Retrograde continuous warm blood cardioplegia: a new concept in myocardial protection

This report presents the results in our first clinical series of patients receiving continuous warm blood cardioplegia through the coronary sinus. Warm oxygenated blood cardioplegia has certain theoretical advantages, such as continuously supplying oxygen and substrates to the arrested heart while avoiding the side effects of hypothermia. Retrograde infusion of cardioplegia also offers certain advantages (eg, in valve operations and in patients with severe coronary artery disease) that are complementary to warm blood cardioplegia. Retrograde warm blood cardioplegia was used in 113 consecutive patients (85 men and 28 women with a mean age of 61 years) undergoing various procedures. Three percent of the patients died, 7% needed transient intraaortic balloon pump support, 6% had evidence of perioperative myocardial infarction, and 96% had spontaneous return of rhythm. There were no coronary sinus injuries. This new technique of retrograde continuous warm blood cardioplegia is a simple, safe, and reliable method of myocardial protection that may change the way we currently protect the heart intraoperatively.     

Endothelial damage during myocardial preservation and storage

Preservation and storage techniques represent two major issues in routine cardiac surgery and heart transplantation. Historically, these methods were conceived to prevent ischemic injury to myocardium after cardiac arrest during heart operations. Evidence shows that endothelium plays a critical role in the maintenance of normal heart function after cardiac operation, mainly by controlling the coronary circulation. Methods for preservation and storage, developed initially to protect cardiomyocyte function, may be deleterious for vascular endothelium and compromise myocardial protection. In this review article the present knowledge about endothelial injury secondary to preservation and storage techniques is discussed.     

Continuous cold blood cardioplegia improves myocardial protection: a prospective randomized study

BACKGROUND: To assess the influence on myocardial protection of the rate of infusion (continuous vs intermittent) of cold blood cardioplegia administered retrogradely during prolonged aortic cross-clamping. The end-points were ventricular performance and biochemical markers of ischemia. METHODS: Seventy patients undergoing myocardial revascularization for three-vessel disease were prospectively randomized to receive intermittent or continuous retrograde cold blood cardioplegia. Hemodynamic measurements were obtained using a rapid-response thermodilution catheter and included right ventricular ejection fraction, cardiac output, left and right ventricular stroke work index, and systemic and pulmonary vascular resistance. Blood samples were obtained from the coronary sinus before cross-clamp application and immediately after cross-clamp removal for determinations of lactate and hypoxanthine. RESULTS: The left ventricular stroke work index trend was significantly superior (p = 0.038) by repeated-measures analysis in continuous cardioplegia. Other hemodynamic measurements revealed a similar trend. The need for postoperative inotropic drugs support was reduced in continuous cardioplegia. The release of lactate in the coronary sinus after unclamping was 2.30 +/- 0.12 mmol/L after intermittent cardioplegia and 1.97 +/- 0.09 mmol/L after continuous cardioplegia (p = 0.036). The release of hypoxanthine was 20.47 +/- 2.74 micromol/L in intermittent cardioplegia and 11.77 +/- 0.69 micromol/L in continuous cardioplegia (p = 0.002). CONCLUSIONS: Continuous cold blood cardioplegia results in improved ventricular performance and reduced myocardial ischemia in comparison with intermittent administration.     

Contrast echocardiography: potential for the in-vivo study of pediatric myocardial preservation

BACKGROUND: Myocardial contrast echocardiography (MCE) has been used successfully during adult cardiac surgery to image myocardial perfusion. Recently it has been suggested this technique is capable of detecting microvascular injury and inflammation because sonicated albumin microbubbles adhere to activated neutrophils and, in the presence of denuded or inflamed endothelium, they persist within the microvasculature rather than passing unimpeded, which results in profound slowing of their transit rates. The technique has not previously been used during congenital heart surgery; however significant potential is suggested in this setting in which myocardial inflammation may contribute to postoperative myocardial dysfunction, a leading cause of morbidity and mortality. We have performed a preliminary study to assess the safety and feasibility of MCE in the pediatric intraoperative environment and to examine myocardial transit rates. METHODS: Sonicated albumin microbubbles were injected with cardioplegia during bypass in 16 children (aged 3 weeks to 8.5 years). Images were collected using transesophageal echocardiography. Complications, post-bypass electrocardiographic, echocardiographic, and outcome data were recorded. Myocardial transit rates were calculated using videointensity analysis, assessed for reproducibility and correlated with demographic and intraoperative variables and postoperative outcome. RESULTS: The technique was performed safely, with good reproducibility. Myocardial persistence of microbubbles, which occurred in 6 patients, was associated with crystalloid cardioplegia, prolonged preischemic bypass (r = 0.72, p = 0.004), or ischemic time (r = 0.69, p = 0.002). CONCLUSIONS: Intraoperative MCE shows potential as an in vivo technique for the study of pediatric myocardial preservation.     

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.     

The effect of sodium concentration on myocardial viability in donor heart preservation using a nondepolarizing solution

This study examined the effect of different sodium concentrations in a nondepolarizing solution on myocardial viability and functional recovery of the canine donor heart. Isolated canine hearts were preserved for 6 h at 5°C, followed by normothermic reperfusion for 2 h. Dogs were divided into two groups of nine dogs each: group 1 received a nondepolarizing solution with 70mm Na⁺ and group 2 with 30mm Na⁺. The myocardial Ca²⁺ concentration at the end of preservation was significantly higher in group 1 than in group 2 and increased after reperfusion in both groups without any intergroup difference. Myocardial concentrations of ATP, ADP, and total adenine nucleotide at the end of reperfusion were significantly higher in group 1 than in group 2. Myocardial cyclic adenosine monophosphate concentration was significantly higher in group 1 than in group 2 at the end of both preservation and reperfusion. The myocardial cyclic guanosine monophosphate concentration in group 1 increased and was higher than in group 2 at the end of preservation, but had returned to normal levels by the end of reperfusion. However, it remained unchanged through preservation and reperfusion in group 2. The left ventricular systolic and diastolic function, assessed by pressurevolume relationship, was better in group 1 than in group 2. Mitochondrial ultrastructural changes were similar. These results suggest that a nondepolarizing solution containing 70mm Na⁺ provides better myocardial protection than a solution containing 30mm Na⁺.     

Experimental studies on myocardial protection with intermittent cross-clamp fibrillation: additive effect of the sodium-hydrogen exchanger inhibitor, cariporide

BACKGROUND: We previously showed that intermittent cross clamping with fibrillation affords myocardial protection equivalent to cardioplegic arrest. In this study, we examined whether cariporide (Aventis Pharma, Frankfurt, Germany), a specific sodium-hydrogen exchanger inhibitor, enhanced the protective effect of intermittent cross-clamp fibrillation (ICCF). METHODS: Isolated rat hearts were Langendorff-perfused (20 mins) with bicarbonate buffer and function (left ventricular developed pressure) measured. In each of three separate protocols that incorporated progressively longer ischemic durations, hearts were randomly allocated to one of three groups: group 1 was the control group with 40, 60, or 80 minutes of continuous global ischemia. Group 2 was the ICCF group with 4, 6, or 8 cycles of 10 minutes ICCF and 10 minutes of reperfusion in sinus rhythm. Group 3 was the ICCF plus cariporide group, which was the same as group 2, but also with 3 micromoles/L cariporide present in perfusate from 10 minutes before the ICCF cycles. Hearts were reperfused for 60 minutes with drug-free buffer and recovery (percentage of initial function) was measured. Hearts were maintained at 37 degrees C throughout the protocols. In protocol 3 (80 minutes ischemia per 8 cycles of ICCF), creatine kinase leakage (myocardial injury) and triphenyl tetrazolium chloride staining (myocardial viability) were also measured. Protocols 1, 2, and 3 had n = 8 hearts, n = 6 hearts, and n = 6 hearts in each group, respectively. RESULTS: In the three protocols, the recoveries of left ventricular developed pressure in the control group, the ICCF group, and the ICCF plus cariporide group, respectively, for protocol 1 were: 26% +/- 3%, 70% +/- 2% (p < 0.05 vs the control group) and 74% +/- 2% (p < 0.05 vs the control group), respectively. For protocol 2 these were: 16% +/- 2%, 55% +/- 1% (p < 0.05 vs the control group), and 70% +/- 3% (p < 0.05 vs the control and ICCF groups), respectively. For protocol 3 these were: 8% +/- 2%, 41% +/- 3% (p < 0.05 vs the control group), and 63% +/- 2% (p < 0.05 vs the control and ICCF groups), respectively. Recovery of left ventricular end-diastolic pressure mirrored that of left ventricular developed pressure in all protocols. In protocol 3, total creatine kinase leakage (international units per gram wet weight) was 88 +/- 12, 47 +/- 4 (p < 0.05 vs the control group), and 17 +/- 1 (p < 0.05 vs the control and ICCF groups), respectively, and triphenyl tetrazolium chloride staining (arbitrary units per gram wet weight) was 0.17 +/- 0.04 in the control group, 0.39 +/- 0.04 (p < 0.05 vs the control group) in the ICCF group, and 0.47 +/- 0.08 (p < 0.05 vs the control group) in the ICCF plus cariporide group, respectively. CONCLUSIONS: Sodium-hydrogen exchanger inhibition with cariporide enhances the myocardial protection afforded by ICCF, with the additive benefit becoming more apparent with increasing severity of the ischemic insult. Sodium-hydrogen exchanger inhibition may provide a significant protective reserve during ICCF, particularly when longer procedures are required.     

Adenosine in myocardial protection in on-pump and off-pump cardiac surgery

Adenosine is most well known for its potent vasodilation of the vasculature. However, it also promotes glycolysis, and activates potassium-sensitive adenosine triphosphate (K(ATP)) channels. Adenosine also strongly inhibits neutrophil function such as superoxide anion production, protease release, and adherence to coronary endothelial cells. Hence adenosine attenuates ischemic injury as well as neutrophil-mediated reperfusion injury. Adenosine has also been implicated in the cardioprotective phenomenon of ischemic preconditioning. Accordingly experimental evidence shows that adenosine reduces postischemic injury when administered before ischemia and at the onset of reperfusion. Clinical studies in cardiology and cardiac surgery show cardioprotective trends with adenosine treatment but the effects are not as dramatic as those reported by experimental studies.     

Norwood operation without circulatory arrest: a new surgical technique

Circulatory arrest (CA) is associated with potential neurologic injury. We have developed a new surgical technique to eliminate CA during the Norwood operation. A modified Blalock-Taussig shunt (BTS) was fully constructed before cannulation for cardiopulmonary bypass. The aortic cannula was inserted in the patent ductus arteriosus to allow systemic cold perfusion. When deep hypothermia was reached, the aortic cannula was redirected into the pulmonary artery (PA) confluence. Both cerebral and systemic perfusion were maintained through the right PA and BTS into the innominate artery.     

Reduction of myocardial reperfusion injury by aprotinin after regional ischemia and cardioplegic arrest

BACKGROUND: Surgical coronary revascularization with cardiopulmonary bypass and cardioplegia has been associated with reperfusion injury. The serine protease inhibitor aprotinin has been suggested to reduce reperfusion injury, yet a clinically relevant study examining regional ischemia under conditions of cardiopulmonary bypass and cardioplegia has not been performed. METHODS: Pigs were subjected to 30 minutes of regional myocardial ischemia by distal left anterior descending coronary artery occlusion, followed by 60 minutes of cardiopulmonary bypass with 45 minutes of cardioplegic arrest and 90 minutes of post-cardiopulmonary bypass reperfusion. The treatment group (n = 6) was administered aprotinin systemically (40,000 kallikrein-inhibiting units [KIU]/kg intravenous loading dose, 40,000 KIU/kg pump prime, and 10,000 KIU x kg(-1) x h(-1) intravenous continuous infusion). Control animals (n = 6) received crystalloid solution. Global and regional myocardial functions were analyzed by the left ventricular+dP/dt and the percentage segment shortening, respectively. Left ventricular infarct size was measured by tetrazolium staining. Tissue myeloperoxidase activity was measured. Myocardial sections were immunohistochemically stained for nitrotyrosine. Coronary microvessel function was studied by videomicroscopy. RESULTS: Myocardial infarct size was decreased with aprotinin treatment (27.0% +/- 3.5% vs 45.3% +/- 3.0%, aprotinin vs control; P <.05). Myocardium from the ischemic territory showed diminished nitrotyrosine staining in aprotinin-treated animals versus controls, and this was significant by grade (1.3 +/- 0.2 vs 3.2 +/- 0.2, aprotinin vs control; P <.01). In the aprotinin group, coronary microvessel relaxation improved most in response to the endothelium-dependent agonist adenosine diphosphate (44.7% +/- 3.2% vs 19.7% +/- 1.7%, aprotinin vs control; P <.01). No significant improvements in myocardial function were observed with aprotinin treatment. CONCLUSIONS: Aprotinin reduces reperfusion injury after regional ischemia and cardioplegic arrest. Protease inhibition may represent a molecular strategy to prevent postoperative myocardial injury after surgical revascularization with cardiopulmonary bypass.     

Endothelial cell injury induced by preservation solutions: a confocal microscopy study

BACKGROUND: We evaluated the effects of standard preservation solutions on cultured human greater saphenous vein endothelial cells. METHODS: Endothelial cells (eight strains) were preincubated for 6 or 24 hours at 4 degrees C in Celsior, Euro-Collins, St. Thomas Hospital II, and University of Wisconsin solutions, reincubated in warm oxygenated culture medium 199, and observed up to 48 hours. Culture viability was assessed through cell counting and confocal microscopy of calcein loaded cells. RESULTS: Incubation in both Euro-Collins and St. Thomas, but not in Celsior or University of Wisconsin solutions, caused significant cells losses and diffuse morphological damages characterized by solution-specific distinctive alterations. Injury caused by 6-hour, but not by 24-hour treatment, was reversible. CONCLUSIONS: The incubation with Celsior and University of Wisconsin solutions substantially preserved endothelial viability and proliferative capability. Conversely, a prolonged incubation in either Euro-Collins or St. Thomas solutions caused severe and potentially irreversible damage referable to the induction of, respectively, apoptotic or necrotic changes.