Effect of milrinone and atrial pacing on stunned myocardium

OBJECTIVE: Most mammalian cardiac muscles show a positive force-frequency relation, which is turned into a negative relation in failinghearts. Stunned myocardium shows similar defects as failing myocardium, ithas a functional reserve recruitable by positive inotropic interventions,and possibly shows a disturbed response to increased heart rate. Thepresent experiments compare in vivo the response of stunned and intactmyocardium to atrial pacing before and during inotropic stimulation bymilrinone. METHODS: In anaesthetised (piritramide) open chest pigs, heartrate, left ventricular and aortic pressure, left descending (LAD) andcircumflex (LCX) coronary artery and aortic blood flow, myocardial systolicshortening in the LAD and LCX area were monitored, and myocardial power wascalculated. The LAD region was subjected to ischaemia and reperfused. Heartrate was raised by right atrial pacing after 90 min reperfusion before andduring i.v. milrinone (105 microg/kg bolus + 8 microg/kg per min infusion).The ischaemic/reperfused area was sliced post mortem and stained bytriphenyl tetrazolium chloride to exclude myocardial infarction. Data fromten experiments are presented. RESULTS: After 90 min LAD reperfusion, LADblood flow and power were 110 and 36% of preischaemic control,respectively, indicating myocardial stunning. The power of the intact areawas not changed (102% of control). Pacing from 87 to 164 per min increasedthe power of the intact area (+96%), the power of the stunned myocardiumdecreased (-64%). Milrinone increased the power of the stunned region to72% of the pre-stunning level and the power of the intact area by +51%.Pacing from 111 to 164 per min during milrinone increased the power of theintact myocardium to the same level as before milrinone, the power of thestunned region did not change. CONCLUSIONS: Stunned myocardium respondspathologically to atrial pacing with a negative staircase in contrast tothe positive staircase of intact myocardium. Inotropic stimulation by thephosphodiesterase inhibitor milrinone recruited the functional reserve ofstunned myocardium. Milrinone did not restore a positive staircase instunned myocardium, but power was maintained during atrial pacing. Thepathological staircase of stunned myocardium may arise from an impairedavailability of cyclic AMP, but the data do not exclude defects in calciumhandling, a dysfunction of the sarcoplasmic reticulum, or an impairedCa-sensitivity of the myofilaments.