Cardioprotection by nisoldipine: Role of timing of administration

Ferrari, Roberto; Curello, Salvatore; Ceconi, Claudio; Cargnoni, A; Pasini, Evasio; Visioli, O

doi:10.1016/0022-2828(92)90289-c

Cited by 1 publication

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“…The aorta was then exposed and suspended on a metal cannula. The hearts were perfused by the non-recirculating Langendorff technique, using a modified Krebs-Henseleit buffer solution, containing 1.5 mM calcium, as previously described [20].…”

Section: Methodsmentioning

confidence: 99%

“…In addition to exclusion of the hemodynamic variability, the isolated heart allows measurements independent of alterations in the central nervous system input to the heart, which are often evoked by dihydropyridines [3]. Previous studies used this model to assess the direct cardioprotective effects of calcium antagonists [20,[37][38][39][40].…”

Section: Experimental Modelmentioning

confidence: 99%

“…Holt et al [39] showed that cardioprotective effects of nicardipine are not correlated with the preservation of high-energy phosphates. Others [8,14,20] reported protection with different calcium antagonists at concentrations that do not exert a negative inotropic effect. For example, nisoldipine, another longacting dihydropyridine, attenuates stunning in the absence of negative inotropism [46,47].…”

Section: Protection With Calcium Antagonistsmentioning

confidence: 99%

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Effects of felodipine on the ischemic heart: Insight into the mechanism of cytoprotection

Ferrari

Cargnoni

Bernocchi

et al. 1996

Cardiovasc Drug Ther

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To assess whether the administration of felodipine protects the myocardium in a dose-dependent manner against ischemia and reperfusion, isolated rabbit hearts were infused with three different concentrations of felodipine: 10(-10), 10(-9), and 10(-8) M. Diastolic and developed pressures were monitored; coronary effluent was collected and assayed for CPK activity and for noradrenaline concentration; mitochondria were harvested and assayed for respiratory activity; and ATP production and calcium content and tissue concentration of ATP, creatine phosphate (CP), and calcium were determined. The occurrence of oxidative stress during ischemia and reperfusion was also monitored in terms of tissue content and release of reduced (GSH) and oxidized (GSSG) glutathione. Treatment with felodipine at 10(-10) and 10(-9) M had no effect on the hearts when perfused under aerobic conditions, whilst the higher dose reduced developed pressure from 57.7 +/- 2.6 to 30.0 +/- 2.6 mmHg (p < 0.01). On reperfusion treated hearts recovered better than the untreated hearts with respect to left ventricular performance, replenishment of ATP and CP stores, and mitochondrial function. Recovery of developed pressure was 100% at 10(-8) M, 55% at 10(-9) M, and 46% at 10(-10) M. The reperfusion-induced tissue and mitochondrial calcium overload, release of CPK and noradrenaline, and oxidative stress were also significantly reduced. The effects of felodipine were dose dependent. Felodipine inhibited the initial rate of ATP-driven calcium uptake but failed to affect the initial rate of mitochondrial calcium transport. It is concluded that felodipine infusion provides dose-dependent protection of the heart against ischemia and reperfusion. Because this protection also occurred at 10(-9) M and 10(-10) M in the absence of a negative inotropic effect during normoxia and of a coronary dilatory effect during ischaemia, it cannot be attributed to an energy-sparing effect or to improvement in oxygen delivery. From our data we can envisage two other major mechanisms-(1) membrane protection and (2) reduction in oxygen toxicity. The ATP-sparing effect occurring at 10(-8) M is likely to be responsible for the further protection.

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Section: Methodsmentioning

confidence: 99%