Aspirin does not improve early arterial patency after streptokinase treatment for acute myocardial infarction.

OBJECTIVE: To investigate the hypothesis that the magnitude of the life saving effect of aspirin in the second international study of infarct survival (ISIS-2) trial cannot be explained solely by prevention of late reocclusion of the infarct related artery. The aim of this study was to discover whether or not aspirin in combination with streptokinase had an adjuvant thrombolytic effect. DESIGN: Aspirin (150 mg) or placebo was given at the start of streptokinase infusion to 200 patients seen within six hours of the start of prolonged ischaemic cardiac pain and ST segment elevation. All patients received active aspirin at three hours. Patency of the infarct related artery was assessed non-invasively by the normalised rise of creatine kinase activity at three hours after starting streptokinase in these 200 patients and in a further 52 patients who had already taken aspirin within one week of the start of infarction. MAIN OUTCOME MEASURE: Rise in creatine kinase activity from baseline to > or = 20% or < 20% of the peak rise of activity in blood taken at three hours after starting infusion of streptokinase. This correlates with patency or occlusion of the infarct related coronary artery at about 2.5 hours after starting streptokinase. RESULTS: Assessed in this way, patency of the infarct related artery was 60% in patients given aspirin, 63% in those given placebo, and 62% in patients who had already taken aspirin within one week of infarction. CONCLUSION: The magnitude of the life saving effect of aspirin remains unexplained. Further investigation is needed into the mechanism of action of antiplatelet treatment in relation to thrombolytic treatment.

Subclinical cardiac dysfunction in acromegaly: evidence for a specific disease of heart muscle.

Acromegaly is associated with an increased cardiac morbidity and mortality, but it is not clear whether this is the result of increased incidence of hypertension and coronary heart disease or of a specific disease of heart muscle. Thirty four acromegalic patients were studied by non-invasive techniques. Seven of these patients had raised plasma concentrations of growth hormone at the time of study; three were newly diagnosed and had not received any treatment. Hypertension was present in nine (26%) but only three (9%) had electrocardiographic left ventricular hypertrophy. Echocardiography showed ventricular hypertrophy in 12 (48%) and increased left ventricular mass in 17 (68%) patients. Holter monitoring detected important ventricular arrhythmias in 14 patients. Thallium-201 scanning showed evidence for coronary heart disease in eight patients. Systolic time intervals were normal except when there was coexistent ischaemic heart disease. A comparison between 19 acromegalic patients with no other detectable cause of heart disease and 22 age matched controls showed appreciably abnormal left ventricular diastolic function in the group with acromegaly. The abnormalities shown did not correlate with left ventricular mass or wall thickness. There was no difference in diastolic function between patients with active acromegaly and those with treated acromegaly. Hypertensive acromegalic patients had worse diastolic function than hypertensive controls, suggesting that hypertension may further impair the left ventricular diastolic abnormality in acromegaly. This is the first study to find evidence of subclinical cardiac diastolic dysfunction in acromegaly and it supports the suggestion that there is a specific disease of heart muscle in acromegaly.

Effects of chronic congestive heart failure secondary to coronary artery disease on the circadian rhythm of blood pressure and heart rate.

In 20 subjects with chronic congestive heart failure due to coronary artery disease, the 24-hour variability of ambulatory intraarterial blood pressure (BP) was studied using an improved Oxford Medilog system, and correlated with left ventricular function at rest. The mean radionuclide ejection fraction was 27% (range 10 to 42), the mean pulmonary arterial wedge pressure was 18 mm Hg (5 to 37) and the mean cardiac index was 2.8 liters/min/m2 (2 to 3.8). The 24-hour systolic BP and heart rate (HR) variability indexes were less than those of 22 normal volunteers (p less than 0.05) and were strongly correlated (p less than 0.05) with ejection fraction at rest and pulmonary arterial wedge pressure. Stepwise regression showed that a combination of the mean nocturnal HR and the standard deviation of the hourly mean systolic BP values accounted for 67% of the variability in ejection fraction between patients. Similarly, 73% of the variation in pulmonary wedge pressure was explained by combining the 24-hour mean HR and the mean nocturnal HR.

First dose response and 24-hour antihypertensive efficacy of the new once-daily angiotensin converting enzyme inhibitor, ramipril.

The reduction in blood pressure (BP) after the first dose and after 8 weeks of treatment with a new once-daily angiotensin converting enzyme (ACE) inhibitor, ramipril, was examined in 12 untreated hypertensive patients, using ambulatory intraarterial BP monitoring. The first period of monitoring began 24 hours before the first dose was given, and continued for 24 hours afterwards. A second 24-hour period of monitoring was carried out after 8 weeks of treatment, commencing immediately after the morning dose. Angiotensin II levels and serum drug levels were measured at 0, 2, 6 and 24 hours after the acute dose. BP decreased progressively from the first hour after the first dose, reached a maximum in the fifth hour (p less than 0.001) and then the effect diminished. The maximum reduction of systolic BP in any patient was 64 mm Hg, the minimum 4 mm Hg. Blood pressure was significantly (p less than 0.05) reduced throughout the 24 hours after dosing, with a mean daytime reduction of 13/12 mm Hg, and a mean nighttime reduction of 15/7 mm Hg. Angiotensin II levels were significantly (p less than 0.02) and maximally reduced by 2 hours after administration, but the reduction was no longer significant after 24 hours. Serum drug levels were also maximal 2 hours after administration. The trial population could be clearly divided into groups of good and poor responders on the basis of BP reduction. The angiotensin II levels were higher before treatment, and decreased further, in all patients with a good response than in those with a poor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of fenoldopam, a specific dopamine receptor agonist, on blood pressure and left ventricular function in systemic hypertension.

1. The effects of fenoldopam, an orally active, specific dopamine-1 receptor agonist, were studied in eleven patients with essential hypertension, using intra-arterial blood pressure recording and equilibrium gated radionuclide angiography. 2. A single dose of fenoldopam 100 mg produced a fall in blood pressure (BP) starting after 20 min. The maximum BP reduction (23/25 mm Hg) occurred after 50 min and was accompanied by a heart rate (HR) increase of 10 beats min-1. The acute effects on BP lasted for 130 min. 3. After 8 weeks of fenoldopam 100 mg, twice daily, only a small, statistically insignificant, hypotensive effect was still apparent after each dose of drug. The duration of the effect was too short to be clinically useful. Tilt-testing produced a BP fall of 24/14 mm Hg and a HR increase of 17 beats min-1. Three patients experienced symptoms of postural hypotension during the study. 4. The drug attenuated the blood pressure rise produced by dynamic cycle exercise and isometric hand grip. 5. Acute administration of fenoldopam increased the left ventricular ejection fraction from 61% to 71% (P less than 0.005) and increased the peak filling rate from 2.52 to 3.86 end diastolic vol s-1 (P less than 0.002). After chronic fenoldopam administration, the left ventricular ejection fraction was 65% (P = NS) pre-dose, rising to 69% (P less than 0.02) post-dose and the peak filling rate was increased from 2.7 to 3.38 end diastolic vol s-1 (P less than 0.01) 60 min post-dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Carvedilol for systemic hypertension.

Twenty-four-hour profiles of intraarterial ambulatory blood pressure (BP) and heart rate were significantly reduced by administration of carvedilol, a new beta-blocking drug with vasodilating properties. Twelve patients were given carvedilol, 25 mg twice daily for 2 weeks; the dose was then increased to 50 mg twice daily if the target BP was not achieved. After 4 weeks of therapy, mean daytime reduction in BP was 25 +/- 3 mm Hg systolic and 19 +/- 3 mm Hg diastolic and mean reduction in heart rate was 22 +/- 3 beats/min. BP at the peak of isometric exercise and during dynamic exercise was also significantly reduced. Radionuclide measurements showed that left ventricular ejection fraction was not affected by treatment, but there was a significant reduction in systolic and diastolic volumes. The drug was well tolerated. This clinical trial suggests that carvedilol will be a useful first-line drug for treatment of essential hypertension, and its vasodilating action may have a more favorable effect on left ventricular function than conventional beta-blocking drugs.

Carvedilol for systemic hypertension.

Twenty-four hour profiles of intraarterial ambulatory blood pressure (BP) and heart rate were significantly reduced by administration of carvedilol, a new beta-blocker with vasodilating properties. Twelve patients were given carvedilol, 25 mg twice daily for 2 weeks; the dose was then increased to 50 mg twice daily if the target BP was not achieved. After 4 weeks of therapy, mean daytime reduction in BP was 25 +/- 3 mm Hg systolic and 19 +/- 3 mm Hg diastolic, and mean reduction in heart rate was 22 +/- 3 beats/min. BP at the peak of isometric exercise and during dynamic exercise was also significantly reduced. Radionuclide measurements showed that left ventricular ejection fraction was not affected by treatment, but there was a significant reduction in systolic and diastolic volumes. The drug was well tolerated. This clinical trial suggests that carvedilol will be a useful first-line drug for treatment of essential hypertension, and its vasodilating action may have a more favorable effect on left ventricular function than conventional beta-blocking drugs.

Once- and twice-daily bevantolol for systemic hypertension using 24-hour ambulatory intraarterial blood pressure recording.

The antihypertensive efficacy of bevantolol, a selective beta 1-adrenoreceptor antagonist, was evaluated in 17 patients with essential hypertension, using continuous ambulatory intraarterial blood pressure (BP) monitoring. The study compared a twice-daily regimen (titrated dose of 200 to 600 mg/day) with the same amount given in a single daily dose. Within-patient comparisons of mean hourly systolic and diastolic BPs and heart rate showed a highly significant effect with twice-daily therapy (p less than 0.001) for all of the 24 hours. Similar significant results were obtained with a single morning dose. There was no difference between the pattern or extent of BP reduction with the 2 regimens. The decrease in BP after bevantolol persisted during the physiologic tests (rest, tilt, isometric and dynamic exercise). Four patients developed minor side effects with the single morning dose, and only 1 patient with the twice-daily regimen. These effects included tiredness, fatigue and dizziness. Unlike pure beta-blocking agents, bevantolol controlled the early morning increase in BP, lending support to the belief that it possesses vasodilatory properties in addition to beta blockade. These results suggest that bevantolol may be useful as first-line therapy in a once-daily dosage for the treatment of essential hypertension.

Acute and chronic effects of nicardipine on systolic and diastolic left ventricular performance in patients with heart failure: a pilot study.

Nicardipine is a new calcium ion antagonist with vasodilating properties which has been shown to be effective in the treatment of hypertension and angina. We have studied its effect on systolic and diastolic left ventricular function in patients with mild to moderate degrees of congestive heart failure. Ten male patients with New York Heart Association Class II and III heart failure underwent acute treatment with an intravenous infusion of nicardipine (10 mg over 10 minutes). A nuclear probe was used to monitor left ventricular ejection fraction, peak filling rate, and relative cardiac output. Blood pressure and heart rate were also measured. The blood pressure (mean +/- SD) fell from 133 +/- 26/86 +/- 11 mmHg to 103 +/- 22/69 +/- 13; the heart rate rose from 67 +/- 9 beats/min to 85 +/- 10; left ventricular ejection fraction from 31 +/- 7 to 38 +/- 6%; relative cardiac output from 24 +/- 9 to 41 +/- 11; peak filling rate from 1.18 +/- 0.4 end-diastolic volume per second to 1.82 +/- 0.4 (p less than 0.001 in all cases) at the end of infusion. After 4 weeks of chronic treatment in eight patients (20 mg to be taken three times daily (tds) in one and 40 mg tds in 7), the blood pressure and heart rate had returned to baseline values but the improvements in left ventricular ejection fraction, relative cardiac output, and peak filling rate were sustained; this was associated with functional improvement in all 8 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of long-acting pinacidil on intra-arterial blood pressure.

We have tested the efficacy of a new long-acting preparation of pinacidil, an arterial vasodilator, using continuous intra-arterial ambulatory blood pressure recording. An acute dose produced a measurable effect lasting for 12 h. The duration of this effect was less during chronic twice daily drug administration. Side effects were common, causing two out of nine patients to withdraw from the study. Tilt testing produced no postural hypotension and there was no evidence of rebound hypertension on the withdrawal day.

Intravenous nicardipine in patients with chronic heart failure: a nuclear stethoscope study.

The effects of intravenous nicardipine (10 mg) on some aspects of left ventricular function have been studied with a radioisotope method in 10 male patients in chronic heart failure (NYHA Class II and III). Blood pressure (mean +/- s.d.) fell from 133 +/- 26/86 +/- 11 mm Hg to 103 +/- 22/69 +/- 13. Heart rate rose from 67 +/- 9 beats per minute to 85 +/- 10. Left ventricular ejection fraction rose from 31 +/- 7% to 38 +/- 6% and relative cardiac output from 24 +/- 9 to 41 +/- 11 (P less than 0.001 in all cases). This suggests that nicardipine has a potent vasodilator effect which results in increased left ventricular pumping activity in patients with mild to moderate heart failure.