@entity460 channel blockers (CCBs) have variable efficacy in the treatment of @entity712 . We hypothesized that modulation of @entity1002 ( @entity1002 ) 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 @entity7863 hamsters (failing hearts) and age-matched @entity329 (normal hearts) were studied. After recording of heart rate, @entity301 ( @entity301 ), @entity1002 and left ventricular systolic pressure (LVSP), hearts were exposed either to @entity1855 or @entity3988 (1 nM-10 microM), mibefradil (1 nM-1 microM) or clentiazem (1 nM-10 microM). Mechanical increase in @entity301 (+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 @entity1002 (+5 to +25 mm Hg). CCBs-induced increment of @entity301 led to a difference in their cardiac response. In normal hearts, the negative inotropic response was more important with @entity3988 and @entity1855 . Failing hearts did not demonstrate increased inotropic sensitivity to first-generation CCBs. On the contrary, at clinically relevant concentrations, @entity1855 resulted in the most pronounced impairment of @entity1002 followed by @entity3988 while @entity946 and clentiazem, at clinically relevant concentrations, preserved @entity1002 . Such findings provide an additional explanation for the variable efficacy of CCBs in @entity712 .

Effects of first and second generation @entity460 channel blockers on diastolic function of the failing hamster heart: relationship with XXXX changes.

@entity712 :: ('MESH:D006333', 'Disease') :: ['heart failure'] @entity301 :: ('MESH:D003327', 'Disease') :: ['coronary flow', 'CF'] @entity1855 :: ('MESH:D014700', 'Chemical') :: ['verapamil'] @entity946 :: ('MESH:D020748', 'Chemical') :: ['mibefradil'] @entity3988 :: ('MESH:D004110', 'Chemical') :: ['diltiazem'] @entity329 :: ('10036', 'Species') :: ['Syrian hamsters'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['Calcium'] @entity7863 :: ('MESH:D044542', 'Disease') :: ['cardiomyopathic'] @entity1002 :: ('MESH:D018487', 'Disease') :: ['LVDP', 'left ventricular diastolic pressure']
@entity301 :: (MESH:D003327,Disease) :: ['coronary flow']
