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  • Pretreatment with catecholamines can suppress severe ventricular arrhythmias in rats: DISCUSSION (part 3)

Delayed protection afforded by administration of noradrenaline seems to resemble the ‘second window of protection’, which also appears after several hours, when the acute effect is already lost . It has been demonstrated that a delayed protective effect could be induced, such as some analogues of adenosine or derivatives of prostacyclin . Pretreatment of animals with a single dose of 7-oxo prostacyclin 48 h before sustained ischemia sufficiently protected the heart of different species against ischemia- and reperfusion-induced arrhythmias, and reduced the extent of cell damage and metabolic disorders . One explanation for this protective effect is that a brief drug-induced stress triggers adaptation to a subsequent long ischemia-induced stress associated with reduced adrenergic response of the heart and myocardial cAMP level, due to cAMP degradation exceeding its generation . Another proposed mechanism of the late antiarrhythmic effect induced by 7-oxo prostacyclin is stimulation of Na+/K+-ATPase activity . This could facilitate better preservation of ionic homeostasis during ischemia, preventing excess calcium influx into the cells.
Because catecholamines and 7-oxo prostacyclin pretreatment afford protection in a similar manner, it is reasonable to investigate catecholamine-induced protection with respect to the possible involvement of Na+/K+-ATPase. In the present study, enzyme activity in heart sarcolemma had not changed either shortly after noradrenaline infusion in vitro or 24 h after in vivo administration. However, the antiarrhythmic effect of preconditioning with noradrenaline was accompanied both in vivo and in vitro by preservation of Na+/K+-ATPase activity after ischemia at the preischemic level (Figure 6A,B). This indicates that a further stimulus (ischemia) may be required to stimulate the activity of the enzyme. Elevated Na+/K+-ATP-ase activity may prevent loss of potassium ions from the cells, which is considered an important factor of arrhythmogenesis during ischemia . Thus, preservation of ionic homeostasis could contribute to the maintenance of electrical stability of cell membranes. This is consistent with the evidence provided by the studies of Clausen that catecholamines can activate electrogenic transport of sodium and potassium ions through the cell membrane and increase intracellular content of potassium ions in skeletal muscle and in other tissues, leading to hyperpolarization both in vitro and in vivo. Online shopping will cost you less money and will take less time, because you can find efficient where to buy nolvadex with generous discounts at the pharmacy that proved its reputability and desire to help by offering best level of service and most efficient drugs.

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