietary lipid modification on alpha- and beta-adrenoceptor-mediated cardiovascular responsiveness, 19 normal volunteers consumed either a high-fat or a low-fat diet for 2 weeks in an open, randomized, crossover study of 6 weeks duration. Diets were balanced for sodium and potassium content. Adrenoceptor-mediated cardiovascular responsiveness was assessed by measuring blood pressure and heart rate responses to incremental infusions of phenylephrine and isoprenaline. Baroreflexes were studied by examining heart rate responses to phenylephrine and to the Valsalva manoeuvre. Total plasma cholesterol and low-density lipoprotein cholesterol levels both fell significantly (by 22% and 26%, respectively), on the low-fat compared with the high-fat diet, as did resting supine blood pressures and heart rate (by 6 mmHg systolic and 3 mmHg diastolic, and 5 beats/min). These changes were accompanied by a significant reduction in the systolic blood pressure response to isoprenaline. Blood pressure responses to phenylephrine and baroreflex sensitivity did not change. These results suggest that dietary fat intake alters cardiac beta-adrenergic reactivity without significant effects on vascular alpha-adrenoceptor mediated responses or baroreflexes.

Atrial Tachyarrhythmias Following Coronary Bypass Surgery: Sympathetic Mechanisms

The development of atrial tachyarrhythmias following cardiothoracic surgery has long been recognised[1]. In an initial series published in 1943, of seventy-eight patients who underwent total pneumonectomy, five developed transient atrial fibrillation (AF) and two atrial flutter, most episodes occurring within two weeks of surgery[1]. None of these patients had organic heart disease and none subsequently developed a sustained atrial arrhythmia. Since then a number of larger series have shown that the incidence of atrial arrhythmias is higher in patients having larger operative procedures, with advancing age, pre-existing cardiovascular disease and with carcinoma of the lung particularly with pericardial involvement[2,3].

Acute effects of exercise on plasma lipids, noradrenaline levels and plasma volume.

1. Total plasma cholesterol, high‐density lipoprotein cholesterol (HDL‐C), low density lipoprotein cholesterol (LDL‐C), noradrenaline, haematocrit, haemoglobin and heart rate were measured in blood sampled from an antecubital vein in nine volunteers after 1 min standing and at intervals up to 1 h following 5 min of vigorous bicycle exercise.

Postural hypotension in elderly patients given carvedilol.

First dose postural hypotension is commonly observed with antihypertensive drugs,1,2 but its incidence may be overstated in clinical trials because of protocol requirements, which may include frequent venesection, fasting, acute withdrawal from caffeine, and frequent changes in posture.1 The s blocker vasodilator drug carvedilol is associated with orthostatic hypotension, particularly in elderly people.*RF 234* We assessed the incidence of first dose hypotension in the absence of possible confounding factors linked to protocol.nnThe study group comprised 16 elderly patients (nine men; mean (SD) age 70 (6) mean weight 73 (17) kg) with uncomplicated mild or moderate hypertension whose supine diastolic blood pressures were 90-110 mm Hg after one weeks washout with placebo after antihypertensive treatment. Previous studies showed that a sample of 10-18 subjects would produce an 80% chance of detecting a difference in response of 10 mm Hg between treatments at the …