THE ROLE OF THE RATE OF VASCULAR COLLAPSE IN ISCHEMIA-INDUCED ACUTE CONTRACTILE FAILURE AND DECREASED DIASTOLIC STIFFNESS

We investigated the contribution of the rate of vascular collapse to t he early contractile failure and decreased diastolic stiffness induced by ischemia. Isolated rat hearts (n = 8/group), perfused at 37 degree s C with blood through a roller pump and paced at 320 beats/min, were subjected to global ischemia either by switching off the roller pump ( slow vascular collapse-group 1) or by reversing the direction of the r oller pump for 5 s prior to switch-off (rapid vascular collapse-group 2). In group 1, residual coronary pressure declined progressively over the first 20 s of ischemia whereas in group 2 the pressure had fallen to zero within 2 s. The profile of ischemia-induced contractile failu re was, however, similar in both groups. Thus, after 2 s of ischemia, when residual perfusion pressure had declined by only 10% in group 1 ( 60.0 +/- 0.0 to 54.9 +/- 0.8 mmHg) but was virtually non-existent in g roup 2 (60.0 +/- 0.0 to 0.4 +/- 12.7 mmHg), left ventricular developed pressure had fallen to a similar extent in both groups (86 +/- 2% and 84 +/- 3%, respectively). Curve-fitting analysis for individual heart s showed that the profile of contractile failure was described by a do uble exponential process that was not significantly affected by the ra pid vascular collapse, Left ventricular end-diastolic pressure in grou p 1 hearts progressively declined over the first 20 s of ischemia, the profile paralleling that of the dissipation of perfusion pressure. In contrast, in group 2 hearts, left ventricular end-diastolic pressure rose rapidly and peaked at 5 s, a period that coincided with the rever sed direction of the perfusion pump. Similarly, in a separate study, t he analysis of ventricular diastolic stiffness (n = 6/group) showed a rapid decline during the first 20 s of ischemia; this decline could be inhibited by the use of rapid vascular collapse. In additional experi ments, hearts (n = 8/group) were paced at 220, 320 or 420 beats/min an d ischemia was induced by reversing (5 s) and then stopping the perfus ion pump. Myocardial oxygen consumption increased in parallel with hea rt rate and was matched by commensurate increases in the rate of contr actile failure. Curve-fitting analysis showed that slow stimulation ra tes (220 beats/min) significantly delayed contractile failure during t he first 60 s of ischemia (first time constant = 14.5 +/- 4.1 s compar ed with 8.1 +/- 1.1 s at 320 beats/min and 6.3 +/- 1.1 s at 420 beats/ min; P<0.05 in both instances). In conclusion, vascular collapse assoc iated with ischemia may contribute to the initial decrease in ventricu lar diastolic stiffness; however, it does not play a major role in det ermining the rate of acute contractile failure. Metabolic processes, a s reflected by oxygen consumption, do, however, appear to be important . (C) 1996 Academic Press Limited