Temporary leukocyte depletion reduces ventricular dysfunction during prolonged postischemic reperfusion.

Leukocyte depletion improves early postischemic ventricular performance in neonatal models of global myocardial ischemia. However, the rate of leukocyte reaccumulation after cardiopulmonary bypass and its subsequent impact on myocardial function is not known. This laboratory study examined the effect of leukocyte depletion on myocardial performance during the initial 6-hour period after bypass in an in situ, in vivo porcine model of neonatal cardiac surgery. Fifteen 3- to 5-day-old piglets (eight control and seven leukocyte depleted animals) were instrumented by placement of left ventricular short-axis sonomicrometry crystals and an intraventricular micromanometer catheter. Mechanical leukocyte depletion was achieved with Pall RC100 filters (Pall Biomedical, Inc., Fajardo, Puerto Rico) in the cardiopulmonary bypass circuit. Neonatal hearts were subjected to 90 minutes of hypothermic ischemia after a single dose of cold crystalloid cardioplegia. Two control animals died after the operation and were excluded from data analysis. Leukocyte filtration reduced the granulocyte count during initial myocardial reperfusion to 0.8% of control values. However, circulating granulocyte counts increased in leukocyte depleted animals throughout the postoperative period, reaching 68% of control values by 6 hours. Despite this rapid return of circulating granulocytes, animals subjected to leukocyte depletion had significantly better preservation of left ventricular performance (measured by preload recruitable stroke work, p < or = 0.02), left ventricular systolic function (measured by end-systolic pressure-volume relationship, p < or = 0.05), and ventricular compliance (p < or = 0.04) during the experiment. These changes in ventricular function were associated with a significant increase in left ventricular water content (p < or = 0.02) and tissue myeloperoxidase activity (p < or = 0.005) in control animals compared with leukocyte depleted animals. This study demonstrates that leukocyte depletion during initial reperfusion results in sustained improvement in postischemic left ventricular function despite the rapid return of granulocytes to the circulation.

Pressure-volume analysis of changes in cardiac function in chronic cardiomyoplasty.

Reports of clinical improvement in human studies of dynamic cardiomyoplasty lack support by consistent objective hemodynamic evidence. Animal studies have also yielded conflicting results, likely due to nonuniform models, particularly the use of unconditioned wraps, and to limitations in commonly used study modalities caused by exaggerated heart motion during wrap stimulation. Our purpose was to assess the primary functional properties of the heart wrapped by conditioned muscle using pressure-volume relation analysis based on conductance catheter volume data. Compared with the unstimulated state, 1:1 stimulation caused an increase in contractility and decreases in end-diastolic volume and stroke work. Assisted beats during 1:2 stimulation showed an increase in contractility and a decrease in end-diastolic volume. Unassisted beats (1:2) showed decreases in end-diastolic volume and stroke work. There was no augmentation of cardiac output or ejection fraction with stimulation (1:1 or 1:2). We conclude that in the nonfailing heart, increased contractility does not augment cardiac output, ejection fraction, and stroke work because of a simultaneous decrease in end-diastolic volume. These changes in contractility and end-diastolic volume may prove therapeutic for dilated cardiomyopathy.

Leukocyte depletion in a neonatal model of cardiac surgery.

Neonatal cardiac surgical procedures continue to be associated with a considerable incidence of severe post-operative ventricular dysfunction. The role of neutrophils in mediating such injury has recently been proposed but remains controversial. The present study was undertaken to examine the potential benefits of leukocyte depletion for myocardial preservation using an in situ, in vivo porcine model of neonatal cardiac surgery. Sixteen 3- to 5-day-old piglets, 8 controls and 8 leukocyte-depleted animals (LD group), underwent 90 minutes of hypothermic ischemia. Mechanical leukocyte filtration during cardiopulmonary bypass reduced the granulocyte count in the initial reperfusate to 0.7% of controls. This was associated with a reduction in leukocyte sequestration in the coronary vascular bed (p < 0.005), a decrease in myocardial creatine kinase release (p < 0.02), and a reduction in coronary vascular resistance (p < 0.03). These changes in physiological response to ischemia were associated with improved postischemic recovery of left ventricular systolic function in LD animals (p < 0.05), although there was no significant improvement in diastolic function. Application of this technique in neonatal cardiac operations may improve myocardial protection and reduce the associated morbidity and mortality.

Systolic and diastolic left ventricular dysfunction due to mild hypothermia.

Postoperative cardiac patients frequently are mildly hypothermic, yet the influence of hypothermia on left ventricular (LV) contractility has received little attention. To study the possible effects of mild hypothermia on LV function, six pigs were placed on partial right ventricular bypass, the hearts were electrically paced to control heart rate, and myocardial temperature was varied between 34 degrees and 38 degrees C. Using two pairs of orthogonally oriented sonomicrometer crystals in the left anterior descending (LAD) and left circumflex (LCX) distributions, we estimated regional work (the area within LV pressure-area loops) over a range of LV preloads. Diastolic function was assessed by measurement of the time constant of LV pressure decay during isovolumic relaxation. Regional work data were expressed as percentages of baseline (38 degrees C and end-diastolic pressure of 10 mm Hg). To control for preload variations, regional work and time constants were calculated from beats with end-diastolic areas within 0.1% of baseline. Regional work (mean +/- SEM) declined from 85.1 +/- 6.7% at 38 degrees C to 31.9 +/- 4.4% at 34 degrees C. Time constants were prolonged from 44.8 +/- 2.5 msec at 38 degrees C to 61.6 +/- 2.7 msec at 34 degrees C. These data demonstrate a marked depression of LV contractility, even at mild levels of hypothermia that may be encountered clinically after cardiac operations.

Does hypothermic fibrillatory arrest improve myocardial protection during emergency revascularization?

Hypothermic fibrillatory arrest (HFA) was compared with conventional hypothermic cardioplegic arrest (HCA) in a model of acute regional ischemia. In 20 pigs, the left anterior descending coronary artery was occluded for 30 minutes before cardiopulmonary bypass. In the HCA group (n = 10), the heart was arrested with a hyperkalemic cold crystalloid solution, whereas in HFA animals (n = 10), the heart was vented and allowed to fibrillate spontaneously without cross-clamping. Miniature pH probes monitored intramyocardial pH during 45 minutes of arrest (HCA or HFA, both with systemic and topical myocardial cooling) and during two hours of coronary reperfusion. Hypothermic fibrillatory arrest did not ameliorate the acidosis in the ischemic (left anterior descending) region; indeed, after two hours of coronary reperfusion, there was a trend toward more acidosis in the postischemic left anterior descending territory in the HFA group. However, HFA did prevent acidosis in the nonischemic (left circumflex) territory. Infarct size expressed as percent of region at risk was 18.1% +/- 3.2% (mean +/- standard error of the mean) in the HCA animals and 18.8% +/- 4.4% in the HFA animals. These results demonstrate that HFA offers no advantage over HCA in protection of regionally ischemic myocardium in a model with minimal collateral circulation.

Free radical scavengers improve functional recovery of stunned myocardium in a model of surgical coronary revascularization.

This study examined whether treatment with the oxygen free radical scavengers, superoxide dismutase and catalase, could improve functional recovery in hearts subjected to regional ischemia and global cardioplegic arrest. Regional left ventricular (LV) function was assessed in open chest pigs with sonomicrometry and micromanometry to calculate an index of regional work from the LV pressure-segment length relationship. After measuring baseline preischemic function, the left anterior descending artery was occluded, creating a region-at-risk in 20% of the LV mass. Cardiopulmonary bypass was begun 15 minutes after initiation of regional ischemia and was followed immediately by cardioplegic arrest for 45 minutes, after which time the coronary artery occluder was removed to simulate coronary revascularization. Starting just before removal of the aortic cross-clamp and continuing for the first 30 minutes of reflow, animals received an aortic root infusion of either superoxide dismutase (3600 U/kg) and catalase (20,000 U/kg) or a control saline solution infusion. In each group, seven animals were successfully weaned from cardiopulmonary bypass without inotropic support. After 2 hour of reperfusion, the recovery of baseline function in the region-at-risk was 44% +/- 7% in the treated animals and 4% +/- 13% in the untreated animals (p less than 0.05). In this experimental model, oxygen free radical scavengers were effective in preserving functional recovery in regionally ischemic myocardium reperfused under conditions simulating surgical revascularization in the setting of acute myocardial ischemia.