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

AbstractThis 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 THORAC CARDIOVASC SURG 1995; 110:1274-86

Echocardiographic Evaluation of Postoperative Coaptation Geometry of Left AV Valve in Complete Atrioventricular Septal Defect

Background: We sought to determine the difference in geometric parameters in the left atrioventricular valve (LAVV) postoperative complete atrioventricular septal defect (CAVSD) compared to the normal heart, and the correlation between geometric and functional parameters for detecting the mechanism of LAVV regurgitation (LAVVR) in CAVSD. Methods: LAVV geometric parameters based on complete and acceptable quality echocardiograms of 18 patients with repaired CAVSD compared with 17 normal controls. LAVVR severity was also quantified by indexed vena contracta (I-VC) (mm) and % jet area/left atrium area (% Jet/LA), and the correlation with LAVV parameters in the CAVSD group was investigated. Results: In the CAVSD group, the posterior closing angle (Pc) was nearly the same as the anterior closing angle (Ac), yet in the normal heart, the Pc angle was double the Ac angle. The anterior opening angle (Ao) and posterior-to-anterior leaflet diameter ratio (a/p) in the CAVSD group was also significantly smaller. The CAVSD group also had a shorter indexed coaptation length (I-CL) and indexed tenting height (I-TH). Displacement length (ΔD) differed completely between the CAVSD and Normal groups, and also showed a strong positive correlation to the functional parameters of LAVVR (% Jet/LA: r  = .70, P  = .02; I-VC: r  = .60, P  = .02). Conclusions: The parameters in this study were applicable to CAVSD AV valve coaptation characteristics. We introduced 2 novel measures that may provide important insights into the differences in geometry and performance of the LAVV in repaired CAVSD as compared to normal hearts

Studies of hypoxemic/reoxygenation injury: Without aortic clamping IV. Role of the iron-catalyzed pathway: deferoxamine

AbstractThis study tests the hypothesis that an iron chelator, deferoxamine, can reduce oxygen-mediated myocardial injury and avoid myocardial dysfunction after cardiopulmonary bypass by its action on the iron-catalyzed Haber-Weiss pathway. Twenty-one immature 2- to 3-week-old piglets were placed on cardiopulmonary bypass for 120 minutes, and five piglets served as biochemical controls without cardiopulmonary bypass. Five piglets underwent cardiopulmonary bypass without hypoxemia (cardiopulmonary bypass control). Sixteen others became hypoxemic while undergoing cardiopulmonary bypass for 60 minutes by lowering oxygen tension to about 25 mm Hg, followed by reoxygenation at oxygen tension about 400 mm Hg for 60 minutes. Oxygen delivery was maintained during hypoxemia by increasing cardiopulmonary bypass flow and hematocrit level. In seven piglets deferoxamine (50 mg/kg total dose) was given both intravenously just before reoxygenation and by a bolus injection (5 mg/kg) into the cardiopulmonary bypass circuit; nine others were not treated (no therapy). Myocardial function after cardiopulmonary bypass was evaluated from end-systolic elastance (conductance catheter) and Starling curve analysis. Myocardial conjugated diene production and creatine kinase leakage were assessed as biochemical markers of injury, and antioxidant reserve capacity was determined by measuring malondialdehyde in postcardiopulmonary bypass myocardium incubated in the oxidant, t -butylhydroperoxide. Cardiopulmonary bypass without hypoxemia caused no oxidant or functional damage. Conversely, reoxygenation (no therapy) raised myocardial conjugated diene levels and creatine kinase production (conjugated diene: 3.5 ± 0.7 absorbance 233 nm/min/100 g, creatine kinase: 8.5 ± 1.5 U/min/100 g; p < 0.05 versus cardiopulmonary bypass control), reduced antioxidant reserve capacity (malondialdehyde: 1115 ± 60 nmol/g protein at 4 mmol/L t -butylhydroperoxide; p < 0.05 versus control), and produced severe postbypass dysfunction (end-systolic elastance recovered only 39% ± 7%, p < 0.05 versus cardiopulmonary bypass control). Deferoxamine avoided conjugated diene production and creatine kinase release and retained normal antioxidant reserve, and functional recovery was complete (95% ± 11%, p < 0.05 versus no treatment). These findings show that iron-catalyzed oxidants may contribute to a reoxygenation injury and imply that deferoxamine may be used to surgical advantage. (J THORAC CARDIOVASC SURG 1995; 110:1190-9

Studies of hypoxemic/reoxygenation injury: With aortic clamping X. Exogenous antioxidants to avoid nullification of the cardioprotective effects of blood cardioplegia

AbstractThis study tests the hypothesis that reoxygenation of cyanotic immature hearts when starting cardiopulmonary bypass produces an “unintended” reoxygenation injury that (1) nullifies the cardioprotective effects of blood cardioplegia and (2) is avoidable by adding antioxidants N -(2-mercaptopropionyl)-glycine plus catalase to the cardiopulmonary bypass prime. Twenty immature piglets (2 to 3 weeks) underwent 30 minutes of aortic clamping with a blood cardioplegic solution that was hypocalcemic, alkalotic, hyperosmolar, and enriched with glutamate and aspartate during 1 hour of cardiopulmonary bypass. Of these, six piglets did not undergo hypoxemia (blood cardioplegic control) and 14 others remained hypoxemic (oxygen tension about 25 mm Hg) for up to 2 hours by lowering ventilator fraction of inspired oxygen before reoxygenation on cardiopulmonary bypass. The primary solution of the cardiopulmonary bypass circuit was unchanged in eight piglets (no treatment) and supplemented with the antioxidants N -(2-mercaptopropionyl)-glycine (80 mg/kg) and catalase (5 mg/kg) in six others ( N -(2-mercaptopropionyl)-glycine and catalase). Myocardial function (end-systolic elastance), lipid peroxidation (myocardial conjugated diene production), and antioxidant reserve capacity were evaluated. Blood cardioplegic arrest produced no biochemical or functional changes in nonhypoxemic control piglets. Reoxygenation caused an approximate 10-fold increase in conjugated production that persisted throughout cardiopulmonary bypass, lowered antioxidant reserve capacity 86% ± 12%, and produced profound myocardial dysfunction, because end-systolic elastance recovered only 21% ± 2%. Supplementation of the cardiopulmonary bypass prime with N -(2-mercaptopropionyl)-glycine and catalase reduced lipid peroxidation, restored antioxidant reserve capacity, and allowed near complete functional recovery (80% ± 8%).** Lipid peroxidation (conjugated diene) production was lower during warm blood cardioplegic reperfusion than during induction in all reoxygenated hearts, which suggests that blood cardioplegia did not injure reoxygenated myocardium. We conclude that reoxygenation of the hypoxemic immature heart causes cardiac functional and antioxidant damage that nullifies the cardioprotective effects of blood cardioplegia that can be avoided by supplementation of the cardiopulmonary bypass prime with antioxidants (* p < 0.05 vs blood cardioplegic control; ** p < 0.05 vs reoxygenation). (J THORAC CARDOIVASC SURG 1995;110:1245-54

The Safety of Simultaneous Arterial and Coronary Sinus Perfusion: Experimental Background and Initial Clinical Results

Concern over myocardial damage from simultaneous arterial (antegrade) and coronary sinus (retrograde) perfusion has led to alternating between these delivery routes to maximize their individual benefits. Based upon predominant retrograde drainage via Thebesian veins, this study: (1) confirms experimentally the safety of simultaneous arterial and coronary sinus perfusion; and (2) reports initial clinical application of this combined strategy in 155 consecutive patients. Experimental: Five mini‐pigs (25 to 30 kg) underwent 1 hour of aortic clamping with simultaneous aortic and coronary sinus perfusion at 200 mUmin with normal blood (37°C) before and after 30 minutes of perfusion with either warm (37°C) or cold (4°C) blood cardioplegia. Coronary sinus pressure was always less than 30 mmHg. There was no right or left ventricular edema, lactate production, or lipid peroxidation as transmyocardial and myocardial conjugated dienes were unaltered, and postbypass recovered left ventricular end‐systolic elastance (conductance catheter) and preload recruitable stroke work Index 101%± 3% and 109%± 90%, respectively. Clinical: Simultaneous arteriaVcoronary sinus perfusion was used in 155 consecutive high risk patients (New York Heart Association Class III to IV) undergoing isolated coronary artery bypass grafting (CABG) (n = 109) and CABG + valve replacementlrepair or aneurysm (n = 46). Included were 16 patients in cardiogenic shock and 24 undergoing reoperation. Mean aortic clamping time averaged 90 ± 4 minutes (range 30 to 207), with 3.5 ± 0.1 grafts per patient; all anastomoses were performed with the aorta clamped. Cold intermittent blood cardioplegia was used for distal anastomoses and valve implantationhepair in 123 patients, and warm continuous blood cardioplegia was used in 32 patients. Following a warm cardioplegic reperfusate, all patients received warm non‐cardioplegic blood perfusion simultaneously via grafts and coronary sinus. Coronary sinus pressure was always less than 40 mmHg. Of 18 patients requiring postoperative mechanical circulatory support (IABP), 16 had IABP placed preoperatively for cardiogenic shock. There were three postoperative myocardial infarctions (2%), and six patients died (3.9% mortality). Conclusion: These experimental and clinical findings overcome perceived concerns about myocardial damage from simultaneous arterial and coronary sinus perfusion, and suggest this approach may add to the armamentarium of cardioprotective strategies. (J Card Surg 1994;9:15–25