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Cardioprotective effects of amlodipine in the ischemic-reperfused heart.
- Source :
-
The American journal of cardiology [Am J Cardiol] 1989 Nov 07; Vol. 64 (17), pp. 101I-115I discussion 115I-116I. - Publication Year :
- 1989
-
Abstract
- Amlodipine is a dihydropyridine derivative belonging to the group of pharmacologic calcium entry blocking agents and is characterized as having a slow onset and relatively long duration of action with minimal effects on cardiac electrophysiology and myocardial contractility. The protective effect of amlodipine was studied in isolated blood-perfused feline hearts made globally ischemic for 60 minutes followed by reperfusion for 60 minutes. Ischemic-induced alterations of left ventricular developed pressure and complicance were monitored. In 11 control and 7 drug-treated hearts, amlodipine produced significant decreases in myocardial oxygen consumption (6.2 +/- 0.4 to 4.4 +/- 0.4 ml oxygen/min/100 g) and coronary vascular resistance, as assessed by changes in perfusion pressure (120 +/- 1 to 100 +/- 4 mm Hg). Amlodipine administered before the onset of global ischemia decreased the development of ischemic contracture as reflected by a progressive increase in resting left ventricular diastolic pressure. The return of contractile function, 60 minutes afer reperfusion, improved significantly in the amlodipine-treated group compared with controls, and there was better maintenance of the tissue concentration of Na+, Ca2+ and K+. A canine model of regional myocardial ischemia (90 minutes) followed by 6 hours of reperfusion was used to assess the cardioprotective effects of amlodipine, 150 micrograms/kg, administered 15 minutes before reperfusion. Infarct size, expressed as a percentage of the area at risk, was smaller in the amlodipine-treated group (n = 10) than in the control group (n = 10) (34.5 +/- 3.8% vs 45.9 +/- 2.8%, p = 0.027). Risk region size did not differ between groups and both groups were comparable with respect to the hemodynamic parameters of heart rate, blood pressure and rate-pressure product. Amlodipine prevented the gradual reduction in coronary blood flow observed in the control group. It is concluded that amlodipine reduces myocardial ischemic injury by mechanism(s) that may involve a reduction in myocardial oxygen demand as well as by positively influencing transmembrane Ca2+ fluxes during ischemia and reperfusion.
- Subjects :
- Amlodipine
Animals
Blood Pressure drug effects
Calcium metabolism
Calcium Channel Blockers
Cats
Compliance drug effects
Coronary Circulation drug effects
Electrophysiology
Female
Heart physiopathology
Heart Ventricles
In Vitro Techniques
Male
Myocardial Contraction drug effects
Myocardial Infarction pathology
Myocardium metabolism
Nifedipine pharmacology
Rest
Heart drug effects
Myocardial Reperfusion Injury prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 0002-9149
- Volume :
- 64
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- The American journal of cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 2530882
- Full Text :
- https://doi.org/10.1016/0002-9149(89)90967-3