Archive for the ‘Cardiology’ Category


ANIMALS AND METHODS

Experiments on rhesus monkeys confirm the association of fetal cardiomegaly with maternal hyperglycemia . However, little information is available regarding the early postnatal development of cardiac contractile function of sucklings from diabetic mothers. The aim of the present study, therefore, was to compare weight parameters, cardiac contractile function and inotropic response to Ca2+ in the offspring of diabetic versus those of control rats during the first week of postnatal life. Results suggest that the sucklings of diabetic mothers suffer from severe growth retardation, decreased magnitude of cardiac contraction and increased cardiac inotropic response to Ca2+ during the first week of life. (more…)

D-sotalol has emerged as the prototype of the so-called class III antiarrhythmic compounds. Its cardiac electro-physiological effects are described as a prolongation of the repolarization period by inhibition of the delayed rectifier potassium current . This property of prolonging the action potential duration, with an accompanying increase in the effective refractory period (ERP), is not due to a blockade of beta-adrenergic receptors because D-sotalol has only 2% of the beta-blocking activity of L-sotalol . D-sotalol further reduced the spontaneous sinus rate, which could be explained by a prolongation of the action potential of sinus node pacemaker cells . This is supported by the observation that the dextroisomer of the drug, which nearly lacks beta-blocking properties, induced the same effect on the repolarization period of the sinus node cells as the levoisomer.
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from diabetic mothers (part 1)

We have previously shown that the cardiac contractile function and its regulation at the level of Ca2+ transport (inotropic response to Ca2+, verapamil, ryanodine and low extracellular sodium) change significantly during the early phases of postnatal ontogeny . This development is obviously due to a disproportion between the rapidly increasing functional demands and the structural and functional ability of the myocardium to fulfil such requirements. These experimental data were obtained in healthy individuals; such an approach differs, however, from the clinical situation, where the pathogenic factors acting during the critical prenatal periods as well as soon after birth (eg, hypoxia, drugs) may have serious consequences for further maturation . It therefore seemed to be useful to follow the myocardial ontogenetic differences in animals exposed to prenatal and early postnatal intervention that may influence the functional properties of the developing heart. (more…)

DISCUSSION (part 3)The neuropathic cases with prolonged QT interval are also often associated with malignant ventricular arrhythmias.  Therefore, the above data seem to be very important. Glibenclamide improves cardiac innervation by acting through the central nervous system, thus on the one hand contributing to its direct antiarrhythmic effect, and on the other hand positively influencing and possibly counteracting the manifestations of cardiac autonomic neuropathy. Although the other second-generation sulphonylurea compounds stimulate only blood pressure depression due to vagal stimulation, this influence could also contribute to their advantageous cardiac effects.
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classical preconditioning (part 16)

Indeed, inhibition of the generation of these substances before short preconditioning occlusions made preconditioning almost impossible. However, when preconditioning was performed in the absence of L-NAME and meclofenamate, and thus the protection was allowed to develop, and when the two inhibitors were then administered only before the prolonged occlusion, antiarrhythmic protection was largely preserved. The effects of complete reversal of the antiarrhythmic effect of preconditioning by the simultaneous inhibition of these two mediators were similar to those seen when the effects of bradykinin were inhibited with an antagonist (icati-bant) at bradykinin (B2) receptors . When icatibant was given before preconditioning, only 50% of the dogs survived the preconditioning procedure. (more…)

One of the possible mechanisms of this antiarrhythmic protection is that nitric oxide may inactivate superoxide radicals during reperfusion . Similarly, inhibition of nitric oxide synthase with L-NAME augmented ischemia-reperfusion injury in rabbit hearts in vivo . Thus, nitric oxide appears to function as an endogenous cardioprotectant not only in the canine but also in rats and rabbits. Maulik and colleagues demonstrated that nitric oxide plays an important role in transmembrane signalling in the ischemic myocardium. This signalling system seems to be transmitted via cGMP and opposes the effects of phosphodiesterase enzymes. A similar mechanism has been suggested to contribute to the protection seen after preconditioning . (more…)

A further way to characterize the differences between the first- and second-generation sulphonylureas is their affinity for membrane channels. Sturgess et al demonstrated the pancreatic sulphonylurea receptor as an ATP-sensitive potassium channel. The affinity of different sulphonylurea compounds to ATP-sensitive potassium channels varies in relation to their hypoglycemic efficacies . Considering that many organs also have ATP-sensitive potassium channels, the sulphonylurea drugs might have direct or indirect cardiac, neurogenic or hormonal actions. Fosset et aldemonstrated a higher affinity of second-generation sulphonylurea  to receptors linked to ATP-dependent potassium channels in myocytes, compared with the first-generation agents. Nevertheless, until now there has been no evidence for any opposite action of first- and second-generation sulphonylurea compounds on extrapancreatic ATP-sensitive potassium channels, which may explain their opposite in vivo effects on arrhythmogeneity.
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classical preconditioning (part 14)

A variety of potentially protective mediators might be released under conditions of myocardial ischemia . These include adenosine, prostacyclin, bradykinin and nitric oxide; each of these may be considered as an endogenous cardioprotective substance . Indeed, there is good evidence that nitric oxide is released into the coronary circulation under both basal and stimulated conditions and that, through the elevation of cGMP, it regulates the coronary circulation. The suggestion that nitric oxide might be involved in the antiarrhythmic effects of ischemic preconditioning in the canine came first from studies in which the generation of nitric oxide or its effect on soluble guanylyl cyclase were prevented by either L-NAME or methylene blue , respectively. (more…)

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