Nicardipine is a potent coronary and systemic vasodilator without depression of ventricular function. We investigated the changes in local myocardial perfusion (LMP) according to the nicardipine administration after coronary reperfusion in a beating canine model. A Doppler probe was placed around the left anterior descending coronary artery (LAD) and thermal diffusion microprobe was implanted in the myocardium perfused by the exposed LAD. To define the nicardipine effects, we compared the two groups (control group, n=7 vs nicardipine group, n=7). In nicardipine group, 5 microgram/kg/min nicardipine was infused continuously. After the release of the LAD occlusion, LAD blood flow were increased compared to the baseline of both groups. However, there was no difference between groups in the LAD blood flow. The LMP after LAD reperfusion did not recover to the baseline level until 30 min after LAD reperfusion in control group (74%, 52% and 70% at 10, 20 and 30 min after LAD reperfusion, respectively). In nicardipine group, however, the LMP recovered to the baseline level at 20 min (99%), and increased more than the baseline level at 30 min (141%) after LAD reperfusion. Our findings suggest that the nicardipine augments the LMP following the release of a coronary occlusion.
Animals ; Coronary Circulation/drug effects* ; Dogs ; Drug Evaluation, Preclinical ; Myocardial Reperfusion* ; Myocardial Reperfusion Injury/prevention & control* ; Nicardipine/pharmacology* ; Nicardipine/therapeutic use ; Vasodilator Agents/pharmacology* ; Vasodilator Agents/therapeutic use

BACKGROUNDCoronary endothelial shear stress (ESS) triggered the development of atherosclerosis. However, the effect of calcium channel antagonist on the distribution of ESS remained unclear.

METHODSTwenty consecutive patients with acute coronary syndrome (ACS) 48 hours after maximal medication with single left anterior descending artery stenosis < 50% were studied. Nicardipine was intravenously injected at 1 µg/kg after a bolus of 10 mg in order to achieve mean blood pressure (MBP) reduced by 10% or more, or the heart rate increased by 10 - 15 beats/min. Hemodynamic variables and angiogram at baseline and during injection of nicardipine were recorded, respectively. Coronary artery 3-D reconstruction was used for the analysis of ESS.

RESULTSDistal reference-vessel-diameter and minimal lumen diameter decreased significantly from (2.42 ± 0.41) mm and (1.47 ± 0.49) mm at baseline to (2.22 ± 0.35) mm and (1.35 ± 0.49) mm at maximal drug-dosage (P = 0.018 and 0.020, respectively). Nicardipine did not change blood velocity. Lowest mean shear stress at segments 2-mm distal to plaque increased significantly from (0.034 ± 0.519) Pa at baseline to (0.603 ± 0.728) Pa (P = 0.013) at peak effect of drug.

CONCLUSIONSNicardipine was associated with the constriction of diseased vessel segment that adapted to the reduction of blood pressure, without dynamic change of blood velocity at each stage of whole cardiac cycle. Increased ESS value at segments distal to plaque reflected the cardioprotection by nicardipine (ChiCTR-TRC-10000964).

Acute Coronary Syndrome ; Aged ; Angina, Unstable ; diagnostic imaging ; drug therapy ; Blood Pressure ; drug effects ; Coronary Angiography ; Coronary Vessels ; drug effects ; Female ; Heart Rate ; drug effects ; Hemodynamics ; drug effects ; Humans ; Male ; Middle Aged ; Nicardipine ; therapeutic use

The authors performed a multicenter prospective study to evaluate the feasibility and safety of intravenous nicardipine hydrochloride for acute hypertension in patients with intracerebral hemorrhage (ICH). This study included 88 patients (mean age: 58.3 yr, range 26-87 yr) with ICH and acute hypertension in 5 medical centers between August 2008 and November 2010, who were treated using intravenous nicardipine. Administration of nicardipine resulted in a decrease from mean systolic blood pressure (BP) (175.4 +/- 33.7 mmHg) and diastolic BP (100.8 +/- 22 mmHg) at admission to mean systolic BP (127.4 +/- 16.7 mmHg) and diastolic BP (67.2 +/- 12.9 mmHg) in 6 hr after infusion (P < 0.001, mixed-effect linear models). Among patients who underwent follow-up by computed tomography, hematoma expansion at 24 hr (more than 33% increase in hematoma size at 24 hr) was observed in 3 (3.4%) of 88 patients. Neurological deterioration (defined as a decrease in initial Glasgow coma scale > or = 2) was observed in 2 (2.2%) of 88 patients during the treatment. Aggressive nicardipine treatment of acute hypertension in patients with ICH can be safe and effective with a low rate of neurological deterioration and hematoma expansion.
Acute Disease ; Adult ; Aged ; Aged, 80 and over ; Antihypertensive Agents/adverse effects/*therapeutic use ; Blood Pressure ; Cerebral Hemorrhage/*drug therapy ; Cohort Studies ; Female ; Follow-Up Studies ; Glasgow Coma Scale ; Hematoma/etiology ; Humans ; Injections, Intravenous ; Male ; Middle Aged ; Nicardipine/adverse effects/*therapeutic use ; Prospective Studies ; Tomography, X-Ray Computed ; Treatment Outcome

AIMTo investigate the antiepileptic effect of dizocilpine (MK-801) on amygdala kindling models in rats and the effects of its combination with general antiepileptic drugs.

METHODSTo establish amygdala kindling models in rats and observe the effect of dizocilpine on kindling models and its combination with general antiepileptic drugs (phenobarbital, valproate and nicardipine) at ineffective dose. The influence of dizocilpine on convulsions induced by semicarbazide (SCZ) in mice were also observed.

RESULTSDizocilpine (0.1-0.25 mg.kg-1, i.p.) was shown to dose-dependently inhibit amygdala kindled seizure, shorten the after discharge duration (ADD) and reduce the Racine's stage (P < 0.01). The combination of dizocilpine with phenobarbital, valproate, nicardipine at ineffective dose shortened ADD or reduced Racine's stages (P < 0.01). Dizocilpine (0.1-0.25 mg.kg-1, i.p.) significantly prolonged the latency and reduced the rate of convulsions and death in mice.

CONCLUSIONDizocilpine inhibits the seizure of the amygdala kindling and improve the antiepileptic activity of phenobarbital, valproate and nicardipine, indicating that these combination may provide a new approach for treating epilepsy.

Amygdala ; drug effects ; physiopathology ; Animals ; Anticonvulsants ; pharmacology ; therapeutic use ; Dizocilpine Maleate ; pharmacology ; therapeutic use ; Electric Stimulation ; Epilepsy ; chemically induced ; drug therapy ; Female ; Kindling, Neurologic ; drug effects ; Male ; Mice ; Nicardipine ; pharmacology ; Phenobarbital ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Semicarbazides ; Valproic Acid ; pharmacology