The effects of potassium channel agonists, cromakalim and adenosine, in diabetic rat hearts

INTRODUCTION: This study was designed to look at ATP sensitive potassium channels (KATP-sc) in diabetic male Sprague-Dawley rat hearts. Diabetes mellitus was induced using streptozocin (ip). KATP-SC can be found in pancreatic B-cells, cardiac muscle, skeletal muscle, neurones, hypothalamus and smooth muscle. Cromakalim and adenosine were used to construct concentration-response curves. These drugs are KATP-SC openers that cause shortening of action potential duration and hyperpolarisation. This is a novel study as there is a sparsity of information on the effect of KATP-SC openers on the hearts of diabetic animals. We therefore hypothesised that cromakalim and adenosine may have both an effect on the electrical activity as well as the contractility in the diabetic myocardium. METHODS: Male Sprague-Dawley rats (150-250 gm) were treated with streptozotocin (STZ) (60 mg/Kg i.p.). All animals were kept under identical living conditions and allowed free access to food and water for 1 week. Animals were then sacrificed after being anaesthetised with 60 mg/Kg pentobarbital containing 1000 Units/ml heparin. Hearts were being rapidly excised, placed in 4 degrees C. Krebs-Henseleit buffer and mounted in a Langendorff system. Concentration-response curves were constructed for cromakalim (0.01nM-0.1uM), and adenosine (0.1uM-100uM). Parameters measured were heart rate (HR), P-R and QRS intervals, systolic pressure (SP), diastolic pressure (DP) and developed pressure (Dev. Pre.). RESULTS: The results found for cromakalim in diabetic rats and adenosine in normal rats mirrored what has been found in previous studies for these drugs in non-diabetic animals, namely, a decrease in HR, an increase in P-R and QRS and a decrease in SP and Dev. Pre. However, adenosine in diabetic rats showed some unexpected results such as a decrease in P-R, and an increase in SP and Dev. Pre. It is possible that the diabetic state interferes significantly with the actions of adenosine but not as significantly with those of cromakalim. Conclusion: The results indicate that adenosine may not be cardioprotective in diabetic animals. This conclusion may be drawn from the fact that P-R interval decreased with increasing concentrations of adenosine. This may lead to the production of arrhythmias such as life threatening ventricular tachycardia or fibrillation (AU)

Supraventricular tachycardia: recent advances in children

Supraventricular tachycardia (SVT) is the most common arrhythmia in children, occurring in about 1/1000 live births. Symptoms may begin in utero or early infancy when there is a significant risk of death. In older children symptoms vary from mild to severely debilitating with a small risk for sudden death in patients with Wolfe-Parkinson-White Syndrome. A better understanding of pathophysiology and cellular mechanisms provided the basis of the new therapeutic strategies. New classes of antiarrhythmic drugs, both for acute termination of SVT (eg. adenosine) and control of recurrence (eg. amiodarone and flecainide), added to older medications such as digoxin and propranolol, resulted in better control in both fetus and child. The greatest innovation in therapy, however, is electrical mapping of atrio-ventricular bypass tracts and their permanent interruption by radio frequency energy catheter ablation. This form of therapy provides a complete cure with 95 percent success and a 1 percent risk for complications in older children and adults. The risk is significantly higher in infants. A thorough knowledge of cardiac anatomy, electrophysiology and natural history is necessary to select appropriate therapy for individual patients to achieve maximum efficacy with minimum complications.(AU)