The objective of the proposed research is to find means of circumventing or delaying, hypoxia, hyperkalemia, acidosis and reperfusion induced arrhythmias in Purkinje fibers, contracture and contractile force related dysfunctions in ventricular muscle tissue, and to study the feasibility of extending the study to isolated cells to answer many of the proposed questions more clearly. Ventricular fibrillation occurs more frequently on reperfusion than during the preceding period of ischemia. Possible mechanisms of enhanced automaticity include phase 4 depolarization characteristics of abnormal Purkinje fibers and abnormal mechanisms like oscillatory afterpotentials (OAPs). The proposed research plans to address the following questions: a) Does the presence of lactate (concentration?) during ischemia and increased potassium concentration during ischemia and reperfusion influence the abnormal events (arrhythmia, OAPs, and contracture in muscle) during reperfusion? b) Are these reperfusion induced abnormalities in Purkinje fibers and ventricular muscles modulated by calcium and magnesium concentrations during ischemia and reperfusion? We shall utilize intracellular recording in canine Purkinje fibers and ventricular muscles along with mechanical tension. Depending on the success of cell isolation, the study may also extend to isolated cells. We shall record changes in action potential parameters, incidences of automaticity and OAPs, force of contraction and changes in resting tension during various interventions (mentioned above). This research may contribute significantly towards the understanding of the nature of reperfusion induced arrhythmias in heart patients.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Minority School Faculty Development Awards (K14)
Project #
5K14HL002480-04
Application #
3088408
Study Section
Special Emphasis Panel (SRC (KR))
Project Start
1990-09-01
Project End
1995-08-31
Budget Start
1993-09-01
Budget End
1994-08-31
Support Year
4
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Meharry Medical College
Department
Type
Schools of Medicine
DUNS #
City
Nashville
State
TN
Country
United States
Zip Code
37208
Bhattacharyya, M L; Sarker, S; Mull, K P et al. (1997) Clofilium-induced block of delayed rectifier type K+ current in atrial tumor cells (AT-1 cells). J Mol Cell Cardiol 29:301-7
Bhattacharyya, M L; Sarker, S; Seth, K (1995) Ryanodine induced block of a cloned human cardiac potassium channel. J Mol Cell Cardiol 27:1931-5
Bhattacharyya, M L; Sarker, S; Seth, K et al. (1994) Modulations of membrane potential oscillations with drive, calcium overload, ryanodine, and caffeine. J Electrocardiol 27:105-13
Bhattacharyya, M L; Sarker, S; Seth, K et al. (1994) Dextrose-, adenosine- and magnesium-induced protective actions during anoxia and reperfusion in canine Purkinje tissue. Clin Exp Pharmacol Physiol 21:631-7