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Biomedical subjects

N A Irvine

Publications and source records attributed to N A Irvine.

11 recordsLinked to original sources
PubMed1991

A dose-ranging study to evaluate the beta 1-adrenoceptor selectivity of bisoprolol.

A dose-ranging study was performed to compare the beta 1-adrenoceptor selectivity of bisoprolol with that of atenolol and nadolol. Seven normal subjects (mean age 26 y) were given single oral doses of bisoprolol 5 mg (B5), 10 mg (B10), 20 mg (B20); atenolol 50 mg (A50), 100 mg (A100); nadolol 40 mg (N40); and placebo (PL), in a single blind randomised cross-over design. Beta 2-adrenoceptor responses were assessed by attenuation of finger tremor and cardiovascular responses to graded isoprenaline infusions. Dose-response curves were constructed, and doses of isoprenaline required to increase finger tremor by 100% (IT100), heart rate by 25 beats/min (IH25), SBP by 25 mmHg (IS25), cardiac output by 35% (IC35), and decrease DBP by 10 mmHg (ID10), after each treatment were calculated. These indices were compared with placebo response and expressed as dose-ratios. Exercise heart rate (EHR) was used to assess beta 1-adrenoceptor blockade. There were dose-related increases in plasma concentrations of bisoprolol and atenolol. Reduction of EHR was significantly less with B5 (16.8%) in comparison with all other treatments: B10 21.9%, B20 23.1%; A50 22.5%, A100 22.6%; N40 22.9%. There were small but significant reductions in isoprenaline-induced tachycardia with bisoprolol and atenolol, although mean dose-ratios were considerably less in comparison with N40 (IH25 dose-ratios): B5 2.55, B10 3.18, B20 3.93, A50 2.91, A100 4.89, N40 17.23. There were similar patterns for the other isoprenaline responses. These results show that conventional doses of bisoprolol (10 mg) and atenolol (50 mg) produced equal antagonism of beta 1 and beta 2-adrenoceptors, and therefore possess equal degrees of beta 1-adrenoceptor selectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1991

The effects of chronic dosing on the beta 1 and beta 2-adrenoceptor antagonism of betaxolol and atenolol.

Six normal subjects were given once daily treatment for 15 days with placebo (PL), betaxolol 10 mg (B10), 40 mg (B40); atenolol 100 mg (A 100); and nadolol 40 mg (N40). Measurements of beta 1-adrenoceptorblockade (reduction of exercise heart rate) and of beta 2-adrenoceptor-blockade (attenuation of isoprenaline induced finger tremor) were made after the first, eighth and fifteenth doses of each drug. Plasma concentrations showed dose related increases between 10 mg and 40 mg doses of betaxolol, and there was significant drug accumulation at steady state compared with after single dosing. The reduction in exercise heart rate (EHR) with B10 was less in comparison with all other treatments. There were no significant differences in effects between single and chronic-dosing for any of the treatments (% reduction EHR compared with placebo, on days 1 and 15): B10 (18.2, 19.0), B40 (28.6, 26.5); A100 (22.7, 23.1); N40 (26.6, 23.8). Dose-ratios for attenuation of isoprenaline-induced finger tremor (IT100) were significantly greater with B40 compared with B10 or A100 (no dose-ratio for finger tremor could be calculated for N40). There were no differences between single and chronic-dosing (IT100 dose-ratios on days 1 and 15): B10 (3.0, 2.5), B40 (4.4, 5.3); A100 (3.0, 3.0). The attenuation of isoprenaline-induced chronotropic response (IH25) by N40 was significantly greater in comparison with all other treatments. IH25 dose-ratios (on days 1 and 15) were as follows: B10 (2.8, 3.6), B40 (5.1, 5.8); A100 (3.6, 3.6); N40 (19.0, 17.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The effects of time and dose on the relative beta 1- and beta 2-adrenoceptor antagonism of betaxolol and atenolol.

1. Six normal subjects were given single oral doses of betaxolol 10 mg (B10), 40 mg (B40), 80 mg (B80); atenolol 50 mg (A50), 200 mg (A200); or placebo (PL). Measurements of beta 1-adrenoceptor blockade (reduction of exercise heart rate) and of beta 2-adrenoceptor blockade (attenuation of isoprenaline responses) were made at baseline, and at 2, 4, 6, 8 and 24 h after drug ingestion. 2. Mean values for Cmax and tmax were as follows: B10 (33 ng ml-1, 3.7 h), B40 (84 ng ml-1, 4.0 h), B80 (179 ng ml-1, 3.7 h); A50 (261 ng ml-1, 2.7 h), A200 (1369 ng ml-1, 2.0 h). 3. Reduction of exercise heart rate (EHR) occurred in dose-dependent fashion up to a ceiling at B40 (as % reduction c.f. placebo, at peak and 24 h): B10 16.2 to 10.2%, B40 27.1 to 16.2%, B80 27.0 to 18.7%; A50 20.9 to 9.1%, A200 28.8 to 15.8%. There were also dose-related increases in beta 2-adrenoceptor antagonism (IT100 dose ratios, at peak and 24 h): B10 2.1 to 1.2, B40 4.7 to 2.6, B80 6.0 to 4.7; A50 2.0 to 1.2, A200 4.7 to 1.8. There were similar trends for attenuation of heart rate and DBP responses to isoprenaline. 4. Ratios of beta 1:beta 2-adrenoceptor antagonism were calculated (as % reduction EHR divided by IT100 dose ratio); to provide an index of beta 1-adrenoceptor selectivity at peak and 24 h: B10 7.7 to 8.5, B40 5.8 to 6.2, B80 4.5 to 4.0; A50 10.5 to 7.6, A200 6.1 to 8.8.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1990

A dose-ranging study to evaluate the beta-adrenoceptor selectivity of single doses of betaxolol.

1. Six normal subjects were given single oral doses of betaxolol 10 mg (B10), 20 mg (B20), 40 mg (B40), 80 mg (B80), propranolol 40 mg (P40), or placebo (PL) in a single-blind randomised cross-over design. 2. beta 1-adrenoceptor blockade was assessed by reductions in exercise heart rate. Betaxolol produced dose-related reductions in exercise heart rate (beats min-1) up to a ceiling at B40, after which B80 showed a lesser effect: (158 +/- 8 PL, 128 +/- 3 B10, 123 +/- 2 B20, 116 +/- 4 B40, 136 +/- 10 B80, 135 +/- 4 P40). All doses of betaxolol (except B80) produced greater reductions compared with P40: (B10 P less than 0.001, B20 P less than 0.005, B40 P less than 0.001). 3. beta 2-adrenoceptor blockade was assessed by attenuation of finger tremor and cardiovascular responses to graded infusions of i.v. isoprenaline. Dose-response curves were constructed and the doses required to increase heart rate by 25 beats min-1, finger tremor by 200%, calf blood flow by 0.5 ml dl-1 min-1, and decrease diastolic blood pressure by 10 mm Hg, after each treatment were calculated. These were then compared with placebo responses and expressed as dose-ratios. 4. Dose-ratios for finger tremor showed significant attenuation by all doses of betaxolol (compared with PL): B10 1.5 +/- 0.18 (P less than 0.05), B20 2.62 +/- 0.45 (P less than 0.005), B40 2.55 +/- 0.33 (P less than 0.001), B80 2.48 +/- 0.48 (P less than 0.01); and by P40 6.49 +/- 1.12 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1989

Long-term prognosis after resuscitation from primary ventricular fibrillation complicating acute transmural myocardial infarction in the north east of Scotland.

The aim of this study is to determine the long-term prognosis of patients successfully resuscitated from primary ventricular fibrillation in the acute phase of transmural myocardial infarction and to identify predictors of mortality. Details of 75 consecutive patients between October 1971 and May 1981 were reviewed in October 1985. The cumulative survival rates at one year, two year, five year and 10 year were 84%, 77% 67% and 40.5% respectively with a median survival time of 8.7 years. Univariate and Cox survival analyses were used to determine predictors of mortality. Only the age of the patient at the time of infarction was found to be highly significant with a greatly increased mortality rate in the older age group (p less than 0.001). The sex, site of infarction (anterior or inferior) and time of entry in the study did not significantly influence long-term prognosis.

Adult↗
PubMed1984

Effect of food on blood hydralazine levels and response in hypertension.

A study with a nonspecific hydralazine assay reported that food increased hydralazine concentrations in plasma. We used a specific HPLC hydralazine assay to determine the effect of food on hydralazine blood levels and hemodynamic responses after oral hydralazine. Six subjects with uncomplicated essential hypertension were given 1 mg/kg hydralazine solution orally on two occasions at least 3 days apart. On 1 study day subjects fasted and on the other they were given a standard meal 45 min before hydralazine. Mean arterial pressure and heart rate were monitored for 2 hr before and for 4 hr after hydralazine and frequent venous blood samples were drawn for hydralazine assay. Hepatic blood flow was estimated by determination of indocyanine green clearance before food, after food, and 30 min after hydralazine. Peak blood hydralazine concentrations fell in all (46.2% +/- 11.5%; means +/- SE) and areas under the blood hydralazine concentration/time curves fell (45.7% +/- 9.5%) after food. This could not be explained by changes in liver blood flow. Food-related reductions in blood levels of hydralazine were associated with reduced vasodepressor effects (41.5% +/- 5.6%). It is possible that food increases intravascular conversion of hydralazine to hydralazine pyruvic acid hydrazone. The reduction in vasodepressor response suggests that patients with hypertension should take hydralazine at a fixed time in relation to meals.

Administration, Oral↗
PubMed1984

Effect of oral dose size on hydralazine kinetics and vasodepressor response.

Levels of hydralazine in blood are log-linearly related to its vasodepressor effect. We examined the effect of oral dose size on the proportion of hydralazine that reaches systemic circulation. Nine subjects with hypertension were given hydralazine in oral doses in the therapeutic range. Blood hydralazine levels, effective liver blood flow, blood pressure, and heart rate were measured. As the hydralazine dose increased, the ratios of the AUC of hydralazine to hydralazine dose and of peak blood hydralazine concentration to hydralazine dose increased, indicating an increase in the proportion of the dose in blood. Liver blood flow tended to increase (maximum 40%) as dose increased above 0.5 mg/kg. Vasodepressor response and degree of tachycardia increased disproportionately with increasing hydralazine dose. There were strong log-linear relationships between peak hydralazine levels and both vasodepressor response and tachycardia that did not change with increasing hydralazine dose. Thus blood hydralazine and vasodepressor response increase disproportionately with increasing hydralazine doses in hypertension.

Acetylation↗
PubMed1983

A non-invasive off-line method of measuring cardiac output.

The measurement of cardiac output has many clinical applications and the development of a reliable, non-invasive measurement technique would be of considerable value to clinicians, cardio-respiratory physiologists and cardiovascular pharmacologists. Currently-used methods of measuring cardiac output are either invasive, and therefore potentially dangerous, or require the use of expensive, sophisticated, complex equipment which often has to be kept exclusively for the purpose of measuring cardiac output. We describe a method based on the recently modified and validated acetylene rebreathing technique which avoids the necessity for on-line computer acquisition of data by employing semi-manual digitization of hard copy recordings. The method is non-invasive, accurate, sensitive and relatively inexpensive. In addition, the whole technique can be rapidly performed by minimally trained personnel.

Adult↗
PubMedDate not supplied

Age and blood pressure determine vasodepressor response to sodium nitroprusside.

Twenty-two patients, aged 33-72 years, with uncomplicated essential hypertension were given sequential incremental intravenous infusions of sodium nitroprusside, each of 10 min duration, to examine the determinants of the vasodepressor response. Changes in mean arterial pressure (delta MAP), heart rate (delta HR), and plasma norepinephrine (delta nc) were determined at the end of each infusion period. The slopes of the dose-response curves obtained were directly proportional to predrug blood pressure (p less than 0.0001) and inversely proportional to baroreflex sensitivity as measured by the slope of the delta HR vs. delta MAP relationship (p = 0.0007). Baroreflex sensitivity was in turn inversely proportional to, and approximately equally dependent on, predrug blood pressure and age (p = 0.0116). Thus, the slopes of the dose-response curves were determined by both predrug blood pressure and patient age. The relationship was such that predrug blood pressure accounted for approximately 75% of the variability in the slope of the dose-response curve, and age for only 25%. This suggests that the age-related reduction in baroreflex sensitivity is mechanistically different from the hypertension-related reduction and is of less importance in modifying homeostatic responses to vasodilation.

Adult↗
PubMedDate not supplied

Differential hemodynamic and sympathoadrenal effects of sodium nitroprusside and hydralazine in hypertensive subjects.

The hemodynamic and sympathoadrenal effects of serial incremental doses of a mixed veno-arteriolar dilator (intravenous sodium nitroprusside 0.0125-0.50 micrograms/kg/min) and a pure arteriolar dilator (bolus injections of hydralazine, 0.05-0.3 mg/kg) were compared in 18 subjects with uncomplicated essential hypertension. Blood pressure was reduced to the same extent over approximately the same time with both drugs. Sodium nitroprusside produced significant reduction in cardiac output (9%) and stroke volume (16%) despite an 11% increase in heart rate. Total peripheral resistance did not change. In contrast, hydralazine produced a significant (39%) reduction in peripheral resistance with a compensatory increase in heart rate (19%), stroke volume (20%), and cardiac output (42%). The catecholamine responses to the drugs differed both quantitatively and qualitatively. Administration of both drugs was associated with gradual increases in plasma norepinephrine, but the levels were consistently 40% higher with sodium nitroprusside for the same fall in blood pressure. No consistent change in plasma epinephrine was found with sodium nitroprusside, whereas with hydralazine, the concentration increased gradually after the blood pressure had been reduced by 9 mm Hg. This threshold was independent of the starting blood pressure. These differences in catecholamine response could reflect different patterns of regional sympathetic activation by the low pressure mechanoreceptors (sodium nitroprusside) and by the arterial baroreceptors (hydralazine). Neither drug has an ideal hemodynamic profile, particularly in subjects with cardiac disease, but a balanced combination of the two may produce a favorable hemodynamic profile and optimal hypotensive effect, minimizing the need for large doses of sympathetic inhibitors.

Adult↗