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Biomedical subjects

C A Howie

Publications and source records attributed to C A Howie.

47 records · Page 3Linked to original sources
PubMed1989

Electrocardiographic evidence of myocardial salvage after thrombolysis in acute myocardial infarction.

There is a need for a simple clinical measurement that will indicate the extent of myocardial salvage after successful thrombolysis. This study examined whether coronary artery reperfusion reduced the infarct size as assessed electrocardiographically after thrombolytic treatment. The sum of the (sigma) ST segment area in leads showing ST segment elevation in the 12 lead electrocardiogram at presentation was used as an index of potential myocardial injury (initial ischaemic index). The evolved infarct size at 48 h was assessed by a QRS scoring system. Two groups of patients, both admitted with anterior myocardial infarction within 6 h of onset, were studied. Group 1 (n = 35) received analgesia only and group 2 (n = 33) received thrombolytic treatment either by the intracoronary (streptokinase, n = 13) or intravenous route (anistreplase, n = 20). Reperfusion was assessed angiographically. The mean (SD) potential infarct size assessed by the initial ischaemic index was similar in both groups (group 1, sigma ST area = 115 (60) mm2 and group 2 = 126 (77 mm2). The QRS score representing evolved infarct size was significantly lower in the treated group (4.1 (2.5] than in group 1 (7.8 (2.6]. The 95% confidence intervals for QRS scores based on the admission sigma ST area from patients with successful reperfusion were applied to a third set of patients (n = 22) to test the ability of the admission ST area (myocardial injury) to predict the QRS score accurately. While patients with successful reperfusion had significantly lower QRS scores than those who did not (4.5 (3.1) versus 9.3 (3.4)), the wide confidence intervals caused by inter-individual variability precluded an accurate prediction of the QRS score in an individual from the sigma ST area at time of presentation. There was no difference in infarct size in patients treated early (</= 3 h) (QRS score 4.2(2.8)) or later (3-6 h) (4.1(2.1)). This study provides evidence that sequential electrocardiographic changes are reduced in patients with anterior infarction who achieve reperfusion after thrombolytic treatment and that this benefit is shown with treatment given up to six hours after infarct onset. None the less, the relation between the initial ischaemic index and the evolved QRS score has wide confidence intervals, reflecting inter-individual variability, and does not allow the prediction of a QRS score in an individual patient.

Acute Disease↗
PubMed1988

Idazoxan and brain alpha 2-adrenoceptors in the rabbit.

The effect of intravenous infusion of idazoxan on the depressor response to intracisternal clonidine 1 microgram/kg and on [3H]yohimbine binding in the fore- and hindbrain of the rabbit was examined. Idazoxan was infused either acutely (30 min) or chronically (5 days) at doses of 0.56 or 1.1 mg/h. Idazoxan 1.1 mg/h reduced the fall in blood pressure after clonidine. This attenuation of the depressor response was observed in the groups that were given the higher dose of idazoxan both acutely and chronically. The extent of attenuation was not modified by the duration of treatment. The low dose of idazoxan given acutely had no significant effect on the response to clonidine but the chronically infused group showed an enhanced response. A significant increase in the number of [3H]yohimbine binding sites (83%) was observed in the forebrain after 5 days infusion of 1.1 mg/h idazoxan with no change in the hindbrain. The lower dose of infusion did not cause any significant change in [3H]yohimbine binding in either brain region. Thus it appears that the susceptibility of the alpha 2-adrenoceptor binding sites to up-regulation by idazoxan may depend on the brain region observed.

Animals↗
PubMed1988

Initial blood pressure as a predictor of the response to antihypertensive therapy.

1. The relationship between fall in systolic blood pressure and initial systolic blood pressure has been investigated in 255 mixed normotensive and hypertensive subjects given placebo or one of five types of antihypertensive drug (ACE inhibitors, calcium antagonists, direct vasodilators, alpha-adrenoceptor blocker, beta-adrenoceptor blocker). 2. In all cases there was a significant correlation between the change in blood pressure and initial blood pressure. When Oldham's transformation was used (replacing the initial blood pressure by the mean of the initial and minimum pressures) the correlation coefficients were all reduced, although five out of six were still statistically significant. 3. In a subset of 43 hypertensive subjects given four antihypertensive agents, concentration-effect analysis was carried out. For three of the agents a linear model was used to relate effect to concentration; for the remaining agent a Langmuir type model was used. 4. For all four sets of data for which concentration-effect analysis was carried out, there was a significant correlation between the sensitivity of response and the initial blood pressure. 5. The observed relationships between initial blood pressure, change in blood pressure and sensitivity of response can be qualitatively explained by postulating a general form of dose-response relationship for all antihypertensive agents.

Antihypertensive Agents↗
PubMed1988

Daily variability of umbilical and lateral uterine wall artery blood velocity waveform measurements.

The daily variability of umbilical artery and lateral uterine wall artery velocity-time waveforms recorded by continuous wave Doppler ultrasound was determined by making three observations in each of 97 women on different days within a 7-day period. There were no significant changes in the maximal:minimal Doppler shift frequency (A/B ratio) or the pulsatility index in either artery over the period of study. Common pregnancy complications did not influence the variability of the recordings. The variability of uterine artery recordings was not affected by gestational age between 17 and 41 weeks but the degree of variability of the umbilical artery recordings was greater before 30 weeks. We conclude that after 30 weeks gestation this technique has an acceptable range of daily variability for clinical and research applications.

Adult↗
PubMed1988

Electrocardiographic prediction of coronary artery patency after thrombolytic treatment in acute myocardial infarction: use of the ST segment as a non-invasive marker.

The predictive value of the measurement of changes in ST segment elevation was assessed as a non-invasive marker of coronary artery reperfusion after thrombolytic treatment. Forty five patients with acute myocardial infarction (23 anterior, 22 inferior) of less than six hours' duration were given thrombolytic treatment by either the intravenous (n = 28) or the intracoronary route (n = 17). A proportional value for the shift in ST segment, termed the fractional change, was calculated both from 12 lead electrocardiograms and from the Holter tape for each patient. Coronary artery patency in an initial group of 22 patients (training group) was associated with a fractional change value of greater than or equal to 0.5 (100% specific, 88% sensitive by Holter analysis; 100% specific, 94% sensitive by 12 lead electrocardiogram). This rule performed well when it was applied to a test group of 17 patients (100% specific, 93% sensitive by Holter analysis; and 67% specific, 93% sensitive by 12 lead electrocardiogram). Linear discriminant analysis was then used to determine which features gave the best separation of those in whom there was reperfusion and those in whom there was not. This gave 100% specificity and 100% sensitivity when applied to the training group for either the 12 lead electrocardiogram or Holter monitoring. When it was applied to the test group, the sensitivity was maintained at 100%, but the specificity dropped to 33% irrespective of whether the basis of the test was Holter monitoring or the 12 lead electrocardiogram. These results suggest that a fractional change of >/= 0.5 calculated from a single lead showing myocardial injury is a useful non-invasive marker of reperfusion. The technique can be applied to either 12 lead electrocardiograms or Holter monitoring. The use of a more complex classification increased the sensitivity of the test at the expense of its specificity.

Adult↗
PubMed1988

Desensitization of vascular and platelet alpha 2-adrenoceptors in rabbits with perinephritis hypertension.

The effects of infusion of alpha-adrenoceptor agonists on blood pressure, pressor responses to bolus doses of agonists and to platelet aggregation were examined in rabbits with perinephritis hypertension and in sham-operated controls. Pressor responses to bolus doses and infusions of phenylephrine, an alpha 1-selective agonist, were greater in hypertensive rabbits. In contrast, responses to boluses but not infusions of alpha-methylnoradrenaline, a selective alpha 2-agonist, were increased in hypertensives. During alpha-methylnoradrenaline infusions pressor responses to bolus doses of alpha-methylnoradrenaline and the aggregatory response of platelets to adrenaline were attenuated in all rabbits, consistent with alpha 2-adrenoceptor desensitization. Attenuation and recovery were observed within minutes of commencing and ceasing infusion. The extent of attenuation and rate of change were generally increased in hypertensive animals. This could explain the apparent increase in pressor responses to bolus doses but not infusions of alpha-methylnoradrenaline in the hypertensive rabbits. It might also contribute to the lability in blood pressure observed in these animals.

Adrenergic alpha-Agonists↗
PubMed1987

Haemodynamic, metabolic, and lymphocyte beta 2-adrenoceptor changes following chronic beta-adrenoceptor antagonism.

We have examined the effects of 7 days treatment with beta adrenoceptor antagonists in 8 healthy volunteers in a placebo controlled, crossover study. We investigated three beta-adrenoceptor antagonists (atenolol, oxprenolol, and propranolol), which have differing profiles of selectivity and partial agonist properties (intrinsic sympathomimetic activity, ISA). We studied adrenaline-induced hypokalaemia, the vasodilator response to an infusion of adrenaline (0.06 micrograms X kg-1 X min-1 for 90 min), and lymphocyte beta 2-adrenoceptor number, determined by (-) [125I]-iodocyanopindolol binding, and measured these variables both before and after 7 days of treatment. The beta 2-mediated depressor response to adrenaline infusion was abolished by propranolol and oxprenolol but persisted after atenolol. In contrast, the hypokalaemia induced by adrenaline was abolished by all three beta-blockers. Lymphocyte beta 2-adrenoceptor number increased significantly following propranolol treatment, but not after oxprenolol for atenolol. We conclude that up-regulation of lymphocyte beta 2-adrenoceptors is dependent on beta 2-receptor blockade and is modified by ISA. The reversal of the hypokalaemic response by atenolol suggests that beta 1 receptors may contribute to the former effect. Alternatively, since different populations of beta 2-adrenoceptors differ in their susceptibility to antagonists there may also be differences in agonist coupling to beta 2-responses between tissues.

Adrenergic beta-Antagonists↗
PubMed1987

Early cardiovascular changes with ibopamine: evidence for a biphasic haemodynamic action.

1. The haemodynamic effects of ibopamine, an oral dopamine derivative, were studied in eight patients with left ventricular dysfunction using invasive catheterisation techniques. 2. An early rise was seen in the mean right atrial pressure (P less than 0.05), the mean capillary wedge pressure (P less than 0.01) and the mean pulmonary arterial pressure (P less than 0.001) which occurred at 15 min and persisted for 30 min. 3. A second, later, positive chronotropic effect was seen as an increase in the heart rate (P less than 0.05) at 45 min with an increased cardiac output (P less than 0.05) persisting above baseline values at 1 h, but with no change in stroke volume. 4. These results support a biphasic mode of action for ibopamine which may be explained by a time phase difference in alpha- and beta-adrenoceptor stimulatory effects.

Aged↗
PubMed1985

Acute and chronic effects of the converting enzyme inhibitors enalapril and lisinopril on reflex control of heart rate in normotensive man.

The effects of enalapril maleate and its lysine analogue, lisinopril, on reflex control of heart rate after acute and chronic administration were examined in 10 normotensive males. Both drugs reduced blood pressure without change in heart rate after acute dosing and after seven days. Both drugs impaired the vagally mediated early cardiac acceleration associated with lying down (standing to lying test). A similar effect was observed following edrophonium. After lisinopril bradycardia induced by facial immersion (diving reflex) was significantly attenuated. Edrophonium similarly attenuated the bradycardia. Both these reflexes are parasympathetically mediated. Neither drug altered heart rate or blood pressure changes following Valsalva's manoeuvre and the cold pressor test. Plasma noradrenaline was unchanged. Absence of reflex tachycardia with blood pressure reduction by converting enzyme inhibitors may be related to increased parasympathetic activity either centrally or peripherally without impairment of baroreflexes or sympathetic function.

Adult↗
PubMed1985

Alpha-adrenoceptor number and function in platelets from treated and untreated patients with essential hypertension and age- and sex-matched controls.

Alpha 2-receptor number was measured on platelets from 19 healthy normotensive volunteers and 19 patients with essential hypertension, using [3H]-yohimbine binding. Platelet function was assessed using the primary aggregation response to adrenaline. The mean alpha 2-receptor number (Bmax fmol/10(8) platelets) in platelets from normotensive controls was 31 (188 sites/cell) and was significantly higher than in age- and sex-matched hypertensive subjects, for whom Bmax = 24 (144 sites/cell) (P < 0.01 by paired t-test). There was no change in the affinity for [3H]-yohimbine binding. Platelet aggregation responses to adrenaline did not differ between hypertensive and normotensive subjects. Blood pressure reduction with prazosin in eight hypertensive subjects did not alter receptor number either acutely or following 1 month of treatment. These findings may be interpreted as evidence for enhanced receptor coupling to functional responses of a significantly smaller receptor population in patients with essential hypertension.

Adult↗