Effects of first and second generation calcium channel blockers on diastolic function of the failing hamster heart: relationship with coronary flow changes
| Autor: | Louis Dumont, Pierre Beaucage, Jean-François Boileau, Julie Massicotte |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Cardiac Output Low Blood Pressure In Vitro Techniques Ventricular Function Left Clentiazem chemistry.chemical_compound Coronary circulation Internal medicine Coronary Circulation Cricetinae medicine Animals Diltiazem Pharmacology Mibefradil business.industry Heart medicine.disease Calcium Channel Blockers Blood pressure medicine.anatomical_structure chemistry Heart failure Cardiology Coronary perfusion pressure Verapamil Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Journal of cardiovascular pharmacology. 42(1) |
| ISSN: | 0160-2446 |
| Popis: | Calcium channel blockers (CCBs) have variable efficacy in the treatment of heart failure. We hypothesized that modulation of left ventricular diastolic pressure (LVDP) may play a role in the variable efficacy of CCBs in this condition. Isolated perfused hearts from 200- to 250-day-old UM-X7.1 cardiomyopathic hamsters (failing hearts) and age-matched Syrian hamsters (normal hearts) were studied. After recording of heart rate, coronary flow (CF), LVDP and left ventricular systolic pressure (LVSP), hearts were exposed either to verapamil or diltiazem (1 nM-10 microM), mibefradil (1 nM-1 microM) or clentiazem (1 nM-10 microM). Mechanical increase in CF (+2 to +10 ml/min) was carried out using a roller pump. Mechanically-augmented flow led to an increase in coronary perfusion pressure (+40 to +90 mm Hg), LVSP (+5 to +40 mm Hg) and LVDP (+5 to +25 mm Hg). CCBs-induced increment of coronary flow led to a difference in their cardiac response. In normal hearts, the negative inotropic response was more important with diltiazem and verapamil. Failing hearts did not demonstrate increased inotropic sensitivity to first-generation CCBs. On the contrary, at clinically relevant concentrations, verapamil resulted in the most pronounced impairment of LVDP followed by diltiazem while mibefradil and clentiazem, at clinically relevant concentrations, preserved LVDP. Such findings provide an additional explanation for the variable efficacy of CCBs in heart failure. |
| Databáze: | OpenAIRE |
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