Pharmacological profile of nicardipine hydrochloride in anesthetized dogs with acute heart failure. Part 1: Hemodynamic effects in normal dogs and dogs with acute heart failure.
Cardiovascular effects of nicardipine hydrochloride (NIC, CAS 54527-84-3, Perdipine), a calcium channel blocker, were investigated in anesthetized normal dogs and dogs with acute heart failure (AHF), and compared with those of nitroglycerin (NTG). In open-chest anesthetized dogs, NIC (0.1-10 micrograms/kg/min i.v.) dose-dependently increased cardiac output (CO) and coronary blood flow as well as decreased mean blood pressure (MBP). NIC had no effect on heart rate (HR) or maximum rate of rise of left ventricular pressure (max. dp/dt). In contrast (0.1-10 micrograms/kg/min i.v.) decreased MBP, but did not change the other cardiovascular parameters. NIC and NTG did not prolong PQ, QRS or QTc intervals. In addition, NIC was effective in the presence of dobutamine. In the anesthetized dog model of ischemic AHF induced by coronary ligation, and ischemia/angiotensin II-induced AHF, NIC (1 and 3 micrograms/kg/min i.v.) increased CO and stroke volume, and reduced total peripheral resistance without decreasing HR or cardiac contractility. Furthermore, in the ischemia/angiotension II-induced AHF model, NIC decreased left ventricular end-diastolic pressure (LVEDP). In contrast, NTG (1-10 micrograms/kg/min i.v.) decreased LVEDP in both AHF models; but did not increase CO. These results suggest that NIC improves hemodynamics in dogs with AHF mainly by reducing afterload without adversely affecting the cardiac contractility or conduction system, while NTG exerts its effect on AHF by reducing preload. NIC injection would thus appear to be beneficial in the treatment of AHF.
Saitoh
C
C
Applied Pharmacology Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Momose
K
K
Tanaka
H
H
Sato
S
S
Taguchi
K
K
Saitoh
M
M
Maehara
J
J
Asano
M
M
Usuda
S
S
D000208:Acute Disease; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000758:Anesthesia; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use*; D004280:Dobutamine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology* / Q000627:therapeutic use*; D005996:Nitroglycerin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D000804:Angiotensin II; D004280:Dobutamine; D009529:Nicardipine; D005996:Nitroglycerin