INTRACELLULAR CA2-FIBRILLATION IN SPONTANEOUSLY HYPERTENSIVE RATS( HANDLING AND VULNERABILITY TO VENTRICULAR)

Spontaneously hypertensive rats (SHR) with ventricular hypertrophy sho w an increased vulnerability for the development of potentially lethal ventricular arrhythmias such as ventricular fibrillation (VF). The me chanisms of this increased vulnerability are not fully understood but may be related to abnormal intracellular Ca2+ ([Ca2+](i)) handling und er stress conditions. We therefore investigated whether [Ca2+](i) hand ling is abnormal in hypertrophied hearts of SHR without heart failure during stimulation stress, and if so whether abnormal [Ca2+](i) handli ng is a determinant of the increased vulnerability to VF in SHR. [Ca2](i) was measured by indo-1 surface fluorescence in perfused hearts of 8- to 10-month-old control Wistar-Kyoto rats (WKY) and age-matched SH R. The state of [Ca2+](i) handling was analyzed during three different forms of stimulation stress: rapid pacing, the long rest period after cessation of rapid pacing, and preprogrammed ventricular stimulation that was simultaneously used for the determination of VF threshold. Th e pulse number VF threshold was used as an index to determine vulnerab ility to VF and to analyze the relationship of [Ca2+](i) handling to v ulnerability. Although VF thresholds were lower in SHR than in WKY, we found that both demonstrated similar [Ca2+]i handling during stimulat ion stress. The extent and rate of [Ca2+](i) accumulation during rapid pacing and those of the [Ca2+](i) decline after cessation of pacing w ere similar in SHR and WKY. In addition, the relationship between [Ca2 +](i) and VF threshold was unaltered in SHR. Thus, we conclude that [C a2+](i) handling is normal in hypertrophied hearts of SHR without hear t failure during stimulation stress and that it is not a determinant o f the increased vulnerability to VF in SHR.