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Biomedical subjects

G Reynolds

Publications and source records attributed to G Reynolds.

At least 55 records · Page 3Linked to original sources
PubMed1987

A haemodynamic and radionuclide assessment of diltiazem in coronary heart disease.

To obtain multiple dose-response haemodynamic and radionuclide data on i.v. diltiazem, 12 ischaemic patients were studied during routine catheterization. At rest, following a 20 min stable control period, the effects of four doses (0.0625, 0.0625, 0.125 and 0.25 mg kg-1 diltiazem at 5 min intervals) were measured in the 3-5 min following i.v. injection. The exercise effects of the cumulative 0.5 mg kg-1 dosage were assessed by comparing a control and post drug period of supine bicycle exercise. The increase in plasma diltiazem levels correlated linearly with the administered dose and achieved therapeutic levels. There were significant dose-related reductions in systemic arterial blood pressure and vascular resistance index; the heart rate fell and cardiac stroke index increased. The calculated double-product (heart rate X systolic blood pressure) was significantly reduced. The left ventricular filling pressures, ejection fraction and cardiac volumes were unaltered. During supine bicycle exercise, the systemic diastolic blood pressure, heart rate and calculated double-product were reduced without change in other parameters. Over the dose range 0.0625-0.5 mg kg-1, diltiazem acutely increased cardiac stroke index and reduced resting heart rate. These haemodynamic data, taken together with its described coronary vasodilator activity suggest that its role in acute vasospastic angina and during angiographic procedures ought to be explored further.

Aged↗
PubMed1987

Immediate effects of bumetanide on systemic haemodynamics and left ventricular volume in acute and chronic heart failure.

1 The haemodynamic and radionuclide effects of i.v. bumetanide (25 micrograms kg-1) were prospectively studied in 24 patients with angiographically documented coronary artery disease and either acute exercise-induced (Group I, n = 12) or chronic (Group II, n = 12) heart failure. 2 Bumetanide at rest increased systemic arterial blood pressure and vascular resistance index; cardiac index and pulmonary artery occluded pressure (PAOP) were reduced at an unchanged heart rate in all patients. The left ventricular ejection fraction fell in patients with normal resting left ventricular filling pressure without change in those with chronic heart failure. The cardiac volumes were unchanged in either group. 3 During constant-load supine bicycle exercise, there were similar effects on systemic arterial pressures, vascular resistance index and PAOP; however the cardiac index was maintained at a reduced left ventricular filling pressure and unchanged ejection fraction and volumes. 4 These data demonstrate immediate mild pressor and vasoconstrictor actions of bumetanide which appear independent of the state of cardiac function; they suggest that any immediate improvement in patient symptomatology following bumetanide may be consequent on the reduction in PAOP; short-term reductions in volume may not occur.

Acute Disease↗
PubMed1987

Comparative haemodynamic dose-response effects of dobutamine and amrinone in left ventricular failure complicating acute myocardial infarction.

The comparative haemodynamic dose-response effects of intravenous (i.v.) amrinone and dobutamine were evaluated in 20 male patients with haemodynamic (pulmonary artery occluded pressure (PAOP) greater than 20 mm Hg) and radiographic left heart failure following a recent myocardial infarction. Following a 1-h control period, 10 patients were each randomised to amrinone (800, 1,600, or 3,200 micrograms/kg/h) or dobutamine (200, 400, or 800 micrograms/kg/h) sequentially infused for 30 min at each dose level; haemodynamic parameters were recorded at the end of each infusion period. Amrinone reduced systemic arterial blood pressure and vascular resistance index with a moderately increased heart rate; PAOP (-10 mm Hg; p less than 0.01) fell substantially without change in cardiac or stroke work indices. Dobutamine increased systemic arterial blood pressure, heart rate, and stroke work index at an unchanged PAOP; cardiac index (+0.7 L/min/m2; 25%; p less than 0.01) increased. Systemic vascular resistance index was significantly reduced by both drugs. Thus, dobutamine increased cardiac index at an unchanged PAOP; myocardial stroke work increased. Amrinone had lesser effect on cardiac pumping but reduced PAOP (preload) at an unchanged stroke work. The implications of these differential actions for the clinical therapy of myocardial infarction deserves further evaluation.

Adult↗
PubMed1986

Pharmacokinetic, haemodynamic and radionuclide studies with nicardipine in coronary artery disease.

Pharmacokinetic, haemodynamic and radionuclide studies explored the acute pharmacokinetic and pharmacodynamic actions of nicardipine in patients with coronary heart disease. Nicardipine infusion resulted in dose-related reductions in systolic and diastolic blood pressure and an increased heart rate. Pharmacodynamic activity was evident between 12 and 24 min following 5 and 10 mg i.v. nicardipine but by 3-6 min following the higher doses of 15 and 20 mg; hypotensive activity persisted for up to 2 h. Post-infusion nicardipine concentrations declined biexponentially; however the limited data precluded formal compartmental analysis. Plasma clearance ranged from 5-12 ml/min/kg, and appeared lower than previously reported volunteer data. The haemodynamic actions of nicardipine (10 mg infusion over 10 min) in 6 patients undergoing diagnostic catheterization were reductions in systolic, diastolic and mean systemic arterial pressure and systemic vascular resistance index. Heart rate and stroke volume index increased, and there was a small but statistically significant increase in pulmonary artery occluded pressure. Radionuclide parameters were measured in 20 patients with stable angina, at rest and during supine bicycle exercise, before and 3-5 min after nicardipine 10 mg intravenously. The left ventricular ejection fraction increased by 4% at rest but not during exercise. The left ventricular rest and exercise ejection and filling rates both increased with a concurrently reduced left ventricular ejection time. There was a highly significant inverse relationship between baseline exercise ejection fraction and the response to nicardipine; ejection fraction increased with low initial values but was either unchanged or fell with higher initial values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Differences in haemodynamic response to beta-blocking drugs between stable coronary artery disease and acute myocardial infarction.

Theoretically the increased sympathoadrenal activity following acute myocardial infarction might augment the haemodynamic impact of beta-adrenoceptor blockade. To evaluate this question 32 haemodynamic studies were performed to compare the effects of equivalent beta-blocking doses of propranolol (8 mg i.v.) and pindolol (0.8 mg i.v.) in patients with a recent acute myocardial infarction (A.M.I.) or stable coronary artery disease (and a presumptive low sympathetic state). In stable coronary artery disease there were clear differences between the haemodynamic impact of propranolol and pindolol. Propranolol decreased both heart rate (delta HR -7 beat/min) and cardiac index (delta CI -0.4 l/min/m2), with an increased pulmonary artery occluded pressure (delta PAOP +4 mmHg) and systemic vascular resistance index (delta SVRI +358 dyn X s X cm-5 m2). However an equivalent beta-blocking dose of pindolol increased PAOP (delta PAOP +3 mmHg) leaving other variables unchanged. These differential actions of propranolol and pindolol have previously been ascribed to the intrinsic sympathomimetic activity (I.S.A.) of pindolol maintaining cardiac pumping function in a low sympathetic state. In contrast following myocardial infarction, both drugs reduced cardiac index to a significantly greater extent compared with stable coronary artery disease (delta CI propranolol -0.81/min/m2; pindolol -0.4 l/min/m2; p less than 0.05); propranolol also reduced the systemic arterial blood pressure (delta systolic -10 mmHg; delta mean -5 mmHg; p less than 0.05). The haemodynamic relevance of the I.S.A. of pindolol appeared attenuated following A.M.I. These data are compatible with experimental evidence of sympathetic nervous activation following coronary occlusion; the resulting hyperadrenergic state appears to condition an augmented haemodynamic response to beta-blocking drugs irrespective of their ancillary pharmacological properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1986

A haemodynamic study of the effects of combined slow-calcium channel blockade (nisoldipine) and beta-blockade (metoprolol) in coronary heart disease.

The interaction of a new slow-calcium blocker (nisoldipine) and the beta-blocker metoprolol was evaluated in 16 patients with stable angina. Haemodynamic parameters were determined in a control rest and exercise period. Patients were then randomised equally to nisoldipine (4-8 micrograms/kg) or metoprolol (10 mg) and the haemodynamics of monotherapy assessed; finally the second drug was administered and the effects of combination determined. At rest nisoldipine reduced systemic blood pressure and vascular resistance (P less than 0.01); heart rate, cardiac and stroke volume indices increased (P less than 0.01) at an unchanged pulmonary artery occluded pressure. Metoprolol alone reduced heart rate (P less than 0.05) and increased the pulmonary artery occluded pressure (P less than 0.05). Combination therapy reduced systemic blood pressure and vascular resistance (P less than 0.01); cardiac index and pulmonary artery occluded pressure increased (P less than 0.01) at an unchanged heart rate. The effect of combination was influenced by the order of administration; an improvement in cardiac performance was particularly evident when nisoldipine was added to metoprolol. The interaction during dynamic exercise was similar to that at rest. Thus these data indicated the haemodynamic safety of concurrent nisoldipine/metoprolol therapy; the addition of nisoldipine to metoprolol appeared to offset in part the cardiodepressant properties of beta-blockade.

Adult↗
PubMed1986

Comparative effects of metoprolol and celiprolol on cardiac hemodynamics and left ventricular volume at rest and during exercise-induced angina.

Celiprolol is a cardioselective beta-adrenoceptor antagonist with attributed cardiostimulant properties. Its hemodynamic profile was compared in a dose-response study with that of metoprolol, which is also cardioselective but lacks cardiostimulatory activity. In 24 patients with angiographically proved coronary artery disease, simultaneous hemodynamic and left ventricular ejection fraction (EF) values were determined at rest in the control (drug-free) state and repeated 3 to 5 minutes after each of four intravenous boluses of celiprolol, 1, 1, 2, and 4 mg, or equivalent beta-blocking doses of metoprolol, 1.25, 1.25, 2.5, and 5.0 mg. The effects of each drug on hemodynamics during exercise-induced angina were determined by exercise testing in the control state and after the maximum cumulative dose of each drug. At rest, metoprolol reduced heart rate, cardiac index, and the left ventricular EF and increased pulmonary artery occluded pressure (PAOP), systemic vascular resistance, and left ventricular end-systolic and end-diastolic volumes. Celiprolol increased cardiac and stroke volume indices and the EF; the PAOP was reduced without change in other measured variables. During exercise, metoprolol significantly increased the PAOP, which was unchanged by celiprolol. At exercise both drugs reduced cardiac index and heart rate, but neither altered the EF. The cardiac function curve demonstrated greater depression at rest after metoprolol than after celiprolol; these differences were attenuated during dynamic exercise. The lesser adverse impact of celiprolol on cardiac function may be attributable to ancillary cardiac stimulatory properties offsetting the cardiac depression after beta-adrenoceptor blockade.

Angina Pectoris↗
PubMed1986

Haemodynamic dose-response effects of intravenous indoramin in acute heart failure complicating myocardial infarction.

The haemodynamic dose-response effects of intravenous indoramin were evaluated in 12 patients with acute heart failure (pulmonary artery occluded pressure of greater than 20 mm Hg) complicating a recent myocardial infarction. Following a 1-h control period with confirmed stable haemodynamics, the effects of three intravenous bolus doses of indoramin (0.125, 0.125, and 0.25 mg/kg at 15-min intervals) were determined in the 10- to 15-min period following each intravenous injection. Plasma drug concentrations rose with the administered dose and were in the previously established therapeutic range. Ten patients tolerated all three doses of the drug; two patients were withdrawn following the second dose owing to clinically evident hypotension (systolic blood pressure of less than 100 mm Hg). Indoramin resulted in progressive falls in systolic, diastolic, and mean systemic arterial pressures (p less than 0.01) without change in cardiac index. There was a dose-related reduction in the heart rate (0.5 mg/kg; -7 beats/min; p less than 0.01). The left ventricular filling pressure showed a significant and quadratic reduction over the dose range (0.5 mg/kg, -5 mm Hg; p less than 0.01). The systemic vascular resistance index was reduced (-333 dynes X s X cm-5 X m2; p less than 0.001) and the stroke volume index increased (+3 ml/m2; p less than 0.05) following the maximum cumulative dosage. These data established the therapeutic safety of indoramin (0.125-0.5 mg/kg) in acute heart failure following myocardial infarction. An improvement in cardiac performance in these patients was compatible with circulatory actions on both cardiac preload and afterload.

Acute Disease↗
PubMed1986

Differential actions of atenolol and celiprolol on cardiac performance in ischemic heart disease.

The therapeutic relevance of differences between beta-adrenoceptor antagonists, related to their ancillary pharmacological properties, is debated. Celiprolol is a novel cardioselective beta-blocking agent with attributed cardio-stimulating properties. Its hemodynamic profile was compared with that of atenolol (cardioselective; no ISA) in a comparative dose-response study of 24 patients with angiographically documented coronary artery disease. Following a stable control period four i.v. boluses of equivalent beta-blocking doses of atenolol (1, 1, 2, and 4 mg) or celiprolol (1, 1, 2, and 4 mg) were administered, and hemodynamics and left ventricular ejection fraction were determined. The comparative actions of the two drugs on the hemodynamics of exercise-induced angina were compared by exercise testing in the control state and following the maximum cumulative dose of each drug. At rest, atenolol reduced heart rate, cardiac index, and left ventricular ejection fraction (EF); systemic vascular resistance index increased without change in systemic arterial or pulmonary artery occluded pressures. Celiprolol increased cardiac index and ejection fraction without change in other variables. During exercise both drugs reduced cardiac index and heart rate; neither altered the exercise EF. The cardiac function curve, relating cardiac index to left ventricular end-diastolic pressure, was significantly depressed by atenolol but was elevated at rest by celiprolol. Thus these studies demonstrated hemodynamic differences between atenolol and celiprolol, presumably related to the ancillary properties of the latter. The relevance of such differences to the therapy of patients with coronary artery disease deserves further examination.

Adrenergic beta-Antagonists↗
PubMed1986

A rest and exercise haemodynamic evaluation of a new cardio-selective beta-adrenoceptor blocker celiprolol alone and in combination with nitroglycerine in ischaemic heart disease.

The symptomatic benefits of combining beta-adrenoceptor blockers and nitrates in angina pectoris are well recognised. Their actions on cardiac haemodynamics and volumes when combined have been poorly characterized. Accordingly this study investigated a new cardioselective beta-adrenoceptor blocking agent celiprolol and buccal nitroglycerine in 24 patients with angiographically documented coronary artery disease. Following a control period, with confirmed stable haemodynamics, three groups (n = 8/group) of prospectively matched patients, were studied following intravenous celiprolol (8 mg), buccal nitrate (10 mg) or their combination. Haemodynamics and left ventricular ejection fraction (nuclear probe) were determined following each intervention. The actions of each regimen on the haemodynamics of exercise-induced angina were compared by exercise testing in the control state and following each regimen. At rest, celiprolol did not alter haemodynamic parameters. Nitrate therapy reduced left ventricular filling pressure (pulmonary artery occluded pressure--PAOP) and volumes; the ejection fraction and heart rate increased. Combination therapy resulted in a highly significant reduction in left ventricular preload and afterload (PAOP and mean arterial blood pressure) at an increased left ventricular ejection fraction and reduced cardiac volumes; there was a trend to reduce cardiac double product (HR X SBP). During exercise celiprolol reduced systolic blood pressure, heart rate and cardiac index; systemic vascular resistance index increased. Nitrate therapy reduced blood pressure and PAOP, and increased ejection fraction. Combination therapy reduced all components of the triple product (heart rate, systolic blood pressure and PAOP) without affecting the other haemodynamic or radionuclide parameters. These data suggest improvements in cardiac function from the combination of celiprolol and nitrate therapy which were not achieved by either agent when used as monotherapy; they afford an interesting insight into the manner in which such widely utilised therapeutic modalities interact in coronary artery disease.

Adrenergic beta-Antagonists↗
PubMed1986

Disposal of lactate during and after strenuous exercise in humans.

Heavy dynamic exercise using both arm and leg muscles was performed to exhaustion by seven well-trained subjects. The aerobic and anaerobic energy utilization was determined and/or calculated. O2 uptake during exercise and during 1 h of recovery was measured as well as splanchnic and muscle metabolite exchange. Glycogen and lactate content in the quadriceps femoris was determined before exercise, immediately after exercise, and after a recovery period. In four male subjects the estimated mean lactate production during exercise was 830 mmol. The splanchnic uptake of lactate during recovery was 80 mmol, and the calculated maximum amount oxidized during the recovery period was 330 mmol. About 60 mmol were accounted for in the body water at the end of the rest period. The remaining 360 mmol of lactate were apparently resynthesized into glycogen in muscle via gluconeogenesis. It is concluded that approximately 50% of the lactate formed during heavy exercise is transformed to glycogen via glyconeogenesis in muscle during recovery and that lactate uptake by the liver is only 10%.

Adult↗
PubMed1986

A haemodynamic dose finding study with a new slow-calcium channel blocker (amlodipine) in coronary artery disease.

The haemodynamic dose-response effects of a new long-acting slow-calcium channel blocking agent, amlodipine were evaluated in 20 patients with angiographically confirmed coronary heart disease. At rest, following a control saline period, four i.v. doses of the drug (cumulative dosage 1.25, 2.5, 5 and 10 mg) were administered to ten patients and haemodynamics determined in the ten to 15 minutes following injection. Effects on circulatory parameters were only evident following the maximum cumulative dosage. Accordingly in a further ten patients, the regimen was doubled (cumulative i.v. dosage 2.5, 5, 10 and 20 mg). In each study the haemodynamic effects during constant load supine bicycle exercise were evaluated by comparison of values during the control exercise period and following the final cumulative dosage. On the higher regimen, amlodipine significantly reduced resting systolic, diastolic and mean (p less than 0.01) systemic arterial pressure and systemic vascular resistance index (p less than 0.01). Heart rate (p less than 0.01), stroke volume index (p less than 0.01) and cardiac index (p less than 0.01) increased; pulmonary artery occluded pressure was unchanged. During constant load bicycle exercise, the mean arterial pressure was significantly reduced (p less than 0.01), and the heart rate and cardiac index increased (p less than 0.01). Thus the immediate impact of amlodipine in stable coronary artery disease was to reduce left ventricular afterload and augment cardiac pumping performance. The minimum effective i.v. dosage appeared to be 10 mg. Amlodipine appears sufficiently promising to warrant longer-term studies in ischaemic heart disease.

Adult↗
PubMed1985

Intravenous amrinone in left ventricular failure complicated by acute myocardial infarction.

Hemodynamic dose-response effects of intravenous amrinone were studied in 22 male patients aged 38 to 62 years with left ventricular failure occurring within 18 hours of acute myocardial infarction. After hemodynamic confirmation of a raised left-sided cardiac filling pressure--pulmonary artery occluded pressure greater than 20 mm Hg--patients were randomized to either low-dose infusion of amrinone (200 micrograms/kg/hr for 30 minutes, 400 micrograms/kg/hr for 30 minutes and then 800 micrograms/kg/hr for 30 minutes) or high-dose infusion of the drug (800, 1,600 and 3,200 micrograms/kg/hr sequentially, each for 30 minutes). Hemodynamic measurements were obtained at 1 hour before amrinone and at the end of each infusion step. Low-dose infusion of amrinone resulted in a progressive increase in cardiac output (p less than 0.05) and stroke volume (p less than 0.05) and progressive reductions in pulmonary artery occluded pressure (p less than 0.01) and systemic vascular resistance (p less than 0.05). Systemic blood pressure and heart rate were unchanged. High-dose infusion resulted in a similar increase in cardiac output (p less than 0.05) but no change in stroke volume owing to associated tachycardia (p less than 0.01). There was a significantly greater decrease in pulmonary artery occluded pressure compared with the low-dose infusion (p less than 0.05), and systemic arterial diastolic and mean pressures were also decreased (p less than 0.05). The decrease in systemic vascular resistance was of a similar order to that induced by the low-dose infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Measurement of fluorescein angiograms of the optic disc and retina using computerized image analysis.

Computerized image analysis was used to quantify objectively fluorescein angiograms of the optic disc, peripapillary choroid, and retina. Techniques were developed to measure fluorescein filling rates of the optic disc and the retinal vessels and the area of fluorescein filling defects within the optic disc. Two subjects, one with glaucoma and the other with ocular hypertension, showed increases of areas of fluorescein filling defects of the optic disc on follow-up and are presented here as examples of the application of these techniques. This methodology can be applied to the longitudinal follow-up of individual patients with glaucoma and retinal diseases, as well as to cross-sectional studies of patient populations.

Adolescent↗
PubMed1985

Hemodynamic dose-response effects of flecainide in acute myocardial infarction with and without left ventricular decompensation.

We evaluated the hemodynamic effects of the class I antiarrhythmic flecainide in 20 patients within 18 hours of an acute myocardial infarction. Equal numbers of patients with normal (group 1) or decompensated (group 2) ventricular function were studied. Both groups received flecainide, 1 mg/kg, as an intravenous bolus over 10 minutes, followed by infusion (1.6 mg/kg/hr) over the next 120 minutes. Plasma concentrations increased linearly with the cumulative flecainide dosage in both groups. There was no difference between the groups in the plasma levels reached, which were within the recognized antiarrhythmic range for flecainide (200 to 1000 ng/ml) throughout the infusion. The hemodynamic effects of flecainide for each group were decreases in systolic blood pressure (maximum 3% fall in group 1 and 8% fall in group 2), cardiac index (9% fall in group 1 and 18% fall in group 2), stroke volume index (13% fall in group 1 and 23% fall in group 2), stroke work index (14% fall in group 1 and 27% fall in group 2), with an increased heart rate (8% rise in group 1 and 5% rise in group 2), pulmonary artery occluded pressure (27% rise in group 1 and 21% rise in group 2), and systemic vascular resistance (11% rise in group 1 and 18% rise in group 2). Diastolic and mean arterial blood pressures did not change. Our data demonstrate that flecainide induced significant cardiodepression in both groups of patients. These effects were not significantly greater in patients with adequately controlled heart failure. These data suggest that the mild negative inotropic properties of flecainide in patients with recent myocardial infarction are comparable to those described for other class I antiarrhythmics.

Adult↗
PubMed1985

Haemodynamic analysis of the effects of nicardipine and metoprolol alone and in combination in coronary artery disease.

The circulatory consequences of concurrent slow-calcium channel (nicardipine) and cardioselective beta blockade (metoprolol) were evaluated in 20 patients with angiographically proven coronary artery disease. The rest and exercise haemodynamic impact of intravenous nicardipine (10 mg) or metoprolol (10 mg) alone was determined by randomly allocating 10 patients to each drug; finally all patients were assessed on combination therapy. The plasma levels of nicardipine (17 +/- 3 to 53 +/- 6 ng ml-1) and metoprolol (36 +/- 5 to 97 +/- 16 ng ml-1) achieved at the time of each study were in the established therapeutic range. At rest nicardipine reduced systemic mean arterial pressure and systemic vascular resistance index; cardiac and stroke volume indices increased without change in pulmonary artery occluded pressure. Metoprolol alone reduced systemic blood pressure, heart rate and cardiac index, and increased systemic vascular resistance index. Combination therapy reduced systemic arterial blood pressure and heart rate with relatively modest effects on cardiac index, systemic vascular resistance index and pulmonary artery occluded pressure. During dynamic exercise nicardipine reduced systemic mean and diastolic arterial pressure and stroke work index without change in other haemodynamic variables. Metoprolol reduced exercise systemic arterial pressures, heart rate and cardiac index, and increased systemic vascular resistance index and pulmonary artery occluded pressure. Combination therapy produced changes similar to those at rest; at peak nicardipine pharmacodynamic activity, the cardiac depressant actions of metoprolol were largely offset by the induced reduction in left ventricular afterload.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Search for cytomegalovirus in postmortem brain tissue from patients with Huntington's chorea and other psychiatric disease by molecular hybridization using cloned DNA.

Postmortem human brain extracts were examined for the presence of human cytomegalovirus (CMV) DNA by molecular hybridization using a dot blot technique. The method was able to detect picogram quantities of homologous DNA, but CMV specific hybridization was detected in only one of 83 brains examined. The positive case came from a patient who had received immunosuppressive therapy. We were not able to confirm the report that CMV is present in the brains of patients with Huntington's chorea, nor was CMV detected in the temporal cortex of brains from schizophrenic patients. Our findings are discussed in relation to the methodology for investigating a possible viral etiology of some neuropsychiatric diseases.

Adult↗