Armand Piwnica

Influence of Temperature on Neutrophil Trafficking During Clinical Cardiopulmonary Bypass

BACKGROUNDnThe adhesion of neutrophils to endothelial cells and their subsequent transendothelial migration play a major role in inflammatory damage elicited by cardiopulmonary bypass (CPB) because these events are linked to the release of cytotoxic proteases and oxidants. However, the patterns of neutrophil trafficking in relation to systemic temperature during clinical CPB have not yet been characterized.nnnMETHODS AND RESULTSnTwenty case-matched patients undergoing warm (31.8 +/- 0.4 degrees C) or cold (26.3 +/- 0.5 degrees C, P < .0001 versus warm) bypass were studied. Blood samples were simultaneously collected from the right and left atria before, at the end of, and 30 minutes after CPB. Plasma levels of C3a, P- and E-selectins, elastase, and interleukin-8 were determined by immunoassays. The results demonstrate: (1) a rise in C3a, reflecting complement activation, (2) a fall in soluble E-selectin consistent with an increased adhesiveness of activated neutrophils, (3) a rise in soluble P-selectin expected to enhance endothelial adhesion of these neutrophils, (4) a rise in elastase, suggesting an adhesion-triggered neutrophil degranulation, and finally (5) a rise in interleukin-8 that is likely to promote transendothelial migration of adherent neutrophils. All of these changes occurred in the two groups of patients and were significant compared with prebypass values. However, in none of the groups was there a significant difference between right and left atrial values for any of the markers. The single difference between cold and warm bypass patients was a significant reduction of elastase release in the cold group (P < .001 versus the warm group).nnnCONCLUSIONSnClinical CPB is associated with biological changes suggesting the occurrence of neutrophil trafficking. Hypothermia provides only partial protection through a reduced release of elastase. Overall, these results reinforce the rationale for the development of therapeutic strategies targeted at blunting the neutrophil-mediated component of bypass-induced inflammatory damage.

Free radicals and myocardial protection: A surgical viewpoint

Oxygen-derived free radicals are now considered important contributors to tissue injury associated with ischemia and reperfusion. Transition metals, primarily iron, greatly enhance the generation of these active species, which can destroy a large variety of biomolecules, in particular the lipid components of cell membranes. This review tries to demonstrate why cardiopulmonary bypass and aortic cross-clamping are situations that predispose to oxygen free radical production, and how anti-free radical agents such as enzymatic scavengers, antioxidants, and iron chelators may prove to be useful therapeutic adjuncts in the clinical setting of open heart surgery.

Increased injury of hypertrophied myocardium with ischemic arrest: Preservation with hypothermia and cardioplegia

Many patients undergoing cardiac surgery have some degree of myocardial hypertrophy. To assess the response of hypertrophied myocardium to simulated cardiac surgery, left ventricular hypertrophy was induced in rats by aortic banding, and ventricular function was measured by means of the isolated, isovolumic heart perfusion technique. The hypertrophied hearts had a greater susceptibility to ischemic injury than nonhypertrophied control hearts, as manifested by a greater degree of diastolic contracture during the recovery period after 30 minutes of ischemic arrest at 37 degrees C. Hypothermia without cardioplegia during a 2-hour arrest did not completely preserve diastolic function in the hypertrophied hearts, but cardioplegia combined with hypothermia completely protected the hypertrophied hearts against 2 hours of ischemia. The results suggest a need for both hypothermic and cardioplegic preservation techniques in patients with myocardial hypertrophy who have cardiac surgical procedures requiring a significant period of myocardial ischemia.

Protective Effect of an Asanguineous Reperfusion Solution on Myocardial Performance Following Cardioplegic Arrest

This study assesses whether an appropriately designed asanguineous initial reperfusate effectively reduces the reperfusion injury following prolonged global ischemia and improves the recovery of cardiac performance after cardioplegic arrest. Forty-eight isolated perfused working rat hearts underwent two hours of hypothermic (15 degrees to 18 degrees C) ischemic arrest followed by 30 minutes of normothermic reperfusion. During ischemic injury, multidose cardioplegia was delivered at 30-minute intervals. The reperfusion solution under study was infused during the last 3 minutes of ischemia, just prior to release of the aortic clamp. The usual hemodynamic variables of this preparation (heart rate, aortic pressure, aortic flow, coronary flow, and stroke volume) were serially recorded and expressed as percent of recovery of control values. The influence of the concentration of Ca2+, pH, and buffer was more specifically investigated. A reperfusate containing 1 mM of Ca2+ was found to result in higher postischemic hemodynamic values than a Ca2+-poor (0.25 mM) reperfusate. The best functional recovery was provided by an alkalotic (pH 7.70 at 28 degrees C), glutamate-enriched initial reperfusate, which, by 30 minutes of reperfusion, yielded a 93.5 +/- 2.3% recovery of aortic flow versus 83.6 +/- 1.8% in the control group receiving unmodified reperfusion (p less than 0.01). We conclude that an appropriate composition of the initial reperfusate can improve the recovery of cardiac function significantly following two hours of cardioplegic arrest and that such an improvement can be achieved by an asanguineous reperfusate provided its composition is properly designed with respect to electrolytes, pH, and substrates.

Effect of nifedipine in hypothermic cardioplegia: a phosphorus-31 nuclear magnetic resonance study

The ability of nifedipine to enhance myocardial protection was assessed on isolated perfused rat hearts subjected to 180 min of hypothermic (20 degrees C), global ischemia, followed by 45 min of normothermic reperfusion. Intracellular pH, ATP, Pi and phosphocreatine content were serially measured at 4 min intervals by phosphorus-31 nuclear magnetic resonance spectroscopy and correlated with simultaneously recorded hemodynamic parameters. Addition of nifedipine (0.075 mumol/l and 0.5 mumol/l) to Saint Thomas cardioplegic solution reduced Pi accumulation during ischemic arrest and increased phosphocreatine levels during reperfusion. Post-ischemic functional recovery was not improved at a drug concentration of 0.075 mumol/l and was depressed at 0.5 mumol/l. These results clearly show that the presence of nifedipine in Saint Thomas cardioplegic solution does not provide significant additional myocardial protection under hypothermic conditions.

Enhanced cardioplegic protection by a fluorocarbon-oxygenated reperfusate: A phosphorus-31 nuclear magnetic resonance study☆

Prolonged global ischemia results in a defect in oxygen extraction during early reperfusion. This study was thus undertaken to assess the effects of maintaining cardioplegia at the onset of reoxygenation in view of channeling available energy toward reparative cell processes rather than mechanical activity. Twenty-four isolated perfused rat hearts were subjected to 120 min of 15 degrees C ischemia. Group I (control) was reperfused with the standard Krebs perfusion medium whereas in groups II and III the initial reperfusate consisted of an oxygenated alkaline cardioplegic solution prior to the resumption of Krebs perfusion. Oxygenation of the cardioplegic reperfusate was ensured by fluorocarbons at a concentration of 10% (O2 content: 5.5 vol %; group II) or 20% (O2 content: 9 vol %; group III). In addition to hemodynamical determinations, high-energy phosphates and intracellular pH were monitored serially by phosphorus-31 nuclear magnetic resonance spectroscopy. After 30 min of reperfusion postischemic recovery of aortic flow was better in group II (74.0 +/- 5.9% of control) than in group I (59.1 +/- 5.4% of control, P less than 0.05). This functional improvement correlated with a higher postischemic increase in phosphocreatine levels (103.21 +/- 11.21% vs 74.12 +/- 3.59%, at 3 min of reperfusion, P less than 0.05) without significant differences in total ATP content. Group III hearts exhibited a slow recovery as evidenced by a severe depression in aortic flow, coronary arteriovenous difference, and total phosphate content during the 15 initial minutes of reperfusion. These results show that the protection provided by cardioplegia can be improved by a fluorocarbon-oxygenated cardioplegic reperfusate.(ABSTRACT TRUNCATED AT 250 WORDS)

31P-NMR study of high-energy phosphorylated compounds metabolism and intracellular pH in the perfused rat heart

Using 31P-NMR and haemodynamical measurements, this work assesses different aspects of myocardial preservation improvement during a global ischaemia, based on a simultaneous and correlated study of high-energy phosphorylated compounds, intracellular pH and left ventricular function. Isolated perfused working rat hearts were subjected to 2 or 3 h of hypothermic ischaemia followed by 30 or 45 min of reperfusion. A study of the influence of pH and buffer used in cardioplegic solutions has demonstrated a better preservation of high-energy phosphates and an improved functional recovery when using a pH 7.0, glutamate - containing solution. Protection provided by cardioplegia can be enhanced by the appropriate use of a fluorocarbon-oxygenated cardioplegic reperfusate. The use of nifedipine, a calcium antagonist, in the cardioplegic solutions, does not provide any additional protection under hypothermic conditions.