Purpose: Assessment of contractile function is a major challenge in patients with left ventricular dysfunction, especially during cardiac surgery. The initial tangent of the femoral arterial pressure increase (tanin) has recently been described to be an estimate of left ventricular (LV) contractility. To confirm these findings tanin was compared to various indices of LV performance in patients undergoing cardiac surgery. Methods: Data from 17 patients were evaluated retrospectively. Myocardial performance was estimated by the echocardiographic indices ejection fraction (EF), shortening fraction (FS), circumferential fiber shortening velocity (Vcf), the parameters of pulse contour analysis area under the curve (AUC) and tanin. Measurements were taken before and after cardiopulmonary bypass (CPB). Results: Tanin increased significantly (813 ± 216 mmHg/s vs. 1490 ± 450 mmHg/s, p in and Vcf correlated strongly (r = 0.70, p in showed only weak correlation with EF (r = 0.36, p = 0.037). There was no significant correlation with FS (r = 0.31, p = 0.079). Tanin and AUC correlated inversely (r = -0.62, p in correlated well with the less preload-dependent parameter Vcf, thus suggesting that tanin may be used as an easily accessible estimate of LV contractility during cardiac surgery.

Purpose: Ex vivo cardiac perfusion can be used as a model for the acute phase after weaning from cardiopulmonary bypass. Dysfunction of the right ventricle is frequently observed after extended cardiopulmonary bypass but in current experimental working heart designs physiologic preload of the right heart is not achieved. Thus we designed an ex-vivo cardiac perfusion system that allows reperfusion of a porcine heart, weaning form circulatory support with a transition to complete work load for the right and left ventricle.

Trotz großer operativer und anästhesiologischer Fortschritte sind die perioperative Morbidität und Letalität in der Gefäßchirurgie häufig deutlich höher als bei anderen operativen Eingriffen. Hierzu tragen sowohl die hohe Prävalenz relevanter Begleiterkrankungen als auch Art und Ausmaß des operativen Eingriffs mit Beeinträchtigungen von Hämodynamik und Organperfusion bei. Das perioperative Management erfordert daher die Kenntnis der patientenbezogenen Risikofaktoren und ein fundiertes Verständnis der pathophysiologischen Zusammenhänge sowie des operativen Vorgehens.

The present study investigates why shedding of the endothelial glycocalyx occurs both in patients undergoing on- and off-pump coronary artery bypass surgery. Release of atrial natriuretic peptide (ANP) was of special interest, because ANP initiates shedding ex vivo. Three major constituents of the glycocalyx (syndecan-1, heparan sulfate and hyaluronan) were measured in arterial blood of patients undergoing coronary artery bypass surgery with (n = 15) and without (n = 15) cardiopulmonary bypass at various phases of the procedure. Additionally, the levels of the inflammatory cytokines interleukin (IL)-6, -8, and -10 and of ANP were evaluated. Elevations of all three components of the glycocalyx were detected in blood of patients undergoing on- (maximum increases: syndecan-1 15-fold, heparan sulfate ninefold, hyaluronan fivefold basal) and off-pump (maximum increases: syndecan-1 fourfold, heparan sulfate twofold, hyaluronan threefold basal) coronary artery surgery. Maximum ANP concentrations increased three- and fourfold basal in on- and off-pump coronary artery surgery, respectively (P < 0.05). There were significant increases in the three cytokine concentrations in both on- (maximum increases: IL-6 146-fold, IL-8 23-fold, IL-10 238-fold basal) and off-pump (maximum increases: IL-6 77-fold, IL-8 eightfold, IL-10 58-fold basal) coronary artery surgery. However, the elevations of ANP preceded those of the cytokines and coincided with or even preceded shedding of the human endothelial glycocalyx in both surgical procedures. These data suggest that release of ANP may lead to perturbation of the endothelial glycocalyx in both on- and off-pump coronary artery bypass surgery.

BACKGROUND:Whilst macrohemodynamic function of porcine xenografts transplanted into baboons has been assessed perioperatively, the ability of the xenograft to maintain systemic microcirculatory perfusion has not been investigated after pig-to-baboon xenotransplantation so far.METHODS:We investigated the sublingual microcirculation of six baboons undergoing orthotopic transplantation of hCD46-transgenic pig hearts using orthogonal polarization spectral imaging. Microvascular measurements were performed after induction of anesthesia, in the early phase of cardiopulmonary bypass (CPB), during reperfusion of the porcine heart and 1 h after the xenograft had resumed its life-supporting function. Microvascular blood flow was analyzed semiquantitatively and the number of visualized cell-to-cell interactions was counted.RESULTS:The proportion of continuously perfused microvessels was 97 (96 to 97) % at baseline and 95 (94 to 97) % in the early phase of CPB. It decreased significantly (P < 0.05) during CPB to 89 (84 to 91), and alterations were still present (P < 0.05) when CPB was terminated and the xenograft had taken over systemic perfusion 83 (81 to 85) %. The microcirculatory changes correlated with the lactate levels (y = 18.1-0.18 x; r(2) = 0.55; P < 0.001), but no correlation with macrohemodynamic parameters was found.CONCLUSION:Microvascular blood flow is altered after orthotopic pig-to-baboon heart transplantation, despite systemic hemodynamic parameters being well maintained by the porcine xenograft. These changes are moderate but persist after termination of CPB. Further studies need to elucidate whether these changes are transient or add to the mortality associated with cardiac xenotransplantation.

BACKGROUND:Displacement of the heart is necessary to expose the target vessel for distal anastomosis to achieve successful multivessel off-pump coronary artery bypass (OPCAB) grafting. In addition to complete revascularisation of the heart, a main challenge during the operation is to maintain haemodynamic stability during this procedure. A new heart positioner (Tentacles) was tested.METHODS:In a prospective clinical study we used the Tentacles device in 50 patients scheduled for multivessel OPCAB procedures and investigated the haemodynamic effects during displacement of the heart and while performing the anastomoses to the anterior, lateral and posterior wall. The following haemodynamic parameters were investigated: mean arterial blood pressure (MAP), cardiac index (CI) and stroke volume index (SVI). The incidence of myocardial ischaemia was monitored by transoesophageal echocardiography (TEE) and by ST-segment analysis in the electrocardiogram (ECG).RESULT:The Tentacles device permitted rapid, secure and excellent exposure of the lateral and posterior wall of the heart. During exposure of the anterior wall there was a small decrease in MAP (77 ± 10 vs.71 ± 9 mmHg, P = 0.02) in combination with an increase in the CI (3.0 ± 0.7 l vs. 3.1 ± 0.8 l/min/m2, P = 0.03). When the lateral and posterior walls of the heart were exposed, the SVI decreased significantly (36 ± 11 and 38 ± 8 mL/m2, P < 0.01 and P = 0.04, respectively) compared to baseline (44 ± 11 mL/m2) while CI and MAP remained stable. The amount of norepinephrine administered during displacement of the heart was significantly higher in all three positions (0.05 ± 0.05, 0.06 ± 0.05 and 0.04 ± 0.03 µg/kg/min, P < 0.01) compared to the physiological position (0.02 ± 0.02 µg/kg/min). Sinus rhythm was maintained throughout the operation. Neither significant changes of the ST-segment in the ECG nor incidences of wall motion abnormality in TEE were observed. Six hours postoperatively the troponin I concentration was 11.7 ± 4.3 ng/mL.CONCLUSION:The Tentacles device provided excellent access in multivessel OPCAB surgery. Haemodynamic stability was maintained in all patients; however additional catecholamine support was used when the heart was displaced. This was the case when carrying out an anastomosis on the anterior, lateral, or posterior wall.

BACKGROUND:Heterotopic thoracic heart transplantation may be an alternative to the established heterotopic abdominal or orthotopic cardiac xenotransplantation model as it combines the safety of heterotopic transplantation with the benefit of a working heart model. METHODS:In a first series of two animals, we tested the surgical feasibility of this procedure with non-transgenic pig hearts transplanted into pre-sensitized baboons (killed after weaning from cardiopulmonary bypass). In a second group (n = 2), double-transgenic alpha(1,3)galactosyl-transferase knock out/hCD46 pig hearts were transplanted into naïve baboons after immunoadsorption. The immunosuppressive regimen consisted of anti-CD20-mAb, tacrolimus, sirolimus, MMF and steroids. RESULTS:The first baboon was successfully transplanted, but died of an air embolism, while in the second animal graft survival was 50 days with the recipient in good physical condition. One rejection reaction was successfully treated by immunoadsorption, ATG and the proteasome inhibitor bortezomib. Post-mortem histopathology showed no evidence for humoral or cellular rejection of the cardiac xenograft. CONCLUSIONS:This is the first description of a heterotopic thoracic pig-to-baboon heart transplantation. The procedure combines the advantages of a working heart model with the safety of heterotopic transplantation. In contrast to orthotopic transplantation, the recipient heart can assist the donor heart during episodes of rejection. We believe that the heterotopic thoracic model may accelerate the progress into the clinical application of cardiac xenotransplantation. However, successful combination of this heterotopic transplantation with an experimental model of cardiac failure may be needed before this technique can be promoted to clinical trials.

BACKGROUND:The implantation of ventricular assist devices is a well-established procedure for the treatment of imminent heart failure. The exact positioning of the left ventricular apical inflow cannula is crucial, because inflow restrictions might occur when the cannula is placed too close to the interventricular septum or a papillary muscle. We report a novel technique using the Tentacles 3-point fixation device for the exposure of the left ventricular apex during ventricular fibrillation under cardiopulmonary bypass.METHODS:We used the Tentacles, a device originally designed for positioning the heart during off-pump coronary artery bypass grafting, for implantation of a biventricular Berlin Heart Excor in a 64-year-old man. The procedure was successful and echocardiographic examinations documented the exact placement of the left ventricular cannula.RESULTS AND CONCLUSION:Our new technique ensures a very precise insertion of apical cannulae, because the left ventricular shape and filling are not impaired.

A healthy vascular endothelium is coated by the endothelial glycocalyx. Its main constituents are transmembrane syndecans and bound heparan sulfates. In vivo the glycocalyx binds plasma proteins, forming the endothelial surface layer, which has a thickness of 500 to 1000 nm in microvessels.1 This large structure maintains the physiologic permeability barrier and prevents leukocyte and platelet adhesion, thereby mitigating inflammation and tissue edema.1,2

In adults with severe sepsis, the disturbances of the sublingual microcirculation can be quantified with orthogonal polarization spectral imaging. We investigated the cutaneous microcirculation of preterm infants with proven infection (PosInf) and with suspected but unproven infection (NegInf). In 25 infants, orthogonal polarization spectral images were obtained daily, videos of the images were blinded, and analyzed off-line. Functional small vessel density (FSVD) was prospectively calculated from day 3 to day 30 of life. There were 17 episodes of proven and nine episodes of suspected but unproven nosocomial late onset infection. Four infants remained healthy. The data were analyzed for the 5 d before the start of antibiotics (day −5 until day −1). FSVD varied widely, but in the PosInf-group, we found a 10% decline from day −5 to day −1 (p = 0.013). There was no significant change over time in the NegInf-group (p = 0.58). Thus, in infants with proven infection, FSVD decreases already 1 d before changes in laboratory parameters. However, these changes in FSVD during infection are not represented by absolute values, but must be identified by daily intraindividual observation.

With great interest, we read the article by Bauer et al. 1on sublingual microvascular perfusion in 47 patients who underwent hypothermic cardiopulmonary bypass surgery. The authors report a 10% decrease in functional capillary density during cardiopulmonary bypass without changes in microvascular diameter or erythrocyte velocity. These results are partly in contrast with our recent findings in a comparable setting.2Although both studies evaluated the sublingual microcirculation by a two-dimensional imaging technique, several differences do exist, of which the imaging technique itself and the subsequent way of analysis are most important. To understand the different results more comprehensively, we would like to comment on several aspects of the study by Bauer et al. First, we used side-stream dark-field imaging, a novel technology based on the orthogonal polarization spectral imaging technique used by the authors. Side-stream dark-field imaging differs from orthogonal polarization spectral technology in terms of magnification and capillary contrast. These differences between the two-dimensional imaging techniques hinder comparison of results obtained by orthogonal polarization spectral versus side-stream dark-field imaging and may explain the differential results. Second, the authors used software to measure microvascular diameter, erythrocyte velocity, and functional capillary density. In our study, a semiquantitative analysis technique was used. Although software can be helpful in decreasing the burden of a time-consuming semiquantitative analysis, we have to look critically at the numbers produced by the software. For example, we would like to learn from the authors whether it was possible to measure erythrocyte velocity in each investigated capillary and venule. Using Microscan Analysis Software (MicroVisionMedical, Inc., Amsterdam, The Netherlands), we experienced that it was impossible to measure high erythrocyte velocities that do exist in a substantial number of capillaries. This problem is probably due to a limited video frame rate: 25 frames/s for phase alternating line standard. Finally, several issues remain unclear after reading the authors’ article. The inclusion criteria used by the authors are not exactly mentioned. Did the authors investigate consecutive, low-risk patients? What was the estimated risk of surgery for the patient population (logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE])? What were the incidences of postoperative morbidity and mortality? We think it might be interesting to investigate a possible relation between intraoperative hypoperfusion of the microcirculation and postoperative outcome. This might be studied in a subgroup of patients with impaired functional capillary density during cardiopulmonary bypass. In addition to this, we wonder why the authors did not separate venules from capillaries, using a cutoff of 20 μm.To conclude, it is of interest to note that both studies reported moderate changes in the sublingual microcirculation that probably reflect a complex pathophysiology during cardiopulmonary bypass. It is expected that novel bedside imaging technology will simplify further microcirculation research in patients based on studies that were performed previously in laboratory animals.3,4We should focus on the questions of which individual stimuli are responsible for the reported changes and whether these changes are of clinical significance. Larger studies, perhaps in high-risk patients, would be helpful to draw stronger conclusions.*Erasmus Medical Center, Rotterdam, The Netherlands. c.denuil@erasmusmc.nl

Changes in microcirculation have been recognized as central to many disease processes. The aim of this study was to evaluate factors, which influence the microcirculation of the skin during the first month of life in premature infants. Red blood cell (RBC) velocity, vessel diameter, and functional small vessel density (FSVD) were measured daily for the first 30 d on the upper arm in preterm infants with gestational age <30 wk. Orthogonal polarization spectral (OPS) images were analyzed off-line with the CapiScope-Image program. In 25 infants, FSVD decreased significantly from week 1 (mean ± SD 236 ± 33 cm/cm2) to week 4 (207 ± 30 cm/cm2) and correlated directly with Hb levels and incubator temperature. Vessel diameters and RBC velocity did not change significantly, nor did clinical parameters such as blood pressure, heart rate or body temperature. Microvascular parameters were not dependent on gestational or postnatal age. The microcirculation of the skin might be an easily accessible window to obtain better understanding of circulatory changes in the postnatal period. Our data are essential as basis for further studies in this field. Hb levels and possible incubator temperatures have a substantial influence on functional small vessel density and therefore need to be taken in account.

The objective of this study was to examine microvascular perfusion during hypobaric hypoxia and physical exercise. We used orthogonal polarization spectral imaging for the non-invasive visualization and assessment of the sublingual mucosal microcirculation in twelve healthy altitude acclimatized mountaineers. Red blood cell velocity (RCV), microvascular diameter (Dia), functional capillary density (FCD) and the number of rolling leukocytes were studied at baseline and after (I) a climb to an altitude of 3196 m, (II) a passive ascent to the same altitude by helicopter and (III) an exercise program at an altitude below 2100 m in the European Alps. Exposure to high altitude and exercise resulted in an increased heart rate (Trial I: 64 (54-66) vs. 95 (84-100); median (interquartile range); P<0.05) and decreased oxygen saturation (Trial I: 98 (98-99) vs. 90 (88-92); P<0.05). However, RCV, Dia and FCD did not change significantly. Furthermore, no enhanced rolling of leukocytes in postcapillary venules could be observed (Trial I: 6.2 (4.4-6.8) vs. 7.8 (4.3-6.7)). In the pooled data of all three trials of this study we could show a significant positive correlation between oxygen saturation and red blood cell velocity (r = 0.25; P = 0.02). These results indicate that orthogonal polarization spectral imaging can be a useful tool for the microcirculatory assessment of man under hypoxic conditions. We could show that in trained, acclimatized subjects microvascular perfusion is well maintained during hypobaric hypoxia at an altitude of 3196 m and no evidence for an increased postcapillary leukocyte adhesion was seen.