Sudden increases in aortic pressure (AoP, mm Hg) are associated with increases in left ventricular (LV) function which persist even after diastolic volume has returned to its initial value (Anrep effect). Likewise, increases in coronary arterial pressure (CAP, mm Hg) are associated with improved LV function (gardenhouse effect). In situ, increases in AoP are paralleled by increases in both CAP and coronary blood flow, i.e., oxygen supply. We investigated the individual contributions of AoP and CAP increases on function (peak systolic pressure: LVPmax, mm Hg; dP/dtmax, mm Hg/s; end-diastolic pressure: LVPed, mm Hg) and end-diastolic geometry (inner diameter: IDed, mm; wall thickness: WTed, mm; sonomicrometry). CAP-induced increases in coronary flow were prevented by admixing dextran to the perfusate. The experiments were performed on isolated, saline-perfused, working rabbit hearts. Increasing CAP from 60 to 80 mm Hg (n = 11) resulted in improved function: LVPmax 89 +/- 3 vs. 94 +/- 3, dP/dtmax 1160 +/- 50 vs. 1250 +/- 50, LVPed 17 +/- 1 vs. 16 +/- 1 (mean +/- SEM). IDed decreased from 9.96 +/- 0.25 to 9.64 +/- 0.33 and WTed increased from 6.02 +/- 0.16 to 6.15 +/- 0.17. In a second series, AoP was increased from 60 to 80 (n = 9). Both LVPmax, dP/dtmax and LVPed increased (90 +/- 4 vs. 97 +/- 3, 1170 +/- 70 vs. 1270 +/- 90 and 18 +/- 1 vs. 19 +/- 1). IDed increased from 9.76 +/- 0.39 to 9.99 +/- 0.37 and WTed decreased from 6.08 +/- 0.22 to 5.86 +/- 0.25. After additionally increasing CAP to 80, function further improved (LVPmax: 101 +/- 3, dP/dtmax: 1310 +/- 80) while LVPed decreased (18 +/- 1). This time, IDed decreased to 9.71 +/- 0.36 and WTed increased to 6.03 +/- 0.26. Increases in CAP improve LV function via the gardenhose effect and likely do not depend on simultaneous increases in coronary flow or oxygen supply. On the other hand, increases in AoP alone improve systolic function via the Frank-Starling mechanism. Increases in both pressures together amplify this effect. Increases in CAP and in AoP have opposing effects on IDed and WTed. In conclusion, the homeometric Anrep effect--at least in part--can be viewed as synergistic action of the Frank-Starling mechanism and the gardenhose effect for this experimental model.

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Improved ventricular function by enhancing the Ca++ sensitivity in normal and stunned myocardium of isolated rabbit hearts.

A possible cause for the decreased function in postischemic reperfused (= stunned) myocardium could be a decrease in Ca++ sensitivity. To test this hypothesis, we used an agent with reportedly Ca++ sensitizing properties (EMD 57033) and performed experiments on a total of 17 isolated rabbit hearts that were perfused with an erythrocyte-containing medium in a modified Langendorff setting (hct = 30%; Ca++ = 2.0 meq/l). The hearts were divided into two groups. In one group (n = 9), the Ca++ sensitizer (30 microM) was administered to nonischemic myocardium, and in a second group (n = 8), the Ca++ sensitizer was administered after 30 min of reperfusion that followed a period of 20 min normothermic, no-flow ischemia. In the nonischemic group, addition of the agent, improved left ventricular (LV) function significantly. In the ischemic group, LV-function was depressed at 30 min reperfusion compared to control. Again, the agent improved LV-function significantly. The increase in systolic and diastolic function was comparable in both groups as well as the oxygen consumption that was significantly increased after administration of the agent. In both groups, the agent neither exhibited significant, positive chronotropic nor arrhythmogenic effects. We summarize that the novel Ca++ sensitizer acts as a potent positive inotropic agent in the isolated blood-perfused rabbit heart. Because of the agent's properties to ameliorate postischemic contractile dysfunction, this general strategy may be useful for treating poorly functioning reperfused myocardium.

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