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Biomedical subjects

Louis P Perrault

Publications and source records attributed to Louis P Perrault.

At least 19 recordsLinked to original sources

Tetrahydrobiopterin and antioxidants reverse the coronary endothelial dysfunction associated with left ventricular hypertrophy in a porcine model.

OBJECTIVE: Endothelium-dependent G-protein mediated relaxations of epicardial coronary arteries is impaired with left ventricular hypertrophy. The objective of this study was to assess the effect of L-arginine, BH(4) and the combination of two antioxidants, superoxide dismutase and catalase, on endothelium-dependent relaxations in a swine left ventricular hypertrophy model. METHODS: Aortic banding was performed 3 cm above the coronary ostia. Vascular reactivity studies were performed in standard organ chamber experiments to assess the NO pathway in the presence of methyltetrahydropterin (a BH(4) analogue), L-arginine, superoxide dismutase and catalase. RESULTS: There was a statistically significant increase in endothelium-dependent relaxation to serotonin and to bradykinin with methyltetrahydropterin and with superoxide dismutase plus catalase (P<0.05) but not with L-arginine compared to untreated coronary arteries from left ventricular hypertrophy animals. Plasma 3-nitrotyrosine level increased significantly from 918+/-122 to 1844+/-300 microM (P<0.05 vs. control) after 60 days of aortic banding. Endothelial dysfunction was not associated with a reduced expression of endothelial nitric oxide synthase 2 months after pressure overload left ventricular hypertrophy. CONCLUSIONS: Treatment with BH(4) and antioxidants constitutes an interesting approach for the prevention of endothelial dysfunction in epicardial coronary arteries associated with left ventricular hypertrophy.

Animals↗

Tricuspid valve replacement: an analysis of 25 years of experience at a single center.

BACKGROUND: Tricuspid valve replacement is seldom used in clinical practice, but the choice between mechanical and biologic prostheses remains controversial. METHODS: Between 1977 and 2002, 97 patients underwent tricuspid valve replacement and were followed at the Montreal Heart Institute Valve Clinic. Patients underwent replacement with bioprostheses (n = 82) and mechanical valves (n = 15). RESULTS: Patients with bioprosthetic tricuspid replacements averaged 53 +/- 13 years of age compared with 48 +/- 11 years in those with tricuspid mechanical valve replacements (p = 0.2). Isolated tricuspid valve replacement was performed in 11 patients (73%) in the mechanical valve group compared with 31 patients (38%. p = 0.01) in the bioprosthetic replacement group. In patients undergoing bioprosthetic tricuspid replacement, 51 (62%) underwent multiple associated valve replacements. The 5-year survival after tricuspid replacement averaged 60% +/- 13% in the mechanical valve group and 56% +/- 6% in the biologic replacement group (p = 0.8). The 5-year freedom rate from tricuspid valve reoperation averaged 91% +/- 9% in patients with mechanical valves and 97% +/- 3% in those with biologic valves (p = 0.2). CONCLUSIONS; Patient survival after tricuspid valve replacement is suboptimal but related to the clinical condition at operation. The use of biologic prostheses for tricuspid valve replacement remains a good option in young patients because of limited life expectancy unrelated to the type of tricuspid prostheses at long-term follow-up.

Bioprosthesis↗

Depression and anxiety and outcomes of coronary artery bypass surgery.

Psychological and psychiatric disorders independently increase the risk of cardiovascular disease and worsen the prognosis in patients with established cardiovascular lesions. The objective of this literature review is to discuss recent data concerning the relationships between depression and anxiety and the outcomes of coronary artery bypass grafting. Pathophysiological hypotheses are put forward to explain observed links. We suggest recommendations aimed at improving the psychological evaluation and management of heart surgery candidates, as well as postbypass patients, in the hope of improving quality of life and cardiovascular outcomes in these patients.

Anxiety↗

Incidence and outcome of radial artery infections following cardiac surgery.

BACKGROUND: Radial artery infections secondary to catheterization for blood pressure monitoring are rare but potentially serious complications. The objective of the study was to evaluate the incidence, the risk factors and the evolution of radial artery infections following cardiac surgery. METHODS: A retrospective review of 8300 patients undergoing cardiac surgery between 1998 and 2002 at the Montreal Heart Institute (MHI) was undertaken. All patients with superficial radial artery infections, infected radial artery pseudoaneurysms, and arterial catheter-related bacteremia were considered using prospective global surveillance of all nosocomial infections over the study period by an infection control nurse. RESULTS: Thirteen patients with radial infections were encountered (0.2%) with bacteremia occurring in 9 patients (0.15%). Five patients developed infected radial artery pseudoaneurysms (0.05%) and 5 patients developed subsequent sternal wound infections. Two patients died in their early postoperative evolution. Mean patient age was 67 years old and mean duration of cannulation was 5.8 days. Only 1 patient had diabetes. Seven of 13 patients were positive for Staphylococcus aureus (54%). All patients had undergone cardiopulmonary bypass (CPB) for various procedures. All superficial infections responded well to antibiotic therapy. Early surgical intervention is essential in cases of infected radial artery pseudoaneurysms. CONCLUSIONS: The postoperative state and cardiopulmonary bypass put patients at risk for infectious complications. Strict systematic changing of arterial lines on a timely basis is unwarranted in our opinion. A high suspicion index, aggressive surgical treatment of bacterial arteritis and appropriate intravenous antibiotics are essential to improve the prognosis.

Aged↗

Surgical radiofrequency ablation induces coronary endothelial dysfunction in porcine coronary arteries.

OBJECTIVES: Surgical radiofrequency ablation is increasingly used during open heart surgery for the treatment of chronic atrial fibrillation. The purpose of this study was to determine the effects of application of radiofrequency on coronary endothelial function and structure and establish the relationship between coronary lesions and distance of radiofrequency application. METHODS: Six Landrace swine (25.9+/-2.0 kg) were included in the study. With the heart kept beating, three epicardial radiofrequency lesions (20 W, 20 s duration, 60 degrees C) 2 cm in length each, were created 1, 5 and 10 mm away from the left anterior descending and the right coronary arteries. The circumflex artery served as control. Coronary rings were placed in organ chambers. After contraction to KCl and prostaglandin F2alpha, endothelium-dependent relaxations to bradykinin were studied. Gomori trichrome and hematoxylin-eosin safran staining were used for histological evaluation. RESULTS: Exposure to radiofrequency 1 mm from the coronary arteries caused a significant decrease in endothelium-independent contractions to KCl and endothelium-dependent relaxations to bradykinin compared to controls (P<0.05). No significant decrease of endothelium-dependent relaxations occurred for rings exposed to radiofrequency at a distance of 5 and 10 mm, compared to controls. Histological examination showed endothelial disruption and medial smooth muscle cells at different stages of necrosis up to 5 mm from the radiofrequency application site. CONCLUSIONS: Radiofrequency may induce coronary endothelial functional and morphological damages when applied less than 5 mm from the artery. Caution must be exerted during left atrial radiofrequency application due to the proximity of the circumflex artery.

Animals↗

Inhibiting the NO pathway with intracoronary L-NAME infusion increases endothelial dysfunction and intimal hyperplasia after heart transplantation.

BACKGROUND: The endothelium protects the vascular wall through the nitric oxide (NO) release. Coronary endothelial dysfunction occurs early after heart transplantation and predicts the development of intimal thickening typical of graft coronary vasculopathy. OBJECTIVE: We designed this study to examine the effect of endothelial NO synthase (eNOS) inhibition on the endothelial dysfunction caused by rejection and on the development of accelerated atherosclerosis after heart transplantation. METHODS: To study the effect on these 2 end-points of inhibiting eNOS with intracoronary L-nitro arginine methyl ester (L-NAME; 1 mg/kg/day), infused with an osmotic pump for 30 days, we used a porcine model of heterotopic heart transplantation with pre-operative immunologic typing, to permit slow rejection without the need for immunosuppression. The endothelium-dependent relaxations of allografted coronary arteries, allografted arteries infused with L-NAME, allografted arteries mounted with the pump, and vehicle and native coronary arteries were compared 30 days after graft implantation using standard organ chamber experiments. We evaluated intimal thickening using a semi-quantitative scale (0-4+ grading). RESULTS: A significant decrease in relaxations to serotonin (5-HT) occurred in allografted arteries infused directly with L-NAME compared with allografted arteries from swine receiving 5-HT, and relaxations in the latter were decreased compared with those of swine receiving the vehicle and native coronary arteries (p < 0.05). We found no significant differences in endothelium-dependent relaxations to bradykinin among coronary rings from all groups. We observed a significant increase in the prevalence and severity of intimal thickening in allografted coronary arteries infused with L-NAME compared with allografts not infused (p < 0.05), which had significantly more intimal thickening compared with native coronary arteries (p < 0.05). CONCLUSION: These results demonstrate that inhibiting the NO pathway worsens the endothelial dysfunction caused by rejection after heart transplantation and accelerates the intimal thickening process, leading to graft coronary vasculopathy. Strategies designed to preserve endothelial integrity and function of the endothelial NO pathway should be used to prevent graft coronary vasculopathy.

Animals↗

Heparin versus danaparoid in off-pump coronary bypass grafting: results of a prospective randomized clinical trial.

OBJECTIVE: The incidence of heparin-induced thrombocytopenia is increasing, and the thrombin inhibitor danaparoid could be a useful alternative. The objective of the present study was to compare danaparoid and heparin in patients undergoing off-pump coronary artery bypass grafting. METHODS: In a prospective, randomized, double-blind clinical trial comparing heparin (bolus of 1 mg/kg) with danaparoid (bolus of 40 U/kg), 71 patients underwent off-pump coronary artery bypass grafting with one of the study drugs. The amount of blood lost, the number of homologous blood products transfused, the troponin T levels, and the amount of anti-Xa activity were monitored. RESULTS: Thirty-four patients underwent 2.6 +/- 0.7 bypasses with danaparoid, and 37 patients underwent 2.5 +/- 0.9 grafts with heparin (P =.8). Postoperative blood losses averaged 1394 +/- 1033 mL in patients receiving danaparoid and 1130 +/- 868 mL in patients receiving heparin (P =.2). The number of homologous blood products transfused averaged 3.6 +/- 7 units in patients receiving danaparoid and 1.9 +/- 4.4 units in patients receiving heparin (P =.2). The number of patients requiring homologous blood transfusion was higher in patients receiving danaparoid (18/34 [53%]) than in patients receiving heparin (10/37 [27%], P =.03). Serum anti-Xa activity averaged 1.6 +/- 0.6 U/mL in patients receiving danaparoid and 1.9 +/- 0.8 U/mL in patients receiving heparin 30 minutes after injection of the drugs (P =.1) and 0.3 +/- 0.1 and 0.04 +/- 0.08 U/mL, respectively, 12 hours after coronary artery bypass grafting (P =.001). Troponin serum levels were similar 48 hours after coronary artery bypass grafting (0.5 +/- 0.6 and 0.4 +/- 0.6 microg/L, respectively). CONCLUSION: Although off-pump coronary artery bypass grafting with danaparoid versus heparin increases the number of patients exposed to homologous blood transfusion (relative risk, 2; 95% confidence limits, 1-4), off-pump coronary artery bypass grafting with danaparoid is a valuable alternative to heparin in patients with thrombocytopenia requiring surgical intervention.

Aged↗

Specific alterations of endothelial signal transduction pathways of porcine epicardial coronary arteries in left ventricular hypertrophy.

Coronary endothelial dysfunction in left ventricular hypertrophy (LVH) can reduce myocardial perfusion and result in an impaired global LV function. The objective of this study was to characterize the specific alterations of endothelial signal transduction of coronary arteries in a swine LVH model. Aortic banding was performed 3 cm above the coronary ostia. Vascular reactivity studies were performed to assess the nitric oxide (NO) and the EDHF-mediated relaxations. There was a significant increase in LV/body weight ratio associated with an increased in LV diastolic and end-diastolic pressure and decrease in dP/dT (P < 0.05), with no significant difference in coronary pressures 60 days after pressure-overload LVH. There was a significant decrease in endothelium-dependent relaxations to serotonin (5-HT) and to bradykinin (BK) (P < 0.05 for both) from LVH animals. There was no significant decrease of relaxations in the presence of BK and Nomega-l-arginine (EDHF pathway). Plasma NO(x) levels decreased significantly from 1.8% +/- 0.2% to 1.2% +/- 0.1% (P < 0.05 versus control). Chronic pressure-overload LVH is associated with an endothelial dysfunction involving both Gi and Gq protein-mediated relaxations in coronary arteries as well as the EDHF pathway.

Animals↗

Interrupted coalescent nitinol clip versus continuous suture coronary anastomosis: a comparative endothelial function study.

BACKGROUND: A new penetrating stapled anastomotic system using nitinol microclips (Coalescent Surgical U-Clip) has been developed to facilitate the construction of compliant interrupted sutures for minimally invasive and robotic surgery as well as for conventional procedures. The purpose of this study was to determine the effect of nitinol U-Clips used for coronary anastomosis in the development of endothelial dysfunction, compared with conventional running sutures. METHODS: In a porcine model, both internal thoracic arteries were harvested, and the heart was removed. In a Krebs solution, 2 anastomoses were realized ex vivo between internal thoracic arteries and the left anterior descending artery. One was carried out with 12 Coalescent microclips, and the other used conventional running 7-0 polypropylene suture material (Prolene). Coronary rings on the anastomotic sites were then placed in organ chambers filled with oxygenated Krebs solution. Vascular reactivity studies were performed in standard organ chamber experiments. After the contraction of the coronary arteries in response to prostaglandin F2alpha, the endothelium-dependent relaxation response to bradykinin was studied. The other coronary arteries served as controls. RESULTS: There was no statistically significant difference among the groups (P >.05) in the amplitude of the contraction response to KCl and prostaglandin F2alpha. There were no statistically significant differences in endothelium-dependent relaxation response to bradykinin between the nitinol microclip group and controls, between the suture group and controls, and between the nitinol microclip and suture groups. CONCLUSIONS: Coalescent nitinol U-Clips used as anastomotic devices do not induce an endothelial dysfunction and allow a compliant anastomosis under satisfactory conditions.

Alloys↗

Influence of intracoronary shunt size on coronary endothelial function during off-pump coronary artery bypass.

OBJECTIVE: The insertion of intracoronary shunts during off-pump coronary artery bypass surgery may induce severe endothelial dysfunction in the target arteries. The purpose of this study was to determine the role of the ratio of the shunt diameter to the target artery diameter in the development of endothelial dysfunction and to develop guidelines for selecting the most appropriate shunt size. METHODS: Nine swine (25 +/- 4 kg) were used for this study. Three ClearView shunts 3 mm, 2 mm, and 1.25 mm in diameter were inserted proximally to distally via 3 arteriotomies into the right coronary artery to obtain oversizing with the 3-mm shunt, undersizing with the 1.25-mm shunt, and a satisfying congruence with the 2-mm shunt. The shunts were left in place for 15 minutes, and the levels of bleeding were quantified. Coronary rings upstream and downstream from the arteriotomies were then harvested and placed in organ chambers to study endothelium-dependent relaxations to serotonin and bradykinin. Noninstrumented coronary arteries served as controls. RESULTS: A decrease of endothelium-dependent relaxation occurred with the 3-mm shunts (P <.005), which were associated with an adequate hemostasis. A decrease of endotheliumdependent relaxation occurred with the 2-mm shunts (P <.05), which were associated with intermittent bleeding, and no significant decrease of endothelium-dependent relaxation occurred with 1.25-mm shunts (P >.05), which were associated with continuous bleeding. CONCLUSIONS: Intracoronary shunts are associated with different disadvantages, depending on the mismatch to the target coronary artery, and whatever their size, shunts are not the ideal device for safely obtaining a satisfactory hemostasis. These results support our clinical attitude of the selective use of intracoronary shunts.

Anastomosis, Surgical↗

Improving neurologic outcome in off-pump surgery: the "no touch" technique.

BACKGROUND: As patients referred for cardiac surgery include increasingly older individuals, the prevalence of comorbid factors, such as previous cerebrovascular disease, carotid disease, aortic atherosclerosis, and reoperations, is on the rise. Avoiding manipulation of the ascending aorta in this high-risk subgroup may become a necessity to perform safe coronary artery bypass grafting (CABG) surgery. METHODS: We retrospectively reviewed our database of 640 off-pump CABG patients and identified 84 patients in whom we adopted the "no touch" technique (NTT). Revascularization was carried out with single or bilateral internal thoracic arteries (ITA) and by connecting additional coronary grafts (saphenous vein, radial artery) in a T or Y configuration. The right gastroepiploic artery was used as a conduit in 2 patients. The brachiocephalic artery was used as an alternative inflow site in 3 patients (reoperation). RESULTS: Age, sex, risk factors, functional class, and history of congestive heart failure were comparable in the two groups. In the NTT group, the frequencies were higher for severe atherosclerosis of the aorta (13% versus 0%; P =.00), carotid disease (25% versus 16%; P =.02), and history of previous cerebrovascular accidents (17% versus 8%; P =.04). Complete revascularization was achieved in 96% of the patients in the off-pump CABG group, compared with 90% in the NTT group (P =.17). No differences in the prevalence of postoperative low cardiac output syndrome, intra-aortic balloon pump use, perioperative myocardial infarction, or operative mortality at 30 days were observed between the two groups. In the NTT group, weak trends toward a lower incidence of postoperative delirium (8% versus 15%; P =.12), a lower incidence of stroke (0% versus 1%; P =.85), and a shorter intensive care unit stay (P =.07) were observed. Hospital stay was also shorter in the NTT group (P =.04). CONCLUSION: Avoiding aortic manipulations in patients with severe atherosclerosis of the aorta, carotid disease, and a previous history of cerebrovascular accidents is technically feasible and is associated with a low risk of mortality and good shortterm results. Adopting this practice may reduce the incidence of stroke and improve early outcome in this subset of patients.

Cardiac Output, Low↗

Comparison of coronary endothelial dysfunction in the working and nonworking graft in porcine heterotopic heart transplantation.

BACKGROUND: The nonworking heterotopic heart transplantation model has been used extensively for the study of rejection and coronary endothelial function in different species. The effect of left ventricular loading in a working heart transplantation model, which may be associated with different coronary flow patterns and local nitric oxide release, on the development of coronary endothelial dysfunction and intimal hyperplasia, is unknown. METHODS: Porcine retroperitoneal "nonworking" heterotopic transplantations (n=10) and "working" heart (with left ventricular filling) transplantations (n=7) were performed. The left ventricular pressure was 0+/-0 mm Hg and 91+/-11 mm Hg in the nonworking and working groups, respectively. In the latter, the left ventricle to systemic arterial pressure ratio was 0.76+/-0.08. RESULTS: Sixty days after transplantation, epicardial coronary arteries from working and nonworking allografts developed a comparable selective endothelial dysfunction of Gi-protein mediated relaxations. There were no statistically significant differences in the prevalence of intimal hyperplasia, but the severity of intimal hyperplasia was significantly greater in allograft coronary arteries from the working hearts. CONCLUSION: Working heterotopic allografts develop an endothelial dysfunction comparable with that of nonworking allografts, which validates the use of the simpler nonworking graft for the study of endothelial function. The similar prevalence of intimal hyperplasia with the development of more severe coronary lesions in working hearts may be due to differences in local nitric oxide release in these two models.

Animals↗

Reduced mortality and strokes with off-pump coronary artery bypass grafting surgery in octogenarians.

BACKGROUND: Off-pump coronary artery bypass surgery (OPCAB) has been revived and has gained popularity, although the exact subsets of patients who might benefit most from this technique are unknown. The aim of this retrospective study was to compare the results of coronary artery bypass grafting surgery (CABG) in octogenarians using cardiopulmonary bypass (CPB) or OPCAB techniques. METHODS AND RESULTS: Over a 5-year period (1995-1999), 125 patients older than 80 years of age were operated for isolated myocardial revascularization (63 using CPB and 62 with OPCAB). There was no statistically significant difference in preoperative comorbidities between groups or in mean left ventricular ejection fraction (54.5+/-15.3% in the CPB group and 50.9+/-13.5% in the OPCAB group, respectively). The mean number of distal anastomosis per patient was 2.9 in CPB group and 2.6 in OPCAB group (P=ns). The majority of patients in both groups had unstable angina and were operated on an urgent basis. The operative mortality was 15.9% in the CPB group and 4.8% in the OPCAB group (P=0.04). There were 4 postoperative strokes (6.3%) in the CPB group and none (0%) in the OPCAB group (P=0.04). The percentage of patients transfused was 92.1% in the CPB group and 72.6% in the OPCAB group (P<0.01). Postoperative myocardial infarction occurred in 11.3% in the CPB group and 14.5% in the OPCAB group (P=NS). For all the parameters entered in the multivariate analysis with logistic regression model, the type of surgery (CPB or OPCAB) was an independent predictor of operative mortality and stroke (P=0.0375). The odds ratio (OR) indicates that operative mortality and stroke occur 4 times (OR=4.171) more often in CPB patients than in OPCAB patients. Follow-up showed no significant difference between the 2 groups in terms of cardiac events and mortality. CONCLUSIONS: This retrospective study suggests a benefit of OPCAB in terms of operative mortality and stroke for octogenarian patients when compared with CPB in our institution.

Aged↗

Long-term results with triple valve surgery.

BACKGROUND: Whether to use biological or mechanical prostheses and whether to repair or replace the tricuspid valve during primary and reoperative triple valve surgery remains controversial. The objective of the present study was to review our experience with primary and reoperative triple valve surgery using CarboMedics (CM) and Carpentier-Edwards (C-E) heart valves. METHODS: All 73 patients undergoing triple valve surgery since 1982 were prospectively followed at the Montreal Heart Institute valve clinic. Aortic valve replacement was performed with CM prostheses (57 patients) and with C-E prostheses (16 patients). Mitral valve replacement was performed with mechanical prostheses (56 patients) and with biological valves (14 patients). Mitral valve repair was done in 3 patients. Tricuspid valve annuloplasty or commissurotomy or both were performed in 66 patients and the tricuspid valve was replaced in 7 patients. Patient survival, complications, and the type of valve procedures were analyzed. RESULTS: Thirty patients averaging 62+/-10 years of age underwent primary triple valve surgery and 43 patients averaging 60+/-10 years of age underwent reoperative triple valve surgery (p = 0.5). Tricuspid repair consisted of annuloplasty with the Bex linear reducer (n = 47), the C-E ring (n = 13), or the De Vega technique (n = 5). Tricuspid valve replacement was done using the C-E pericardial prostheses. The 30-day mortality was 17% and 12% in patients with primary and reoperative surgery, respectively (p = 0.5) and patient survival averaged 80%+/-7%, 75%+/-8%, and 41%+/-15%, and 70%+/-7%, 57%+/-9%, and 50%+/-10%, respectively 1, 5, and 10 years following surgery (p = 0.5). The freedom rate from thromboembolism and from bleeding complications were 87%+/-6% and 95%+/-3% in primary and reoperative patients, respectively, 5 years following surgery. CONCLUSIONS: Triple valve surgery, either as a primary or a reoperative procedure, results in acceptable long-term survival with both mechanical and biological prostheses.

Aged↗

Cardioplegic arrest with L-arginine improves myocardial protection: results of a prospective randomized clinical trial.

BACKGROUND: Blood cardioplegic arrest remains the method of choice for myocardial protection. L-arginine has been suggested to improve protection through an increase in nitric oxide production. METHODS: A prospective, randomized, double-blinded clinical trial comparing standard blood cardioplegic solution to L-arginine-enriched solution (7.5 g/500 mL) enrolled 200 patients undergoing coronary artery bypass grafting. Clinical data and biochemical markers of ischemia were recorded. Warm blood cardioplegia (33 degrees C) was administered in 74% of patients and cold blood (20 degrees C) was used in 26% of patients. Both groups averaged three grafts per patient. RESULTS: There were two (2%) deaths in both groups. There were four (4%) myocardial infarctions (MI) in the control group and six (6%) infarctions in the L-arginine group (p = 0.5). For the 190 patients without MI, serum levels of troponin T averaged 0.40+/-0.43, 0.38+/-0.42, and 0.39+/-0.50 microg/L in control patients compared with 0.28+/-0.22, 0.24+/-0.18, and 0.27+/-0.20 microg/L in L-arginine patients, respectively, 12, 24 and 48 hours after coronary artery bypass grafting (p = 0.03). The cardiac index averaged 2.7+/-0.8 L x min(-1) x m(-2) in control patients and 2.9+/-0.7 L x min(-1) x m(-2) in arginine patients immediately after surgery (p = 0.09). Intensive care unit and hospital length of stay averaged 3.5+/-5 days and 7.3+/-6 days in control patients compared with 2.5+/-3 days and 6.1+/-4 days in arginine patients (p = 0.09). CONCLUSIONS: L-arginine-supplemented blood cardioplegic solution is associated with reduced release of biochemical markers of myocardial damage, suggesting improved myocardial protection.

Aged↗