We investigated the effects of in vivo treatment with the angiotensin-converting enzyme inhibitor (ACE-I) captopril and/or of in vitro administration of L-arginine on the metabolism and ischemia-reperfusion injury of the isolated perfused rat myocardium. Captopril (50 mg/l in drinking water, 4 weeks) raised the myocardial content of glycogen. After 25-min global ischemia, captopril treatment, compared with the controls, resulted in lower rates of lactate dehydrogenase release during reperfusion (8.58 +/- 1.12 vs. 13.39 +/- 1.88 U/heart/30 min, p<0.05), lower myocardial lactate contents (11.34 +/- 0.93 vs. 21.22 +/- 4.28 micromol/g d.w., p<0.05) and higher coronary flow recovery (by 25%), and prevented the decrease of NO release into the perfusate during reperfusion. In control hearts L-arginine added to the perfusate (1 mmol/l) 10 min before ischemia had no effect on the parameters evaluated under our experimental conditions, presumably because of sufficient saturation of the myocardium with L-arginine. In the hearts of captopril-treated rats, L-arginine further increased NO production during reperfusion and the cGMP content before ischemia. Our results have shown that long-term captopril treatment increases the energy potential and has a beneficial effect on tolerance of the isolated heart to ischemia. L-arginine added into the perfusate potentiates the effect of captopril on the NO signaling pathway.
- MeSH
- arginin farmakologie MeSH
- guanosinmonofosfát cyklický metabolismus MeSH
- inhibitory ACE farmakologie MeSH
- kaptopril farmakologie MeSH
- krysa rodu Rattus MeSH
- myokard metabolismus MeSH
- oxid dusnatý metabolismus MeSH
- potkani Wistar MeSH
- reperfuzní poškození myokardu farmakoterapie metabolismus MeSH
- synergismus léků MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- arginin MeSH
- guanosinmonofosfát cyklický MeSH
- inhibitory ACE MeSH
- kaptopril MeSH
- oxid dusnatý MeSH
The increase of radical forms of mitochondrial respiratory chain compounds (MRCC) is an indicator of an increased risk of the formation of oxygen radicals. Using electron paramagnetic resonance (EPR), we found an increase of signals corresponding to ubisemichinone radical (.QH) and ironsulfur proteins radical forms (-FeS) of these respiratory chain compounds during ischemia in the isolated perfused rat heart (.QH increased from 1.51 to 3.08, .FeS1 from 1.14 to 2.65 arbitrary units). During the 5-min reperfusion, the signals returned to normoxic levels. In isolated mitochondria exposed to anoxia and reoxygenation the radical forms of .QH and FeS2 changed in a similar manner as in the intact heart. A combination of in vivo captopril treatment and in vitro L-arginine administration significantly decreased the levels of MRCC radicals in the isolated myocardium (.QH from 2.61 to 1.72 and .FeS, from 1.82 to 0.46 under normoxia; .QH from 4.35 to 2.66 and .FeS1 from 1.93 to 1.35 during ischemia). This decrease in MRCC radical forms was associated with increased NO levels in the perfusate, determined as NO2- / NO3-, as well as tissue NO levels determined using EPR as the dinitrosyl iron complex (DNIC). These results provide new information about the cardioprotective effects of ACE inhibitors and L-arginine.
- MeSH
- arginin farmakologie MeSH
- elektronová paramagnetická rezonance MeSH
- inhibitory ACE farmakologie MeSH
- ischemická choroba srdeční metabolismus MeSH
- kaptopril farmakologie MeSH
- koenzymy MeSH
- krysa rodu Rattus MeSH
- kyslík aplikace a dávkování MeSH
- oxid dusnatý metabolismus MeSH
- potkani Wistar MeSH
- proteiny obsahující železo a síru metabolismus MeSH
- srdeční mitochondrie účinky léků metabolismus MeSH
- transport elektronů * MeSH
- ubichinon analogy a deriváty metabolismus MeSH
- volné radikály MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- arginin MeSH
- coenzyme Q10 MeSH Prohlížeč
- inhibitory ACE MeSH
- kaptopril MeSH
- koenzymy MeSH
- kyslík MeSH
- oxid dusnatý MeSH
- proteiny obsahující železo a síru MeSH
- ubichinon MeSH
- volné radikály MeSH
Chronic renal insufficiency (CRI) is often associated with cardiovascular disease; however, its underlying mechanisms are not completely understood. Therefore, in the present study, myocardial functions and metabolic changes were investigated using an animal model of CRI in subtotally nephrectomized rats. In addition, some other parameters, considered risk factors of cardiovascular diseases, were determined. Subtotal nephrectomy led to an elevation in blood pressure (144 +/- 2.8 vs 114 +/- 2.5 mm Hg), left ventricular hypertrophy (290 +/- 12 vs 200 +/- 40 mg/100 g b.w.), hypertriglyceridaemia (2.96 +/- 0.31 vs 0.77 +/- 0.07 mmol/l), and impaired glucose tolerance (AUC 836 +/- 12.4 vs 804 +/- 10.4 mmol x l(-1) x 120 min). Isolated perfused hearts of uraemic rats exhibited diminished basal functions (coronary and aortic flow, stroke volume) by 20-30% compared with the controls. Interestingly, the tolerance of isolated heart to global 20-min no-flow ischaemia was improved in uraemic rats. The most marked differences in heart function recovery during reperfusion concerned aortic flow (90 +/- 2.3 vs 66 +/- 10%) and stroke volume (97 +/- 2.7 vs 68 +/- 5.6% of pre-ischaemic values). Pre-ischaemic myocardial glycogen content was distinctly increased (by 50%) in uraemic rats compared with the controls.
- MeSH
- adenosintrifosfát metabolismus MeSH
- chronické selhání ledvin komplikace metabolismus patofyziologie MeSH
- glykogen metabolismus MeSH
- krysa rodu Rattus MeSH
- myokard metabolismus MeSH
- nefrektomie MeSH
- potkani Wistar MeSH
- reperfuzní poškození myokardu metabolismus patofyziologie MeSH
- srdce patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adenosintrifosfát MeSH
- glykogen MeSH
- MeSH
- dietní sacharidy aplikace a dávkování MeSH
- dietní tuky nenasycené aplikace a dávkování farmakologie MeSH
- glukosa metabolismus MeSH
- hypertriglyceridemie metabolismus MeSH
- inzulin farmakologie MeSH
- krysa rodu Rattus MeSH
- kyseliny mastné omega-3 aplikace a dávkování farmakologie MeSH
- myokard metabolismus MeSH
- potkani Wistar MeSH
- sacharosa aplikace a dávkování MeSH
- srdce účinky léků MeSH
- triglyceridy metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dietní sacharidy MeSH
- dietní tuky nenasycené MeSH
- glukosa MeSH
- inzulin MeSH
- kyseliny mastné omega-3 MeSH
- sacharosa MeSH
- triglyceridy MeSH
Using a model of the isolated beating rat heart, the authors compared the protective effect of St. Thomas Hospital cardioplegic solution enriched with glucose and mannitol (StTH-M) and Bretschneider solution (HTK-B). Results showed that, during 120-minute global ischaemia in cardioplegia, StTH-M was able to maintain levels of high-energy phosphates comparable with those found in a group of hearts perfused with HTK-B at 20 degrees C only when the temperature had been decreased to 12-15 degrees C. Under these conditions, repair of metabolic and functional parameters during post-ischaemic perfusion was also similar in both groups.
- MeSH
- chlorid draselný farmakologie MeSH
- chlorid sodný farmakologie MeSH
- chlorid vápenatý farmakologie MeSH
- energetický metabolismus MeSH
- glukosa farmakologie MeSH
- hořčík farmakologie MeSH
- hydrogenuhličitany farmakologie MeSH
- kardioplegické roztoky farmakologie MeSH
- krysa rodu Rattus MeSH
- mannitol farmakologie MeSH
- myokard metabolismus MeSH
- potkani Wistar MeSH
- prokain farmakologie MeSH
- reperfuze myokardu MeSH
- srdce fyziologie MeSH
- techniky in vitro MeSH
- teplota MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- Bretschneider cardioplegic solution MeSH Prohlížeč
- chlorid draselný MeSH
- chlorid sodný MeSH
- chlorid vápenatý MeSH
- glukosa MeSH
- hořčík MeSH
- hydrogenuhličitany MeSH
- kardioplegické roztoky MeSH
- mannitol MeSH
- prokain MeSH
- St. Thomas' Hospital cardioplegic solution MeSH Prohlížeč
One of the methods of donor heart protection against ischemia is a substantial lowering of temperature of the heart perfused with cardioplegic solution (CS). The achieved conservation of energetically rich compounds, however, does not guarantee the full restoration of heart function during reperfusion. Another possibility for heart preservation is repeated application of CS at 20 degrees C. This variant was tested in our experiments on isolated rat hearts perfused under constant pressure with the Krebs-Henseleit solution according to Langendorff. During global ischemia (180 min at 20 degrees C) we applied the St. Thomas Hospital CS lx or 4 x at 60 min intervals. During the ischemia, glycogen, ATP, lactate, Na+, K+ were assessed in the heart. The heart injury was monitored as the release of lactate dehydrogenase (LD) during the 60 min reperfusion. Repeated CS perfusion of the heart during ischemia lowers the contents of lactate and maintains ATP and glycogen content at elevated levels throughout ischemia. The improved condition of the heart after repeated CS application demonstrated as prevention of the gain of Na+ in the cells at the end of ischemia as well as after reperfusion. This was associated with reduced intracellular potassium depletion and LD release into the perfusate.
- MeSH
- adenosintrifosfát metabolismus MeSH
- energetický metabolismus * MeSH
- glykogen metabolismus MeSH
- kardioplegické roztoky aplikace a dávkování MeSH
- krysa rodu Rattus MeSH
- kyselina mléčná MeSH
- laktáty metabolismus MeSH
- myokard metabolismus MeSH
- reperfuze myokardu * MeSH
- techniky in vitro MeSH
- transplantace srdce * MeSH
- uchovávání orgánů metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adenosintrifosfát MeSH
- glykogen MeSH
- kardioplegické roztoky MeSH
- kyselina mléčná MeSH
- laktáty MeSH
31P NMR spectroscopy was used to study the time course of changes in the concentration of high-energy metabolites and intracellular pH in the dog myocardium during hypothermic ischaemia at 9 degrees C in Bretschneider (HTK-B) and St. Thomas' Hospital (StTH) cardioplegic solutions. It was found that ATP and phosphocreatine degrade slowlier in HTK-B than in StTH, with phosphocreatine depletion occurring within 7.9 +/- 1.4 h in HTK-B and within 6.2 +/- 1.4 h in StTH. The values are virtually identical with the time intervals at which ATP concentration falls below the critical level (60% of initial ATP concentration). In agreement with biochemical analysis, a higher concentration of phosphomonoesters was noted until the 180th minute of ischaemia in HTK-B, a finding suggesting more rapid glycogen degradation in HTK-B. Even though HTK-B contains a high concentration of histidine buffer, higher values of intracellular pH were found during ischaemia in StTH. The effect of extracellular concentration of sodium ions on intracellular pH is discussed.
- MeSH
- adenosintrifosfát metabolismus MeSH
- chlorid draselný farmakologie MeSH
- chlorid sodný farmakologie MeSH
- chlorid vápenatý farmakologie MeSH
- fosfáty metabolismus MeSH
- glukosa farmakologie MeSH
- glykogen metabolismus MeSH
- hořčík farmakologie MeSH
- hydrogenuhličitany farmakologie MeSH
- kinetika MeSH
- koncentrace vodíkových iontů MeSH
- kyslík metabolismus MeSH
- magnetická rezonanční spektroskopie MeSH
- mannitol farmakologie MeSH
- myokard metabolismus MeSH
- prokain farmakologie MeSH
- psi MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- psi MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- adenosintrifosfát MeSH
- Bretschneider cardioplegic solution MeSH Prohlížeč
- chlorid draselný MeSH
- chlorid sodný MeSH
- chlorid vápenatý MeSH
- fosfáty MeSH
- glukosa MeSH
- glykogen MeSH
- hořčík MeSH
- hydrogenuhličitany MeSH
- kyslík MeSH
- mannitol MeSH
- prokain MeSH
- St. Thomas' Hospital cardioplegic solution MeSH Prohlížeč
- MeSH
- chlorid draselný MeSH
- chlorid sodný MeSH
- chlorid vápenatý MeSH
- hořčík MeSH
- hydrogenuhličitany MeSH
- kardioplegické roztoky * MeSH
- kontrakce myokardu * MeSH
- krysa rodu Rattus MeSH
- mannitol MeSH
- myokard metabolismus patologie MeSH
- transplantace srdce * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chlorid draselný MeSH
- chlorid sodný MeSH
- chlorid vápenatý MeSH
- hořčík MeSH
- hydrogenuhličitany MeSH
- kardioplegické roztoky * MeSH
- mannitol MeSH
- St. Thomas' Hospital cardioplegic solution MeSH Prohlížeč
- MeSH
- adeninnukleotidy metabolismus MeSH
- adenosintrifosfát metabolismus MeSH
- energetický metabolismus * MeSH
- glykogen metabolismus MeSH
- inbrední kmeny potkanů MeSH
- kardioplegické roztoky aplikace a dávkování MeSH
- krysa rodu Rattus MeSH
- kyselina mléčná MeSH
- laktáty metabolismus MeSH
- myokard metabolismus patologie MeSH
- reperfuzní poškození myokardu metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adeninnukleotidy MeSH
- adenosintrifosfát MeSH
- glykogen MeSH
- kardioplegické roztoky MeSH
- kyselina mléčná MeSH
- laktáty MeSH
- MeSH
- chlorid draselný farmakologie MeSH
- chlorid sodný farmakologie MeSH
- chlorid vápenatý farmakologie MeSH
- glukosa farmakologie MeSH
- hořčík farmakologie MeSH
- hydrogenuhličitany farmakologie MeSH
- kardioplegické roztoky farmakologie MeSH
- krysa rodu Rattus MeSH
- mannitol farmakologie MeSH
- myokard metabolismus MeSH
- prokain farmakologie MeSH
- reperfuzní poškození myokardu metabolismus MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- Bretschneider cardioplegic solution MeSH Prohlížeč
- chlorid draselný MeSH
- chlorid sodný MeSH
- chlorid vápenatý MeSH
- glukosa MeSH
- hořčík MeSH
- hydrogenuhličitany MeSH
- kardioplegické roztoky MeSH
- mannitol MeSH
- prokain MeSH
- St. Thomas' Hospital cardioplegic solution MeSH Prohlížeč
