Energy conservation by nisoldipine in ischaemic heart

Jong, Jan Willem de; Huizer, Tom; Tijssen, Jan G.P.

doi:10.1111/j.1476-5381.1984.tb16535.x

Cited by 32 publications

(6 citation statements)

References 14 publications

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“…Adsorption of dihydropyridines to PVC and silicone infusion lines has been reported (Jakobsen & Mikkelsen, 1986;de Jong et al, 1984). In an in vitro experiment the extent and reproducibility of adsorption of nisoldipine to the PVC infusion lines used (Talas, Ommen, The Netherlands) were studied.…”

Section: Adsorption Of Nisoldipine To Infusion Linesmentioning

confidence: 99%

The influence of infusion rate on the pharmacokinetics and haemodynamic effects of nisoldipine in man.

Harten¹,

Brummelen²,

Zeegers³

et al. 1988

Brit J Clinical Pharma

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1 The pharmacokinetics and haemodynamic effects of nisoldipine on long term i.v. infusion of 2.40 mg and 9.59 mg in 25 h were studied in six healthy subjects. Liver blood flow at 0.8 and 24 h was assessed by measuring indocyanine green (ICG) clearance.2 After high-dose nisoldipine, systemic clearance was 0.99 ± 0.16 1 min-', volume of distribution was 5.8 ± 1.5 1 kg-' and elimination half-life was 10.7 ± 2.4 h. The pharmacokinetic parameters were similar after low-dose nisoldipine. 3 No significant changes in apparent liver blood flow were observed after either highdose or low-dose nisoldipine. 4 Systolic blood pressure did not change, whereas diastolic blood pressure decreased by approximately 10% during both treatments. Maximal increase in heart rate was approximately 37% at high-dose infusion, whereas this was one half lower during the low-dose regimen. 5 Increased infusion rate results in an unfavourable shift in the haemodynamic effect profile of nisoldipine.

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Section: Adsorption Of Nisoldipine To Infusion Linesmentioning

confidence: 99%

The influence of infusion rate on the pharmacokinetics and haemodynamic effects of nisoldipine in man.

Harten¹,

Brummelen²,

Zeegers³

et al. 1988

Brit J Clinical Pharma

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“…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%

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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“…In the isolated rat heart, nisoldipine initiates dosedependent coronary vasodilation [33]. In ca nine coronary arteries in situ, intravenous infusion of nisoldipine abolishes seroto nin and potassium-induced vasoconstriction [34], while in anesthetized pigs, nisoldipine (2-4 pg/kg/min) reduces left ventricular sys tolic pressure, vascular resistance during sys tole, and left ventricular dP/dt max, with no change in cardiac output [35].…”

Section: Discussionmentioning

confidence: 99%

Effect of Nisoldipine on Large Coronary Arteries in situ: Inhibition of Vasoconstriction Induced by Vasopressin

1988

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The effects of nisoldipine on myocardial performance and large coronary artery diameter, resistance and cross-sectional area were studied in rabbit hearts in situ. Changes in mean internal diameter of coronary artery segments were visualized using color arteriography; changes were computer-calculated. Nisoldipine had a direct dilatory effect on large coronary arteries in situ and it attenuated the vasoconstriction induced by vasopressin. It shifted the dose-response curve of vasopressin to the right in a noncompetitive manner. Nisoldipine reduced the effect of vasopressin on maximum left ventricular dP/dt, mean aortic pressure, left ventricular end-systolic pressure and heart rate. The results demonstrate that nisoldipine is an effective dilator of large epicardial coronary arteries in situ and inhibits the vasoconstriction induced by vasopressin.

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Energy conservation by nisoldipine in ischaemic heart

Cited by 32 publications

References 14 publications

The influence of infusion rate on the pharmacokinetics and haemodynamic effects of nisoldipine in man.

The influence of infusion rate on the pharmacokinetics and haemodynamic effects of nisoldipine in man.

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

Effect of Nisoldipine on Large Coronary Arteries in situ: Inhibition of Vasoconstriction Induced by Vasopressin

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