CHARACTERIZATION OF LEFT-VENTRICULAR RELAXATION IN THE ISOLATED GUINEA-PIG HEART

The time constant of left ventricular pressure fall, tau, has frequent ly been used as a measure of myocardial relaxation in the blood-perfus ed, ejecting heart. The aim of the present study was to characterise t au in relation to beta-adrenergic activation, coronary perfusion press ure and flow as well as cardiac oxygen supply and demand in the isolat ed, isovolumically beating heart. Therefore, tau was analysed from dig itised left ventricular pressure data in a total of 23 guinea pig hear ts perfused with saline at constant pressure (60 cmH(2)O). The coronar y venous adenosine concentration ([ADO]) served as an index of myocard ial oxygenation. Isoprenaline (0.4-3.2 nmol l(-1)) decreased and propr anolol (3-9 mu mol l(-1)) increased tau dose-dependently (linear regre ssion tau vs lg ([isoprenaline]), r = 0.74; tau vs. lg ([propranolol]) , r = 0.66, both P<0.05). During graded reductions in cardiac oxygen s upply from 96.1+/-12.6(SEM) to 44.4+/-4.4 mu l min(-1) g(-1), tau was prolonged from 61.5+/-12.7 to 109.9+/-22.6 ms while left ventricular d eveloped pressure (LVDP) decreased from 90.7+/-7.2 to 40.7+/-5.1 mmHg. In parallel, [ADO] increased from 23.7+/-9.1 to 58.0+/-19.1 pmol ml(- 1) (P<0.05). Increasing oxygen supply to 165.4+/-32.4 mu l min(-1) g(- 1) augmented LVDP to 102.7+/-7.3 mmHg but did not change tau or [ADO]. There was a dual response of tau to changes in cardiac oxygen supply or demand. As long as oxygen supply and demand matched, tau remained c onstant. However, when the oxygen supply was less than 100 mu l min(-1 ) g(-1), left ventricular relaxation was prolonged in parallel to the reduction in oxygen supply. In addition,. a close relationship was obs erved between [ADO] as an indicator of myocardial oxygenation and tau (Spearman correlation, r = 0.99, P<0.005). We conclude that the time c onstant of left ventricular pressure fall, tau; sensitively reflects m yocardial relaxation in the isolated, isovolumically beating guinea pi g heart. Moreover, in this model left ventricular relaxation is not in fluenced by alterations in coronary perfusion pressure or flow as long as cardiac oxygen demand is matched by an adequate supply. Rather, re laxation is strictly coupled to myocardial oxygenation as reflected by coronary venous adenosine concentrations.