Arterial pressure during cardiopulmonary bypass is not associated with acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) after cardiac surgery is common and is associated with increased mortality. We wanted to investigate if the arterial pressure or the use of norepinephrine during cardiopulmonary bypass were associated with AKI. METHODS: A retrospective analysis of patients who underwent coronary artery bypass grafting with or without concomitant procedures was conducted. AKI was defined using the RIFLE criteria. Data on arterial pressure and use of norepinephrine during cardiopulmonary bypass were entered in a binary logistic regression model to control for possible perioperative confounders. RESULTS: A total of 623 patients were included. Mean age was 68.3 ± 9.7 years and 81% were males. AKI was observed in 198 patients (32%). Mean arterial pressure was 47 ± 6 mmHg and 45 ± 6 mmHg (P = 0.008) in the AKI and no-AKI group, respectively. Norepinephrine was used more frequently and in higher amounts, during cardiopulmonary bypass, in patients who developed AKI. These differences in arterial pressures and use of norepinephrine between the groups were not found to be significant when entered in the binary logistic regression model. CONCLUSION: No independent relationship between arterial pressure or use of norepinephrine and AKI was found.

Assessment of coronary artery disease using coronary computed tomography angiography in patients with aortic valve stenosis referred for surgical aortic valve replacement.

BACKGROUND: In patients referred for aortic valve replacement (AVR) a pre-surgical assessment of coronary artery disease is mandatory to determine the possible need for additional coronary artery bypass grafting. The diagnostic accuracy of coronary computed tomography angiography (coronary CTA) was evaluated in patients with aortic valve stenosis referred for surgical AVR. METHODS: Between March 2008 and March 2010 a total of 181 consecutive patients were included. All patients underwent pre-surgical coronary CTA (64- or 320-detector CT scanner) and invasive coronary angiography (ICA). The analyses were performed blinded to each other. RESULTS: The mean ± SD age of the included patients was 71 ± 9 years and 59% were male. The prevalence of significant coronary artery stenosis >70% by ICA was 36%. Average heart rate during coronary CTA was 65 ± 16 b pm. In a patient based analysis 94% of the patients (171/181) were considered fully evaluable. Coronary CTA had a sensitivity of 68%, a specificity of 91%, a positive predictive value of 81%, and a negative predictive value of 83%. Advanced age, obstructive lung disease, NYHA function class III/IV, and high Agatston score were found to be significantly associated with disagreement between ICA and coronary CTA in univariate analysis. CONCLUSION: In patients with aortic valve stenosis referred for surgical AVR the diagnostic accuracy of coronary CTA to identify significant coronary artery disease is moderate. Coronary CTA may be used successfully in a subset of patients with low age, no chronic obstructive lung disease, NYHA function class

Rapid decline in 51Cr-EDTA measured renal function during the first weeks following lung transplantation.

We previously described a 54% decline in renal function at 6 months after lung transplantation (LTx). We hypothesized that this decline is a very early event following LTx. Thirty-one consecutive patients (16 females/15 males), mean age 49 (+/-13) years, with emphysema, cystic fibrosis/bronchiectasis or idiopathic pulmonary fibrosis were included in an analysis of renal function before and after LTx. The glomerular filtration rate (GFR) was measured using the (51)Cr-ethylenediaminetetra acetic acid plasma clearance single injection technique (mGFR) at baseline before transplantation and at 1, 2, 3 and 12 weeks postoperatively. Mean mGFR declined from 103 +/- 18 to 65 +/- 22, 53 +/- 16 and 57 +/- 18 mL/min/1.73m(2) at 1-, 3- and 12-weeks post-LTx (p < 0.0001), respectively. In a time-dependent repeated measures ANOVA, risk factors for a decline in mGFR posttransplant included: time (p < 0.0001), acute renal failure within 2 weeks post-LTx (p = 0.0003), use of heart and lung machine (p = 0.04), and the use of ephedrine (p = 0.048), as well as increasing age, older than 18 years at LTx (p = 0.006). These data demonstrate that renal function, measured with an isotope method, decreases dramatically during the first week after LTx.

Postoperative treatment with low molecular weight heparin after right heart assist for coronary artery bypass grafting.

Right heart assist (RHA) was used for coronary artery bypass grafting (CABG). We explored the affection of the coagulation system during surgery and evaluated two different antithrombotic treatments postoperatively. The pilot study comprised 14 patients. During surgery activated clotting time (ACT) was kept > 200 sec. By random the patients were selected to different postoperative treatments. The control group received acetyl salicylic acid (ASA) 150 mg daily, the intervention group received ASA 150 mg daily and Low Molecular Weight Heparin (LMWH) 5000 IU x2 for three days. Serum levels of prothrombin fragment 1 and 2 (F 1 + 2), plasmin-antiplasmin product (PAP), anti-Xa activity and functional antithrombin (ATIII) were measured. During surgery there was no increase of F 1 + 2 or PAP. After protamin was administered there was a significant increase of F 1 + 2 but not in PAP during the next 6 hours. Postoperative antithrombotic treatment with LMWH seems to normalise F1 + 2 while ASA does not. ACT level > 200 sec. seems sufficient for RHA-CABG surgery. Fibrinolytic agents are not necessary. It seems that postoperative LMWH treatment prevents increased thrombin formation. General recommendations with respect to antithrombotic treatment beyond ASA can not be made based on study.

Acute myocardial hypoxia increases BNP gene expression.

It is well established that cardiac failure increases cardiac B-type natriuretic peptide (BNP) expression due to myocardial stretching. However, patients with ischemic heart disease also display increased plasma BNP and proBNP concentrations despite preserved cardiac function. In this study, we examined whether acute myocardial hypoxia increases cardiac BNP expression. Surgical reduction of the blood flow to an area of the anterior ventricular wall in pigs reduced the myocardial oxygen tension from 46 +/- 4 to 13 +/- 5 mmHg. The tissue contents of VEGF and BNP mRNA increased 1.8-fold and 3.5-fold, respectively (n=10, P<0.005) in hypoxic compared with normoxic ventricular myocardium after 2.2 +/- 0.2 h; the magnitude of the increase in BNP mRNA expression was positively correlated with that of VEGF in hypoxic myocardium (r=0.66, P<0.05). In support of a hypoxia-induced increase of BNP gene transcription, the content of a premature BNP mRNA was increased in hypoxic myocardium (4.8-fold, P<0.005) and in freshly harvested ventricular myocytes when kept in culture flasks and oxygen-deprived for 3 h (2.2-fold, P=0.002). ProBNP peptide accumulated in the medium of freshly harvested ventricular myocyte cultures but was undetectable in ventricular myocardium, indicating rapid release of the newly synthesized proBNP peptide. Accordingly, the plasma proBNP concentration increased after 2 h of myocardial hypoxia (P=0.028). Cumulatively, the data suggest that acute hypoxia stimulates cardiac BNP expression.

Right heart assist for beating heart coronary artery bypass grafting.

OBJECTIVE: Cardiopulmonary bypass used in conventional coronary artery bypass surgery (cCABG) entails a risk of complications. Consequently, the trend is moving towards off-pump coronary artery bypass (OPCAB). This procedure, however, may lead to haemodynamic instability due to kinking of the right ventricle when the posterior aspect of the heart is exposed. The aim of the study was to establish if a right-sided circulatory assist device (RHA) was able to maintain haemodynamic stability during OPCAB procedures. METHOD: In a prospective study 50 RHA-OPCAB patients and a control group of 50 cCABG patients were examined. Before accessing the marginal arteries, an RHA was established in the RHA-OPCAB patients. RESULTS: A stable haemodynamic condition was achieved for 98% of the RHA-OPCAB patients. The study group had less postoperative chest drain bleeding (P<0.001), shorter ventilation time (P=0.001), and lower blood levels of creatine kinase (CK) and brain CK (P<0.001) compared to the control group. CONCLUSION: The results indicate that RHA-OPCAB is a realistic alternative to cCABG. The procedure can be safely performed most likely resulting in reduced postoperative bleeding, myocardial damage, and ventilation time.

Platelet function after coronary artery bypass grafting: is there a procoagulant activity after off-pump compared with on-pump surgery?

OBJECTIVE: After off-pump coronary artery bypass (OPCAB) haemostasis might be better preserved compared with on-pump coronary artery bypass grafting (CABG). The aim of this study was to investigate whether this possibly better preserved haemostasis results in a procoagulant activity of the platelets. DESIGN: Thirty patients were studied prospectively, 15 undergoing on-pump CABG and 15 undergoing OPCAB. Platelet function was evaluated four times within the first 24 h: preoperatively, postoperatively, 4 h and 1 day after surgery with a bedside whole blood clotting test. RESULTS: A significant increase of platelet-activating-factor-induced platelet aggregation was observed postoperatively after OPCAB (p < 0.01). Only two patients did not reach preoperative values within 1 day postoperatively and four patients had a more than twofold increase. Platelet aggregation immediately after on-pump CABG was reduced to near half of preoperative values, but within 1 day postoperatively normal platelet aggregation was regained in half of the patients. CONCLUSION: This study has mainly indicated that platelets after OPCAB were more easily activated in the early postoperative period. After CABG with cardiopulmonary bypass we found a temporary platelet dysfunction which seemed to be overcome within the first postoperative day.

The pulmonary vasculature in a neonatal porcine model with increased pulmonary blood flow and pressure.

INTRODUCTION: Hypertension and hyperperfusion of the pulmonary vascular bed in the setting of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the understanding of the basic mechanisms of this disease, there is a need for clinically relevant animal models which reflect the disease process. MATERIAL AND RESULTS: We randomly allocated 45 newborn pigs, at the age of 48 hrs, to groups in which there was either construction of a 3 mm central aorto-pulmonary shunt, undertaken in 9, or ligation of the left pulmonary artery, achieved in 13. Controls included sham operations in 13, or no operations in 10 pigs. Follow-up was continued for three months. The interventions were compatible with survival in most pigs. The shunts resulted in an acute 85% increase in systolic pulmonary arterial pressure, and a more than twofold increase in pulmonary blood flow. By three months of age, nearly all shunts had closed spontaneously, and haemodynamics were normal. Ligation of the left pulmonary artery resulted in a normal total pulmonary blood flow, despite only the right lung being perfused, and a 33% increase in systolic pulmonary arterial pressure. These haemodynamic changes were maintained throughout the period of study. In both groups, histomorphometry revealed markedly increased muscularity of the intra-acinar pulmonary arteries. Circulating levels of endothelin were normal in the shunted animals, and elevated in those with ligation of the left pulmonary artery. CONCLUSION: In neonatal porcine models of pulmonary vascular disease, created by construction of 3 mm central aorto-pulmonary shunts and ligation of one pulmonary artery, we observed histopathological changes of the pulmonary vasculature similar to early hypertensive pulmonary vascular disease in humans. Elevated circulating levels of endothelin were associated with abnormal haemodynamics rather than abnormal pathology. These findings could be valuable for future studies on the pathogenesis of hypertensive pulmonary vascular disease associated with congenital cardiac malformations.

Right heart assist ensures hemodynamic stability during beating heart coronary surgery on marginal arteries. An animal experimental porcine study.

OBJECTIVES: In many heart centers myocardial revascularization using beating heart coronary surgery has partly replaced conventional coronary artery bypass grafting (cCABG) using cardiopulmonary bypass. However, access to the marginal arteries is problematic and hampered by space limitations, which might compromise the quality of the anastomoses and it entails a significant risk of hemodynamic instability subsequent to the manipulations of the heart. Hemodynamic impairment may be caused by dislocation of the low-pressure right atrium and ventricle. Therefore, it was hypothesized that the use of Right Heart Assist (RHA) may be able to ensure hemodynamic stability when tilting and manipulating the heart. DESIGN: In an animal experimental model RHA was implemented in order to study the hemodynamic impact of dislocating the heart in a standardized fashion. RESULTS: Dislocation of the unassisted heart to expose the first and second marginal branches caused a decline in arterial blood pressure, cardiac output and venous saturation of 38-48%. Supported by RHA this decrease was minimized to 0-17%. CONCLUSION: RHA for beating heart procedures indicates several advantages: ample time and safety while making the anastomoses at the marginal branches, less space limitations and enhanced control of hemodynamic stability compared with no RHA. This operation technique is challenging current practice and indications, and may potentially replace cCABG for the majority of patients.

[Coronary bypass surgery without heart-lung-machine. First experiences and results after two years]. / Koronar bypasskirurgi uden hjerte-lunge-maskine. Første erfaringer og resultater efter to år.

Results and experiences two years after the introduction of off-pump coronary artery bypass (OPCAB) are presented. The material includes 95 patients, where 24 patients had a high preoperative risk due to unstable angina, concomitant diseases or relative contraindications to conventional bypass surgery. Per- and postoperative course was characterized by low morbidity with ultra fast track recovery, no detectable levels of coronary enzyme release in the majority of patients, no reoperations for bleeding and early discharge from the hospital. There were two in-hospital deaths, both patients from the high risk group, where one patient died due to a preoperative myocardial infarction, while the other death was not related to cardiac disease. Follow-up results were fully satisfactory, where 86% of the patients were free from anginal symptoms three months after surgery. As a consequence of these positive experiences, OPCAB surgery is offered to an increasing number of patients, currently 25% of our CABG procedures.

Blood velocity patterns after aortic valve replacement with a pulmonary autograft.

OBJECTIVE: Besides several other advantages, aortic valve replacement with a pulmonary autograft may result in improved hemodynamic characteristics compared to other valve replacement procedures. However, this plausible assumption has never been verified. Therefore, the aim of this study was to determine turbulent blood velocity energies in the ascending aorta after aortic valve replacement with a pulmonary autograft. METHODS: Blood velocity measurements were performed using a specialized pulsed Doppler ultrasound technique in the ascending aorta immediately after weaning from extracorporeal circulation. Six patients were included in the study. Determination of radial velocity components in 17 measuring points evenly distributed in the cross sectional area allowed computation of turbulence energies and a quantitative display of the spatial and temporal turbulence energy distribution during systole. RESULTS: The maximum turbulence energies were below 13 N/m2 in all patients and in all measuring positions in the cross sectional area. Color coded mapping of the spatial and temporal turbulence energy distribution displayed no consistent areas with markedly enhanced turbulence. These data are moderately elevated compared to turbulence energy values for normal aortic valves, which are below 4 N/m2, while artificial or xenovalves typically show values in the range of 40-60 N/m2. CONCLUSIONS: Turbulence energy levels after aortic valve replacement with a pulmonary autograft are considerably lower than those found for artificial aortic valves. From a fluid dynamic point of view this procedure provides excellent hemodynamic conditions in the ascending aorta.

Anti-CD4 monoclonal antibody treatment in combination with total lymphoid irradiation and cyclosporin A in hamster-to-rat cardiac transplantation. Morphological features of heart grafts, recipient spleens and lymph nodes.

Significantly prolonged graft survival (GS) of hamster hearts transplanted heterotopically into rats can be achieved by different immunosuppressive treatment strategies. The exact mechanism of graft rejection is unclear, but it seems to be a primarily humoral, antibody-mediated type of rejection. The histopathology of long-term surviving grafts is controversial and the morphology of lymphoid tissue in spleens and lymph nodes as the possible site of anti-donor antibody formation has not previously been investigated. This report demonstrates a significantly prolonged GS in hamster-to-rat cardiac transplantation after combined treatment with total lymphoid irradiation (TLI), cyclosporin A (CyA) and anti-CD4 monoclonal antibodies (MAb), where long-term GS (> 100 days) could be achieved in a few animals. The histopathology of heart grafts showed predominantly chronic vascular changes with endothelial proliferation, intimal thickening and vessel obliteration. No substantial cellular reactivity in terms of mononuclear/lymphoid cell infiltration could be demonstrated in rejected grafts. Spleens and lymph nodes were characterized by a profound global reduction in lymphoid tissue after preoperative TLI. Although subsequent lymphoid regeneration was depressed due to postoperative immunosuppression, a significant increase in IgM-positive plasma cells was observed, supporting evidence of an antibody-mediated mechanism of graft rejection. The role of CD4+ cells is unclear, but anti-donor antibody formation might involve T-cell help.