Calcium en cardioplegie

Coronary perfusion with a calcium-free solution, followed by reperfusion with a calcium containing solution, may result in acute myocardial cell death and in irreversible loss of the e1ectrical and mechanical activity of the heart. This phenomenon is known as the calcium paradox. A number of cardioplegic solutions that have been developed for clinical practice, are free of calcium (e.g. the Bretschneider solution). Animal experiments have demonstrated that under certain circumstances coronary perfusion with the Bretschneider solution can predispose the heart to the calcium paradox. During cardiac surgery, however, calcium-free cardioplegic solutions can be used without risk of inducing the calcium paradox during reperfusion of the heart with calcium-containing blood, provided that temperature during cardioplegia is low, and flow and duration of infusion are limited. It is recommended, nevertheless, to avoid the use of calcium-free cardioplegic solutions in clinical practice

Calcium paradox and calcium entry blockers

Reperfusion of isolated hearts with calcium-containing solution after a short period of calcium-free perfusion results in irreversible cell damage (calcium paradox). This phenomenon is characterized by an excessive influx of calcium into the cells, the rapid onset of myocardial contracture, exhaustion of tissue high-energy phosphates, massive release of cell constituents, and extensive ultrastructural damage. The calcium paradox can be regarded as the most severe form of myocardial necrosis that can be produced experimentally. Under the experimental conditions described in this study, the calcium entry blockers verapamil, nifedipine, diltiazem and lidoflazine failed to reduce the massive release of enzymes that occurs in the severe form of the calcium paradox. Calcium entry blockers, however, may alter the time course of the events that occur during the development of the calcium paradox. Calcium entry blockers may have a protective effect in a mild form of the calcium paradox. This is of interest for cardiac surgery where calcium-free cardioplegic solutions are widely used. Calcium entry blockers may decrease the potential hazard of the use of these solutions

Protective effect of pretreatment with the calcium antagonist anipamil on the ischemic-reperfused rat myocardium;a phosphorus-31 nuclear magnetic resonance study

To assess whether the prophylactic administration of anipamil, a new calcium antagonist, protects the heart against the effects of ischemia and reperfusion, rats were injected intraperitoneally twice daily for 5 days with 5 mg/kg body weight of this drug. The heart was then isolated and perfused by the Langendorff technique. Phosphorus-31 nuclear magnetic resonance spectroscopy was used to monitor myocardial energy metabolism and intracellular pH during control perfusion and 30 min of total ischemia (37°C), followed by 30 min of reperfusion. Pretreatment with anipamil altered neither left ventricular developed pressure under normoxic conditions nor the rate and extent of depletion of adenosine triphosphate (ATP) and creatine phosphate during ischemia. Intracellular acidification, however, was attenuated. On reperfusion, hearts from anipamil-pretreated animals recovered significantly better than untreated hearts with respect to replenishment of ATP and creatine phosphate stores, restitution of low levels of intracellular inorganic phosphate and recovery of left ventricular function and coronary flow. Intracellular pH recovered rapidly to preischemic levels, whereas in untreated hearts a complex intracellular inorganic phosphate peak indicated the existence of areas of different pH within the myocardium. It is concluded that anipamil pretreatment protects the heart against some of the deleterious effects of ischemia and reperfusion. Because this protection occurred in the absence of a negative inotropic effect during normoxia, it cannot be attributed to an energy-sparing effect during ischemia. Therefore, alternative mechanisms of action are to be considered

Low Ca2+ reperfusion and enhanced susceptibility of the postischemic heart to the calcium paradox

This study was designed to define the effect of postischemic low Ca2+ perfusion on recovery of high-energy phosphates, intracellular pH, and contractile function in isolated rat hearts. Phosphorus-31 nuclear magnetic resonance spectroscopy was used to follow creatine phosphate, adenosine triphosphate, intracellular inorganic phosphate, and intracellular pH during control perfusion (15 minutes), total ischemia (30 minutes), and reperfusion (30 minutes). In Group I the perfusate [Ca2+] was 1.3 mmol/l throughout the experiment, whereas in Group II the perfusate [Ca2+] was reduced to 0.05 mmol/l during the first 10 minutes of reperfusion. Hearts from Group III were not made ischemic but were subjected to 10 minutes of low Ca2+ perfusion followed by 20 minutes of normal Ca2+ perfusion. During low Ca2+ reperfusion (Group II) recovery of high-energy phosphates and pH was significantly better than in controls (Group I). However, after reexposure to normal Ca2+, metabolic recovery was largely abolished, coronary flow was suddenly impaired, and contracture developed without any rhythmic contractions. These observations indicated the occurrence of a calcium paradox rather than postponed ischemia reperfusion damage. On the other hand, normoxic hearts (Group III) tolerated temporary perfusion with 0.05 mmol/l Ca2+ very well with respect to left ventricular developed pressure, coronary flow, and metabolic parameters. In conclusion, postischemic low Ca2+ (0.05 mmol/l) perfusion may reduce reperfusion damage, but at the same time ischemia appears to enhance the susceptibility of the heart to the calcium paradox

Post-extra systolic potentiation: influence of calcium and verapamil in rat and rabbit hearts

The interactions of the inotropic effects of verapamil (0.05-2.0 µmol/l-1, calcium (0.33-5.2 mmol/l-1) and post extra systolic potentiation (PESP) as induced by paired stimulation were studied in isolated rabbit and rat hearts under isovolumic and isotonic conditions. At low doses of verapamil, contractions were depressed, but those elicited by paired stimulation showed less depression than contractions of the same rate during single stimulation and even exceeded the unpotentiated contractions without verapamil. At high doses of verapamil contractility could not be restored by paired stimulation. Although contractions were restored to control level by an increase in extra-cellular calcium they were still abnormal in the sense that PESP could not be elicited. The excitation-contraction (e-c) uncoupling due to low calcium perfusion could be counteracted by paired stimulation but e- c uncoupling due to high dose verapamil could not be reversed by paired stimulation. Our results support the view that PESP does not only depend on augmented slow channel calcium influx but also on an enhanced calcium shift within the sarcoplasmic reticulum. We are doubtful about the idea that PESP can be used clinically to counteract the negative inotropic effect of high doses of verapamil

Bestudering van de effecten van calciumantagonisten tijdens ischemie en reperfusie met behulp van NMR

Het principe van kernspinresonantie of NMR (nuclear magnetic resonance) wordt al meer dan 30 jaar in de chemie gebruikt bij de opheldering van moleculaire structuren en processen. De laatste jaren wordt NMR in toenemende mate ook iI,1 het medisch wetenschappelijk en diagnostisch onderzoek toegepast, waarbij een onderscheid gemaakt dient te worden tussen MRS (magnetic resonance spectroscopy) en MRI (magnetic resonance imaging). Bij beide toepassingen wordt door middel van radiogolven op non-destructieve en non-invasieve wijze informatie verkregen over lokale dichtheid en eigenschappen van bepaalde atoomkernen in biologisch materiaal dat zich in een sterk magneetveld bevindt. Met MRI worden afbeeldingen van weefsels en organen verkregen; MRS daarentegen levert een biochemische analyse van het onderzochte materiaal in de vorm van een spectrum

31P NMR study of intracellular pH during the calcium paradox

Reperfusion of an isolated mammalian heart with a calcium-containing solution after a brief calcium-free perfusion results in irreversible cell damage: the calcium paradox. It has been suggested that acidification of the cytosol, as a result of hydrolysis of ATP and accumulation of calcium by mitochondria, is an important factor in the development of the calcium paradox. Phosphorus nuclear magnetic resonance (31P NMR) spectroscopy was used to investigate the course of intracellular pH during the calcium paradox in isolated rabbit heart at 37°C. Intracellular pH was measured from the chemical shift of the intracellular inorganic phosphate (Pi) peak. During control perfusion and the subsequent calcium-free period intracellular pH amounted to 7.1. After induction of the calcium paradox by readmitting calcium to the perfusion fluid, intracellular pH amounted to 7.0. It is concluded that acidification of the cytosol does not play a causal role in the development of the calcium paradox