The role of leukocyte depletion in reducing injury to myocardium and lung during cardiopulmonary bypass

Activated leukocytes and oxygen free radicals have been implicated in the pathogenesis of heart and lung injury after reperfusion and during cardiopulmonary bypass. This study was designed to determine whether leukocyte depletion prevents injury to the heart and lung during cardiopulmonary bypass. Twenty-eight open heart surgeries were performed in this study. In Group F, leukocyte depletion was performed with an LG-6 arterial line filter after aortic declamp (n = 14). Leukocyte depletion was not performed during cardiopulmonary bypass in Group C (n = 14). Thereafter, cardiac and lung function were assessed in the 24 hr after reperfusion. The total catecholamine dose used for 24 hr after reperfusion (r) was 61.9 +/- 13.4 in Group C and 43.9 +/- 19.2 in Group F (p < 0.05). CK-MB at 3 and 6 hr after reperfusion was 65.9 +/- 13.5 and 64.8 +/- 15.8 in Group C and 45 +/- 11.8 and 38 +/- 10.8 in Group F, respectively (p < 0.05). The pulmonary index after reperfusion at 3 and 6 hr was 1.7 +/- 0.5 and 1.3 +/- 0.4 in Group C and 0.7 +/- 0.3 and 0.6 +/- 0.4 in Group F, respectively (p < 0.05). There was significantly better preserved lung function in Group F. In conclusion, leukocyte depletion was significantly effective in preserving heart and lung function during cardiopulmonary bypass.     

Strategies of myocardial protection for operation in chronic model of cyanotic heart disease

BACKGROUND: Cyanotic congenital hearts have an increased susceptibility to ischemia and subsequent reperfusion. The role of platelet-activating factor antagonism and mechanical neutrophil depletion with leukocyte-depleting filters for control of ischemia-reperfusion injury was assessed in corrective surgical procedures for cyanotic heart disease. METHODS: A swine model of cyanotic heart disease was evaluated with three study groups: a control group; a group given a platelet-activating factor antagonist (PAFA group); and a group with leukocyte-depleting filtration (LDF group). The cyanotic model was created with a left atrial appendage-pulmonary artery fistula with peripheral banding through a left anterior thoracotomy in weanling swine. The experimental procedure was performed 5 to 7 weeks later when body weight was greater than 20 kg and oxygen saturation was 85% or less. The corrective procedure was performed through a median sternotomy on cardiopulmonary bypass with repair of the shunt. Myocardial protection was accomplished with hypothermic blood-crystalloid (4:1) cardioplegia; the period of ischemic arrest was 90 minutes. In the PAFA group, the platelet-activating factor antagonist CV-6209 was delivered intravenously 15 to 20 minutes before aortic cross-clamping. In the LDF group, Pall leukocyte-depleting filters were used in the CPB arterial line. Hemodynamic data were taken before operation and 10 and 30 minutes after CPB with impedance ventriculography. RESULTS: There were four deaths in the control group within 30 minutes after CPB; all animals in the treated groups survived longer than 60 minutes (p < 0.05). The ventricular assessment of end-systolic elastance revealed superior performance in the LDF group 30 minutes after CPB compared with the control group (p < 0.05) (controls, 4.0+/-9; PAFA group, 6.5+/-3.7; and LDF group, 12.0+/-4.6). CONCLUSIONS: Both leukocyte-depleting filters and platelet-activating factor antagonism provided myocardial protection, and the filters afforded superior postoperative myocardial contractility.     

Modified ultrafiltration improves left ventricular systolic function in infants after cardiopulmonary bypass

OBJECTIVE: Our objective was to test the hypothesis that use of modified ultrafiltration after cardiopulmonary bypass improves intrinsic left ventricular systolic function in children. METHODS: Twenty-one infants undergoing cardiopulmonary bypass were instrumented with ultrasonic dimension transducers, to measure the anteroposterior minor axis diameter, and a left ventricular micromanometer. Patients were randomized to modified ultrafiltration (n = 11, age 226 +/- 355 days, weight 6.7 +/- 3.1 kg) or control (n = 10, age 300 +/- 240 days, weight 7.0 +/- 2.5 kg) (all differences p > 0.05 between groups). Left ventricular systolic function was assessed by means of the slope of the preload-recruitable stroke work index. Myocardial cross-sectional area was measured by echocardiography. Data were acquired immediately after separation from bypass, at steady state, and during transient vena caval occlusion. Data acquisition was repeated after 13 +/- 5 minutes of modified ultrafiltration or after 12 +/- 5 minutes without modified ultrafiltration in the control group. Inotropic drug support was the same at both study points. RESULTS: In the modified ultrafiltration group, the filtrate volume was 363 +/- 262 ml. The hematocrit value increased from 26.0% +/- 2.7% to 36.7% +/- 9.5% (p = 0.018), myocardial cross-sectional area decreased from 3.72 +/- 0.35 cm2 to 3.63 +/- 0.36 cm2 (p = 0.04), end-diastolic length increased from 25.6 +/- 9.0 mm to 28.8 +/- 9.9 mm (p = 0.01), and end-diastolic pressure fell from 5.6 +/- 0.8 mm Hg to 4.2 +/- 0.8 mm Hg (p = 0.005), suggesting an improved diastolic compliance. In the control group, the hematocrit value, myocardial cross-sectional area, end-diastolic length, and pressure did not change (all p > 0.05). Mean ejection pressure increased in the ultrafiltration group (p = 0.001) but did not change in the control group (p = 0.22). The slope of the preload-recruitable stroke work index increased after ultrafiltration from 52.3 +/- 52.0 to 74.2 +/- 66.0 (10[3] erg/cm3) (p = 0.02) but did not change in the control group (p = 0.07). One patient from each group died in the postoperative period. Patients in the ultrafiltration group received less inotropic drug support in the first 24 hours after the operation (156.62 +/- 92.31 microg/kg in 24 hours) than patients in the control group (865.33 +/- 1772.26 microg/kg in 24 hours, p = 0.03). CONCLUSIONS: Use of modified ultrafiltration after cardiopulmonary bypass improves intrinsic left ventricular systolic function, improves diastolic compliance, increases blood pressure, and decreases inotropic drug use in the early postoperative period.     

Thromboxane A2 receptor-specific antagonism in hypothermic cardiopulmonary bypass

Using a thromboxane A2 receptor-specific antagonist, SQ 30,741, this study was undertaken to define the role of thromboxane A2 in postischemic myocardial reperfusion injury and in the heparin-protamine reaction. Eighteen heparinized (300 units/kg) sheep were placed on cardiopulmonary bypass (CPB) after complete instrumentation, cooled to 28 degrees C, and had their aortas crossclamped for 1 hour. They were then rewarmed to 36 degrees C and weaned from CPB without inotropic support. Control sheep (n = 6) received a saline infusion throughout the procedure. Bolus animals (n = 6) received 5 mg/kg of SQ 30,741 at 5 minutes after discontinuation of CPB and before protamine sulfate administration. Infusion animals (n = 6) received an SQ 30,741 bolus of 5 mg/kg followed by a continuous infusion of 5 mg.kg-1 hr-1 of SQ 30,741 initiated before CPB. All animals received 5 mg/kg of protamine sulfate over a 15-second period 15 minutes after being weaned from CPB. Control animals exhibited significantly decreased global myocardial function after the 1-hour ischemic interval. Further significant functional decline and increase in pulmonary pressure occurred after protamine sulfate administration. Bolus animals experienced a similar postischemic injury, but had no further decrease in function following protamine infusion. Infusion animals had significantly improved global myocardial function after bypass compared with both other groups and were also protected from the deleterious effects of protamine sulfate administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bradykinin and functional vasodilatation in the salivary gland

The relationships between left ventricular function and myocardial O2 availability and metabolism were studied in cats with hemorrhagic shock (AP=30 mm. Hg) with the use of a right heart bypass preparation. Aortic flow and heart rate were held constant. Oxygen-carrying capacity was reduced by diluting donor blood with an equal volume of 5 per cent glucose in saline. Oxygen availability was estimated as the product of arterial O2 content and coronary blood flow. All shock animals showed a progressive metabolic acidemia with time, and a fall in coronary flow concomitantly. Four control animals (AP=75 mm. Hg) as well as two shock animals with high arterial oxygen content and hematocrit showed no significant changes in myocardial O2 metabolism or performance over a period of 90 minutes. Nine shock animals with reduced hematocrit demonstrated a progressive reduction in ventricular function, myocardial O2 metabolism, and O2 availability. As O2 availability fell below 10 ml. per minute per 100 Gm. of heart weight, cardiac failure uniformly appeared and was accompanied by a reduction in O2 extraction and consumption. The correlation between left ventricular dP/dt max and O2 availability was highly significant (r = 0.75, p less than 0.01) in shock animals but not in controls. Thus a close relationship between myocardial O2 metabolism and function during the course of hemorrhagic shock has been demonstrated. Reduced myocardial O2 availability is directly linked with the appearance of cardiac failure.     

Deleterious effects of cardiopulmonary bypass on early graft function after single lung allotransplantation: evaluation of a heparin-coated bypass circuit

Clinical lung transplantation may necessitate the use of cardiopulmonary bypass during the procedure, resulting in increased morbidity with more severe early graft dysfunction and increased blood loss. A heparin surface-coated cardiopulmonary bypass circuit is now available with improved biocompatibility and reduced systemic heparin requirements and may offer advantages compared with standard uncoated cardiopulmonary bypass circuits. This study investigates in a canine model of single-lung allotransplantation whether cardiopulmonary bypass adversely affects early graft function and whether a heparin-coated cardiopulmonary bypass circuit with reduced systemic heparin dosage improves results compared with standard uncoated cardiopulmonary bypass systems. Fifteen dogs underwent left single-lung allotransplantation with occlusion of the contralateral pulmonary artery and bronchus 1 hour after reperfusion. In one group, five animals underwent the procedure without cardiopulmonary bypass. In the group with uncoated circuits, five animals underwent the procedure with the use of standard uncoated cardiopulmonary bypass circuits with full systemic heparin dosage. In the group with heparin-coated circuits, five animals underwent the procedure with the use of heparin-coated cardiopulmonary bypass circuits and reduced systemic heparin dosage. Early graft function was evaluated by arterial oxygenation, pulmonary mechanics, lung water measurements, and histologic analysis. Hemodynamics and postoperative blood loss were also measured. Two hours after reperfusion, partial pressure of oxygen in arterial blood on an inspired oxygen fraction = 1.0 was significantly greater (p < 0.001) in the group without cardiopulmonary bypass (467 +/- 58 mm Hg) than in the group with uncoated circuits (114 +/- 90 mm Hg) and the group with heparin-coated circuits (193 +/- 105 mm Hg), with no significant difference between the groups undergoing bypass procedures. Lung compliance decreased and lung water increased in all transplanted lungs without significant differences between groups. Histologic analysis did not differentiate between the groups. After reperfusion, cardiac index and mean arterial pressure were significantly reduced in the groups with uncoated circuits and with heparin-coated circuits compared with the group that did not undergo cardiopulmonary bypass (p < 0.001). Postoperative blood loss was significantly less (p < 0.002) in the group that did not undergo cardiopulmonary bypass (90 ml +/- 38 ml) compared with both the group with uncoated circuits (750 +/- 15 ml) and the group with heparin-coated circuits (690 +/- 387 ml), with no significant difference between the groups that underwent bypass. The use of cardiopulmonary bypass with systemic heparinization is detrimental to early graft function in this canine model of left single-lung allotransplantation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of depletion of leukocytes and platelets on cardiac dysfunction after cardiopulmonary bypass

BACKGROUND: This study examined the effects of the depletion of leukocytes and platelets from circulated blood on cardiac function after cardiopulmonary bypass in 37 patients who underwent coronary artery bypass grafting or aortic valve replacement. METHODS: Leukocytes and platelets were removed continuously using a blood cell separator, beginning immediately after the start of the operation and ending 1 hour after the release of the aortic cross-clamp in 19 patients (LPD group), but not in the remaining 18 patients (control group). Blood cell counts and levels of thromboxane B2, 6-keto-prostaglandin F1alpha, leukocyte elastase, complements C3a and C4a, thrombin-antithrombin III complex, and D-dimer were determined periodically during and after the operation. The cardiac index, the difference between the central and peripheral core temperatures, and the doses of catecholamines and vasodilators required to support the circulation in the early postoperative period also were assessed. RESULTS: Leukocyte and platelet counts and levels of leukocyte elastase, thromboxane B2, thromboxane2/6-ketoprostaglandin F1alpha, thrombin-antithrombin III complex, and D-dimer were significantly lower in the LPD group than in the control group before and after the release of the aortic cross-clamp and during the perioperative period. There were no significant differences in the levels of 6-keto-prostaglandin F1alpha or complements C3a and C4a between the two groups. The catecholamine dose was significantly lower in the LPD group than in the control group (1.1 +/- 2.5 versus 5.0 +/- 5.2 mg/kg, respectively). Fewer patients required the use of nitroprusside as a vasodilator in the LPD group than in the control group (1/19 versus 12/18, respectively). CONCLUSIONS: The depletion of leukocytes and platelets using a blood cell separator prevents the deterioration of cardiac function after cardiac operations using cardiopulmonary bypass.     

Antitumor activity of human umbilical cord blood cells: A comparative analysis with peripheral blood and bone marrow cells

OBJECTIVES: To determine the predictive value of quantitative evaluation of myocardial viability on changes in left ventricular function, exercise capacity, and quality of life after coronary artery bypass grafting in patients with ischemic heart failure (congestive heart failure, New York Heart Association class > or = III) with and without angina. METHODS: Thirty-five patients, 14 with congestive heart failure and angina (CHF-angina) and 21 with congestive heart failure without angina (CHF-no angina) were studied at baseline and 6 months after coronary bypass grafting. Left ventricular function was evaluated with transthoracic echocardiography and radionuclide ventriculography. Myocardial viability was assessed with [18F]-2-fluoro-2-deoxy-D-glucose using positron emission tomography. Peak aerobic capacity (peak oxygen consumption) and anaerobic threshold were assessed with treadmill exercise test and quality of life with a questionnaire. RESULTS: A total of 286 of 336 dysfunctional left ventricular segments were viable. There were two perioperative deaths (5.7%) and three late deaths. Left ventricular ejection fraction increased from 23% +/- 7% to 32% +/- 9% (p < 0.0001), and a linear correlation was found between the number of viable segments and the changes in ejection fraction (r = 0.65; p = 0.0001). Receiver operating characteristics curve identified eight viable segments as the best predictor for increase of ejection fraction more than 5 percentage points. Peak oxygen consumption increased from 15 +/- 4 to 22 +/- 5 ml/kg per minute (p < 0.0001). Preoperatively, anaerobic threshold was identified in one patient from the CHF-angina group and in all from the CHF-no angina group and increased from 13 +/- 4 to 19 +/- 4 ml/kg per minute (p < 0.0001). Quality of life scores improved significantly in both groups. No correlation was found between the amount of viable dysfunctional myocardium and changes in exercise capacity or quality of life. CONCLUSIONS: In patients with postischemic congestive heart failure the amount of viable myocardium dictates the degree of improvement in left ventricular function after revascularization.     

Ischemic and reperfusion injury of cyanotic myocardium in chronic hypoxic rat model: changes in cyanotic myocardial antioxidant system

OBJECTIVE: The objective was to evaluate the effect of left ventricular function on cyanotic myocardium after ischemia-reperfusion and to determine the effect of cyanosis on the myocardial antioxidant system. METHODS: Cyanotic hearts (cyanotic group) were obtained from rats housed in a hypoxic chamber (10% oxygen) for 2 weeks and control hearts (control group) from rats maintained in ambient air. Isolated, crystalloid perfused working hearts were subjected to 15 minutes of global normothermic ischemia and 20 minutes of reperfusion, and functional recovery was evaluated in the two groups. Myocardial superoxide dismutase, glutathione peroxidase, glutathione reductase activity, and reduced glutathione content were measured separately in the cytoplasm and mitochondria at the end of the preischemic, ischemic, and reperfusion periods. RESULTS: Mean cardiac output/left ventricular weight was not significantly different between the two groups. Percent recovery of cardiac output was significantly lower in the cyanotic group than in the control group (56.1% +/- 5.7% vs 73.0% +/- 3.1%, p = 0.001). Mitochondrial superoxide dismutase, mitochondrial and cytosolic glutathione reductase activity, and cytosolic reduced glutathione were significantly lower in the cyanotic group than in the control group at end-ischemia (superoxide dismutase, 3.7 +/- 1.3 vs 5.9 +/- 1.5 units/mg protein, p = 0.012; mitochondrial glutathione reductase, 43.7 +/- 14.0 vs 71.0 +/- 30.3 munits/mg protein, p = 0.039; cytosolic glutathione reductase, 13.7 +/- 2.0 vs 23.2 +/- 4.2 munits/mg protein, p < 0.001; and reduced glutathione, 0.69 +/- 0.10 vs 0.91 +/- 0.24 microgram/mg protein, p = 0.037). CONCLUSIONS: Cyanosis impairs postischemic functional recovery and depresses myocardial antioxidant reserve during ischemia. Reduced antioxidant reserve at end-ischemia may result in impaired postischemic functional recovery of cyanotic myocardium.     

Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations

We studied the inflammatory reaction related to cardiopulmonary bypass in 24 neonates (median age 6 days) undergoing the arterial switch operation for simple transposition of the great arteries, with respect to the development of postoperative capillary leak syndrome. Complement proteins, leukocyte count, tumor necrosis factor-alpha, and histamine levels were determined before, during, and after cardiopulmonary bypass. Additionally, protein movement from the intravascular into the extravascular space during cardiopulmonary bypass was assessed by the measurement of plasma concentrations of proteins with molecular weights ranging from 21,200 to 718,000. Capillary leak syndrome developed in 13 of the 24 neonates. Patients with capillary leak syndrome, as compared with those without, had preoperatively higher C5a levels (C5a, 3.0 +/- 0.6 microgram/L vs 0.9 +/- 0.2 microgram/L) (mean +/- standard error of the mean) (p < 0.05) and higher leukocyte counts (leukocytes, 17.9 +/- 2.1 X 10(3) cells/ml versus 11.7 +/- 0.8 X 10(3) cells/ml) (p < 0.05), suggesting in these neonates a preoperative inflammatory state. Preoperative clinical and operative data were identical in both patient groups. Before cardiopulmonary bypass, serum protein concentrations were similar in all patients. Ten minutes after institution of cardiopulmonary bypass, protein concentrations fell to significantly lower values in patients with capillary leak syndrome than in those without: albumin (19% +/- 1.5% vs 30% +/- 6% of the prebypass value, p < 0.05), immunoglobulin G (17% +/- 1.5% vs 29% +/- 5.5%, p < 0.001), and alpha 2-macroglobulin (15% +/- 1.2% vs 25% +/- 4%, p < 0.02). During cardiopulmonary bypass, albumin concentrations remained significantly lower in patients with capillary leak syndrome than in those without, whereas hematocrit values were similar in both groups. During cardiopulmonary bypass, patients with capillary leak syndrome also had lower concentrations of complement proteins C3 and C4 but not C1 inhibitor. C3d/C3 ratio and C5a levels were similar in both patient groups. In contrast, histamine liberation during cardiopulmonary bypass was significantly more pronounced in patients with capillary leak syndrome than in those without (725.2 +/- 396.7 pg/ml vs -54.1 +/- 58.4 pg/ml, p < 0.05). Tumor necrosis factor-alpha levels after protamine administration were also significantly higher in patients with capillary leak syndrome (38.1 +/- 10.0 pg/ml vs 15.3 +/- 3.4 pg/ml, p < 0.05). Leukocyte count during and after cardiopulmonary bypass was similar in both patient groups. This study demonstrates increased protein leakage as early as 10 minutes after initiation of.     

Coronary surgery on the beating heart under extracorporeal circulation in high-risk patients. An acceptable compromise?

Coronary artery surgery with cardioplegia in high risk patients carries a risk of myocardial ischaemia and, without cardiopulmonary bypass, is not always technically feasible. The authors assessed an alternative, surgery on the beating heart with haemodynamic assist by cardiopulmonary bypass in 43 consecutive patients with poor left ventricular function (mean ejection fraction: 0.26), evolving myocardial ischaemia or acute myocardial infarction, old age (mean: 79.5 years) and comorbid conditions. Results were assessed mainly on clinical criteria. In addition, 9 patients had pre- and post-cardiopulmonary bypass measurements of markers of myocardial ischaemia (troponine Ic) and systemic inflammation (interleukines 6 and 10, elastase). In 6 cases, right atrial biopsy was analysed for expression of messenger ribonucleic acid coding for heat shock protein (HSP) 70; the data were compared with those of patients operated under warm blood cardioplegia. There was one cardiac death and one myocardial infarction. Myocardial conservation was confirmed by the minimal increase in troponine Ic levels and the significant increase in HSP 70 in RNA suggesting myocardial adaptation to stress. On the other hand, the minimal concentrations of mediators of inflammation were not significantly changed. In selected high risk patients, coronary revascularisation on the beating heart under cardiopulmonary bypass could be a valuable alternative. It conserves the potentially deleterious effects of cardiopulmonary bypass but peroperative global myocardial ischaemia, an important factor in the aggressivity of cardiac surgery, is eliminated.     

Implementation of legislative requirements for emergency medical services in prepaid group practice organizations

This study was based on the concept that intracellular accumulation of calcium plays a role in mediating ischemic myocardial injury and that inhibition of entry of calcium into cells may have a salutary effect on the ischemic heart. Nifedipine, a potent vasodilator and inhibitor of transmembrane calcium flux, was infused into the aortic root of 6 dogs (5 microgram/kg/hr) during 2 hours of myocardial ischemia while on cardiopulmonary bypass. Seven control animals received normal saline at the same flow rate and temperature (20 degrees C). The results showed that none of the 7 control animals were able to maintain adequate aortic pressure or cardiac output after 30 to 60 minutes of normothermic reperfusion. All had marked left ventricular failure and were unresponsive to large doses of inotropic agents. In contrast, the 6 dogs treated with nifedipine were weaned from bypass either without difficulty or requiring small doses of calcium chloride and norepinephrine. Light microscopy demonstrated more marked ischemic damage in the control group than in the group of drug-treated dogs. We conclude that the concept of inhibition of transmembrane calcium flux offers a new and potent method for myocardial preservation during ischemia.     

Histologic localization of indocyanine green dye in aging primate and human ocular tissues with clinical angiographic correlation

OBJECTIVE: Because C5a induces tissue injury by activating polymorphonuclear leukocytes, the hypothesis was that inhibition of C5a activity would reduce cardioplegia-related injury. METHODS: Pigs were placed on cardiopulmonary bypass. The hearts were arrested for 1 hour with hyperkalemic cardioplegia. Pigs were then separated from bypass, and the hearts were reperfused for 2 hours. Anti-porcine C5a monoclonal antibody (1.6 mg/kg, intravenously; n = 6) was administered 20 minutes before the onset of cardiopulmonary bypass. Six pigs received saline solution vehicle. Reactivity of coronary arterioles was studied in vitro with videomicroscopy. Microvessels from uninstrumented pigs served as controls for vascular studies. RESULTS: Endothelium-dependent relaxation to adenosine diphosphate (percent relaxation of precontraction) was reduced after cardioplegic reperfusion (63% +/- 14% vs 77% +/- 10% in control at 10 micromol/L; P =.01). This impairment in endothelium-dependent relaxation was improved with anti-porcine C5a monoclonal antibody (80% +/- 22%; P =.01 vs saline solution), as was the impaired endothelium-dependent relaxation to clonidine (64% +/- 12% control; 26% +/- 17% saline solution; 55% +/- 24% anti-porcine C5a monoclonal antibody at 10 micromol/L; P =.01 saline solution vs control or anti-porcine C5a monoclonal antibody). Myeloperoxidase activity was significantly decreased (0.2 +/- 0.2 units/g protein; P =.04) in the anti-porcine C5a monoclonal antibody group compared with 5.2 +/- 2.7 in the saline solution group. CH50 2 hours after bypass was not statistically different (0.57 +/- 0.41 unit and 0.65 +/- 0.41 unit, respectively) between the anti-porcine C5a monoclonal antibody and saline solution groups. Despite less myocardial polymorphonuclear leukocyte infiltration after C5a inhibition, maximum rate of rise of left ventricular pressure, percent segmental shortening, and blood flow through the left anterior descending coronary artery were similar in the anti-porcine C5a monoclonal antibody and saline solution groups. CONCLUSIONS: Inhibition of C5a limits neutrophil-mediated impairment of endothelium-dependent relaxation after cardiopulmonary bypass and cardioplegic reperfusion, but it has no effect on short-term myocardial functional preservation.     

Software assessment under consideration of validation aspects: PPS and PMS systems

BACKGROUND: The use of cardiopulmonary bypass (CPB) in coronary bypass grafting is associated with a generalized inflammatory response. This negative impact of CPB may be avoided by using new surgical techniques recently introduced to perform coronary bypass grafting 'off-pump', i.e. without CPB. METHODS: Since the specific effects of CPB on the immunorelevant cells have still not been fully investigated, we measured the changes in leukocyte subsets of the circulating blood in patients who underwent coronary bypass surgery with a conventional sternotomy approach and CPB (group A, n = 10), in patients who underwent the same surgical procedure but without CPB (group B, n = 10), and in patients who underwent a minimally invasively performed single bypass to the left anterior descending artery (LAD) (group C, n = 10). RESULTS: Leukocyte subsets showed a similar change during and after coronary bypass grafting in all three groups. The total number of leukocytes was increased soon after reperfusion in the CPB group. A similar but delayed increase was observed in both off-pump groups. Changes in lymphocyte subsets and T-lymphocyte subsets were similar in all three groups, with a drop of lymphocytes during the first 24 postoperative hours mainly caused by a drop of T4-helper cells. CONCLUSION: The results indicate a reaction of the leukocyte subsets to coronary bypass surgery which is more related to the surgical trauma in general than to CPB in particular.     

Complete unloading alone may not adequately protect the left ventricle

BACKGROUND: The benefit of left ventricular (LV) unloading for preserving LV function is commonly accepted, but its efficacy remains incompletely defined. METHODS: We studied the influence of complete LV unloading on LV systolic and diastolic mechanics using an in situ isovolumic preparation with two different coronary perfusion pressures (CPPs) in 12 dogs during prolonged normothermic cardiopulmonary bypass. RESULTS: Multivariate analysis of covariance with time as a covariate revealed that a high CPP (143 +/- 36 mm Hg; n = 6) was associated with better preservation of systolic LV function over time as assessed by LV end-systolic elastance (p < 0.001) and the end-systolic pressure-volume relation physiologic intercept (p < 0.001) compared with a moderate CPP (107 +/- 18 mm Hg; p < 0.005 versus a high CPP by t-test; n = 6). Dobutamine (2 micrograms.kg-1.min-1) improved LV end-systolic elastance (p < 0.005) and LV physiologic intercept (p < 0.01) only in the high-CPP group. Conversely, impaired LV diastolic function (as measured by LV stiffness) was observed (p < 0.001) with a high CPP, but did not change with a moderate CPP. CONCLUSIONS: These observations in canine hearts suggest that complete LV unloading may not preserve LV systolic function adequately over time when CPP is maintained in the accepted clinical range. A higher CPP is required to prevent deterioration over prolonged cardiopulmonary bypass times, but diastolic dysfunction still occurs.     

Emergency percutaneous cardiopulmonary bypass support for acute myocardial infarction

We assessed the efficacy of emergency percutaneous cardiopulmonary bypass support (PCPS) in the treatment of patients with acute myocardial infarction complicated by cardiogenic shock. Emergency PCPS was instituted in 21 consecutive patients beginning in 1991. After the stabilization of the hemodynamics, coronary reperfusion was performed by means of coronary artery bypass grafting or percutaneous transluminal coronary angioplasty. Of the seven patients with acute myocardial infarction involving either the left main or two-vessel territories, five survived more than 1 month, but only one patient remained alive and well after 20 months. The main cause of death for this group was low output syndrome. Four of 12 patients with acute left main trunkal occlusion in the catheter laboratory survived and showed a preserved cardiac function (mean followup 28.5 months). The main cause of death for this group was brain damage. Two patients with single-vessel territory acute myocardial infarction underwent PCPS to treat refractory ventricular fibrillation. Both patients were still alive and well at a 12-month followup. Percutaneous cardiopulmonary bypass support successfully stabilized the hemodynamics, allowing time to perform revascularization for all three groups of patients with life-threatening acute myocardial infarction. Recanalization was nevertheless unable to salvage the damaged myocardium in cases of prolonged ischemic time.     

Safety and cost-effectiveness of MIDCABG in high-risk CABG patients

BACKGROUND: Myocardial revascularization without cardiopulmonary bypass has been proposed as a potential therapeutic alternative in high-risk patients undergoing coronary artery bypass grafting. To evaluate this possibility we compared 15 high-risk (HR) patients in whom minimally invasive direct coronary artery bypass grafting was used as the method of revascularization with 41 consecutive patients who underwent conventional coronary artery bypass grafting during 1 month. METHODS: Patients undergoing myocardial revascularization without cardiopulmonary bypass were significantly older than their low-risk (LR) counterparts (72.2 +/- 11.6 versus 63.3 +/- 9.7 years, p = 0.006). The demographic profile for HR versus LR patients was as follows: female patients, 60.0% versus 26.8%, p = 0.02; diabetes, 20.0% versus 24.4%, p = 0.7; prior stroke, 33.3% versus 7.4%, p = 0.03; chronic obstructive pulmonary disease, 60.0% versus 9.8%, p < 0.0001; peripheral vascular disease, 33.3% versus 12.2%, p = 0.03, congestive heart failure, 26.6% versus 9.8%, p = 0.09; impaired left ventricular (ejection fraction < 0.40), 40.0% versus 17.0%, p = 0.07; urgent operation, 86.6% versus 46.3%, p < 0.0001; and redo operation, 20.0% versus 0%, p = 0.003. RESULTS: There were no deaths in the HR group and one death in the LR group. The average intensive care unit stay was 1.1 +/- 0.5 days in HR patients versus 1.6 +/- 1.6 days in LR individuals (p = 0.2), and the average hospital stay was 6.1 +/- 1.8 versus 7.3 +/- 4.4 days, respectively (p = 0.3). We used an acuity risk score index developed by the Adult Cardiac Care Network of Ontario to predict outcome in the HR group. The expected intensive care unit stay in HR patients was 4.1 +/- 1.2 days (versus the observed stay of 1.1 +/- 0.5 days, p < 0.0001), and the expected hospital stay was 12.5 +/- 1.5 days (versus the observed stay of 6.1 +/- 1.8 days, p < 0.0001). The expected mortality in the HR group was 6.1% versus 0%, p = 0.3. A cost regression model was used to examine predicted versus actual cost (in Canadian dollars) for the HR patient cohort (based on Ontario Ministry of Health funding). The expected cost for the HR cohort would have been $11,997 per patient. In contrast, the average cost for these 15 patients was $5,997 per patient, an estimated cost saving of 50%. CONCLUSIONS: Myocardial revascularization without cardiopulmonary bypass appears to be a safe and cost-effective therapeutic modality for HR patients requiring myocardial revascularization.     

Assessment of preload reserve in myocardial ischemia--the relation between preload reserve and ischemic size differs between anterior descending and circumflex coronary artery occlusions in a canine model

The role of changes in preload in maintaining stable hemodynamics during coronary obstruction was assessed in the presence of myocardial ischemia due to occlusions of the left anterior descending (LAD) and left circumflex (LCX) coronary arteries. Changes in preload (mean left atrial pressure) to maintain a constant stroke volume after coronary occlusion were examined in 18 anesthetized dogs (LAD occlusion in 9 dogs, LCX occlusion in 9 dogs). The level of ischemia was assessed sonomicrometrically. Ventricular function curves relating left atrial pressure to stroke volume were assessed during a control state and after 1 min of coronary occlusion. The extent of preload reserve after coronary occlusion was examined on the ventricular function curves and was defined as the change in mean left atrial pressure required to maintain stroke volume at the level of the control state under conditions of regional ischemia. Ischemic size was determined by a stereo-angiogram after the animals were sacrificed. The extent of preload reserve (X) was linearly related to the ischemic size (Y) in both LAD (Y = 0.90 + 0.16X, r = 0.76, p < 0.001) and LCX (Y = -1.79 + 0.19X, r = 0.79, p < 0.001) occlusions. The slopes of the regression lines in LAD and LCX occlusions were the same. The X intercepts of these lines were -5.6% and 9.4% of the left ventricular weight in LAD and LCX ischemia (p < 0.001), respectively. Thus, the presence of systolic wall motion abnormalities due to coronary occlusion can be compensated for hemodynamically by changes in the preload reserve.(ABSTRACT TRUNCATED AT 250 WORDS)     

Left ventricular volume reduction for end-stage heart failure: intrapapillary or extrapapillary resection, mitral valve repair or replacement?

We report on two patients with end-stage dilated cardiomyopathy and functional mitral valve insufficiency who underwent left ventricular volume reduction. Intrapapillary resection and correction of the mitral valve regurgitation produced inadequate reduction of the ventricular cavity and resulted in inability to wean the patients from cardiopulmonary bypass. Following extension of the resection to include the papillary muscles and mitral valve replacement, there was a significant improvement in cardiac function. Both patients survived surgery; subsequent echocardiography provided evidence of improved myocardial function and NYHA functional class.     

Differential regulation of vitamin D receptors in clonal populations of a chronic myelogenous leukemia cell line

BACKGROUND: Both crystalloid and blood cardioplegia result in cardiac dysfunction associated with myocardial edema. This edema is partially due to the lack of myocardial contraction during cardioplegia, which stops myocardial lymph flow. As an alternative, acceptable surgical conditions have been created in patients undergoing coronary artery bypass operations with esmolol-induced minimal myocardial contraction. We hypothesized that minimal myocardial contraction during circulatory support using either standard cardiopulmonary bypass (CPB) or a biventricular assist device would prevent myocardial edema by maintaining cardiac lymphatic function and thus prevent cardiac dysfunction. METHODS: We placed 6 dogs on CPB and 6 dogs on a biventricular assist device and serially measured myocardial lymph flow rate and myocardial water content in both groups and preload recruitable stroke work only in the CPB dogs. In all dogs we minimized heart rate with esmolol for 1 hour during total circulatory support. RESULTS: Although myocardial lymph flow remained at baseline level during CPB and increased during biventricular assistance, myocardial water accumulation still occurred during circulatory support. However, as edema resolved rapidly after separation from circulatory support, myocardial water content was only slightly increased after CPB and biventricular assistance, and preload recruitable stroke work was normal. CONCLUSIONS: Our data suggest that minimal myocardial contraction during both CPB and biventricular assistance supports myocardial lymphatic function, resulting in minimal myocardial edema formation associated with normal left ventricular performance after circulatory support. The concept of minimal myocardial contraction may be a useful alternative for myocardial protection, especially in high-risk patients with compromised left ventricular function.