Left ventricular dysfunction and disturbed O(2)-utilization in stunned myocardium: influence of ischemic preconditioning.
OBJECTIVE
Myocardial dysfunction during postischemic reperfusion is frequently reported only in terms of left ventricular (LV) systolic properties. We additionally assessed diastolic properties, the cardiovascular tone and in particular, the relation between ventricular function and myocardial oxygen consumption. Moreover, these measures are investigated after cardioprotection via ischemic preconditioning (IP). However, this phenomenon is not fully understood, and therefore cardioprotective methods like ischemic preconditioning might provide only insufficient protection.


METHODS
In a total of 17 isolated rabbit hearts, perfused with an erythrocyte suspension (Hct 30%), we investigated the effect of 20 min low-flow ischemia also on diastolic properties, coronary resistance and cardiac energetics (n=9). During control and 30 min after the onset of reperfusion, LV systolic function was assessed in terms of aortic flow, dP/dt(max) and the end-systolic pressure-volume relation (ESPVR). Early relaxation was evaluated via dP/dt(min) and diastolic properties were assessed via the end-diastolic pressure-volume relation (EDPVR), i.e. using the equation LVP(ed)=c.exp(m.LVV(ed)), where c equals the LVP(ed)-axis intercept and m equals LV stiffness. In addition, coronary resistance (R(cor)) and the pressure-volume area (PVA) were calculated. Total oxygen consumption (MVO(2)) was calculated as well as the contractile efficiency (E = inverse slope of the MVO(2)-PVA relation). In a second series (n=8) the effect of ischemic preconditioning (3 min no-flow and 8 min reperfusion before the 20 min low-flow ischemia) was tested.


RESULTS
In the first series, systolic function was impaired during reperfusion: aortic flow to 32% of control, dP/dt(max) to 74% and the slope of ESPVR to 73%. Early relaxation in terms of dP/dt(min) decreased to 76%. The slope of the EDPVR was steeper in stunned myocardium with an increase of the ventricular stiffness (m increased from 3.2 to 4.1) and with an upward shift of the EDPVR (c from 0.6 to 2.4 mmHg). Coronary resistance was increased (from 0.9 to 1.4 mmHg/ml per min) and PVA was significantly decreased to 68%, whereas MVO(2) was not, indicating also a decrease in contractile efficiency E from 28 to 14%. In the second series, recovery of systolic function was significantly improved by IP compared with the first series (aortic flow 56% of preischemic control, dP/dt(max) to 91% and ESPVR to 78%). LV stiffness m was also slightly increased from 3.1 to 3.9 and again, c was elevated, indicating no beneficial effect for diastolic properties including dP/dt(min) (77%). But IP improved R(cor) significantly (from 0.9 to only 1.0 mmHg/ml per min) and efficiency E to 21% (from 27% during control).


CONCLUSIONS
Brief episodes of ischemia not only induce systolic but also diastolic and vascular stunning at almost maintained MVO(2). The decreased contractile efficiency clearly indicates an impaired O(2)-utilization of the contractile apparatus. Ischemic preconditioning did not improve diastolic function during reperfusion, but it provided protection with respect to vascular stunning and myocardial energetics.
Sunderdiek
U
U
Department of Thoracic and Cardiovascular Surgery, Heinrich-Heine University, Düsseldorf, Germany. usunderdiek@aol.com
Schmitz-Spanke
S
S
Korbmacher
B
B
Gams
E
E
Schipke
J D
JD
D000818:Animals; D003971:Diastole / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D017682:Myocardial Stunning / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D010477:Perfusion; D011817:Rabbits; D013599:Systole / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology*; D016277:Ventricular Function, Left / Q000502:physiology