Cardioprotective effects of carnitine in extensive aortocoronary bypass grafting: a double-blind, randomized, placebo-controlled clinical trial

The cardioprotective effects of carnitine were tested in patients undergoing multiple aortocoronary bypass grafting. Intermittent aortic cross-clamping at 28 degrees C was used. Mean total cross-clamping time was 30 +/- 11 min. Patients were randomized into three groups: a control group receiving placebo (group 1), a group pretreated with 3 g carnitine intravenously before cardiopulmonary bypass (CPB) (group 2), and a group pretreated with 6 g carnitine intravenously (group 3). The markers of myocardial ischemia included levels of adenosine triphosphate, its catabolites, and creatine phosphate in transmural left ventricular biopsy specimens taken at the beginning and end of CPB, as well as hemodynamic recovery during weaning from CPB and for the next 24 h. The intravenous infusion of carnitine (3 or 6 g) had no hemodynamic effect. At the end of CPB myocardial tissue levels of adenosine triphosphate and creatine phosphate did not differ significantly among the groups (P greater than 0.05). Recovery of cardiac function during weaning from CPB and for the following 24 h was similar in all three groups (P greater than 0.05). It is concluded that pretreatment with carnitine neither facilitates weaning from cardiopulmonary bypass in patients undergoing aortocoronary bypass surgery nor favorably affects hemodynamic function during the next 24 h.     

Effects of cardiopulmonary bypass and cardioplegia on regional and global cardiac actions of halothane in dogs

Cardiopulmonary bypass (CPB) with aortic cross-clamping represents a controlled period of global cardiac ischemia. We hypothesized that CPB (asanguineous prime), with aortic cross-clamping and repeated cardioplegia, alters myocardial function, which would be manifested as an exaggerated myocardial depression caused by halothane after CPB. In nine dogs anesthetized with fentanyl and midazolam, halothane dose-response curves (0.0%-2.0%) were compared before and after CPB. A reduced mean arterial blood pressure (46.4 +/- 3.7 vs 85.8 +/- 5.9 mm Hg), associated with a marked hemodilution (hematocrit, 19% +/- 1% vs 41% +/- 2%), was observed after CPB. Cardiac output and systolic shortening were not significantly different after versus before CPB during fentanyl-midazolam anesthesia. Normalized to fentanyl-midazolam hemodynamics, halothane dose-response curves before and after CPB were identical for all variables except cardiac output, where halothane caused a slight but statistically significantly more pronounced decrease after CPB compared with before CPB. The effect of halothane on left ventricular function, therefore, is relatively unaffected by CPB with cardioplegia.     

Influence of milrinone on internal mammary artery grafts]

To evaluate the effects of milrinone on blood flow in the left internal mammary artery (LIMA) grafts and hemodynamic variables, we conducted a prospective randomized study. Twenty-four patients undergoing coronary artery bypass grafting were randomized to receive milrinone treatment (Milrinone; n = 12) or no milrinone treatment (Control; n = 12). Milrinone was given after induction of anesthesia at a speed of 0.5 microgram/kg/min for 24 hours. After start of cardiopulmonary bypass (CPB), CPB perfusion flow was adjusted to 2.4 l/m2 and LIMA blood flow was measured. Blood samples for determination of plasma cAMP levels were collected and hemodynamic measurements were also assessed perioperatively. LIMA blood flow was significantly greater in Milrinone than that in Control (40 +/- 4 vs 29 +/- 4 ml/min/m2, p < 0.05). Plasma levels of cAMP were significantly (p < 0.05) greater in Milrinone than those in Control at tha start of CPB (18 +/- 1 vs 13 +/- 1 pmol/ml) and at the end of CPB (24 +/- 2 vs 17 +/- 2 pmol/ml). Systemic vascular resistance was significantly (p < 0.05) lower and cardiac index was significantly (p < 0.05) greater in Milrinone than those in Control postoperatively. With its positive inotropic and systemic vasodilator activities, milrinone may have direct vasodilator effect on LIMA.     

Pretreatment with aminophylline reduces release of Troponin I and neutrophil activation in the myocardium of patients undergoing cardioplegic arrest.

OBJECTIVE: Cardioplegic arrest and subsequent reperfusion results in myocardial injury partly related to local inflammation in the heart. It has been proven that aminophylline has numerous anti-inflammatory effects. This study has been designed to evaluate the effects of aminophylline used as a cardioprotective agent for patients undergoing cardiopulmonary bypass (CPB) for valve replacement. METHODS: Thirty patients undergoing elective valve replacement were randomized to receive either aminophylline (n=15), or normal saline (control n=15). Administration of aminophylline (5mg/kg) was injected intravenously after induction of anesthesia. The cardiac Troponin I (cTnI), myocardial myeloperoxidase (MPO) activity, atrial cyclic AMP, and a coronary sinus neutrophil count were measured before and after cardioplegic arrest. RESULTS: There were no differences between the two groups with regard to clinical variables. The cTnI concentration increased significantly after aortic declamping in both groups. However, it was significantly lower, 8h after aortic declamping, in aminophylline group (1.00+/-0.41 vs 2.37+/-1.35 ng/ml p=0.038). The atrial cAMP was significantly higher before aortic cross-clamping in aminophylline group (42.5+/-6.7 pmol/g tissue vs 30.6+/-12.4 pmol/g tissue p=0.04). In addition, we found that the aminophylline group had a significantly lower MPO after reperfusion (1.50+/-0.58 U/g tissue vs 0.86+/-0.24 U/g tissue p=0.003), and a significantly lower neutrophil count 30 min after aortic declamping (0.68+/-0.11x10(3) cell/ml vs 0.32+/-0.16x10(3) cell/ml, p=0.023). CONCLUSIONS: Pretreatment with intravenous aminophylline reduces the subclinical myocardial injury and neutrophil activation in patients undergoing CPB for valve replacement.     

Prevention of TNFalpha-associated myocardial dysfunction resulting from cardiopulmonary bypass and cardioplegic arrest by glucocorticoid treatment.

OBJECTIVE: Cardiac surgery on cardiopulmonary bypass (CPB) results in progressive myocardial dysfunction, despite unimpaired coronary blood flow, and is associated with increased myocardial tumor necrosis factor-alpha (TNFalpha) expression. We investigated whether anti-inflammatory treatment prevents increased TNFalpha expression and myocardial dysfunction after CPB. METHODS AND RESULTS: Baseline systemic hemodynamics, myocardial contractile function, aortic and coronary blood flow were measured in anesthetized pigs. Then, placebo (PLA; saline; n=7) or methylprednisolone (MP; 30 mg/kg; n=6) was infused intravenously and CPB was instituted. Global ischemia was induced for 10 min by aortic cross-clamping, followed by 1 h of cardioplegic cardiac arrest. After declamping and reperfusion, CPB was terminated after a total of 3 h. Measurements were repeated at 15 min, 4 h, and 8 h following termination of CPB. Systemic TNFalpha-plasma concentrations and left ventricular TNFalpha expression were analyzed. With unchanged coronary blood flow in both groups, a progressive loss of myocardial contractile function to 38+/-2% of baseline (p<0.01) and cardiac index to 48+/-6% of baseline (p<0.01) at 8 h after CPB in PLA was attenuated in MP (myocardial function: 72+/-3%, p<0.01 vs PLA; cardiac index: 78+/-6%, p<0.05 vs PLA). Systemic TNFalpha was increased at 8 h in PLA compared to MP (243+/-34 vs 90+/-34 pg/ml, p<0.05). Myocardial TNFalpha was increased at 8 h after CPB compared to baseline and MP (p<0.05). Myocardial TNFalpha immunostaining was more pronounced in PLA than in MP (p<0.05), with TNFalpha-mRNA localization predominantly to cardiomyocytes. CONCLUSIONS: Methylprednisolone attenuates both systemic and myocardial TNFalpha increases and progressive myocardial dysfunction induced by cardiac surgery, suggesting a key role for TNFalpha.     

Milrinone, not epinephrine, improves left ventricular compliance after cardiopulmonary bypass

OBJECTIVE: To compare the effects of milrinone versus epinephrine administered after cardiopulmonary bypass (CPB) on left ventricular compliance. DESIGN: Prospective and randomized. SETTING: University-affiliated hospital. PARTICIPANTS: Twenty consenting adult patients. INTERVENTIONS: Patients undergoing aortocoronary bypass surgery were randomized to receive 50 microg/kg of milrinone (group M; n = 10) or 0.03 microg/kg/min of epinephrine (group E; n = 10) shortly after separation from CPB. Left ventricular compliance was assessed by observing changes in left ventricular end-diastolic area (LVEDA) in the short-axis view with transesophageal echocardiography, while maintaining a constant left atrial pressure. Measurements were performed (1) before CPB, (2) after separation from CPB, and (3) after either milrinone or epinephrine. MEASUREMENTS AND MAIN RESULTS: Baseline LVEDA decreased by 20% after CPB in the milrinone group (from 16.6 +/- 3.1 cm2 to 14.3 +/- 2.4 cm2; p < 0.05) and by 22% in the epinephrine group (from 19.4 +/- 4.1 cm2 to 17.2 +/- 3.8 cm2; p < 0.05). LVEDA increased by 15% after milrinone (from 14.3 +/- 2.4 cm2 to 15.6 +/- 2.8 cm2; p < 0.05) but remained unchanged after epinephrine (from 17.2 +/- 3.8 cm2 to 17.1 +/- 4.2 cm2; p = ns). CONCLUSIONS: Left ventricular compliance was decreased after CPB. The administration of milrinone, but not epinephrine, was associated with a partial return to prebypass values. The exact mechanism of action remains to be determined.     

Adenosine for cardioplegic induction: a comparison with St Thomas solution

OBJECTIVE: To determine if quicker cardiac standstill obtained by adding adenosine to potassium crystalloid cardioplegia translated into better myocardial preservation and cardiac function in the early postoperative period compared with the same cardioplegia without adenosine. DESIGN: A prospective study. SETTING: Cardiac center of a teaching institute. PARTICIPANTS: Sixty consecutive patients with left main vessel or triple-vessel disease undergoing coronary artery bypass surgery under moderate hypothermia. INTERVENTIONS: The study comprised two groups of patients. Group N (n = 15) was the control group, given St Thomas cardioplegic solution after aortic cross-clamping, without adenosine; whereas group A (n = 45) received 250 microg/kg of adenosine into the aortic root after aortic cross-clamping, followed by the same St Thomas cardioplegia as in group N. The two groups were otherwise similar in all aspects of perfusion management. MEASUREMENTS AND MAIN RESULTS: Time taken to achieve cardiac standstill after aortic cross-clamping was significantly greater, 18.7+/-3.1 seconds, in the control group compared with the adenosine group, 3.4+/-0.9 seconds (p<0.001). The quicker arrest of the adenosine group led to better postoperative function, in the form of higher cardiac index (p<0.01), lower filling pressures (pulmonary artery wedge pressure) (p<0.05), and lower mean pulmonary artery pressure (p<0.05) at 6 hours. In the adenosine group, only 3 of 45 (6.6%) patients had elevated creatine phosphokinase (CPK) (MB) values greater than 50 U/L over preoperative CPK values compared with 3 of 15 (20%) in the control group (p<0.01). CONCLUSIONS: Injection of 250 microg/kg of adenosine into the aortic root before administration of cold crystalloid St Thomas cardioplegia solution after cross-clamping, in patients with severe coronary artery disease, produces significantly faster cardiac standstill, better myocardial preservation, and better cardiac function in the early postoperative period.     

Inhibitory effect of milrinone on cytokine production after cardiopulmonary bypass

BACKGROUND: It has been suggested that cyclic adenosine monophosphate-elevating agents suppress cytokine production. To evaluate the effects of milrinone, a phosphodiesterase III inhibitor, on cytokine production after cardiopulmonary bypass, we conducted a prospective randomized study. METHODS: Twenty-four patients undergoing coronary artery bypass grafting were randomized to receive either milrinone treatment (milrinone, n = 12) or no milrinone treatment (control, n = 12). Administration of milrinone (0.5 microg x kg(-1) x min(-1)) was started after induction of anesthesia and was continued for 24 hours. Blood samples for determination of plasma cyclic adenosine monophosphate, tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-8 levels were collected perioperatively. RESULTS: No significant differences were observed in tumor necrosis factor-alpha and interleukin-8 levels between the groups. Interleukin-1beta and interleukin-6 levels after cardiopulmonary bypass were significantly (p < 0.05) lower in the milrinone group than in the control group. Plasma levels of cyclic adenosine monophosphate increased significantly (p < 0.05) after the administration of milrinone and the levels correlated inversely (r = -0.55, p < 0.01) with interleukin-6 levels. CONCLUSIONS: The results indicate that milrinone suppresses cytokine production by elevating cyclic adenosine monophosphate levels in patients undergoing cardiopulmonary bypass. With its positive inotropic and vasodilator activities, milrinone may have antiinflammatory effects.     

Nifedipine as an adjunct to St. Thomas' Hospital cardioplegia. A double-blind, placebo-controlled, randomized clinical trial

The cardioprotective effect of the addition of the slow calcium-channel blocker nifedipine to cardioplegic solution was tested in two double-blind placebo controlled randomized studies. The first study included 24 patients undergoing aortic-coronary bypass grafting, and the second included 24 patients undergoing aortic valve replacement. Nifedipine at a dose of 200 micrograms/L or placebo was added to St. Thomas' Hospital cardioplegic solution. The following markers of ischemia were used: adenosine triphosphate and its catabolites, creatine phosphate and inorganic phosphate, determined in transmural left ventricular biopsy specimens taken before, at the end of, and after aortic cross-clamping; hemodynamic recovery 15 minutes after cessation of cardiopulmonary bypass; clinical outcome in terms of the incidence of arrhythmias, low cardiac output, positive inotropic support immediately after operation, and follow-up at 15 months. The main difference between the two studies was that myocardial temperature during cross-clamping remained constant at 14 degrees C in coronary bypass grafting but increased to 25 degrees C in valve operations despite the application of the same amounts of cardioplegic solutions. This lower temperature resulted in better preservation of high-energy phosphates in coronary bypass operations as compared to the placebo group having valve replacement operations. According to analysis of variance, a drug effect could be demonstrated only in the aortic valve replacement study: Accumulation of breakdown products of the adenine nucleotide pool was less in the nifedipine group than in the placebo group (p less than 0.05). Adenosine triphosphate decreased only to 84% in the nifedipine group and to 72% in the placebo group. Despite this adenosine triphosphate-sparing effect, weaning from cardiopulmonary bypass was more difficult in the nifedipine group. Left ventricular stroke work index 15 minutes after bypass was decreased to 72% of the prebypass value in the nifedipine group (t test, p less than 0.01) and only to 86% in the placebo group (p = NS). In contrast, after the patients were admitted to the intensive care unit, the incidence of low cardiac output tended to be lower in the nifedipine group than in the placebo group: 33% versus 58% (p = NS). In conclusion, ischemia-induced degradation of nucleotides as it occurs when myocardial cooling is inadequate can be prevented by the addition of nifedipine to the St. Thomas' Hospital cardioplegic solution. This effect, however, is not associated with an improved clinical outcome.     

Milrinone enhances systolic, but not diastolic function during coronary artery bypass grafting surgery

PURPOSE: To evaluate the effect of milrinone on diastolic function during coronary artery bypass grafting surgery (CABG). METHODS: Fifty patients undergoing CABG were randomized to receive a bolus and infusion of milrinone or placebo before cardiopulmonary bypass (CPB) until skin closure. Hemodynamic and transesophageal echocardiographic measurements of systolic and diastolic function were obtained. Pulsed wave Doppler measurements of the early (E wave) and atrial components (A wave) of the transmitral (TMF) and transtricuspid (TTF) flows, and systolic (S wave), diastolic (D wave) and atrial components (Ar) of the pulmonary (PVF) and hepatic venous blood flow (HVF) velocities were performed. Early and atrial components of the mitral (Em and Am waves) and tricuspid annulus velocities (Et and At waves) were assessed by tissue Doppler imaging (TDI). Assessment of diastolic dysfunction was graded from normal to severe using a scale score. RESULTS: Cardiac index and heart rate were higher in the milrinone group compared to placebo after the administration of study drug (2.8 +/- 0.6 vs 2.1 +/- 0.5 L.min(-1)m(-2)) (P < 0.0001) and (67 +/- 8 vs 60 +/- 12 beats.min(-1)) (P < 0.05) respectively. There were no changes in left and right ventricular diastolic dysfunction scores between study groups. Higher PVF S wave, HVF S wave, TTF A wave and At measured by TDI in the milrinone group compared with placebo suggested an improvement in ventricular systolic and atrial contraction. CONCLUSION: Distinct from its effects on systolic function, milrinone administered before CPB is not with associated improved biventricular diastolic function in patients undergoing CABG.     

Cardiomyocyte apoptosis and ischemic preconditioning in open heart operations

BACKGROUND: The aim of the present study was to ascertain the percentage of left apical myocardial apoptosis in three-vessel coronary artery bypass grafting patients quantitatively and the impact of ischemic preconditioning. METHODS: Twenty-one patients with three-vessel disease who had elective coronary artery bypass grafting were randomized in a ratio of 2:1 to ischemic preconditioning (n = 14) or a control group (n = 7). The ischemic preconditioning protocol was established by two cycles of ascending aorta occlusion for 2 minutes followed by 3 minutes of reperfusion. Myocardial samples from the apex of the left ventricle were taken using a Tru-Cut needle before aortic cross-clamping and immediately after declamping. The percentage of apoptosis was analyzed by TUNEL methods. Data on hemodynamics and biochemical markers were collected. RESULTS: Low levels of myocardial apoptosis were found before the operation (0.01% +/- 0.00%). During the early reperfusion period, the percentage of myocardial apoptotic cells significantly increased (0.15% +/- 0.05%, p = 0.008). Ischemic preconditioning significantly improved cardiac index and right ventricular ejection fraction recovery after the operation (p = 0.036 and 0.001 respectively, repeated measure) but had no effect on myocardial apoptosis before and after the operation (0.01 +/- 0.00 versus 0.01 +/- 0.00, p = 0.658 and 0.12% +/- 0.04% versus 0.23% +/- 0.14%, p = 0.302). CONCLUSIONS: Cardioplegic myocardial ischemia during open heart operation was associated with induction of cardiomyocyte apoptosis in humans. Attenuation of postoperative cardiac dysfunction by ischemic preconditioning appeared to be independent of apoptosis.     

Does adenosine pharmacologically precondition human myocardium during coronary bypass surgery?

AIM: Adenosine (Ado) triggers ischemic preconditioning. We investigated whether Ado provides additional myocardial protection in patients during intermittent aortic cross-clamping (IAC) bypass surgery. METHODS: The placebo group was made of 15 male of 66+/-8 years while the Ado group was made of 19 male of 65+/-10 years. The patients of the Ado group had a 3-vessel heart disease and were treated with elective surgery. With the aortic cross-clamping, Ado or vehicle were infused over 10 min at systemic pressure together with sufficient blood via the aortic root. Blood samples before anaesthesia and onset of ECC, 1 hour after end of surgery, and on day 1 and 2 post-surgery to assess CK-MB and troponin I were performed. Hemodynamic measures (heart rate, left ventricular pressure, max/min pressure rise, central venous pressure) before installation and 15 min after completion of the coronary artery bypass. Different ECGs for electrophysiological analyses were performed. RESULTS: Hemodynamic and laboratory measures revealed no significant advantages of either protocol. Mortality rate was zero in both groups. CONCLUSIONS: The comparable outcome is likely due to cardioprotection provided by both IAC bypass surgery and hypothermia, which might obscure beneficial effects of pharmacological preconditioning in patients with good left ventricular function (ejection fraction >50%). As the benefit might have been marginal, it may well become apparent in a larger study on patients with more severe left ventricular dysfunction.     

Myocardial adenosine triphosphate content as a measure of metabolic and functional myocardial protection in children undergoing cardiac operation

In an effort to quantitate the metabolic and functional response to global myocardial ischemia as a prelude to specific interventions to improve myocardial protection in children, the following data were collected. Twenty children (age, 1.16 +/- 0.3 years) underwent repair of congenital intracardiac malformations using aortic cross-clamping and cold potassium cardioplegia (ischemic time, 56.1 +/- 4.5 minutes). Metabolic protection was assessed by measuring the myocardial adenosine triphosphate (ATP) content by microbioluminescence. Before and after ischemia 10-mg myocardial samples were obtained from the left ventricular apex using a Tru-cut biopsy needle. In 15 patients, postoperative ventricular function was measured by radionuclide ventriculography at 72 to 96 hours following operation. Five of 6 patients with a postischemic ATP level less than 40% of control (26.3 +/- 2.8) had a left ventricular ejection fraction (EF) lower than 55% (50.3 +/- 2.3). Seven of 9 patients with an ATP level greater than 40% of the preischemic level (98.0 +/- 14.4) had a normal EF (61.8 +/- 2.9; p less than 0.04). Two other patients with postischemic ATP levels lower than 40% of control died of low cardiac output and had no postoperative ventricular function studies. Thus, of 7 patients with postischemic ATP levels lower than 40% of preischemic levels, 2 died and 5 had depressed left ventricular function. These data support the concept that low postischemic ATP levels correlate with death or poor postoperative ventricular function, and indicate that this variable will be useful to assess future improvements in myocardial protection during pediatric cardiac operations.     

Cardioprotective effects of lidoflazine in extensive aorta-coronary bypass grafting

The cardioprotective effects of lidoflazine, a calcium entry blocker, were tested in patients undergoing multiple aorta-coronary bypass grafting (at least four grafts). Intermittent aortic cross-clamping at 25 degrees to 28 degrees C was used. Mean cross-clamp time was 11 minutes for one distal anastomosis. Patients were randomized into three groups: a control group (I), a group (II) pretreated with 0.5 mg . kg-1 lidoflazine intravenously before cardiopulmonary bypass (CPB), and a group (III) pretreated with 1 mg . kg-1 lidoflazine intravenously. The following markers of ischemia are used: (1) adenosine triphosphate (ATP), creatine phosphate (CP) and glycogen determined in transmural left ventricular biopsy specimens taken at the beginning and end of CPB; (2) ultrastructure in a similar pair of specimens; and (3) hemodynamic recovery 15 minutes after cessation of CPB. At the end of the intervention, ATP decreased to 73% in Group I but remained unchanged in Groups II (98%) and III (88%). CP decreased to 82% in Group I and remained unaltered in Groups II (100%) and III (110%). Glycogen decreased in Group I (to 44%) and in Group II (78%) but remained unchanged in Group II (138%). Ultrastructural study showed better preservation of the glycocalyx and sarcolemma in Group III than in Group I. Left ventricular stroke work index remained unaltered after CPB in Group III but decreased in Groups I and II to about 60% of its initial value. Thus lidoflazine pretreatment protects the myocardium in a dose-dependent manner against deterioration of myocardial function and structure.     

Effects of simulated clinical cardiopulmonary bypass and cardioplegia on mass of the canine left ventricle

Myocardial edema is a well-documented response to ischemia and reperfusion in dogs and can be detected as an increase in left ventricular (LV) mass measured echocardiographically. Investigation in human beings has failed to demonstrate similar increases in LV mass after routine cardiac operations. However, direct comparison of these observations is not possible, because dogs have not been studied under conditions of cardiopulmonary bypass (CPB) and global ischemia that rigorously reproduce those of a clinical operation. Accordingly, clinical CPB and global ischemia were simulated in 8 adult dogs. Multisection two-dimensional echocardiograms and a computerized light pen were used to calculate LV volume and mass. The data were analyzed during four periods: before CPB; CPB before cross-clamping; CPB after cross-clamping, and after CPB. Echocardiographic LV mass increased significantly from 89.5 +/- 7.4 gm (before CPB) to 94.6 +/- 8.5 gm (CPB before cross-clamping) (p less than 0.05) and from 94.6 +/- 8.5 gm to 100.4 +/- 8.1 gm (CPB after cross-clamping) (p less than 0.05). Overall, mass increased 13.9% (p less than 0.05). Mean wall thickness increased 0.08 cm (p less than 0.05) overall and correlated with the increase in mass (r = 0.79). Postmortem mass correlated well with late echocardiographic mass (r = 0.95). Interobserver correlation of 98 separate mass determinations was high (r = 0.84) with a coefficient of variation of 10.5%. We conclude that canine LV mass increases significantly with CPB and global ischemia maintained within clinical standards and that human beings and dogs may differ in extent of edema during CPB.     

Transapical aortic cannulation via left lateral thoracotomy for descending thoracic and thoracoabdominal aortic surgery

Two patients underwent surgery for a chronic type B dissection using a total cardiopulmonary bypass (CPB) with transapical arterial cannulation. At surgery, a total CPB was established by cannulating the left femoral artery and the ascending aorta via the ventricular apex. The patients were cooled to 30°C. The proximal anastomosis was done after cross-clamping the aortic arch between the left carotid artery and the left subclavian artery in both cases. In the first case, the entire descending thoracic aorta was replaced, and two pairs of intercostal arteries were reconstructed. The other patient underwent replacement of the proximal descending thoracic aorta. Neither patient experienced any complications. Transapical aortic cannulation is a useful option during descending thoracic and thoracoabdominal aortic surgery. It can provide more stable circulation during the cross-clamping, more gentle manipulation of the aorta by nonpulsatile flow, and more liberty in temperature control.     

Ischemic preconditioning in myocardial revascularization with intermittent aortic cross-clamping

BACKGROUND: This study tests the hypothesis that initial brief periods of ischemia can increase the protection obtained by intermittent aortic cross-clamping. METHODS: In the control group (n = 18), the procedure was performed under intermittent aortic cross-clamping at 32 degrees C. Patients in the preconditioned gorup (n = 17) received a stimulus of two 3-minute periods of cross-clamping followed by 2 minutes of reperfusion prior to standard operation. CKMB, troponin 1, adenosine, and lactate were obtained from the great cardiac vein at the onset of cardiopulmonary bypass (CPB), at the end of the first anastomosis, and at the end of CPB. RESULTS: CKMB and troponin I were slightly higher at the end of CPB in the control group, while there was no difference between adenosine and lactate levels. [table: see text]. CONCLUSION: There was no difference between groups in terms of myocardial protection.     

Bronchial artery perfusion during cardiopulmonary bypass does not prevent ischemia of the lung in piglets: assessment of bronchial artery blood flow with fluorescent microspheres.

OBJECTIVE: Blood supply of the lungs during total cardiopulmonary bypass (CPB) is limited to flow through the bronchial arteries. This study was undertaken to assess the bronchial artery blood flow during CPB with fluorescent microspheres in a piglet model. METHODS: We subjected ten piglets (mean weight 5.0+/-0.5 kg) to 120 min of normothermic, total CPB without aortic cross-clamping, followed by 60 min of post-bypass perfusion. Fluorescent microspheres were injected into the left atrium or the aortic cannula or distal to the cannula to assess bronchial artery blood flow before, during and after CPB. The reference samples were taken from the descending aorta. We compared the different sites of injection. Tissue samples of the lungs were taken before and 60 min after CPB. RESULTS: Before CPB, total bronchial artery perfusion was 43.6+/-14.1 ml/min (4.8+/-1.3% of cardiac output) as by injection distal to the aortic cannula. These values were not different when microspheres were injected into the left atrium or the aortic cannula. There was no difference in scatter or in the amount of microspheres in the reference samples among the three injections sites. During CPB, bronchial artery perfusion was significantly decreased (4.4+/-2.4 ml/min vs. 40.0+/-5.0 ml/min before CPB) and returned to baseline values 60 min after CPB. Light microscopy of the tissue samples revealed alveolar septal thickening and a decrease in alveolar surface area after 60 min of reperfusion which was associated with a decreased capacity to oxygenate blood. CONCLUSIONS: (1) Bronchial artery blood flow can quantitatively be assessed during CPB when microspheres are injected into the ascending aorta and the reference samples are taken from the descending aorta. (2) Despite adequate perfusion pressure bronchial artery blood flow is decreased substantially during CPB. (3) The decrease in blood flow and the ultrastructural changes present at the end of CPB suggest the presence of low-flow ischemia of the lung during total CPB.     

Myocardial apoptosis prevention by radical scavenging in patients undergoing cardiac surgery

BACKGROUND: Reactive oxygen-derived species, including those generated during myocardial ischemia and reperfusion induced by cardioplegia, have been suggested to be involved in myocardial apoptosis induction. The purpose of our study was to investigate (1) whether cardioplegic arrest initiates apoptosis in the hearts of cardiac surgery patients and (2) whether reactive oxygen-derived species scavenging with N-acetylcysteine attenuates myocardial apoptosis initiation. METHODS: In transmural left ventricular biopsy samples collected before and at the end of cardiopulmonary bypass, we densitometrically determined cardiac myocyte staining intensity for active caspases-3 and -7, the apoptosis signal pathway central effector enzymes. The left ventricular biopsy samples had been obtained from 36 coronary artery bypass graft patients randomized in a double-blind fashion to receive either N-acetylcysteine (100 mg/kg into cardiopulmonary bypass prime followed by infusion at 20 mg.kg(-1).h(-1); n = 18) or placebo (n = 18). RESULTS: The change in left ventricular cardiac myocyte staining (end of cardiopulmonary bypass minus before cardiopulmonary bypass) differed significantly between groups for both measures: caspase-3, -3.1 +/- 4.5 gray units (mean +/- SD; N-acetylcysteine group) versus 7.1 +/- 8.1 gray units (placebo); 95% confidence interval, 6.4 to 14.4; P <.0001; caspase-7, -5.1 +/- 6.1 gray units (N-acetylcysteine) versus 5.1 +/- 5.7 gray units (placebo); 95% confidence interval, 6.3 to 15.0; P <.0001. Clinical outcome did not differ between N-acetylcysteine and placebo. CONCLUSIONS: Our data show that cardioplegic arrest initiates the apoptosis signal cascade in human left ventricular cardiac myocytes. This apoptosis induction can effectively be prevented by N-acetylcysteine.     

Acadesine (AICA-riboside) improves postischemic cardiac recovery.

To test if acadesine (5-aminoimidazole-4-carboxamide riboside), a purine precursor, has cardioprotective effects, 16 dogs were placed on total cardiopulmonary bypass and subjected to global myocardial ischemia. Hemodynamic recovery was compared between a control (n = 8) group receiving standard cardioplegia and an acadesine (n = 8) group pretreated with intravenous acadesine (2.5 mg.kg-1.min-1 for 5 minutes, then 0.5 mg.kg-1.min-1) before ischemia, during ischemia, and until 10 minutes after removal of the aortic cross-clamp. Additionally, in the acadesine group the cardioplegia also contained 20 mumol/L acadesine. While the dogs were on cardiopulmonary bypass, global warm myocardial ischemia was induced by aortic cross-clamping for 5 minutes under normothermic conditions to simulate an angioplasty accident. Five minutes after aortic cross-clamping, hypothermic cardioplegia (30 mL/kg) was administered. The left anterior descending coronary artery was occluded before the first infusion of cardioplegia to simulate poor cardioplegia delivery that can occur during an emergency coronary artery bypass procedure after an angioplasty accident. The left anterior descending artery occlusion was released, and additional cardioplegia (15 mL/kg) infusions were made every 30 minutes thereafter during 120 minutes of cardioplegic ischemia. Thirty minutes after reperfusion, all animals in both groups were weaned from bypass and recovery data were obtained to compare with baseline preischemic values. There were no significant differences in heart rate, left atrial pressure, or systemic vascular resistance between groups after weaning from bypass. Peak developed pressure recovered to 79% +/- 19% (mean +/- standard deviation) of baseline in the acadesine group compared with 56% +/- 22% in the control group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)