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J W De Jong

Publications and source records attributed to J W De Jong.

At least 19 recordsLinked to original sources
PubMed2000

Does resveratrol induce pharmacological preconditioning?

Resveratrol is a grape component with complex pharmacology related to its antioxidant activity. Little is known about the direct effects of resveratrol on the myocardium. We tested whether resveratrol administration before ischemia could attenuate ischemic/reperfusion damage. We examined how resveratrol affects high-energy phosphate metabolism (31P-nuclear magnetic resonance) and contractility of isolated Langendorff perfused rat hearts subjected to 20 min no-flow ischemia and 30 min reperfusion. During 10 min resveratrol infusion (10 microM) before ischemia, basal phosphorylation potential dropped by 40% (p < 0.05 vs. preinfusion value) without affecting contractility. The level of effluent adenosine was increased by 68%, parallel to a 50% increase in coronary flow. Resveratrol significantly improved postischemic recovery of rate-pressure product (62 +/- 5.2 vs. 23 +/- 8.1% of controls; p < 0.05). The metabolic pattern following resveratrol infusion was similar to that produced by ischemic preconditioning, suggesting that an increase in adenosine availability is involved in cardioprotection.

Adenosine↗
PubMed1994

Loss of elastic recoil in postischemic myocardium induces rightward shift of the systolic pressure-volume relationship.

Ischemia-induced systolic dysfunction has been ascribed to changes in cellular excitation-contraction coupling and diastolic dysfunction because of disruption of the extracellular collagen matrix. Therefore, systolic and diastolic pressure-volume relationships and O2 consumption were determined before and after 5 min of global ischemia in isolated blood-perfused porcine hearts. The slope of the systolic pressure-volume relationship was 7.2 +/- 0.6 (SE) mmHg.ml-1.100 g-1 (n = 18) at baseline and did not change during reperfusion, but the systolic volume intercept shifted from 1.0 +/- 0.4 ml/100 g at baseline to 3.7 +/- 1.4, 4.1 +/- 1.1, and 4.2 +/- 0.9 ml/100 g at 15, 30, and 60 min of reperfusion, respectively (all P < 0.05). The diastolic volume intercept was 8.2 +/- 0.7 ml/100 g at baseline and remained unchanged during reperfusion. Therefore, the difference of the systolic-diastolic volume intercepts, an index of elastic recoil forces, was decreased to 57 +/- 8, 49 +/- 7, and 47 +/- 9% of baseline values (P < 0.05). The shift of the systolic pressure-volume relationship was accompanied by a transient decrease of contractile efficiency (slope of O2 consumption-pressure-volume-area relationship) at 15 min of reperfusion (from 43 +/- 6 to 27 +/- 7%). We hypothesize that the rightward shift of the systolic pressure-volume relationship was compatible with a decrease of elastic-restoring forces, probably induced by alterations in the extracellular collagen matrix and/or the cytoskeleton, and thereby our data imply that left ventricular dysfunction of postischemic myocardium does not result solely from disturbances in excitation-contraction coupling.

Animals↗
PubMed1991

Does xanthine oxidase cause damage during myocardial ischemia?

Xanthine oxidase is the pathological form of xanthine oxidoreductase, which generates free oxygen radicals, when it converts (hypo)xanthine to urate. We studied 1. developmental changes in rat heart, 2. urate production in catheterized patients, and 3. species differences of cardiac xanthine oxidase. First, we measured the activity of the enzyme at various ages. In rat-heart homogenate, xanthine oxidoreductase increased from 0.5 mU/g (newborn) to 25 mU/g (15 weeks, P less than 0.001). In the second part of the study, we demonstrated that patients undergoing coronary angioplasty showed some cardiac urate production. In the last part of our investigations we showed that in explanted human hearts perfused with hypoxanthine, the enzymatic activity was low, contrasting findings in some other species. The apparent xanthine oxidoreductase activity (mU/g) was: 33 (mouse), 28 (rat), 14 (guinea pig), 0.59 (rabbit), less than 0.1 (pig), 0.31 (man) and 3.7 (cow). We conclude that in several species, cardiac damage due to xanthine oxidase cannot be excluded; however in man it is unlikely to occur.

Aging↗
PubMed1986

Myocardial adenosine cycling rates during normoxia and under conditions of stimulated purine release.

Formation and rephosphorylation of adenosine (adenosine cycling) was studied in isolated rat hearts during normoxia and under conditions of stimulated purine formation. Hearts were infused with an inhibitor of adenosine kinase (5-iodotubercidin, 2 microM). In addition, perfusions were carried out with or without acetate, which is converted into acetyl-CoA, with simultaneous breakdown of ATP to AMP and purines. We found a linear, concentration-dependent, increase in normoxic purine release by acetate (5-20 mM). Differences in total purine release with or without iodotubercidin were taken as a measure of adenosine cycling. In normoxic hearts, iodotubercidin caused a minor increase in purine release (2.7 nmol/min per g wet wt.). Acetate (12.5 mM) increased purine release by 4.9 nmol/min per g, and its combination with inhibitor gave a large increase, by 14.2 nmol/min per g. This indicates a strongly increased adenosine cycling rate during acetate infusion. However, no significant differences in purine release were observed when iodotubercidin was infused during hypoxia, anoxia or ischaemia. The hypothesis that adenosine cycling is near-maximal during normoxia was not confirmed. Increased myocardial adenosine formation appears to be regulated by the availability of AMP and not by inhibition of adenosine kinase. This enzyme mainly functions to salvage adenosine in order to prevent excessive loss of adenine nucleotides.

Acetates↗
PubMed1985

Timely administration of nisoldipine essential for prevention of myocardial ATP catabolism.

Calcium entry blockers can effectively preserve high-energy phosphates in ischemic heart. However, little is known about the optimal timing of drug therapy. The moment of nisoldipine administration in relation to its protective efficacy during ischemia and reperfusion was studied in rat hearts. Nisoldipine (50 nM), given some time before a reduction of about 90% in coronary flow diminished ATP-catabolite efflux during both ischemia and reperfusion by up to 85%. In contrast, drug administration at the onset of ischemia, or during ischemia or during reperfusion was completely without protective effect. Similarly, early nisoldipine application gave rise to ischemic ATP, adenylate charge and creatine phosphate values higher than those in untreated or late-treated hearts. Nisoldipine decreased the tension developed before ischemia by up to 66%, without affecting (post)ischemic function. Nisoldipine spares energy effectively only if administered to the heart prior to ischemia. This presumably has to do with its negative inotropy before flow reduction.

Adenosine Diphosphate↗
PubMed1984

Diltiazem administered before or during myocardial ischemia decreases adenine nucleotide catabolism.

Calcium antagonists potentially prevent ATP breakdown, but literature data on this subject are conflicting. We studied the effect of diltiazem on ATP catabolism in rat heart, perfused according to Langendorff. Administration of the drug took place either before or during ischemia, induced by lowering the perfusion pressure. The reduction in flow without diltiazem was 85%. We observed a significantly (P less than 0.001) lower production of purine nucleosides and oxypurines by the ischemic heart, when we gave diltiazem in a dose range of 1 to 100 microM before ischemia. The highest drug concentration reduced purine release by 85%. Due to ischemia, myocardial adenine nucleotide content decreased by 40% (P less than 0.001); this was partially prevented by 5 microM diltiazem (P = 0.4 v. untreated hearts). The drug also effectively reduced purine release, when applied five minutes after the induction of ischemia, but higher concentrations were needed.

Adenine Nucleotides↗
PubMed1984

Energy conservation by nisoldipine in ischaemic heart.

We studied the effect of the calcium entry blocker nisoldipine on ATP catabolism in the rat heart, perfused according to Langendorff. Even 1 nM nisoldipine induced vasodilatation; concentrations of 30 nM and higher caused significant negative inotropy. The drug had a very strong affinity for silicon rubber tubing. Myocardial ischaemia was induced by lowering the perfusion pressure, which reduced flow without nisoldipine by 85%. The efflux of purine nucleosides and oxypurines rose 14 fold. Nisoldipine reduced this efflux of ATP catabolites dose-dependently. The highest concentration, 300 nM, suppressed ischaemic purine production completely. The action of the drug was antagonized by an increase in Ca2+-concentration in the perfusion fluid. We also showed the protective effect of nisoldipine on adenine nucleotides in freeze-clamped hearts. A concentration of 20 nM partially prevented the reduction of ATP and adenylate energy charge due to ischaemia. We conclude that relatively low doses of nisoldipine effectively prevent ATP breakdown in ischaemic rat heart.

Adenosine Triphosphate↗
PubMed1984

Xanthine oxidase in rabbit plasma after application of a bovine milk preparation to small intestine.

The absorption of xanthine oxidase into the bloodstream was studied in rabbits given a milk/cream preparation, fortified with 130 U bovine milk xanthine oxidase or the milk/cream preparation alone (control). The preparations were injected trans-abdominally into the intestines. The rise of plasma xanthine oxidase/dehydrogenase activity was studied with a radioenzymatic assay with and without NAD+. In rabbits, which received the fortified mixture, the plasma xanthine oxidase increase in 8 h was six times more than the increase in control animals (P less than 0.001). In both groups plasma xanthine dehydrogenase activity increased 3-4 times (P less than 0.001), without a significant difference between the two groups. We estimate that only 0.003%, or about 3 micrograms, of the xanthine oxidase added, is absorbed as an active enzyme from the intestine.

Animals↗
PubMed1983

Myocardial xanthine oxidase/dehydrogenase.

High-energy phosphates in heart muscle deprived of oxygen are rapidly broken down to purine nucleosides and oxypurines. We studied the role of xanthine oxidase/dehydrogenase (EC 1.2.3.2/EC 1.2.1.37) in this process with novel high-pressure liquid chromatographic techniques. Under various conditions, including ischemia and anoxia, the isolated perfused rat heart released adenosine, inosine and hypoxanthine, and also substantial amounts of xanthine and urate. Allopurinol, an inhibitor of xanthine oxidase, greatly enhanced the release of hypoxanthine. From the purine release we calculated that the rat heart contained about 18 mU xanthine oxidase per g wet weight. Subsequently, we measured a xanthine oxidase activity of 9 mU/g wet wt. in rat-heart homogenate. When endogenous low molecular weight inhibitors were removed by gel-filtration, the activity increased to 31 mU/g wet wt. Rat myocardial xanthine oxidase seems to be present mainly in the dehydrogenase form, which upon storage at -20 degrees C is converted to the oxidase form.

Animals↗
PubMed1983

Synergistic effect of nifedipine and propranolol on adenosine (catabolite) release from ischemic rat heart.

Both nifedipine a calcium antagonist, and propranolol a beta-adrenergic blocker, are used as protective agents of the ischemic myocardium. In the clinical setting, the combination of the two drugs is used successfully although several case reports indicate potential dangers of the combination. For this reason we decided to study the combined effect of nifedipine and DL-propranolol in the isolated rat heart made ischemic for a short period of time. Apex displacement was taken as a measure of contractility. Release of the AMP catabolites adenosine, inosine, (hypo)xanthine and uric acid was used as a marker of ATP breakdown. Contractility during ischemia was not affected by the drugs. DL-Propranolol (30 or 150 micrograms/l) had no effect on ischemic myocardial purine release, while nifedipine (15 micrograms/l) reduced purine release during ischemia by 33% (P less than 0.02). The combination of 15 micrograms/l nifedipine and 150 micrograms/l DL-propranolol decreased purine release by 53% (P less than 0.005 vs. nifedipine). We conclude from these results that propranolol has a synergistic effect, adding to the beneficial action of nifedipine on ischemic myocardium.

Adenosine↗
PubMed1983

Regulation of porcine heart and skeletal muscle AMP-deaminase by adenylate energy charge.

1. Cytosol from pig skeletal muscle, but not heart, contains an inhibitor of AMP-deaminase (AMP-D, EC 3.5.4.6) which reduces AMP-D activity 8-fold. 2. Heart and skeletal muscle AMP-D have been purified to apparent homogeneity by cellulose phosphate and DEAE-Sephacel chromatography. 3. AMP-D from skeletal muscle is inhibited more severely than the heart enzyme by an increase in adenylate energy charge to levels exceeding 0.4. Nevertheless both enzymes seem to be regulated by the energy charge, which contrasts with reports for rabbit heart AMP-D.

AMP Deaminase↗
PubMed1982

Nifedipine reduces adenine nucleotide breakdown in ischemic rat heart.

An ATP-sparing effect has been demonstrated for a number of calcium antagonists. Nifedipine probably has a similar action, but data supporting this view are limited. Therefore we decided to study the effect of nifedipine on high-energy phosphate (and carbohydrate) metabolism in the ischemic rat heart. Langendorff preparations were made ischemic for less than 15 min. The reduction in coronary flow was 60 or 70%. Apex displacement during ischemia, a measure of contractility, was comparable for nifedipine-treated and untreated hearts. Ischemia caused a considerable release of the AMP catabolites adenosine, inosine and (hypo)xanthine, and of lactate. Nifedipine (10-100 micrograms/l) prevented this in a dose-dependent way. The highest dose reduced the release of purines and lactate by 90% (P less than 0.01) and 60% (P less than 0.001), respectively. The drug acted in a similar way during reperfusion. Due to ischemia, the adenylate energy charge (ATP + 0.5 ADP)/(ATP + ADP + AMP), decreased 15% (P less than 0.001); nifedipine at a concentration of 100 micrograms/l prevented this decrease (P less than 0.05). We conclude that nifedipine exerts a beneficial effect on myocardial adenine nucleotide metabolism during ischemia and reperfusion.

Adenine Nucleotides↗
PubMed1978

Antiarrhythmic, metabolic and hemodynamic effects of Org 6001 (3alpha-amino-5alpha-androstan-2beta-ol-17-one-hydrochloride) after coronary flow reduction in pigs.

The antiarrhythmic activity of the aminosteroid Org 6001 was investigated in young pigs (20-28 kg). Ventricular arrhythmias were induced by restriction of the flow in the left anterior descending coronary artery (LAD) to 25% of its control value during a period of 30 minutes. Nine out of 30 control animals died in this period due to ventricular fibrillation. None of the 19 animals treated with Org 6001 (5-10 mg/kg) or the 12 animals treated with lidocaine (2.75-3.50 mg/kg) fibrillated. Moreover, the number of premature ventricular beats was greatly reduced in pretreated groups compared with the untreated group (P less than .001). The first derivative of left ventricular pressure decreased with 25% (P less than 0.001) after administration of Org 6001. However, during 30 minutes of LAD flow reduction to 25% of control, the adverse effects of Org 6001 were less than those of lidocaine. Myocardial lactate production indicated some delay in onset of ischemia. However, there was no indication that this beneficial effect was long-lasting. When after 30 minutes of LAD flow reduction to 25% of control, the LAD was completely occluded between its second and third branch, all untreated animals fibrillated within 120 minutes, whereas 4 of the 19 animals treated with Org 6001 and 3 of the 12 treated with lidocaine survived. It is concluded that Org 6001 has antiarrhythmic properties in the ischemic pig heart which compare favorably with those of lidocaine.

17-Ketosteroids↗
PubMed1977

Partial purification and properties of rat-heart adenosine kinase.

The activity of myocardial adenosine kinase (E.N. 2.7.1.20) in a number of species was assayed. Rat heart contained the highest specific activity. From this source adenosine kinase was purified in a simple way 80-fold, until it was free of adenosine deaminase activity. A molecular weight of about 39 000 was measured. NSC 113939 (1), NSC 113940 and 8-azaadenosine inhibited myocardial adenosine kinase. Dipyridamole stimulated the enzyme at high adenosine levels, and inhibited at low substrate concentrations. A number of divalent cations could (partially) substitute for Mg2+. The optimal concentration of MgCl2 or MnCl2 was about 0.5 mM; concentrations exceeding 1 mM inhibited severely. An apparent Km for ATP of 0.1 mM was measured, whereas an apparent Km for adenosine of 0.5 muM was was found. The latter increased to 3.3 muM, when dipyridamole was added. Replacement of ATP by GTB or ITP increased the activity, and UTP and CTP were inferior as a phosphate donor.

Adenosine Kinase↗