Serotonin markers show altered transcription levels in an experimental pig model of mitral regurgitation.

Serotonin (5-hydroxytryptamine, 5-HT) signalling is implicated in the pathogenesis of myxomatous mitral valve disease (MMVD) through 5-HT1B receptor (R), 5-HT2AR and 5-HT2BR-induced myxomatous pathology. Based on increased tryptophan hydroxylase-1 (TPH-1) and decreased serotonin re-uptake transporter (SERT) in MMVD-affected valves, increased valvular 5-HT synthesis and decreased clearance have been suggested. It remains unknown how haemodynamic changes associated with mitral regurgitation (MR) affect 5-HT markers in the mitral valve, myocardium and circulation. Twenty-eight pigs underwent surgically induced MR or sham-operation, resulting in three MR groups: control (CON, n = 12), mild MR (mMR, n = 10) and severe MR (sMR, n = 6). The gene expression levels of 5-HT1BR, 5-HT2AR, 5-HT2BR, SERT and TPH-1 were analysed using quantitative PCR (qPCR) in the mitral valve (MV), anterior papillary muscle (AP) and left ventricle (LV). MV 5-HT2BR was also analysed with immunohistochemistry (IHC) in relation to histological lesions and valvular myofibroblasts. All 5-HTR mRNAs were up-regulated in MV compared to AP and LV (P <0.01). In contrast, SERT and TPH-1 were up-regulated in AP and LV compared to MV (P <0.05). In MV, mRNA levels were increased for 5-HT2BR (P = 0.02) and decreased for SERT (P = 0.03) in sMR vs. CON. There were no group differences in 5-HT2BR staining (IHC) but co-localisation was found with α-SMA-positive cells in 91% of all valves and with 33% of histological lesions. In LV, 5-HT1BR mRNA levels were increased in sMR vs. CON (P = 0.01). In conclusion, these data suggest that MR may affect mRNA expression of valvular 5-HT2BR and SERT, and left ventricular 5-HT1BR in some pigs.

Hypertrophied hearts: what of sevoflurane cardioprotection?

BACKGROUND: Recent studies have demonstrated that inhalation anaesthetics, like sevoflurane, confer cardioprotection both experimentally and clinically. However, coexisting cardiac disease might diminish anaesthetic cardioprotection and could partly explain why the clinical results of cardioprotection with anaesthetics remain controversial--in contrast to solid experimental evidence. Concomitant left ventricular hypertrophy is found in some cardiac surgery patients and could change cardioprotection efficacy. Hypertrophy could potentially render the heart less susceptible to sevoflurane cardioprotection and more susceptible to ischaemic injury. We investigated whether hypertrophy blocks sevoflurane cardioprotection, and whether tolerance to ischaemia is altered by left ventricular hypertrophy, in an established experimental animal model of ischaemia-reperfusion. METHODS: Anaesthetized juvenile pigs (n=7-12/group) were subjected to 45 min distal coronary artery balloon occlusion, followed by 120 min of reperfusion. Controls were given pentobarbital, while sevoflurane cardioprotection was achieved by 3.2% inhalation throughout the experiment. Chronic banding of the ascending aorta resulted in left ventricular hypertrophy development in two further groups and these animals underwent identical ischaemia-reperfusion protocols, with or without sevoflurane cardioprotection. Myocardial infarct sizes were compared post-mortem. RESULTS: The mean myocardial infarct size (% of area-at-risk) was reduced from mean 55.0 (13.6%) (+/-SD) in controls to 17.5 (13.2%) by sevoflurane (P=0.001). Sevoflurane reduced the infarct size in hypertrophied hearts to 14.6 (10.4%) (P=0.001); however, in hypertrophic controls, infarcts were reduced to 34.2 (10.2%) (P=0.001). CONCLUSION: Sevoflurane abrogated ischaemic injury to similar levels in both normal and left ventricular hypertrophied hearts.

Sevoflurane improves myocardial ischaemic tolerance in a closed-chest porcine model.

AIMS: Volatile anaesthetics prevent experimental myocardial ischaemia-reperfusion injury (I/R) in several species, but this finding is partially inconsistent with clinical evidence. Some experimental models may not accurately represent the complex signal transduction pathways triggered by volatile anaesthetics. We therefore investigated sevoflurane I/R prevention in vivo in a porcine model with greater likeness to human physiology than models previously used and compared it with neutral anaesthetic. METHODS AND RESULTS: Myocardial infarct size [IS/AAR] was compared in three groups of pigs (N=35) randomised to Control anaesthesia (pentobarbital infusion, n=12), sevoflurane inhalation alone (end-tidal concentration 3.2%) (Sevo, n=9), or both Combined (n=14), throughout ischaemia and reperfusion. Anterior/septal myocardial infarcts resulted from distal LAD coronary artery occlusion by balloon catheter for 45 min followed by 120 min of reperfusion. [IS/AAR] was measured in tetrazolium-stained heart slices after standardised image processing with computer-assisted planimetry. Measurements included full invasive monitoring. Control animals developed infarction in 55.0 +/- 3.9% (SEM) of the area at risk, Sevo in 17.5 +/- 4.4% (P=0.0002), and Combined with pentobarbital in 24.3 +/- 3.8% (P=0.0001) of the AAR, sevoflurane reducing infarct size significantly (68% and 60%, respectively). CONCLUSIONS: Sevoflurane markedly decreased myocardial infarct size after prolonged coronary occlusion in a porcine model. In addition to novel sevoflurane cardioprotection in the closed-chest model, which is more comparable to normal human hearts than models previously used, sevoflurane cardioprotection is substantiated in the juvenile intact organism. The perspectives underline recommending volatile anaesthetics in risk patients and in cardiac surgery.

Increased expression of endothelin B receptor in static stretch exposed porcine mitral valve leaflets.

The aim of this study was to evaluate the effect of mechanical stretch on the expression of ET-1 and ET(A)- and ET(B)-receptors in porcine mitral valve leaflets. Leaflet segments from 10 porcine mitral valves were exposed to a static stretch load of 1.5 N for 3.5h in buffer at 37 degrees C together with matching control segments. Subsequently, the mRNA expression of ET-1, ET(A)-R and ET(B)-R was measured by real-time RT-PCR in the chordal insertion areas. The analyses showed an increased transcription of ET(B)-receptors in stretch-exposed leaflet segments compared to unstretched segments median 2.23 (quartiles 1.37 and 2.70) vs. median 1.56 (quartiles 1.38 and 2.17, P=0.03) whereas the mRNA expression of ET(A)-receptors (P=0.90) and ET-1 (P=0.51) remained unchanged. Stretch increased the expression of ET(B)-receptors in porcine mitral valve leaflets. The finding could lead to a better understanding of the pathogenesis of myxomatous mitral valve disease.

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.

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.

Influence of anterior mitral leaflet second-order chordae on leaflet dynamics and valve competence.

BACKGROUND: Chordal transposition is used in mitral valve repair, yet the effects of second-order chord transection on valve function have not been extensively studied. We evaluated leaflet coaptation, three-dimensional anterior mitral valve leaflet shape, and valve competence after cutting anterior second-order chordae. METHODS: In 8 sheep radiopaque markers were affixed to the left ventricle, mitral annulus, and leaflets. Animals were studied immediately with biplane videofluoroscopy and echocardiography before (Control) and after (Cut2) severing two anterior second-order "strut" chordae. Leaflet coaptation was assessed as separation between leaflet edge markers in the midleaflet and near each commissure (anterior commissure, posterior commissure). Anterior leaflet geometry was determined 100 milliseconds after end-diastole from three-dimensional coordinates of 13 markers. RESULTS: Anterior leaflet geometry changed only slightly after chordal transection without inducing mitral regurgitation. Leaflet coaptation times were 79+/-17 and 87+/-22 milliseconds at the anterior commissure; 72+/-21, 72+/-19 milliseconds at midleaflet, and 71+/-12 and 75+/-8 milliseconds at the posterior commissure (p = NS) for Control and Cut2, respectively. CONCLUSIONS: Cutting anterior second-order chordae did not cause delayed leaflet coaptation, alter leaflet shape, or create mitral regurgitation. These data indicate that transposition of second-order anterior chordae ("strut" chordae) is not deleterious to anterior leaflet motion per se.

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.

Downstream turbulence and high intensity transient signals (HITS) following aortic valve replacement with Medtronic Hall or St. Jude Medical valve substitutes.

OBJECTIVE: High intensity transient signals (HITS) representing microembolization to the brain have been found to contribute to cognitive impairment and psychoneurological dysfunction in patients carrying a mechanical aortic valve. It is unknown, whether HITS represent gaseous or solid emboli. This animal study evaluates the impact of valve orientation on HITS for two different mechanical valves with both valves implanted in their best and worst orientation, which has been defined in previous studies with respect to downstream turbulence. METHODS: In four pigs a rotation device carrying either a Medtronic Hall (MH) or St. Jude Medical (SJM) valve size 23 mm was implanted. The device allowed rotation of the implanted valves without reopening of the aorta. Approximately 30 min after weaning from extracorporeal circulation, a Doppler probe was placed on both common carotid arteries. In different orientations of the implanted valves (best and worst position), HITS were detected by the Doppler probe and recorded for ten min by a transcranial Doppler sonography device (Medilab Inc., Estenfeld, Germany). RESULTS: HITS showed significant change with rotation for both valve designs. With the major orifice of the MH oriented towards the non-coronary leaflet (optimum position) very low HITS-counts (0.8-1.7/min) were observed. In the worst orientation HITS rose to 43-66/min. For the SJM the HITS count in the optimum position was 23.4-24/min and in the worst orientation 38-48/min. CONCLUSIONS: Valve orientation has an important impact on microembolization to the brain. In the optimum orientation (large orifice facing the non-coronary leaflet) the Medtronic Hall valve showed negligible incidence of HITS. The St. Jude Medical bileaflet valve showed less variation but demonstrated significant HITS counts at any orientation. As the MH in the worst position shows significantly higher turbulent stresses than the SJM but no higher incidence of HITS, a strong correlation between turbulence and HITS was not demonstrated by this study.

Prosthetic heart valve evaluation by magnetic resonance imaging.

OBJECTIVE: To evaluate the potential of magnetic resonance imaging (MRI) for evaluation of velocity fields downstream of prosthetic aortic valves. Furthermore, to provide comparative data from bileaflet aortic valve prostheses in vitro and in patients. METHODS: A pulsatile flow loop was set up in a 7.0 Tesla MRI scanner to study fluid velocity data downstream of a 25 mm aortic bileaflet heart valve prosthesis. Three dimensional surface plots of velocity fields were displayed. In six NYHA class I patients blood velocity profiles were studied downstream of their St. Jude Medical aortic valves using a 1.5 Tesla MRI whole-body scanner. Blood velocity data were displayed as mentioned above. RESULTS: Fluid velocity profiles obtained from in vitro studies 0.25 valve diameter downstream of the valve exhibited significant details about the cross sectional distribution of fluid velocities. This distribution completely reflected the valve design. Blood velocity profiles in humans were considerably smoother and in some cases skewed with the highest velocities toward the anterior-right ascending aortic wall. CONCLUSION: Display and interpretation of fluid and blood velocity data obtained downstream of prosthetic valves is feasible both in vitro and in vivo using the MRI technique. An in vitro model with a straight tube and the test valve oriented orthogonally to the long axis of the test tube does not entail fluid velocity profiles which are compatible to those obtained from humans, probably due to the much more complex human geometry, and variable alignment of the valve with the ascending aorta. With the steadily improving quality of MRI scanners this technique has significant potential for comparative in vitro and in vivo hemodynamic evaluation of heart valves.

High-frequency pressure fluctuations measured in heart valve patients.

BACKGROUND AND AIM OF THE STUDY: Due to the risk of thromboembolic complications, mechanical heart valve patients require life-long anticoagulant therapy, in contrast to bioprosthetic valves. The reason for this is still not fully understood. In vitro studies have demonstrated the presence of cavitation bubbles in the vicinity of mechanical heart valves, but not of bioprosthetic valves. When cavitation bubbles collapse, they release a significant amount of energy, which may damage the formed elements of the blood. A correlation between the presence of cavitation bubbles and high-frequency pressure oscillations has been established in vitro. Thus, the aim of this study was to measure and quantify high-frequency pressure oscillations in patients with normal, bioprosthetic or mechanical aortic valves. METHODS: Measurements were performed in six patients with normal aortic valves after coronary bypass surgery, in five patients fitted with a Carpentier-Edwards pericardial bioprosthesis, and in nine patients fitted with a St. Jude Medical or CarboMedics aortic valve. High-frequency pressure fluctuations were measured intraoperatively using a hydrophone placed near the aortic annulus. The root mean square (RMS) value of the high-frequency pressure signals were calculated in the frequency range 35-150 kHz. RESULTS: High-frequency pressure fluctuations, with intensities above the noise floor, were registered only in the vicinity of mechanical heart valve prostheses, and not in the vicinity of normal or bioprosthetic valves. The mean value of RMS pressure fluctuations was 0.5 Pa for normal aortic valves, 0.8 Pa for bioprosthetic valves, and 67 Pa for mechanical valves. CONCLUSIONS: This study is the first to show the presence of high-frequency pressure fluctuations in patients with mechanical valves.

In vivo analysis of dynamic tensile stresses at arterial end-to-end anastomoses. Influence of suture-line and graft on anastomotic biomechanics.

OBJECTIVE: to determine the influence of an anastomotic suture line and a graft on dynamic tensile stresses of vascular end-to-end anastomoses in vivo. MATERIAL AND METHODS: the abdominal aorta of twelve 35-kg pigs was used as an experimental model. Simultaneous recordings of internal arterial diameter and pressure were performed on each pig at 3 successive stages: (1) The genuine artery (REF), (2) artery-artery (A-A) and (3) graft-artery (G-A) anastomosis at 1-mm increments in the immediate perianastomotic area. Thereby, RD (relative distension), CC (compliance coefficient), E(p)(dynamic pressure-strain elastic modulus) and hysteresis loop areas could be calculated for every measuring point. RESULTS: the graft was significantly stiffer than REF. A-A and G-A anastomoses were significantly less compliant than REF. Maximum E(p), minimum CC and hysteresis loop areas were found at the anastomotic line due to minimum anastomotic RD. Downstream of the G-A anastomosis, the RD, CC, E(p)and loop areas were significantly different from REF, but significantly different from A-A. CONCLUSION: an animal model for acute studies of mechanical properties of vascular end-to-end anastomoses was developed. The main determinant for anastomotic biomechanics was the suture-line itself.

Animal experimental implantation of an atrial septal defect occluder system.

OBJECTIVE: To establish the implantation technique for the atrial septal defect occluder system (ASDOS) device in an experimental animal model and to determine long term mechanical stability of the device and its in vivo properties in terms of biocompatibility and tissue reaction. MATERIALS AND METHODS: An atrial septal defect was created and the device implanted in 17 pigs (mean weight 30 kg). The implantation technique was refined and modified because of initial technical and anatomical complications during nine acute pilot studies. The technique proved to be feasible in eight subsequent survival studies. Four pigs were electively killed three months after implantation (group 1). The remaining four pigs were killed six months after implantation (group 2). RESULTS: Necropsy showed all devices were embedded in soft tissue three months after implantation. Microscopic examination of atrial septal tissue showed an acute granulomatous inflammatory reaction in group 1 and fibrosis in group 2. The intensity of the inflammatory reaction around the device was clearly milder in group 2, indicating a decline in the inflammatory response with time. Clinical and biochemical investigations indicated acceptable biocompatibility of the device. CONCLUSION: The implantation technique for the ASDOS device in a chronic pig model has been established. Biocompatibility of the device was acceptable.

Self management of oral anticoagulant therapy after heart valve replacement.

OBJECTIVE: Patients with mechanical heart valves require lifelong oral anticoagulant treatment which entails frequent blood sampling and dosage adjustment. The purpose of this study was to investigate the feasibility of letting heart valve operated patients manage blood specimen analysis and dosage adjustment themselves. METHODS: A total of 21 patients were enrolled in the study and followed for at least 9 months postoperatively. Immediately after the heart valve operation they were trained in operating a CoaguChek international normal ratio (INR) monitor to analyze capillary whole blood samples. Subsequently training in dosage adjustment was accomplished and all patients were considered fully capable of self management after 30 weeks. In the training period, parallel laboratory INR measurements were made at 3-4 week intervals for reference. A control group of 20 patients was matched, respectively, to the study group. The INR target range was 2.0-3.0. RESULTS: Out of the 21 study patients 19 continued self management beyond 9 months. The median INR value obtained with the monitor was within therapeutic target range for all study patients and only 15 out of 20 control patients were within this range. The mean systematic deviation between laboratory and CoaguChek INR was 7.8% but each patient had a constant characteristic deviation from -11 to +21%. The study patients were within therapeutic target range 77% of the time compared with 53% for the control patients. CONCLUSIONS: Self management of oral anticoagulation is feasible for selected patients and constitutes a significant service improvement compared with conventional management. The CoaguChek monitor seems sufficiently accurate and reliable for self testing and the treatment quality is comparable or even better than conventional management. Assessment of the rate of bleeding and thrombo-embolic events shall be settled in studies comprising larger number of patients.

Clinical evaluation of Duraflo II heparin treated extracorporeal circulation circuits (2nd version). The European Working Group on heparin coated extracorporeal circulation circuits.

OBJECTIVES: To evaluate whether the application of heparin treated circuits for elective coronary artery surgery improves postoperative recovery, a European multicenter randomised clinical trial was carried out. METHODS: In 11 European heart centers, 805 low-risk patients underwent cardiopulmonary bypass (CPB) with either an untreated circuit (n = 407) or an identical but heparin treated circuit (n = 398, Duraflo II). RESULTS: Significant differences were found among participating centers with respect to patient characteristics, blood handling procedures and postoperative care. The use of heparin treated circuits revealed no overall changes in blood loss, blood use, time on ventilator, occurrence of adverse events, morbidity, mortality, and intensive care stay. These results did not change after adjustment for centers and (other) prognostic factors as analysed with logistic regression. In both groups no clinical or technical (patient or device related) side effects were reported. Because female gender and aortic cross clamp time appeared as prognostic factors in the logistic regression analysis, a subgroup analysis with these variables was performed. In a subpopulation of females (n = 99), those receiving heparin treated circuits needed less blood products, had a lower incidence of rhythm disturbances and were extubated earlier than controls. In another subgroup of patients with aortic cross clamp time exceeding 60 min (n = 197), the amount of patients requiring prolonged intensive care treatment (> 24 h) was significantly lower when they received heparin treated circuits versus controls. CONCLUSION: These findings suggest that improved recovery can be expected with heparin treated circuits in specific higher risk patient populations (e.g. females) and when prolonged aortic cross clamp time is anticipated. Further investigations are recommended to analyses the clinical benefit of heparin treated circuits in studies with patients in different well defined risk categories and under better standardised circumstances.

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.

New method for monitoring the functional state of a dynamic cardiomyoplasty.

OBJECTIVE: To assess the impact of a dynamic cardiomyoplasty on failing hearts, it is essential to estimate the contraction force of the skeletal muscle and how its contraction is synchronized with the heart cycle. METHODS: In a 6-month study a small fluid-filled, balloon-mounted catheter was placed between the myocardium and the muscular wrap in five adult female Boor goats and two female domestic pigs. The catheter was connected to a subcutaneous measuring chamber whereby pressure monitoring could be accomplished. Distinct pressure signals as a result of function of the dynamic cardiomyoplasty and the heart were detected initially in all animals. RESULTS: Maximal relative pressure from the dynamic cardiomyoplasty was calculated as 336.2% +/- 69.4% on day 24 +/- 6.1 (n = 7) and end-stage pressure as 59.8% +/- 9.7% on day 174.6 +/- 13.1 (n = 4). A functional loss of pressure signals from the dynamic cardiomyoplasty was correlated to severe histologic muscle damage (n = 3). Pressure signals transferred from the contracting myocardium to the catheter showed defined segments of contraction, ejection, and filling periods, allowing a mechanical synchronization of the dynamic cardiomyoplasty to the heart cycle. CONCLUSIONS: This monitoring catheter enabled the assessment of the functional state of the dynamic cardiomyoplasty and allowed a synchronization to the heart cycle. It will promote understanding and might help to avoid muscle damage in dynamic cardiomyoplasty for an improved outcome of the surgical treatment of end-stage heart failure.

Arteriovenous fistulas aggravate the hemodynamic effect of vein bypass stenoses: an in vitro study.

PURPOSE: The purpose of this study was to assess the impact of arteriovenous fistulas combined with varying degrees of stenosis on distal bypass hemodynamics and Doppler spectral parameters. METHODS: In an in vitro flow model bypass stenoses causing 30%, 55%, and 70% diameter reduction were induced 10 cm upstream of a fistula with low outflow resistance. Flow and intraluminal pressure were measured proximal to the stenosis and downstream of the fistula. The waveform parameters peak systolic velocity, end-diastolic velocity, pulsatility index, and pulse rise time were determined from midstream Doppler spectra obtained 10 cm downstream of the fistula. All measurements were carried out with open and clamped fistula. RESULTS: At 30% diameter reducing stenosis opening of the fistula induced a 12% systolic pressure drop across the stenosis but had no adverse effect on the Doppler waveform parameters. At 55% stenosis the pressure drop increased from 16% to 31% after fistula opening. This increased pressure drop was associated with a further reduction in peak systolic velocity, a decrease in pulsatility index, and an enhanced pulse rise time prolongation. Fistula opening at 70% stenosis increased the systolic pressure drop from 31% to 48% and had significant impact on all waveform parameters. CONCLUSIONS: Distal arteriovenous fistulas enhance pressure loss across stenoses and affect downstream velocity waveform configuration. The presence of a combined fistula and a stenosis mimics the distal hemodynamic conditions of a more severe stenosis. Assessment of the hemodynamic impact of fistulas must be undertaken in the evaluation of in situ vein bypass stenoses.

Monitoring thrombin generation with prothrombin fragment 1.2 assay during cardiopulmonary bypass surgery.

UNLABELLED: Despite high plasma levels of heparin during cardiopulmonary bypass surgery, activation of the coagulation system has been reported. We hypothesize that the coagulation system activity most appropriately could be assessed by molecular markers of thrombin generation. The aim of the present study was to describe the changes in thrombin generation during CPB, using prothrombin fragment F1 + 2 (F1.2) as an indicator and evaluate different blood sampling regimens for interpretation of the F1.2 measurements. Twenty patients, operated under extracorporeal circulation with coronary artery bypass grafting (CABG), comprised the study material. The heparin levels were maintained above 2.5 IU/ml throughout the bypass procedure and the functional AT-III level was kept above 0.5 U/ml. Despite of this anticipated inactivation of the coagulation system, the concentrations of F1.2 and FpA increased throughout CPB, particularly after release of the aortic crossclamp. F1.2 and FpA correlated significantly (R = 0.69). No statistically significant correlation was found between F1.2 formation rate and age, bodyweight, baseline ACT, ACT after 200 IU heparin/kg, average heparin concentration during CPB or average AT-III level during CPB. CONCLUSIONS: Thrombin formation seems to be a continuous process during CPB despite adequate heparinization. The pattern of thrombin generation can be assessed most appropriately in terms of F1.2 generation rate. Extraordinary high levels of F1.2 were seen after release of the aortic crossclamp, indicating that the periods before and after aortic crossclamping should be evaluated separately.