Hemodynamic comparison of dopexamine and nitroprusside at high and low doses in patients with coronary artery disease and impaired left ventricular function.

Pure vasodilator drugs are currently the preferred agents for treatment of acute and chronic heart failure of all grades of severity. In contrast, the role of drugs that combine vasodilation with inotropic action remains highly controversial despite their several advantageous physiological actions and long therapeutic history in heart failure. We hypothesize that this uncertainty might be due first to subtle unfavorable hemodynamic effects not detectable by the relatively crude hemodynamic methods by which these agents are usually analyzed, particularly with regard to the quantification of afterload, and secondly to the narrow therapeutic range of these drugs, such that the dose administered is critical. We tested this hypothesis by comparing several refined hemodynamic measurements of dopexamine, an inotropic vasodilator, with a pure arteriovenous dilator (sodium nitroprusside, SNP) on left ventricular (LV) systolic and diastolic function, large arterial behavior, and coupling of the left ventricle to the arterial system at two dose levels in 35 patients with ischemic heart disease. The study protocol was a fixed order of 15-min infusions of saline, dopexamine 1 microg/kg/min, and dopexamine 3 + ++microg/kg/min, or saline, SNP 1 microg/kg/min, and SNP 3 microg/kg/min. Detailed hemodynamic observations were made at the end of each 15-min infusion period. Both drugs produced equivalent arterial vasodilation, as measured by the decrease in systemic vascular resistance index (SVRI), but dopexamine resulted in a significantly greater increase in cardiac index (CI). Myocardial contractility, assessed by several load-independent indexes, increased with dopexamine, as anticipated with an inotropic drug, but did not alter with SNP. Arterial compliance, a measure of the distensibility of large conduit arteries, was increased by SNP but not by dopexamine. Arterial wave reflection was increased by dopexamine, especially at high doses, but reduced by SNP. Increased arterial compliance and reduced wave reflection reduce LV afterload. SNP reduced preload, whereas dopexamine had no effect on this aspect of ventricular function. Vasodilator drugs and those which combine vasodilator and inotropy increase cardiac output (CO) and reduce SVR. Therapy with inotropic vasodilators has no effect on preload and does not reduce the dynamic components of ventricular afterload, although it does reduce its static components. These effects are dose dependent; there is less perturbation of afterload at lower doses. In contrast, vasodilator therapy reduces preload and both static and dynamic parts of afterload.

Angiotensin converting enzyme inhibition in chronic stable angina: effects on myocardial ischaemia and comparison with nifedipine.

OBJECTIVES: To determine the anti-ischaemic effects of a new angiotensin converting enzyme inhibitor, benazepril, compared with nifedipine, alone and in combination, in chronic stable angina caused by coronary artery disease. DESIGN: Placebo controlled, double blind, latin square design. SETTING: Regional cardiology service for a mixed urban and rural population. SUBJECTS: 40 patients with stable exertional angina producing at least 1 mm ST segment depression on exercise test with the Bruce protocol. 34 patients completed all four phases of the trial. INTERVENTIONS: Each patient was treated with placebo, benazepril (10 mg twice daily), nifedipine retard (20 mg twice daily), and a combination of benazepril and nifedipine in the same doses, in random order for periods of two weeks. MAIN OUTCOME MEASURES AND RESULTS: Total duration of exercise was not increased by any treatment. Exercise time to the development of 1 mm ST segment depression was not significantly changed with benazepril alone or in combination with nifedipine but was increased with nifedipine from 4.18 (1.8) min to 4.99 (1.6) min (95% confidence interval (95% CI) 0.28 to 1.34; p < 0.05). There was a significant relation between increase in duration of exercise and resting renin concentration (r = 0.498; p < 0.01). Myocardial ischaemia during daily activity, as assessed by ambulatory electrocardiographic monitoring, was reduced by benazepril and by the benazepril and nifedipine combination. This was significant for total ischaemic burden (451(628) min v 231(408) min; 95% CI -398 to -41 min; p < 0.05) and maximal depth of ST segment depression (-2.47(1.2) mm v -2.16 mm; 95% CI 0.04 to 0.57; p < 0.05) for the combination and for maximal ST segment depth for benazepril monotherapy (-2.47 (1.2) mm v -1.96(1.2) mm; 95% CI 0.18 to 0.91; p < 0.05). Benazepril significantly altered the circadian rhythm of cardiac ischaemia, abolishing the peak ischaemic periods at 0700 to 1200 and 1700 to 2300 (p < 0.05). CONCLUSIONS: Benazepril, an angiotensin converting enzyme inhibitor, had a modest anti-ischaemic effect in effort angina, but this effect was not as pronounced as with nifedipine. The anti-ischaemic action was more noticeable in asymptomatic ischaemia during daily activity, whereas nifedipine had little effect on this aspect of myocardial ischaemia. The combination of benazepril and nifedipine reduced ischaemia of daily activity.

Acute haemodynamic effects of dopexamine in patients with coronary arterial disease.

We assessed the acute haemodynamic effects of dopexamine 1 microgram/kg/min and 3 micrograms/kg/min in 21 patients with coronary arterial disease following routine catheterisation. Patients were aged 38 to 72 years and left ventricular ejection fraction ranged from 23 to 79%. Dopexamine was well tolerated in all patients except one in whom transient ventricular arrhythmias occurred with 3 micrograms/kg/min. No patient developed angina. Dopexamine increased cardiac index (2.6 +/- 0.4 to 3.2 +/- 0.1 (P less than 0.001) and 4.0 +/- 1.0 1/min/m2 (P less than 0.001), control to 1 microgram/kg/min and 3 micrograms/kg/min, respectively) and decreased systemic vascular resistance index (3356 +/- 1506 to 2318 +/- 809 (P less than 0.001) and 2252 +/- 1973 dyne.sec.cm-5/m2 (P less than 0.001], but did not affect systemic arterial, pulmonary arterial or right atrial pressure. Maximum positive dP/dt was increased (1294 +/- 324 to 1597 +/- 505 (P less than 0.001) and 2199 +/- 819 mmHg/sec (P less than 0.001] as was left ventricular stroke work index (44 +/- 20 to 51 +/- 21 (P less than 0.05) and 56 +/- 27 g.m/m2 (P less than 0.001) control to 1 microgram/kg/min and 3 micrograms/kg/min, respectively). Left ventricular end diastolic pressure fell with 3 micrograms/kg/min from 19.8 +/- 6.9 to 12.4 +/- 4.6 mmHg (P less than 0.05) in patients with preserved left ventricular ejection fraction (greater than 50%, n = 6), but not in those with impaired left ventricular ejection fraction (less than 50%, n = 15), otherwise the effects in these two subgroups were similar. We conclude that dopexamine has both inotropic and vasodilator properties.(ABSTRACT TRUNCATED AT 250 WORDS)

The early diagnosis of acute myocardial infarction.

Latex agglutination for serum myoglobin (Rapitex) was compared with the initial ECG for the early diagnosis of acute myocardial infarction. Forty patients suspected of myocardial infarction were prospectively evaluated by initial electrocardiogram and Rapitex serum myoglobin. The initial ECG was categorised into one of three groups: Group 1 had ST segment elevation of at least 1 mm in a limb lead or 2 mm in a precordial lead (with or without Q waves); Group 2 had abnormalities other than those seen in Group 1; and Group 3 had no particular abnormalities present that is, a normal ECG. Myocardial infarction was confirmed by a rise in creatine kinase to greater than or equal to twice the upper limit of normal for our laboratory range and with a CKMB fraction of greater than 6%. Nineteen of 40 patients sustained myocardial infarction; nine ECG group 1, six ECG group 2, and four ECG group 3. Eleven of the 19 patients with myocardial infarction had positive serum myoglobin agglutination. The initial ECG was the most predictive of a subsequent rise in CK (p = 0.003), while Rapitex serum myoglobin determination was the least predictive (p = 0.8517). We conclude that the Rapitex serum myoglobin test offers little diagnostic or economic advantage over the initial electrocardiogram.