The Journal of thoracic and cardiovascular surgery
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J. Thorac. Cardiovasc. Surg. · Oct 1995
Randomized Controlled Trial Multicenter Study Clinical TrialAcadesine: a new drug that may improve myocardial protection in coronary artery bypass grafting. Results of the first international multicenter study. Multinational Acadesine Study Group.
The effect of acadesine, an adenosine-regulating agent, on the incidence of myocardial infarction, all adverse cardiovascular outcomes (myocardial infarction, cardiac death, left ventricular dysfunction, life-threatening arrhythmia, or cerebrovascular accident) and mortality was assessed in 821 patients undergoing coronary artery bypass grafting. Patients were prospectively stratified to a high-risk group (age > 70 years, unstable angina, previous coronary bypass, unsuccessful angioplasty, or ejection fraction < 30%) or a non-high-risk group. They were randomized in a double-blind manner to placebo (n = 418) or acadesine (n = 403) by intravenous infusion over 7 hours (0.1 mg/kg per minute) and in the cardioplegic solution (placebo or acadesine; 5 micrograms/ml). ⋯ However, acadesine reduced the incidence of cardiac related events that contributed to deaths occurring during the first 3 postoperative days so that the incidence of death in this period was lower (placebo, 1.9%; acadesine, 0.2%; p = 0.038). No adverse events were related to acadesine treatment. Although overall there were no statistically significant between-group differences for the primary study end points, a secondary analysis in a prospectively defined high-risk subgroup suggests that acadesine may be beneficial in some patients.
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J. Thorac. Cardiovasc. Surg. · Oct 1995
Randomized Controlled Trial Clinical TrialRecombinant aprotinin in coronary artery bypass graft operations.
To evaluate the role of recombinant bovine aprotinin in reducing blood loss in coronary artery bypass graft surgery. ⋯ We conclude that, at the dosages given, recombinant bovine aprotinin decreases surgical blood loss and transfusion requirements in patients undergoing coronary artery bypass grafting, but its use requires appropriate monitoring of heparin use during bypass. Whether higher dosages of aprotinin increase the risk of graft thrombosis must be further assessed with a larger patient sample.
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J. Thorac. Cardiovasc. Surg. · Oct 1995
Protective effect of nicorandil as an additive to the solution for continuous warm cardioplegia.
Experiments were designed to assess whether (1) nicorandil given before global low-flow ischemia or (2) included in low-flow continuous cardioplegia improved the recovery of cardiac function in the isolated rat heart. The first investigated the effect of nicorandil (2, 10, or 100 mumol/L), given for 3 minutes before 30 minutes of normothermic global ischemia, on recovery after 30 minutes of reperfusion. In aerobically perfused hearts, doses of 10 and 100 mumol/L significantly increased coronary flow; the dose of 100 mumol/L exerted a negative inotropic effect. ⋯ Ventricular compliance (the ventricular volume required to achieve a left ventricular end-diastolic pressure of 4 mm Hg) was better preserved in the nicorandil-containing noncardioplegia group (133 +/- 6 microliters) than in the control group (88 +/- 10 microliters; p < 0.05). In conclusion, nicorandil has been shown to (1) reduce ischemic contracture, (2) lessen the effects of ischemic arrest, and (3) improve the postischemic recovery of contractile function. In this species and preparation it may, however, enhance vulnerability to reperfusion-induced arrhythmias.
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J. Thorac. Cardiovasc. Surg. · Oct 1995
Constitutive nitric oxide release is impaired after ischemia and reperfusion.
Myocardial ischemia and reperfusion may result in endothelial dysfunction and reduced release of nitric oxide. With the use of an amperometric sensor, the first direct measurements of constitutive nitric oxide release from a beating heart were measured from the coronary effluent of isolated working rat hearts subjected to ischemia and reperfusion. Rats, six to eight per group, were randomly studied as follows: control (no pretreatment) and pretreatment with the nitric oxide donor L-arginine (3 mmol/L), its enantiomer D-arginine (3 mmol/L), nitric oxide inhibitor N omega-nitro-L-arginine methyl ester (100 mumol/L), and combined N omega-nitro-L-arginine methyl ester/L-arginine. ⋯ We conclude that after ischemia/reperfusion, endothelial dysfunction results in decreased nitric oxide release, which can be ameliorated with L-arginine pretreatment. The direct cytoprotective properties of nitric oxide may contribute to improved functional recovery in hearts pretreated with L-arginine. Augmentation of the L-arginine/nitric oxide pathway may provide a new approach for improved recovery after cardiovascular operations.
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J. Thorac. Cardiovasc. Surg. · Oct 1995
Studies of hypoxemic/reoxygenation injury with aortic clamping: XI. Cardiac advantages of normoxemic versus hyperoxemic management during qardiopulmonary 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. ⋯ 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.(ABSTRACT TRUNCATED AT 400 WORDS)