Sarcoplasmic reticulum Ca-release channel and ATP-synthesis activities are early myocardial markers of heart failure produced by rapid ventricular pacing in dogs

Abstract

The contraction-relaxation cycle of the heart is dependent on a cycle of ATP production and utilization and a cycle of Ca uptake and Ca release by the sarcoplasmic reticulum (SR). Heart failure (HF) is associated with abnormalities of myocardial Ca and ATP cycling, but the time course of their development is unknown. This study tested the hypothesis that, compared with ATP-utilizing and Ca-uptake activities, decreases in ATP-synthesis and Ca-release activities occurred earlier in the development of HF and persisted longer during recovery from HF. HF was induced by right ventricular pacing of dogs at 250 beats/min. Dogs were studied after 1 week of pacing (n = 8, early HF), at HF (n = 11, severe HF), and 4 weeks after cessation of pacing (n = 9) and were compared with dogs not subjected to pacing. At early HF, there were decreased activities (p < 0.05) of the SR Ca-release channel (rate constant from 199 +/- 36 x 10(-4) to 90 +/- 16 x 10(-4) s-1), mitochondrial ATP synthesis (from 11.2 +/- 2.4 to 7.0 +/- 2.2 international units (IU)/g), and creatine kinase (CK) from 2028 +/- 266 to 1811 +/- 79 IU/g). The decreased Ca-channel activity was due to a 32% decrease in maximal activity (rate constant from 249 +/- 50 x 10(-4) to 170 +/- 29 x 10(-4) s-1) and to a 2-fold increase (from 19.1 +/- 12.4 to 42.0 +/- 14.2%) in inhibition of maximal channel activity (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)