Anion-channel blockade with alinidine: a specific bradycardic drug for coronary heart disease without negative inotropic activity

In 14 patients undergoing cardiac catheterization for suspected coronary artery disease, alinidine, 0.6 mg/kg, was administered intravenously to determine its effects on left ventricular (LV) function, coronary blood flow and myocardial oxygen consumption. To assess effects independent of changes in heart rate (HR), measurements were made at spontaneous and matched pacing HRs. At spontaneous HR, alinidine decreased HR from 70 +/- 2 to 61 +/- 3 beats/min (p less than 10(-6]. Peak rate of LV pressure decreased from 1,652 +/- 92 to 1,371 +/- 80 mm Hg/s (p less than 10(-5] and Vmax decreased from 47 +/- 3 to 41 +/- 2 s-1 (p less than 10(-4]. Coronary sinus blood flow decreased from 109 +/- 9 to 89 +/- 7 ml/min (p less than 0.01) and myocardial oxygen consumption from 10.9 +/- 1.0 to 9.0 +/- 0.8 ml O2/min (p less than 0.05). At a matched pacing HR of 98 +/- 3 beats/min before and after alinidine administration, peak rate of LV pressure decreased from 1,984 +/- 124 to 1,793 +/- 106 mm Hg/s (p less than 10(-4] and Vmax from 60 +/- 5 to 56 +/- 4 s-1 (p less than 0.02). Coronary sinus blood flow and myocardial oxygen consumption were not significantly changed at matched pacing HRs. The time constant of the first 40 ms of LV isovolumic relaxation was prolonged by alinidine only during spontaneous HR. Thus, alinidine results in a bradycardia-dependent decrease in myocardial oxygen consumption. It has negative inotropic properties independent of changes in HR and so is not a pure bradycardia-specific agent

Acute effects of intravenous nisoldipine on left ventricular function and coronary hemodynamics

The hemodynamic effects of nisoldipine were investigated in 16 patients with suspected coronary artery disease who underwent routine cardiac catheterization. Nisoldipine was given intravenously in a dose of 6 micrograms/kg over 3 minutes and measurements made before and after drug administration during spontaneous and matched atrial paced heart rate. During sinus rhythm, nisoldipine produced a significant increase in heart rate (19%, p less than 10(-5]. Left ventricular systolic pressure decreased 28% (p less than 10(-6) and left ventricular end-diastolic pressure did not change significantly (5%, difference not significant). Coronary sinus and great cardiac vein blood flow increased by 21% (p less than 0.02) and 25% (p less than 0.005), respectively, after nisoldipine administration. Simultaneously, mean aortic pressure decreased 33% (p less than 10(-6]; consequently, the global and regional coronary vascular resistances decreased by 50% (p less than 10(-4]. The decreases in global (-8%) and regional (-4%) myocardial oxygen consumption did not reach statistical significance. A 6% (not significant) increase in end-diastolic volume and an 11% (p less than 0.002) decrease in end-systolic volume resulted in an increase of 21% in stroke volume (p less than 10(-4] with a consistent increase in ejection fraction (+16%, p less than 10(-5]. Total systemic vascular resistance was reduced by 30% (p less than 0.0002). During spontaneous heart rate and matched atrial pacing, the time constant of isovolumic relaxation as assessed by a biexponential model, was significantly shortened.(ABSTRACT TRUNCATED AT 250 WORDS

Acute effects of intravenous nisoldipine on left ventricular function and coronary hemodynamics

The hemodynamic effects of nisoldipine were investigated in 16 patients with suspected coronary artery disease who underwent routine cardiac catheterization. Nisoldipine was given intravenously in a dose of 6 micrograms/kg over 3 minutes and measurements made before and after drug administration during spontaneous and matched atrial paced heart rate. During sinus rhythm, nisoldipine produced a significant increase in heart rate (19%, p less than 10(-5]. Left ventricular systolic pressure decreased 28% (p less than 10(-6) and left ventricular end-diastolic pressure did not change significantly (5%, difference not significant). Coronary sinus and great cardiac vein blood flow increased by 21% (p less than 0.02) and 25% (p less than 0.005), respectively, after nisoldipine administration. Simultaneously, mean aortic pressure decreased 33% (p less than 10(-6]; consequently, the global and regional coronary vascular resistances decreased by 50% (p less than 10(-4]. The decreases in global (-8%) and regional (-4%) myocardial oxygen consumption did not reach statistical significance. A 6% (not significant) increase in end-diastolic volume and an 11% (p less than 0.002) decrease in end-systolic volume resulted in an increase of 21% in stroke volume (p less than 10(-4] with a consistent increase in ejection fraction (+16%, p less than 10(-5]. Total systemic vascular resistance was reduced by 30% (p less than 0.0002). During spontaneous heart rate and matched atrial pacing, the time constant of isovolumic relaxation as assessed by a biexponential model, was significantly shortened.(ABSTRACT TRUNCATED AT 250 WORDS

Short-term assessment of left ventricular function, coronary hemodynamics, and catecholamine balance in severe congestive heart failure after a single oral dose of milrinone

Systemic and coronary hemodynamics were measured before and every 10 min after oral milrinone (10 mg) administration for 50 min, together with the drug plasma level in 14 patients with congestive heart failure. Left ventricular pressure (tip manometry), volume (angiography), and derived indexes were simultaneously assessed before and 60 min after milrinone treatment. Peak positive dP/dt, Vmax, and peak velocity of contractile element significantly increased 30 min after milrinone administration by 15%, 37%, and 30%, respectively. An increase in cardiac output (25%) with a consistent decrease in systemic vascular resistance (20%) occurred after 40 min without major changes in heart rate and aortic pressure. Right atrial pressure and minimal and end-diastolic left ventricular pressures decreased significantly after 50 min, by 30%, 25%, and 20%, respectively. Peak -dP/dt increased despite a slight change in end-systolic pressure. The time constants of relaxation, tau 1 and tau 2, significantly decreased by 15% after 50 min and by 16%. A transient but significant increase of 40% in coronary sinus blood flow was observed after 30 min, while myocardial oxygen consumption was unchanged 50 min after milrinone treatment. No changes were observed in catecholamine balance with milrinone. Ejection fraction increased significantly (22%) after milrinone administration, as well as the net work of left ventricle (27%). The increase of inotropism in failing hear

The haemodynamic and myocardial effects of dopexamine: a new B2-adrenoceptor and dopaminergic agonist

Dopexamine increases inotropic state and rate of relaxation independent of changes in heart rate. Dopexamine has a chronotropic effect and results in a decrease in systemic vascular resistance. Dopexamine has a spectrum of action that should be useful in patients with severe heart failure

Effect of a single oral dose of milrinone on left ventricular diastolic performance in the failing human heart

In 14 patients with severe congestive heart failure, left ventricular pressure (measured by tip manometer) and derived variables were measured before and every 10 minutes after administration of oral milrinone (10 mg) for 50 minutes along with measurements of coronary sinus blood flow and drug plasma levels. Arterial and coronary sinus catecholamines were measured only before and 50 minutes after milrinone. Left ventricular pressure, volume (as determined by angiography) and derived indexes were simultaneously assessed at matched atrial paced heart rate before and 60 minutes after milrinone. Three patients who did not achieve a therapeutic plasma level (less than 150 ng/ml) were excluded. Peak negative first derivative of left ventricular pressure (-dP/dt) progressively and significantly increased (10%) together with a decrease in the two exponential time constants of relaxation, namely, Tau 1 (19%) and Tau 2 (22

Epicardial wall motion and left ventricular function during coronary graft angioplasty in humans

Epicardial wall motion and left ventricular function changes during temporary coronary artery occlusion were assessed in a patient at the time of percutaneous transluminal angioplasty performed on a previously placed stenotic coronary artery bypass graft. Epicardial wall motion was analyzed using biplane cineradiography with frame to frame measurements of distances between pairs of radiopaque epicardial markers placed at the time of previous cardiac surgery. Bypass graft occlusion after initial dilation led to the early onset of a biphasic epicardial late systolic lengthening and early diastolic shortening similar to the regional wall motion abnormality preceding the procedure

Effects of short-term intravenous administration of diltiazem on left ventricular function and coronary hemodynamics in patients with coronary artery disease

The hemodynamic effects of diltiazem were investigated in 15 patients with suspected coronary artery disease undergoing routine cardiac catheterization. Diltiazem was given in a high dose of 500 micrograms/kg over a period of 5 min and measurements made before and after drug administration during spontaneous heart rate and during matched atrial pacing. Spontaneous heart rate did not change (-5%; NS). Left ventricular (LV) systolic pressure decreased 24% (p less than 10(-6)) and LV end-diastolic pressure (LVEDP) did not change (-5%; NS). During coronary blood flow measurement, mean aortic pressure decreased 30% (p less than 10(-6)) as global (coronary sinus) and regional (great cardiac vein) coronary vascular resistance diminished with no change in coronary blood flow. Myocardial oxygen consumption decreased 19% (p less than 0.02). During matched pacing, although no change occurred in calculated systolic isovolumic indexes of contractility, end-systolic pressure-volume index decreased 15% (p less than 0.05). The time constant of isovolumic relaxation assessed by a biexponential model decreased. No net change occurred in either global or regional wall motion. In summary, high-dose diltiazem was administered safely to patients with coronary artery disease. It is concluded that, at this dose, diltiazem acted as a peripheral and coronary vasodilator. Hemodynamic changes consistent with a direct negative inotropic and chronotropic effect of the drug were observed. Myocardial oxygen consumption decreased with no change in coronary blood flow