Minutes Of Blood Cardioplegic Arrest Research Articles

Aprotinin Decreases Ischemic Damage During Coronary Revascularization

This study sought to determine whether the favorable anti-inflammatory effects of aprotinin might limit ischemic damage during the revascularization of ischemic myocardium. Twenty pigs underwent 90 minutes of coronary occlusion followed by 45 minutes of blood cardioplegic arrest and 180 minutes of reperfusion. Ten animals received a loading dose of aprotinin (40,000 kallikrein inhibiting units/kg) during the start of coronary occlusion followed by an infusion of 20,000 kallikrein inhibiting units/kg/hour. Ten other animals received no aprotinin. Summary statistics are expressed as the mean +/- standard error. The aprotinin-treated animals required less cardioversions for ventricular arrhythmias (1.0 +/- 0.7 vs. 3.6 +/- 0.6; p < 0.001), accumulated less lung water (1.0 +/- 0.2% change vs. 6.2 +/- 0.9% change; p = 0.038), had more complete coronary relaxation to bradykinin (34.1 +/- 5.9% change vs. 9.2 +/- 3.5% change; p = 0.01), and had reduced infarct size (area necrosis/area risk = 20 +/- 1.1% vs. 39 +/- 1.2%; p = 0.003). Aprotinin limits ischemic injury during acute coronary revascularization by decreasing ventricular arrhythmias and lung edema, preserving endothelial function, and minimizing myocardial necrosis.

Pretreatment with statins enhances myocardial protection during coronary revascularization

Objective: This experimental study was undertaken to determine whether pretreatment with statins would enhance myocardial protection and minimize ischemic injury during revascularization of acutely ischemic myocardium. Methods: In 20 pigs the second and third diagonal arteries were occluded for 90 minutes, followed by 45 minutes of blood cardioplegic arrest and 180 minutes of reperfusion. Ten pigs received atorvastatin (40 mg orally every day) for 21 days before surgical intervention; 10 others received no statins. Ischemic damage was assessed on the basis of the need for cardioversions for ventricular arrhythmias, regional wall-motion scores (4 = normal to −1 = dyskinesia) were determined by means of 2-dimensional echocardiography, endothelial function was assessed on the basis of bradykinin-induced coronary artery relaxation, and infarct size was calculated by determining the area of necrosis to the area of risk by means of histochemical staining. Results are given as means ± SE. Results: Statin-treated animals required fewer cardioversions (0.11 ± 0.01 vs 2.87 ± 0.20, P = .0001), had improved wall-motion scores (2.81 ± 0.10 vs 1.52 ± 0.08, P = .01), had lower infarct size (21% ± 2% vs 41% ± 2%, P = .0001), and had more complete coronary artery relaxation (34% ± 5% vs 8% ± 4%, P = .01). Total serum cholesterol levels were similar between the groups (62 ± 5 mg/dL for statin-treated animals vs 68 ± 5 mg/dL for non-statin-treated animals, P = .30). Conclusions: Pretreatment with statins enhances myocardial protection during revascularization by means of mechanisms that are independent of their cholesterol-lowering properties.J Thorac Cardiovasc Surg 2003;125:1037-42

Blood cardioplegic protection in profoundly damaged hearts: role of Na +-H + exchange inhibition during pretreatment or during controlled reperfusion supplementation

Background Inhibition of the Na +/H + exchanger before ischemia protects against ischemia-reperfusion injury, but use as pretreatment before blood cardioplegic protection or as a supplement to controlled blood cardioplegic reperfusion was not previously tested in jeopardized hearts. Methods Control studies tested the safety of glutamate-aspartate–enriched blood cardioplegic solution in 4 Yorkshire-Duroc pigs undergoing 30 minutes of aortic clamping without prior unprotected ischemia. Twenty-four pigs underwent 30 minutes of unprotected normothermic global ischemia to create a jeopardized heart. Six of these hearts received normal blood reperfusion, and the other 18 jeopardized hearts underwent 30 more minutes of aortic clamping with cardioplegic protection. In 12 of these, the Na +/H + exchanger inhibitor cariporide was used as intravenous pretreatment (n = 6) or added to the cardioplegic reperfusate (n = 6). Results Complete functional, biochemical, and endothelial recovery occurred after 30 minutes of blood cardioplegic arrest without preceding unprotected ischemia. Thirty minutes of normothermic ischemia and normal blood reperfusion produced 33% mortality and severe left ventricular dysfunction in survivors (preload recruitable stroke work, 23% ± 6% of baseline levels), with raised creatine kinase MB, conjugated dienes, endothelin-1, myeloperoxidase activity, and extensive myocardial edema. Blood cardioplegia was functionally protective, despite adding 30 more minutes of ischemia; there was no mortality, and left ventricular function improved (preload recruitable stroke work, 58% ± 21%, p < 0.05 versus normal blood reperfusion), but adverse biochemical and endothelial variables did not change. In contrast, Na +/H + exchanger inhibition as either pretreatment or added during cardioplegic reperfusion improved myocardial recovery (preload recruitable stroke work, 88% ± 9% and 80% ± 7%, respectively, p < 0.05 versus without cariporide) and comparably restored injury variables. Conclusions Na +/H + exchanger blockage as either pretreatment or during blood cardioplegic reperfusion comparably delays functional, biochemical, and endothelial injury in jeopardized hearts.

Can l-arginine improve myocardial protection during cardioplegic arrest? Results of a phase I pilot study

Background. l-Arginine appears to improve myocardial protection during cardioplegic arrest in animal models. Methods. To study the clinical effect and safety of l-arginine in humans, a phase I pilot study was performed with 50 patients who underwent coronary artery bypass grafting. We randomly assigned half to a treatment group, which received 1 g of l-arginine administered during the first 30 minutes of cardioplegic arrest induced by either warm or cold blood cardioplegia, and half to a control group, which did not receive l-arginine supplementation. Results. Age, sex, and preoperative clinical status were similar in both groups. Seventeen patients of each group were administered intermittent warm antegrade blood cardioplegia, whereas the solution needed to be cooled to obtain complete standstill of the remaining eight hearts in each group. An internal thoracic artery graft to the left anterior descending coronary artery was performed in all patients. There was no death and no myocardial infarction in the treatment group, but there were one death and two infarctions in the control group. The amount of serial release of troponin I during the first 72 hours after the operation was similar between the l-arginine group and the control group ( p > 0.05). Peak serum troponin levels averaged 4.9 ± 1.0 μg/L in the arginine group and 3.9 ± 1.0 μg/L in the control group ( p > 0.05). A multivariate analysis of variance showed no effect of l-arginine ( p > 0.05) but a significant effect of the temperature of the cardioplegic solution on the release of troponin I ( p < 0.05). Serum troponin I levels averaged 2.2 ± 0.4 μg/L, 4.5 ± 0.4 μg/L, and 6.9 ± 0.4 μg/L in the patients with cold cardioplegia and 1.4 ± 0.3 μg/L, 2.4 ± 0.3 μg/L, and 3.3 ± 0.3 μg/L in the patients with warm cardioplegia 1, 2, and 6 hours, respectively, postoperatively. Conclusions. The administration of 1 g of l-arginine during the first 30 minutes of blood cardioplegic arrest did not result in a decrease in the postoperative release of cardiac enzyme; however, cold cardioplegic arrest significantly increased the release of cardiac troponin I postoperatively. There was no significant side effect related to the addition of l-arginine to the cardioplegic solution.

Studies of hypoxemic/reoxygenation injury with aortic clamping: XI. Cardiac advantages of normoxemic versus hyperoxemicmanagement during cardiopulmonary bypass

The conventional way to start cardiopulmonary bypass is to prime the cardiopulmonary bypass circuit with hyperoxemic blood (oxygen tension about 400 mm Hg) and deliver cardioplegic solutions at similar oxygen tension levels. This study tests the hypothesis that an initial normoxemic oxygen tension strategy to decrease the oxygen tension–dependent rate of oxygen free radical production will, in concert with normoxemic blood cardioplegia, limit reoxygenation damage and make subsequent hyperoxemia (oxygen tension about 400 mm Hg) safer. Thirty-five immature (3 to 5 kg, 2 to 3 week old) piglets underwent 60 minutes of cardiopulmonary bypass. Eleven control studies at conventional hyperoxemic oxygen tension (about 400 mm Hg) included six piglets that also underwent 30 minutes of blood cardioplegic arrest. Of 25 studies in which piglets were subjected to up to 120 minutes of ventilator hypoxemia (reducing fraction of inspired oxygen to 5% to 7%; oxygen tension about 25 mm Hg), 11 underwent either abrupt (oxygen tension about 400 mm Hg, n = 6) or gradual (increasing oxygen tension from 100 to 400 mm Hg over a 1-hour period, n = 5) reoxygenation without blood cardioplegia. Fourteen others underwent 30 minutes of blood cardioplegic arrest during cardiopulmonary bypass. Of these, nine were reoxygenated at oxygen tension about 400 mm Hg, and five others underwent normoxemic cardiopulmonary bypass and blood cardioplegia (oxygen tension about 100 mm Hg) with systemic oxygen tension raised to 400 mm Hg after aortic unclamping. Measurements of lipid peroxidation (conjugated dienes and antioxidant reserve capacity) and contractile function (pressure-volume loops, conductance catheter, end-systolic elastance) were made before and during hypoxemia and 30 minutes after reoxygenation. Hyperoxemic cardiopulmonary bypass did not produce oxidant damage or reduce functional recovery after cardiopulmonary bypass in nonhypoxemic controls. In contrast, abrupt and gradual reoxygenation without blood cardioplegia produced significant lipid peroxidation (84% increase in conjungated dienes), lowered antioxidant reserve capacity 68% ± 5%, 44% ± 8%, respectively, and decreased functional recovery 75% ± 6% ( p < 0.05), 66% ± 4% ( p < 0.05). Similar impairment followed abrupt reoxygenation before blood cardioplegic myocardial management, because conjungated diene production increased 13-fold, antioxidant reserve capacity fell 40%, and contractility recovered only 21% ± 2% ( p < 0.05). Conversely, normoxemic induction of cardiopulmonary bypass and blood cardioplegic myocardial management reduced conjungated diene production 73%, avoided impairment of antioxidant reserve capacity, and resulted in 58% ± 11% recovery of contractile function. We conclude that these data suggest that reoxygenation damage is (1) oxygen tension dependent, (2) occurs whether reoxygenation is abrupt or gradual in the absence of blood cardioplegia, and (3) can be reduced by normoxemic management when CPB is started and during blood cardioplegic administration before subsequent reintroduction of hyperoxemia. (J T HORAC C ARDIOVASC S URG 1995; 110:1255-64)

Studies of hypoxemic/reoxygenation injury: With aortic clamping: XIII. Interaction between oxygen tension and cardioplegiccomposition in limiting nitric oxide production and oxidant damage

This study tests the interaction between oxygen tension and cardioplegic composition on nitric oxide production and oxidant damage during reoxygenation of previously cyanotic hearts. Of 35 Duroc-Yorkshire piglets (2 to 3 weeks, 3 to 5 kg), six underwent 30 minutes of blood cardioplegic arrest with hyperoxemic (oxygen tension about 400 mm Hg), hypocalcemic, alkalotic, glutamate/aspartate blood cardioplegic solution during 1 hour of cardiopulmonary bypass without hypoxemia (control). Twenty-nine others were subjected to up to 120 minutes of ventilator hypoxemia (oxygen tension about 25 mm Hg) before reoxygenation on CPB. To simulate routine clinical management, nine piglets underwent uncontrolled cardiac reoxygenation , whereby cardiopulmonary bypass was started at oxygen tension of about 400 mm Hg followed by the aforementioned blood cardioplegic protocol 5 minutes later. All 20 other piglets underwent controlled cardiac reoxygenation , whereby cardiopulmonary bypass was started at the ambient oxygen tension (about 25 mm Hg), and reoxygenation was delayed until blood cardioplegia was given. The blood cardioplegia solution was kept normoxemic (oxygen tension about 100 mm Hg) in 10 piglets and made hyperoxemic (oxygen tension about 400 mm Hg) in 10 others. The cardioplegic composition was also varied so that the cardioplegic solution in each subgroup contained either KCl only (30 mEq/L) or components that theoretically inhibit nitric oxide synthase by including hypocalcemia, alkalosis, and glutamate/aspartate. Function (end-systolic elastance) and myocardial nitric oxide production, conjugated diene production, and antioxidant reserve capacity were measured. Blood cardioplegic arrest without hypoxemia did not cause myocardial nitric oxide or conjugated diene production, reduce antioxidant reserve capacity, or change left ventricular functional recovery. In contrast, uncontrolled cardiac reoxygenation raised nitric oxide and conjugated diene production 19- and 13-fold, respectively ( p < 0.05 vs control), reduced antioxidant reserve capacity 40%, and contractility recovered only 21% of control levels. After controlled cardiac reoxygenation at oxygen tension about 400 mm Hg with cardioplegic solution containing KCl only, nitric oxide and conjugated diene production rose 16- and 12-fold, respectively ( p < 0.05 vs control), and contractility recovered only 43% ± 5%. Normoxemic (oxygen tension of about 100 mm Hg) controlled cardiac reoxygenation with the same solution reduced nitric oxide and conjugated diene production 85% and 71%, and contractile recovery rose to 55% ± 7% ( p < 0.05 vs uncontrolled reoxygenation). In comparison, controlled cardiac reoxygenation with an oxygen tension of about 400 mm Hg hypocalcemic, alkalotic, glutamate/aspartate blood cardioplegic solution reduced nitric oxide and conjugated diene production 85% and 62%, respectively, and contractility recovered 63% ± 4% ( p < 0.05 vs KCl only). Normoxemic delivery of this solution resulted in negligible nitric oxide and conjugated diene production and 83% ± 8% recovery of contractility ( p < 0.05 vs all other groups). These data show correlation between nitric oxide production during initial reoxygenation and the extent of oxidant damage (i.e., conjugated diene production) and link functional recovery to suppression of excessive nitric oxide production and limitation of lipid peroxidation by the interaction of oxygen tension and cardioplegic composition during initial reoxygenation. (J T HORAC C ARDIOVASC S URG 1995; 110:1274-86)