Pulse conductance and flow-induced hemolysis during pulsatile cardiopulmonary bypass.

In this study, the hypothesis was tested that a low-resistant, high-compliant oxygenator provides better pulse conductance and less hemolysis than a high-resistant, low-compliant oxygenator during pulsatile cardiopulmonary bypass. Forty adults undergoing coronary artery bypass surgery were randomly divided into two groups using either an oxygenator with a relatively low hydraulic resistance (Quadrox BE-HMO 2000, Maquet Cardiopulmonary AG, Hirrlingen, Germany) or with a relatively high hydraulic resistance (Capiox SX18, Terumo Cardiovascular Systems, Tokyo, Japan). The phase shift between the flow signals measured at the inlet and outlet of the oxygenator was used to assess compliance. Pulse conductance in terms of pressure attenuation was calculated by dividing the outlet pulse pressure of the oxygenator by the inlet pulse pressure. A normalized index was used to assess hemolysis. The phase shifts in time of the flow pulses were 36 +/- 6 ms in the low-resistant (high-compliant) oxygenator, and 14 +/- 2 ms in the high-resistant (low-compliant) oxygenator group (P < 0.001). The low-resistant, high-compliant oxygenator provided 27% better pulse conductance compared with the high-resistant, low-compliant oxygenator (0.84 +/- 0.02 and 0.66 +/- 0.01, respectively, P < 0.001). Inlet pulse pressures were significantly higher (29%) in the high-resistant, low-compliant (Capiox) group than in the low-resistant, high-compliant (Quadrox) group (838 +/- 38 mm Hg and 648 +/- 25 mm Hg respectively, P < 0.001), but no significant difference in hemolysis was found. A low-resistant, high-compliant oxygenator provides better pulse conduction than a high-resistant, low-compliant oxygenator. However, the study data could not confirm the association of high pressures with increased hemolysis.

Intrapericardial delivery of amiodarone and sotalol: atrial transmural drug distribution and electrophysiological effects.

Amiodarone and sotalol are frequently used in the treatment of atrial fibrillation. However, oral and intravenous (IV) therapy with these drugs has suboptimal efficacy and is associated with serious extracardiac side effects. We hypothesized that intrapericardial (IPC) delivery produces antiarrhythmic effects at lower plasma drug concentrations than IV delivery. Goats (n = 27) were randomised into 5 groups receiving either IPC vehicle, amiodarone (IV or IPC) or dl-sotalol (IV or IPC). Epicardial and endocardial atrial effective refractory period and atrial response to burst pacing (rapid atrial response, RAR) were assessed before and after 3 hours of drug infusion at 2 mg.kg.h. IPC delivery produced steeply decreasing drug concentrations from epicardium to endocardium in both atria and ventricles. Plasma drug concentrations were significantly lower in IPC than in IV groups. IPC amiodarone and sotalol reduced epicardial RAR inducibility (-74% +/- 20% and -66% +/- 30%, respectively) compared with IV delivery (-11% +/- 17% and -17% +/- 28%, respectively; P < 0.05). Endocardial RAR inducibility was only reduced in the IPC amiodarone group (-70% +/- 17%, P < 0.05). In conclusion, IPC delivery of amiodarone and sotalol increases atrial drug concentration and antiarrhythmic effects at reduced plasma drug concentrations. These potential benefits are particularly prominent for IPC delivered amiodarone.

Laboratory performance testing of venous cannulae during inlet obstruction.

Venous cannulae undergo continuous improvements to achieve better and safer venous drainage. Several cannula tests have been reported, though cannula performance during inlet obstruction has never been a test criterion. In this study, five different cannulae for proximal venous drainage were tested in a mock circulation that enabled measurement of hydraulic conductance after inlet obstruction by vessel collapse. Values for hydraulic conductance ranged from 1.11 x 10(-2) L/min/mm Hg for a Thin-Flex Single Stage Venous Cannula with an open-end lighthouse tip to 1.55 x 10(-2) L/min/mm Hg for a DLP VAD Venous Cannula featuring a swirled tip profile, showing a difference that amounts to nearly 40% of the lowest conductance value. Excessive venous drainage results in potentially dangerous high-negative venous line pressures independent of cannula design. Cannulatip design featuring swirled and grooved tip structures increases drainage capacity and enhances cannula performance during inlet obstruction.

New ultrasonic radiation reduces cerebral emboli during extracorporeal circulation.

OBJECTIVE: Cardiac surgery is associated with intraoperative cerebral emboli, which can result in postoperative neurological complications. A new ultrasonic transducer (EmBlocker) can be positioned on the ascending aorta and activation of the EmBlocker is expected to divert emboli to the descending aorta, thereby decreasing emboli in the cerebral arteries. In this preliminary animal study, safety and efficiency of this technology were examined. METHODS: In 14 pigs (+/-70 kg), a median sternotomy was performed and the EmBlocker was positioned on the aorta ascendens at the level of the bifurcation of the aorta and the innominate artery. In one animal temperature measurements were performed. During these measurements, the EmBlocker was activated for four periods of 120 s of high power (1.5 W/cm(2)) and for four periods of 600 s of low power (0.5 W/cm(2)). In the safety study (n=6), the EmBlocker was activated twice the expected clinical duration (eight periods of 120 s of high power and, subsequently, one period of 20 min of low power). Tissue samples (control and sonicated) were collected after 1 week for histopathological evaluation (aorta, trachea, esophagus, vagus nerves). In the efficiency study (n=7), extracorporeal circulation was installed. Emboli (air and solid (1200, size 500 microm-750 microm)) were introduced in the proximal ascending aorta and the EmBlocker was alternately activated with high power for solid emboli injections and low power for air emboli injections. Transcranial Doppler (TCD) was used to analyse middle cerebral artery blood flow for occurrence of embolic signals, which were manually counted offline. RESULTS: Histopathology revealed no difference between control and sonicated tissue. There is a rise in temperature during EmBlocker activation, but in all measured tissues it was within limits; less then 42 degrees C for 2 min in the aorta wall directly under the EmBlocker. Use of the EmBlocker significantly reduced emboli in the cerebral arteries in an animal model; air emboli with 65% (left) and 69% (right) and solid emboli with 49% (left) and 50% (right). CONCLUSIONS: The new ultrasound technology can safely be applied and is capable of reducing emboli in the cerebral arteries during extracorporeal circulation. Use of the EmBlocker in cardiac surgery bears the potential to lower the risk of postoperative neurological complications. Clinical feasibility studies are in progress.

Combined Impella and intra-aortic balloon pump support to improve both ventricular unloading and coronary blood flow for myocardial recovery: an experimental study.

Some patients in need of hemodynamic support do not respond to intra-aortic balloon pump (IABP) therapy. Hemodynamic stability can then be obtained by a more potent cardiac assist device, like the Impella catheter pump. Whether additional IABP support additional to Impella support can provide more optimal hemodynamic myocardial conditions is examined in this study. Seven sheep were implemented with IABP and Impella. An acute myocardial infarction was induced. Hemodynamic performance was assessed during baseline, during Impella support and IABP support individually, and during the combined Impella plus IABP support. The Impella support provided a reduction of afterload with 30% and an increase of coronary artery flow with 47%. The IABP increased coronary artery flow (13%), carotid artery flow (16%), and aortic ascending blood pressure (6%); a similar (but stronger) effect was provided when using the IABP support additional to Impella support and, respectively, increases of 33, 21, and 19% were established. The oxygen demand-supply ratio decreased by 25% due to the extra use of the IABP. A combination of IABP and Impella provides the most optimal hemodynamic myocardial conditions compared to either stand-alone support.

Synchronously counterpulsating extracorporeal life support enhances myocardial working conditions regardless of systemic perfusion pressure.

OBJECTIVE: A new pulsatile extracorporeal life support (pECLS) system has entered the market. We wanted to investigate what potential advantages pECLS may have over current non-pulsatile systems (NPS). Our research was focused on the pump's functional interaction with the left ventricle and the coronary circulation. METHODS: Extensive hemodynamic measurements were performed during asynchronous and synchronous pECLS in 10 calves. The two extremes regarding LV afterload, namely systolic arrival (SA) and diastolic arrival (DA) of the pump pulse were studied. RESULTS: SA was associated with increased oxygen consumption (+57%) and decreased diastolic coronary perfusion (-43%). DA increased left ventricular output (DA: 4.5+/-2.4 l/min vs SA: 3.5+/-2.2 l/min), LV ejection fraction (+10%), and ventricular efficiency (+17%). Mean aortic pressure and mean coronary flow were only marginally affected by pulse incidence. Systolic impairment was more pronounced with higher bypass flows. These results indicate that myocardial working conditions can be optimized by phasing pECLS ejection into cardiac diastole. CONCLUSION: We conclude that during pECLS, myocardial working conditions can be improved by avoidance of systolic impairment. Synchronously counterpulsating pECLS could be a more economic and versatile alternative to NPS or NPS combined with intra-aortic balloon pumping. The potential benefits of synchronously counterpulsating pECLS over the current alternatives remain to be investigated.

Intra-aortic balloon pumping in acute mitral regurgitation reduces aortic impedance and regurgitant fraction.

Acute mitral regurgitation (MR) is present in 10% of patients presenting with cardiogenic shock. To stabilize these patients, intra-aortic balloon pumping (IABP) is recommended, but the mechanism of IABP support in these patients is unknown. This animal study was designed to describe the hemodynamic effect of intra-aortic balloon pumping during cardiogenic shock induced by acute MR. In eight calves, left ventricular pressure-volume loops, aortic and left atrial pressure, and aortic, carotid artery, and coronary blood flow were recorded. Acute MR (range 36%-79%) was created by placing a metal cage in the mitral valve. Hemodynamic data was obtained at control, during acute MR, and during acute MR with 1:1 IABP support. Acute MR caused a decrease in cardiac output (-32%, P = 0.018), blood pressure, and carotid artery flow, whereas left ventricular output (+127%, P = 0.018), end-diastolic volume, and left atrial pressure all significantly increased. Stroke work, ejection fraction, and coronary blood flow were not significantly changed, and no signs of ischemia were seen on the ECG. The IABP raised average cardiac output by 31% (P = 0.012) and significantly raised blood pressure and flow to the brain while decreasing systemic vascular resistance. Left ventricular function and mean coronary blood flow did not change, but diastolic coronary flow became more important as shown by the increase in diastolic fraction from 64% to 95%. (P = 0.028). Average MR dropped by 7.5% (P = 0.025). In conclusion, application of the IABP during acute MR lowers aortic impedance, resulting in less MR and more output toward the aorta without changing left ventricular function.

Miniature intracardiac assist device provides more effective cardiac unloading and circulatory support during severe left heart failure than intraaortic balloon pumping.

BACKGROUND: Hemodynamic assistance with a miniature intracardiac pump may fill the treatment gap between use of an intraaortic balloon pump (IABP) and the current, more invasive ventricular assist devices. The objective of this study was to compare the hemodynamic efficacy of a miniature intracardiac pump device with that of IABP. METHODS AND RESULTS: Reversible acute mitral regurgitation (AMR) was induced in eight calves by stenting the mitral valve using a vena cava filter. Full and partial AMR assist were compared with maximum IABP support in each animal. In full-support mode, both assist systems increased cardiac output (miniature intracardiac pump, 13% [p < 0.05]; IABP, 3% [p < 0.05]), mean aortic pressure (miniature intracardiac pump, 13% [p < 0.05]; IABP, 8% [p < 0.05]), carotid artery flow (miniature intracardiac pump, 29% [p < 0.05]; IABP, 5% [difference not significant]), and coronary blood flow (miniature intracardiac pump, 25% [difference not significant]; IABP, 34% [p < 0.05]). Again in full-support mode, both systems reduced left atrial pressure (miniature intracardiac pump, 2.4 mm Hg [p < 0.05]; IABP, 0.7 mm Hg [p < 0.05]), peak left ventricular (LV) pressure (miniature intracardiac pump, 13% [p < 0.05]; IABP, 5% [p < 0.05]), and external LV work (miniature intracardiac pump, 29% [p < 0.05]; IABP, 3% [p < 0.05]). Only full miniature intracardiac pump support reduced both end-diastolic LV volume (7%; p < 0.05) and end-systolic LV volume (10%; p < 0.05). IABP mainly improved coronary perfusion, while the miniature intracardiac pump proved more capable of genuinely unloading the LV. CONCLUSIONS: We conclude that during severe acute LV failure, the miniature intracardiac pump is capable of more effective cardiac unloading and circulatory support than IABP.

Use of novel nonfluoroscopic three-dimensional electroanatomic mapping system to monitor and analyze heart surgery in animal models.

BACKGROUND: The new method of three-dimensional (3D) electroanatomic mapping was presented as an important tool for cardiac imaging and intervention. We present herein the first use of this technology for the monitoring, analysis, and development of cardiac surgery at the preclinical stage. METHODS: The method is based on utilizing a locatable catheter connected to an endocardial mapping and navigating system, to accurately establish the location and orientation of the tip of the mapping catheter and simultaneously record its local electrogram. The 3D geometry of the beating cardiac chamber is reconstructed in real time. The system was tested on six goats that underwent dynamic cardiomyoplasty. Two maps of each animal were performed: preoperative and postoperative during the stimulation protocol of the skeletal muscle. RESULTS: The electroanatomic mapping system provided detailed maps of the left ventricle during the stimulation protocol, which demonstrated a striking geometric difference between the assisted and the unassisted beats. These geometric changes are best described by referring to left ventricular long-axis movements (22.3 +/- 3.8 degrees vs 3.4 +/- 1.6 degrees, p < 0.001), center-of-mass movements (10.4 +/- 3.0 mm vs 3.9 +/- 1.6 mm, p < 0.005), and the changes in upward movement viewed along the base (7.9 +/- 1.9 mm vs 3.6 +/- 1.7 mm, p < 0.01), middle (13.8 +/- 4.0 mm vs 7.3 +/- 1.8 mm, p < 0.005), and the apex of the heart (28.1 +/- 4.5 vs 5.3 +/- 2.3 mm, p < 0.001) [mean +/- SD]. CONCLUSIONS: The 3D electroanatomic mapping system allows detailed reconstruction of the left ventricular geometry and a clear view of the difference between the assisted and the unassisted beats. This novel monitoring system may serve as an important tool for the analysis and development of new techniques in cardiac surgery.

Stability of radiopaque iodine-containing biomaterials.

Stability tests have been performed on two typical iodine-containing radiopaque poly(methacrylate) copolymers. Material A is a terpolymer of methylmethacrylate (MMA), 2-hydroxyethyl methacrylate (HEMA) and 2-[4-iodobenzoyl]-oxo-ethylmethacrylate (4-IEMA); material B is a copolymer of MMA and 4-IEMA. Cylindrical specimens of material A were implanted subcutaneously and intraperitoneally in Wistar rats. The implants were retrieved after 2 years. Histology showed that the material was well-tolerated. Detailed analysis of the surface of the implants by electron spectroscopy for chemical analysis (ESCA) revealed that the material remained stable. No differences could be detected between the ESCA spectra of the explants, and those of the control specimens, which were from the same synthetic batch and which were stored in dry form during the entire experimental period. Material B was also stable upon irradiation with X-rays in vitro, even at high doses, compared to the clinical situation. Exposure of material B to gamma-radiation, however, was found to lead to structural degradation. This was evident from clear yellowing, and also from the ESCA spectra. The spectra revealed that material B deteriorates during gamma-irradiation through rupture of C-C and or C-O chemical bonds, not via C-I bond disruption. It can be concluded that iodine is tightly bound to these radiopaque biomaterials. This is important with regard to potential applications of these materials as implant biomaterials.

Effects of chronic cardiomyoplasty on ventricular remodeling in a goat model of chronic cardiac dilatation: part 2.

BACKGROUND: Reduction of ventricular dilatation, rather than direct improvement of pump function, has been suggested to be the main working mechanism of dynamic cardiomyoplasty (CMP). This working mechanism was examined in the goat using a chronic cardiac dilatation model induced by the creation of a cervical arteriovenous shunt and submitted to passive and active CMP. METHODS: Fourteen female goats underwent surgical creation of a shunt between the left carotid artery and the jugular vein. Seven goats had no additional operation (control group). The other 7 goats (CMP group) underwent CMP approximately 8 weeks after the creation of the shunt. The wrapped left latissimus dorsi muscle was left unstimulated for 2 weeks, and subsequently stimulated electrically for a 3-month period, using a 1:4 muscle-to-heart contraction ratio. Hemodynamic measurements included heart catheterization and determination of left ventricular (LV) pressure-volume relations by means of the conductance catheter method at baseline, after 8 weeks (only in the CMP group), and after 5 months. Transthoracic echocardiography was performed just before opening the AV shunt and every 2 weeks thereafter. RESULTS: Significant ventricular enlargement, as well as persistent increase in filling pressures, were observed after 8 weeks. Animals in the control group dilated further beyond 2 months (LV end-diastolic diameter from 39 +/- 2 to 67 +/- 6 mm). In contrast, the ongoing LV dilatation process was stopped by passive CMP, and LV end-diastolic diameter significantly decreased after electrical activation of the wrapped skeletal muscle (from 63 +/- 7 to 42 +/- 6 mm). Cardiomyoplasty also significantly increased the slope of the end-systolic pressure-volume relation (elastance) when compared with pre-CMP values (from 0.9 +/- 0.2 to 1.7 +/- 0.5 mm Hg/mL), which indicated an improvement of the LV contractile state. No significant hemodynamic effects could be observed at the tuned stimulation settings on a beat-to-beat basis during electrical muscle stimulation. CONCLUSIONS: The contribution of CMP to LV dimension and contractility appeared to be either passive or active, and this study suggests the importance of stimulating the latissimus dorsi muscle to enhance the girdling effects of the wrapped latissimus dorsi muscle and to improve LV contractility.

Effects of acute dynamic cardiomyoplasty in a goat model of chronic ventricular dilatation: part 1.

BACKGROUND: The acute effects of cardiomyoplasty in an experimental model of chronic dilated heart have not been thoroughly investigated. Therefore, a model of chronic left ventricular (LV) dilatation was created to accurately determine actual changes shortly after passive and active wrapped skeletal muscle. METHODS: A carotid-jugular shunt model in 8 goats was used to induce progressive dilatation of the cardiac ventricles. Geometric modifications induced by the arteriovenous shunt were monitored by transthoracic echocardiography. After 8 weeks, cardiomyoplasty was performed, and the acute hemodynamic changes obtained with static cardiomyoplasty soon after the wrapping procedure were determined. Hence, hemodynamic variables recorded during assisted cardiac beats were then compared with data collected with unassisted cardiac beats using the conductance catheter method to generate pressure-volume loops. RESULTS: During electrical stimulation of the unconditioned skeletal muscle wrapped around the dilated left ventricle, a significant increase in stroke volume (117 +/- 48 mL versus 87 +/- 38 mL; p < 0.05) was observed. Early wrapped latissimus dorsi muscle activation also induced a reduction in LV end-systolic volume (from 51 +/- 28 mL to 27 +/- 14 mL; p < 0.05) when compared with unassisted LV contraction. CONCLUSIONS: In a chronic model of cardiac dilatation, acute dynamic cardiomyoplasty was shown to increase LV contractile performance and reduce LV volume. Further evaluation is necessary to show the effects of a conditioned wrapped muscle on LV systolic function and dimensions in the long-term.

Pressure-volume loops in patients with aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Preoperative left ventricular (LV) function is the strongest predictor of outcome after valve replacement for aortic stenosis (AS). Although pressure-volume analysis with the conductance catheter technique can provide detailed information on LV systolic and diastolic function, this technique has not yet been used in AS patients. The present study examined the potential use of LV function measurements using pressure-volume analysis with a conductance catheter during surgery for AS. METHODS: In six patients with severe symptomatic AS, a conductance catheter was placed under transesophageal echocardiographic guidance in the left ventricle via the right superior pulmonary vein. RESULTS: The procedure was successful in all patients and lengthened the duration of surgery by <30 min, but with no increase in bypass or aortic cross-clamp times. Pressure-volume analysis showed that systolic function was normal in all patients (ejection fraction 42-59%, end-systolic elastance 1.6-4.5 mmHg/ml), while diastolic dysfunction was found in all patients (Tau 32-96 ms, LV end-diastolic pressure 7-42 mmHg, atrial kick 25-60%). After valve replacement, systolic function improved, but diastolic function did not. CONCLUSION: The conductance catheter placed via the pulmonary vein can determine LV systolic and diastolic dysfunction in detail in an individual patient with AS before and after valve replacement. The technique may be used to extend diagnostic data from less-invasive modalities and to determine prognosis in the individual patient.

Hemodynamic analysis of descending versus ascending aortomyoplasty, and comparison with intra-aortic balloon pump.

OBJECTIVE: Descending and ascending aortomyoplasty are two surgical procedures intended to induce hemodynamic benefits similar to those of the intra-aortic-balloon-pump (IABP). To date, there have been no studies comparing the two surgical techniques. The objective of this study was to compare coronary blood flow augmentation and afterload reduction as produced by descending and ascending aortomyoplasty counterpulsation METHODS: Twenty-two mongrel dogs (18-35 kg) underwent IABP application (n=7), descending (n=8), or ascending (n=7) aortomyoplasty. Left anterior descending (LAD) coronary artery blood flow was measured using a Transonic Doppler flow probe. Left ventricular pressure as well as aortic pressures proximal and distal to either the aortomyoplasty site or the IABP position were monitored continuously. RESULTS: Descending aortomyoplasty induced higher elevation in the LAD blood flow during assisted beats (27% from 10.8+/-4 to 13.8+/-6 ml/min, P<0.001) than that induced by either ascending aortomyoplasty (19% from 11.7+/-5 to 14+/-5 ml/min, P<0.001) or IABP counterpulsation (18% from 8.6+/-3 to 10.2+/-4 ml/min, P<0.001). Conversely, while ascending aortomyoplasty reduced the left ventricular end-diastolic pressure by 16% (from 60+/-18 to 50+/-22 mmHg, P<0.001), similar to the 16% after load reduction achieved by the IABP counterpulsation, descending aortomyoplasty failed to induce afterload reduction. CONCLUSIONS: Descending aortomyoplasty produces higher coronary blood flow augmentation than either ascending aortomyoplasty or IABP. However, afterload reduction comparable to that achieved by IABP was observed only with ascending aortomyoplasty and not with descending aortomyoplasty.

Cytokine removal on extracorporeal life support for treatment of acute endotoxemia: a randomized controlled animal study.

BACKGROUND: We prospectively evaluated the effectiveness of resin adsorption incorporated in an extracorporeal life support (ELS) circuit in an animal model of sepsis for removal of cytokines and prevention of hemodynamic deterioration during the treatment of septic shock. METHODS: Twelve female landrace pigs were randomly assigned to two groups, a study group(n=6), treated with high-flow resin adsorption (300 mL/min) and ELS, and a control group (n=6), treated only with ELS. Septic shock was induced by intravenous 0.02 µg/kg/min infusion was of Escherichia coli lipopolysaccharide (LPS). Measurements were carried out in the study group at baseline, at the end of LPS injection(t0) at 30(t1), 60(t2), 90(t3) and 120 min (t4) and 60 min after stopping resin-adsorption (t5). In the control group measurements were performed at baseline (t0), t1 and only t2, as no control animal survived beyond this latter experimental timepoint. RESULTS: The final population consisted of 9 animals, five in the study group and 4 in the control group. Plasma values of both tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) were reduced during resin-adsorption (t1-t4) while these mediators increased in controls undergoing ELS only. With a clearance of TNF-α of 15,233 pg/min and IL-6 of 10,233 pg/min, 79.2% of TNF-α and 95.3% of IL-6 produced were adsorbed. Systemic vascular resistance decreased significantly in both groups at t0. While it further was reduced during the control experiments at t1 and t2, it returned to normal in the study animals. Cardiac output increased at t0, t1 and t2 in the control experiments. In contrast, in study animals after a peak at t0, it returned to the baseline value and did not vary thereafter. CONCLUSIONS: Combined resin-adsorption and ELS improved hemodynamics resulting from effective removal of inflammatory mediators in a pig model of septic shock.

Increased coronary blood flow and cardiac contractile efficiency with intraaortic balloon counterpulsation in a porcine model of myocardial ischemia-reperfusion injury.

The evaluation of the impact of intraaortic balloon pump (IABP) on postischemic coronary perfusion and myocardial contractile impairment has been so far limited to early reperfusion phase. Therefore, we analyzed the 24-hour effects of IABP on coronary blood flow (CBF) and left ventricular performance in an animal model of acute myocardial ischemia-reperfusion injury. Healthy swine (n = 20) underwent 120-minute ligation of the left anterior descending coronary artery followed by 24 hours of reperfusion. We randomly assigned the animals to have IABP placed in the descending aorta 5 minutes after reperfusion onset (n = 10) or to undergo no implantation (n = 10). We measured CBF, coronary resistance, cardiac cycle efficiency (CCE), and maximal pressure/time ratio before ischemia was induced and at 30 minutes and 1, 6, 12, and 24 hours after reperfusion began. During diastole, CBF was significantly increased in IABP compared with baseline and controls at all time points (all p < 0.001). This was also true during systole in IABP only for the first hour after reperfusion began. Additionally, both CCE and pressure/time ratio were significantly increased in IABP compared with baseline at 30 minutes and 1 hour after reperfusion began (p < 0.001). IABP was associated with enhanced CBF and cardiac efficiency in a model of acute ischemic-reperfusion injury.

Hydrophilic surface coatings with embedded biocidal silver nanoparticles and sodium heparin for central venous catheters.

Central venous catheters (CVCs) have become indispensable in the treatment of neonates and patients undergoing chemotherapy or hemodialysis. A CVC provides easy access to the patient's circulation, thus enabling facile monitoring of hemodynamic parameters, nutritional support, or administration of (cytostatic) medication. However, complications with CVCs, such as bacterial bloodstream infection or thromboembolism, are common. Bloodstream infections, predominantly caused by Staphylococcus aureus, are notoriously difficult to prevent and treat. Furthermore, patients receiving infusion therapy through a CVC are at risk for deep-vein thrombosis, especially of the upper limbs. Several recent clinical trials have shown that prophylactic anticoagulation (low-molecular-weight heparin or vitamin K antagonists) is not effective. Here, we report on the systematic development of a new bifunctional coating concept that can -uniquely- be applied to make CVC surfaces antimicrobial and antithrombogenic at the same time. The novel coating consists of a moderately hydrophilic synthetic copolymer of N-vinylpyrrollidinone (NVP) and n-butyl methacrylate (BMA), containing embedded silver nanoparticles (AgNPs) and sodium heparin. The work demonstrates that the AgNPs strongly inhibit adhesion of S. aureus (reference strain and clinical isolates). Surprisingly, heparin not only rendered our surfaces practically non-thrombogenic, but also contributed synergistically to their biocidal activity.

Epicardial application of an amiodarone-releasing hydrogel to suppress atrial tachyarrhythmias.

BACKGROUND: Amiodarone is currently the most effective antiarrhythmic drug for sinus rhythm maintenance. However, due to serious extracardiac adverse effects, prophylactic amiodarone therapy is only appropriate for patients at high risk for postoperative atrial fibrillation (AF). We hypothesized that epicardial application of an amiodarone-releasing hydrogel would produce therapeutic myocardial drug concentrations, while systemic levels would remain low. METHODS: Goats were fitted with right atrial epicardial patch electrodes. A poly(ethylene glycol)-based hydrogel with amiodarone (1mg/kg bw) (n=10) or without drug (n=6) was applied to the right atrial epicardium. Atrial effective refractory period (AERP), conduction time and atrial response to burst pacing (rapid atrial response, RAR) were assessed up to 28days in awake goats. Myocardial, plasma and extracardiac tissue amiodarone concentrations were analysed by high-performance liquid chromatography. RESULTS: The amiodarone-loaded hydrogel produced therapeutic drug concentrations in the right atrium up to 21days after application. In this period, AERP and conduction time were prolonged, while RAR inducibility was reduced (P<0.05) compared to animals treated with drug-free hydrogel. Mean amiodarone concentrations in the right atrium were 1 order of magnitude higher than in other heart chambers and 2 orders of magnitude higher than in extracardiac tissues. Plasma amiodarone levels remained below the detection limit (<10ng/mL) during the 28-day follow-up. CONCLUSIONS: Epicardial application of an amiodarone-releasing hydrogel reduces atrial vulnerability to tachyarrhythmias up to 3weeks, while extracardiac drug levels remain low. Therefore, amiodarone-releasing hydrogel could be applied during cardiac surgery to prevent postoperative AF at minimal risk for extracardiac adverse side effects.

Quantitative assessment of cardiac load-responsiveness during extracorporeal life support: case and rationale.

We describe a case of a patient assisted by extracorporeal life support, in which we obtained the dynamic filling index, a measure for venous volume during extracorporeal life support, and used this index to assess cardiac load-responsiveness during acute reloading. While reloading, the obtained findings on cardiac pump function by the dynamic filling index were supported by trans-esophageal echocardiography and standard pressure measurement. This suggests that the dynamic filling index can be used to assess cardiac load-responsiveness during extracorporeal life support.

Atrium-targeted drug delivery through an amiodarone-eluting bilayered patch.

OBJECTIVE: Clinical studies have demonstrated the efficacy of oral and intravenous amiodarone therapy to prevent postoperative atrial fibrillation. However, because of significant extracardiac side effects, only high-risk patients are eligible for prophylactic amiodarone therapy. This study addressed the hypothesis that atrium-specific drug delivery through an amiodarone-eluting epicardial patch reduces vulnerability to atrial tachyarrhythmias, whereas ventricular and plasma drug concentrations are minimized. METHODS: Right atrial epicardiums of goats were fitted with electrodes and a bilayered patch (poly[ethylene glycol]-based matrix and poly[lactide-co-caprolactone] backing layer) loaded with amiodarone (10 mg per patch, n = 10) or without drug (n = 6). Electrophysiologic parameters (atrial effective refractory period, conduction time, and rapid atrial response to burst pacing) and amiodarone levels in plasma and tissue were measured during 1 month's follow-up. RESULTS: Epicardial application of amiodarone-eluting patches produced persistently higher drug concentrations in the right atrium than in the left atrium, ventricles, and extracardiac tissues by 2 to 4 orders of magnitude. Atrial effective refractory period and conduction time increased, whereas rapid atrial response inducibility decreased significantly (P < .05) during the 1-month follow-up compared with that seen in animals treated with drug-free patches. Amiodarone concentrations in plasma remained undetectably low (<10 ng/mL). CONCLUSIONS: Atrium-specific drug delivery through an amiodarone-eluting patch produces therapeutic atrial drug concentrations, whereas ventricular and systemic drug levels are minimized. This study demonstrates that sustained targeted drug delivery to a specific heart chamber is feasible and might reduce the risk for ventricular and extracardiac adverse effects. Epicardial application of amiodarone-eluting patches is a promising strategy to prevent postoperative atrial fibrillation.