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PubMed1988

Cardiovascular and renal hemodynamic effects of intravenous infusions of the selective DA1 agonist, fenoldopam, used alone or in combination with dopamine and dobutamine.

Fenoldopam (0.1 and 0.2 microgram/kg/min i.v.) was administered to pentobarbital-anesthetized dogs alone and combined with dopamine (DA) and dobutamine. Renal blood flow, heart rate, and mean arterial pressure were measured. Both dosages of fenoldopam increased renal blood flow without altering blood pressure, similar to the effects of DA (1 and 2 micrograms/kg/min). Administration of fenoldopam with only DA (1 microgram/kg/min) produced further increase in renal blood flow. After administration of phenoxybenzamine (15 mg/kg i.v.), DA produced significant increments in renal blood flow and reductions in renal vascular resistance when compared with experiments without phenoxybenzamine, suggesting even low dosages of DA exert alpha-adrenoceptor agonist activity. Dobutamine (2 and 4 micrograms/kg/min) increased renal blood flow about 37% of that produced by DA. Fenoldopam added to dobutamine produced similar increments in renal blood flow as DA. Fenoldopam did not affect the increase in cardiac contractile force produced by DA and dobutamine. Thus, fenoldopam alone or in combination with DA had no advantage over 2 and 4 micrograms/kg/min DA to further increase renal blood flow. In contrast, fenoldopam with dobutamine produced greater increments in cardiac contractile force than DA and equivalent increases in renal blood flow as DA.

Adrenergic alpha-Antagonists↗
PubMed1992

Low blood-to-cerebrospinal fluid passage of sorbitol after intravenous infusion.

BACKGROUND AND PURPOSE: Compared with mannitol, the osmotherapeutic agent sorbitol is less prone to accumulate in the blood and the same quantity may be infused in a smaller volume. Because of these advantageous characteristics, we studied the pharmacokinetics of sorbitol in serum and cerebrospinal fluid. METHODS: Six patients (five women and one man; age range, 46-70 years) with an external ventriculostomy and suffering from brain edema due to cerebrovascular disease received sorbitol as part of their therapy. Before and after the first dose of 50 g infused over 20 minutes, sorbitol concentrations in serum and cerebrospinal fluid were determined repeatedly using an enzymatic procedure. RESULTS: Maximal sorbitol concentrations ranged from 2,705 to 5,821 (median, 3,227) mg/l in serum compared with 6.7-130.7 (median, 19.5) mg/l in cerebrospinal fluid. Cerebrospinal fluid maxima were observed 0.17-3 hours after the end of the infusion. Sorbitol elimination in serum was adequately described by a two-compartment pharmacokinetic model (distribution half-life, 0.05-0.14 hour; elimination half-life, 0.23-0.61 hour). Elimination in cerebrospinal fluid followed a single-exponential decay and was considerably slower than that in serum (half-life, 1.3-7.7 hours). CONCLUSIONS: The maximal cerebrospinal fluid concentration/maximal serum concentration ratio was low for sorbitol, thus suggesting a small potential risk of inducing an increase of intracranial pressure after osmotherapy (rebound effect).

Aged↗
PubMed2001

Pharmacological stress myocardial perfusion imaging with the potent and selective A(2A) adenosine receptor agonists ATL193 and ATL146e administered by either intravenous infusion or bolus injection.

BACKGROUND: Adenosine (Ado) and dipyridamole are alternatives to exercise stress for myocardial perfusion imaging. Though generally safe, side effects frequently occur that cause patient discomfort and sometimes lead to premature termination of the study or require aminophylline administration. Recently, a new class of A(2A) Ado receptor agonists was synthesized. ATL193 and ATL146e are 2-propynylcyclohexyl-5'-N-ethylcarboxamido derivatives of Ado. The study goals were to evaluate the potency and selectivity of these new compounds on recombinant canine Ado receptors and to evaluate their hemodynamic properties in dogs to assess their usefulness as vasodilators for myocardial perfusion imaging. METHODS AND RESULTS: In assays of recombinant canine Ado receptors, ATL-193 and ATL-146e were highly selective for the A(2A) over the A(1) and A(3) receptors and were more potent than MRE-0470 and CGS-21680. In 16 anesthetized dogs, the agonists were administered by infusion (ATL-193; n=7 normal) or bolus injection (ATL-146e; n=9 critical left anterior descending coronary artery stenosis), and hemodynamic responses were compared with those of Ado. Both agonists produced dose-dependent coronary flow (CF) elevation without provoking the hypotension observed with Ado. After an ATL-146e bolus, the CF increase was sustained for several minutes, providing ample time for injection and myocardial uptake of (99m)Tc-sestamibi, and CF returned to baseline within 20 minutes. The CF increase was completely blocked by the selective A(2A) antagonist ZM241385 (3 microgram. kg(-1). min(-1)). CONCLUSIONS: ATL-193 and ATL-146e are highly potent and selective Ado A(2A) receptor agonists with excellent potential for use as vasodilators for myocardial perfusion imaging. An important advantage of ATL-146e is the ability to administer it by bolus injection.

Adenosine↗
PubMed1989

Precordial ECG mapping in acute myocardial infarction (AMI) after intravenous infusion of streptokinase (s).

Repeated precordial ECG mapping (42 leads) and CK-MB serum measurements were done in 40 patients with anterior and/or anterolateral acute myocardial infarction. Twenty patients serving as controls, were treated with routine anticoagulant therapy. In 20 patients (the s group), randomly selected, a short-term IV infusion of 1,500,000 IU streptokinase was administered and followed by the same anticoagulant treatment as in controls. Ten subjects from each group underwent coronary arteriography one month later. From the analysis of ECG mapping the number of leads (N) and the sum of measurements (sigma) for each parameter were calculated. Before treatment there were no significant differences for all measured parameters between the two groups of patients. Seven days later, ST elevations were statistically different for NST and sigma ST with lower values for the s group. Higher values for NR and sigma R were also noted in this group. No statistically significant difference was found for NQ and sigma Q. CK-MB curve showed an earlier peak in the s group than in the control group. Five patients from the s group showed a patency of the infarct-related vessel. In conclusion, the results of this study show that patients receiving s have a significant benefit with ECG improvement. On the other hand, the CK-MB curve indicates an eventual recanalization to a certain degree in the obstructed coronary artery, which is the final goal.

Creatine Kinase↗