Systemic effects of carbon dioxide insufflation technique for de-airing in left-sided cardiac surgery.

OBJECTIVE: Systemic effects of carbon dioxide (CO2) insufflation during left-sided cardiac surgery were evaluated in a prospective randomized study, with regard to acid-base status, gas exchange, cerebral hemodynamics, and red blood cell morphology. METHODS: Twenty patients undergoing elective left-sided cardiac surgery were randomized to de-airing procedure either by CO2 insufflation technique (CO2 group, n = 10) or by Lund technique without CO2 insufflation (Lund group, n = 10). Groups underwent assessment of acid-base status by intermittent arterial blood gases and in-line blood gas monitoring. Capnography was used to determine volume of CO2 produced. Cerebral hemodynamics was measured by transcranial Doppler sonography and near-infrared spectroscopy. Red cell morphology from cardiotomy suction and vent tubing was studied by scanning electron microscopy. RESULTS: Patients in the CO2 group consequently developed significantly higher levels of hypercapnia with a concomitant increase in the volume of CO2 produced despite significantly higher oxygenator gas flows compared with the Lund group. Effects on cerebral hemodynamics were observed in the CO2 group with significantly higher blood flow velocities in the middle cerebral artery and higher regional cerebral saturation. Red blood cell damage was observed in the CO2 group by scanning electron microscopy (97% in CO2 group vs 18% in Lund group). CONCLUSIONS: Insufflation of CO2 into the cardiothoracic wound cavity during left-sided cardiac surgery can induce hypercapnic acidosis and increased cerebral blood flow and local blood cell damage. These systemic effects should be monitored by in-line capnography and acid-base measurements for early and effective correction by increase in gas flows to the oxygenator.

Functional and pharmacological characteristics of permeability transition in isolated human heart mitochondria.

The objective of the present study was to validate the presence and explore the characteristics of mitochondrial permeability transition (mPT) in isolated mitochondria from human heart tissue in order to investigate if previous findings in animal models of cardiac disorders are translatable to human disease. Mitochondria were rapidly isolated from fresh atrial tissue samples obtained from 14 patients undergoing Maze surgery due to atrial fibrillation. Human heart mitochondria exhibited typical mPT characteristics upon calcium overload such as swelling, evaluated by changes in light scattering, inhibition of respiration and loss of respiratory coupling. Swelling was a morphologically reversible event following transient calcium challenge. Calcium retention capacity (CRC), a quantitative measure of mPT sensitivity assayed by following extramitochondrial [Ca(2+)] and changes in respiration during a continuous calcium infusion, was significantly increased by cyclophilin D (CypD) inhibitors. The thiol-reactive oxidant phenylarsine oxide sensitized mitochondria to calcium-induced mPT. Release of the pro-apoptotic intermembrane protein cytochrome c was increased after, but not before, calcium discharge and respiratory inhibition in the CRC assay. From the present study, we conclude that adult viable heart mitochondria have a CypD- and oxidant-regulated mPT. The findings support that inhibition of mPT may be a relevant pharmacological target in human cardiac disease and may underlie the beneficial effect of cyclosporin A in reperfusion injury.

Circulating cardio-enriched microRNAs are associated with long-term prognosis following myocardial infarction.

BACKGROUND: Increased levels of cardio-enriched microRNAs (miRNAs) have been described in patients with myocardial infarction (MI). We wanted to evaluate the diagnostic and prognostic potential of cardio-enriched miRNAs in patients presenting with a suspected acute coronary syndrome (ACS). METHODS: Cardio-enriched miRNAs (miR-1, miR-208b and miR-499-5p) were measured using real time PCR in plasma samples from 424 patients with suspected ACS treated in a coronary care unit. miRNAs were assessed for discrimination of a clinical diagnosis of myocardial infarction and for association with 30-day mortality and diagnosis of heart failure. Correlation with left ventricular systolic dysfunction as measured by the ejection fraction (LVEF) was also assessed. To confirm myocardial origin miRNA was measured during coronary artery bypass surgery. RESULTS: miRNAs were higher in MI patients and correlated with LVEF (p < 0.001). Discrimination of MI was accurate for miR-208b (AUC = 0.82) and miR-499-5p (AUC = 0.79) but considerable lower than for Troponin T (AUC = 0.95). Increased miRNA levels were strongly associated with increased risk of mortality or heart failure within 30 days for miR-208b (OR 1.79, 95% CI = 1.38-2.23, p = 1 × 10(-5)) and miR-499-5p (OR 1.70, 95% CI = 1.31-2.20, p = 5 × 10(-5)) but the association was lost when adjusting for Troponin T. During surgery miR-208b and miR-499-5p was released in the coronary sinus after cardioplegia-reperfusion to markedly higher levels than in a peripheral vein. CONCLUSIONS: Our findings confirm increased levels of cardio-enriched miRNAs in the blood of MI patients and establish association of increased miRNA levels with reduced systolic function after MI and risk of death or heart failure.

Comparison of the effectiveness and safety of a new de-airing technique with a standardized carbon dioxide insufflation technique in open left heart surgery: a randomized clinical trial.

OBJECTIVE: We have compared the effectiveness, time required for de-airing, and safety of a newly developed de-airing technique for open left heart surgery (Lund technique) with a standardized carbon dioxide insufflation technique. METHODS: Twenty patients undergoing elective open aortic valve surgery were randomized prospectively to the Lund technique (Lund group, n = 10) or the carbon dioxide insufflation technique (carbon dioxide group, n = 10). Both groups were monitored intraoperatively during de-airing and for 10 minutes after weaning from cardiopulmonary bypass by transesophageal echocardiography and online transcranial Doppler for the severity and the number of gas emboli, respectively. The systemic arterial partial pressure of carbon dioxide and pH were also monitored in both groups before, during, and after cardiopulmonary bypass. RESULTS: The severity of gas emboli observed on transesophageal echocardiography and the number of microembolic signals recorded by transcranial Doppler were significantly lower in the Lund group during the de-airing procedure (P = .00634) and in the first 10 minutes after weaning from cardiopulmonary bypass (P = .000377). Furthermore, the de-airing time was significantly shorter in the Lund group (9 vs 15 minutes, P = .001). The arterial pH during the cooling phase of cardiopulmonary bypass was significantly lower in the carbon dioxide group (P = .00351), corresponding to significantly higher arterial partial pressure of carbon dioxide (P = .005196) despite significantly higher gas flows (P = .0398) in the oxygenator throughout the entire period of cardiopulmonary bypass. CONCLUSIONS: The Lund de-airing technique is safer, simpler, and more effective compared with the carbon dioxide insufflation technique. The technique is also more cost-effective because the de-airing time is shorter and no extra expenses are incurred.

Inotropic support during experimental endotoxemic shock: part I. The effects of levosimendan on splanchnic perfusion.

BACKGROUND: Septic shock may cause splanchnic hypoperfusion. We hypothesized that levosimendan would improve systemic and hepatosplanchnic perfusion during endotoxemic shock. METHODS: In 16 anesthetized pigs (31.4 +/- 3.4 kg), a jugular vein, a carotid artery, the pulmonary artery (thermodilution), the portal vein, and a hepatic vein were cannulated for hemodynamic monitoring and blood sampling. Ultrasonic flowprobes were placed around the portal vein, the hepatic artery, and the superior mesenteric artery (SMA). In addition to 30 mL/kg of dextran 70 given before baseline, all animals received 10 mL x kg(-1) x h(-1) of IV fluids throughout the experiment. An endotoxin infusion (2 microg x kg(-1) x h(-1)) was given for 300 min; 100 min after the start of endotoxin, the pigs were randomized to receive levosimendan (50 microg x kg(-1) x h(-1), n = 8) or placebo (n = 8). To evaluate the isolated effects of endotoxemia, all data before randomization were pooled into one group. Data were analyzed by analysis of variance and presented as mean +/- sem. RESULTS: Endotoxemia (t = 90 min, pooled data) decreased systemic vascular resistance (SVR, 2526 +/- 203 to 1946 +/- 122 dyn x s x cm(-5), P = 0.003) and mean arterial blood pressure (MAP, 109 +/- 6 to 84 +/- 3 mm Hg, P < 0.05), whereas heart rate (66 +/- 4 to 98 +/- 8 bpm), and mean pulmonary arterial pressure (MPAP, 20 +/- 1 to 38 +/- 2 mm Hg) increased (P < 0.001). Cardiac output (CO, 3.4 +/- 0.2 L/min) and systemic oxygen delivery (414 +/- 33 mL/min) were unchanged, but blood flows in the SMA (575 +/- 34 to 392 +/- 38 mL/min) and the portal vein (881 +/- 62 to 568 +/- 39 mL/min) decreased (P < 0.001). Although hepatic arterial blood flows increased (36 +/- 8 to 219 +/- 38 mL/min), gut (114 +/- 11 to 84 +/- 7 mL/min) and hepatic (94 +/- 11 to 67 +/- 8 mL/min) oxygen deliveries decreased (P < 0.05). At t = 300 min, the levosimendan group showed lower MPAP (39 +/- 3 vs 49 +/- 2 mm Hg, P = 0.025), lower SVR (2158 +/- 186 vs 3069 +/- 370 dyn x s x cm(-5), P = 0.052), and lower MAP (55 +/- 9 vs 87 +/- 9 mm Hg, P < 0.001) than the control group. In both groups, CO, portal vein, and hepatic arterial blood flows decreased (P < 0.001); the mean values for the levosimendan group at t = 300 min were 2.0 +/- 0.4 L/min, 390 +/- 83 mL/min, and 36 +/- 12 mL/min, respectively. SMA blood flow decreased only in the levosimendan group (432 +/- 40 to 320 +/- 78 mL/min, P < 0.001), whereas gut oxygen delivery decreased in the levosimendan (85 +/- 12 to 63 +/- 12 mL/min, P < 0.001) and in the control (83 +/- 6 to 59 +/- 3 mL/min, P = 0.03) groups. CONCLUSION: Levosimendan administered after the establishment of endotoxemic shock to pigs receiving moderate fluid resuscitation prevented further increases in MPAP and maintained a low SVR. There were, however, no improvements in CO, MAP decreased, and levosimendan neither prevented the development of circulatory shock nor improved hepatosplanchnic perfusion.

Inotropic support during experimental endotoxemic shock: part II. A comparison of levosimendan with dobutamine.

BACKGROUND: We compared the association of levosimendan or dobutamine with norepinephrine for the maintenance of systemic and hepatosplanchnic perfusion during early endotoxemic shock. METHODS: Twenty anesthetized pigs (26.8 +/- 0.5 kg) were instrumented with flow probes and catheters to monitor systemic and regional perfusion as described in our companion article in this issue of the journal. Two animals were excluded because of surgical complications. Oxygen consumption (VO(2)) was measured by indirect calorimetry. Starting 1 h after instrumentation, an endotoxin infusion (Escherichia coli lipopolysaccharide, 2 microg x kg(-1) x h(-1)) was administered for 300 min. Sixty minutes after the start of endotoxin, the animals were fluid resuscitated (20 mL/kg dextran 70); at 120 min, they were randomized into three groups of six animals each: levosimendan (25-50 microg x kg(-1) x h(-1)), dobutamine (10-20 microg x kg(-1) x min(-1)), and control. In the first two groups, norepinephrine (0.5-2 microg x kg(-1) x min(-1)) was added when mean arterial blood pressure (MAP) or= baseline. The data were divided into two subsets: before (0-120 min, all animals) and after (120-300 min, three groups) randomization, and analyzed by analysis of variance. P < 0.05 was considered significant. RESULTS: At 120 min, cardiac output was 15% higher (P < 0.001), systemic vascular resistance was 30% lower (P < 0.001), and MAP decreased 12.5% (P = 0.004); blood flow in the hepatic artery, superior mesenteric artery, and portal vein had increased by 100% (P = 0.004), 60% (P < 0.001), and 20% (P < 0.001), respectively. Between 120 and 300 min, cardiac output and systemic oxygen delivery decreased 50% in control animals (P < 0.05), remained unchanged in the levosimendan group, and increased 60% with dobutamine (P = 0.05). MAP (P = 0.043) and VO(2) (P = 0.001) decreased 20% in the control group. Portal vein flow decreased in the control (50%) and levosimendan (30%) groups (P < 0.001) and was therefore higher in the dobutamine group (P = 0.003) at 300 min. Hepatic and gut oxygen deliveries decreased in the levosimendan (50%, and 30%, respectively, P < 0.001) and control groups (70% and 45%, respectively, P < 0.05); thus, regional oxygen deliveries were greater in the dobutamine group (P < 0.05). In this group, mixed venous and hepatic vein oxygen saturation were maintained; the latter variable was higher than in the other groups (P < 0.05). Although unchanged with dobutamine, arterial (P = 0.020), portal (P = 0.020), and hepatic vein (P = 0.034) lactate concentrations increased twofold with levosimendan. CONCLUSION: In volume-resuscitated endotoxemic pigs, the association of either levosimendan or dobutamine with norepinephrine preserved systemic blood flow, oxygen delivery, and VO(2). However, only dobutamine-norepinephrine maintained portal blood flow, which was associated with preservation of splanchnic and hepatic oxygen homeostasis and stable lactate concentrations.

A new de-airing technique that reduces systemic microemboli during open surgery: a prospective controlled study.

OBJECTIVE: We have evaluated a new technique of cardiac de-airing that is aimed at a) minimizing air from entering into the pulmonary veins by opening both pleurae and allowing lungs to collapse and b) flushing out residual air from the lungs by staged cardiac filling and lung ventilation. These air emboli are usually trapped in the pulmonary veins and may lead to ventricular dysfunction, life-threatening arrhythmias, and transient or permanent neurologic deficits. METHODS: Twenty patients undergoing elective true left open surgery were prospectively and alternately enrolled in the study to the conventional de-airing technique (pleural cavities unopened, dead space ventilation during cardiopulmonary bypass [control group]) and the new de-airing technique (pleural cavities open, ventilator disconnected during cardiopulmonary bypass, staged perfusion, and ventilation of lungs during de-airing [study group]). Transesophageal echocardiography and transcranial Doppler continually monitored the air emboli during the de-airing period and for 10 minutes after termination of the cardiopulmonary bypass. RESULTS: The amount of air embolism as observed on echocardiography and the number of microembolic signals as recorded by transcranial Doppler were significantly less in the study group during the de-airing time (P < .001) and the first 10 minutes after termination of cardiopulmonary bypass (P < .001). Further, the de-airing time was significantly shorter in the study group (10 vs 17 minutes, P < .001). CONCLUSION: The de-airing technique evaluated in this study is simple, reproducible, controlled, safe, and effective. Moreover, it is cost-effective because the de-airing time is short and no extra expenses are involved.

The kinetics of lipid micro-emboli during cardiac surgery studied in a porcine model.

OBJECTIVE: To study the kinetics of lipid micro-emboli during cardiac surgery. DESIGN: Eleven pigs were studied. Seven of these were put on extracorporeal circulation. A shed blood phantom consisted of blood, saline and radioactive triolein was added to the circuit. Both venous and arterial blood samples were taken at short intervals. Four animals were used to study renal kinetics without extracorporeal circulation. The same kind of shed blood phantom was infused into the ascending aorta. Samples were taken from the renal artery and vein. All samples were analyzed for radioactivity by scintillation counting. RESULTS: A median 130-fold increase in radioactivity was seen in the blood and was quickly eliminated. Systemic first-pass wedging was found to be 62%. The first-pass elimination in the kidney was 77%. No radioactivity was found in urine. CONCLUSIONS: This study shows that the turnover of lipid micro-emboli is fast, and that the majority of the emboli are trapped on their first passage through the capillary system. No evidence was found of a renal excretion of these lipid emboli.

Cardiovascular effects of levosimendan in the early stages of endotoxemia.

Sepsis-associated myocardial depression is associated with calcium desensitization and adrenergic uncoupling. We conducted a prospective randomized investigation on the effects of the calcium sensitizer, levosimendan, on hemodynamics, myocardial blood flow, and myocardial lactate metabolism during porcine endotoxemia. Twelve pigs were studied. Oxygen consumption was measured by indirect calorimetry, and myocardial blood flow was measured by retrograde thermodilution. Pulmonary, arterial, and venous indwelling catheters allowed measurements of cardiac output, vascular pressures, and blood sampling. Fluids were given at an average of 15 mL . kg . h. After baseline measurements (0 min), an infusion of Escherichia coli LPS (2 microg . kg . min) was started in all animals. Beginning at 100 min, six animals received levosimendan (50 microg . kg . h), whereas six control animals received placebo. The study lasted for 300 min. All animals responded to endotoxin with pulmonary hypertension, a transient decrease in cardiac output, tachycardia, and systemic hypotension. Levosimendan infusion decreased systemic vascular resistance (P = 0.001), coronary vascular resistance (P = 0.004), and mean arterial (P < 0.001) and coronary perfusion pressures (P < 0.001), whereas pulmonary hypertension was unaffected. Heart rate progressively increased in both groups and was significantly higher in the levosimendan group (P = 0.048). Myocardial blood flow remained unchanged in both groups; however, 80 min after the start of levosimendan infusion, left ventricular myocardial hypoxia ensued, as evidenced by a negative myocardial lactate gradient (P = 0.01). Two control and five levosimendan animals died before the end of the study. Early administration of levosimendan during porcine endotoxemia increased heart rate, caused arterial vasodilation, and decreased coronary perfusion pressure, resulting in myocardial hypoxia.

Controversial significance of early S100B levels after cardiac surgery.

BACKGROUND: The brain-derived protein S100B has been shown to be a useful marker of brain injury of different etiologies. Cognitive dysfunction after cardiac surgery using cardiopulmonary bypass has been reported to occur in up to 70% of patients. In this study we tried to evaluate S100B as a marker for cognitive dysfunction after coronary bypass surgery with cardiopulmonary bypass in a model where the inflow of S100B from shed mediastinal blood was corrected for. METHODS: 56 patients scheduled for coronary artery bypass grafting underwent prospective neuropsychological testing. The test scores were standardized and an impairment index was constructed. S100B was sampled at the end of surgery, hourly for the first 6 hours, and then 8, 10, 15, 24 and 48 hours after surgery. None of the patients received autotransfusion. RESULTS: In simple linear analysis, no significant relation was found between S100B levels and neuropsychological outcome. In a backwards stepwise regression analysis the three variables, S100B levels at the end of cardiopulmonary bypass, S100B levels 1 hour later and the age of the patients were found to explain part of the neuropsychological deterioration (r = 0.49, p < 0.005). CONCLUSIONS: In this study we found that S100B levels 1 hour after surgery seem to be the most informative. Our attempt to control the increased levels of S100B caused by contamination from the surgical field did not yield different results. We conclude that the clinical value of S100B as a predictive measurement of postoperative cognitive dysfunction after cardiac surgery is limited.

Vacuum-assisted closure therapy guided by C-reactive protein level in patients with deep sternal wound infection.

BACKGROUND: Deep sternal wound infection is a serious and potentially lethal complication of cardiac surgery when performed through a median sternotomy. We describe the outcome of a new treatment strategy with C-reactive protein level-guided vacuum-assisted closure used at our department. METHODS: Data from 16 consecutive adult patients who had deep sternal wound infections after cardiac surgery were reviewed. Patients with superficial infection or sterile dehiscence were not included. All patients with postoperative deep sternal wound infections were treated with first-line vacuum-assisted closure therapy, followed by direct surgical closure. A purpose-built vacuum-assisted closure system consisting of polyurethane foam pieces and a special pump unit was used. The foam was placed in the wound after debridement of foreign material and necrotic tissue. The wound was covered with adhesive drape and connected to the pump unit, which was programmed to create a continuous negative pressure of 125 mm Hg in the wound cavity. Intravenous antibiotics were given according to tissue-culture results. The patients were immediately extubated after the operation. When ingrowth of granulation tissue was observed in all parts of the wound and the plasma C-reactive protein level showed a steady decline to 30 to 70 mg/L or less without confounding factors, such as tissue injuries or concomitant infections, the sternotomy was rewired, and the wound was closed. RESULTS: All patients were alive and free from deep sternal wound infection 3 months after the operation. The median vacuum-assisted closure treatment time until surgical closure was 9 days (range, 3-34 days), and the median C-reactive protein level at closure was 45 mg/L (range, 20-173 mg/L). The median hospital stay was 22 days (range, 12-120 days). CONCLUSIONS: Early vacuum-assisted closure treatment, followed by surgical closure guided by the plasma C-reactive protein level, is a reliable and easily applied new strategy in patients with postoperative deep sternal wound infection.