Frederik H. van der Veen

The relationship between the antimicrobial effect of catheter coatings containing silver nanoparticles and the coagulation of contacting blood

It is well known that surface coatings for medical devices can be made antimicrobial through introduction of silver nanoparticles. By virtue of their extremely large surface-to-volume ratio, the silver particles serve as a depot for sustained release of silver ions, despite the fact that silver is not readily oxidized. Antimicrobial coatings are especially important in connection with indwelling catheters with a high risk of bacterial line infections, such as central venous catheters (CVCs). This study specifically addressed the question what the impact of silver nanoparticles (exposed at the coatings surface) and/or the release of silver ions would be on coagulation of contacting blood. Studies, performed in vitro with fresh platelet-rich blood plasma (PRP) from 5 different healthy volunteer donors, clearly pointed out that: (i) the presence of silver nanoparticles correlates with accelerated thrombin formation upon contact of the coating with PRP; (ii) platelet activation is stronger as a result from the contact with silver nanoparticle-containing coatings as compared to other coatings which are devoid of silver. A series of titration experiments, in which the potential effect of silver ions is mimicked, revealed that the observed activation of blood platelets can be best explained through a collision mechanism. The results suggest that platelets that collide with silver, exposed at the surface, become activated without adhering to the surface. These new results point, rather unexpectedly, at a double effect of the silver nanoparticles in the coating: a strong antimicrobial effect occurs simultaneously with acceleration of the coagulation of contacting blood. This new information is, evidently, most relevant for the development of improved surface coatings for indwelling catheters (such as CVCs) which should combine antimicrobial features and close-to-zero thrombogenicity.

Long-term follow-up (12 to 35 weeks) after dynamic cardiomyoplasty

OBJECTIVES To obtain information on the long-term effects of dynamic cardiomyoplasty on hemodynamics and muscle histology, this surgical method was evaluated in goats. BACKGROUND Dynamic cardiomyoplasty has been introduced as a new method to treat patients with severe cardiac failure. METHODS In 24 goats, the left latissimus dorsi muscle was wrapped around the heart. The muscle was then subjected to progressive electrical stimulation. In 16 goats, invasive transesophageal Doppler echocardiographic measurements and histologic evaluation of the latissimus dorsi muscle were performed at > or = 12 weeks after the wrapping. RESULTS Only two goats showed an increase in aortic and left and right ventricular pressures concomitant with increased aortic flow during latissimus dorsi muscle stimulation both before and after induction of cardiac failure using imipramine. This was accompanied by a preserved latissimus dorsi muscle structure and nearly complete transformation to type I muscle fibers. The remaining 14 goats showed extensive lipomatosis in the latissimus dorsi muscle, with severe intimal hyperplasia and proliferation of smooth muscle cells in the walls of the thoracodorsal artery and its branches. An increase in endoneural and endomysial connective tissue was observed, with some goats showing destroyed nerve branches near the electrodes. These findings differed from those observed after long-term electrical stimulation of goat latissimus dorsi muscle in situ. CONCLUSIONS Dynamic cardiomyoplasty is of use in the treatment of severe heart failure if the histologic structure of the wrapped latissimus dorsi muscle remains intact. Long-term results in goats suggest that the current approach used in dynamic cardiomyoplasty may lead to deterioration of the wrapped muscle.

Acute and short-term effects of partial left ventriculectomy in dilated cardiomyopathy: assessment by pressure-volume loops.

OBJECTIVES The aim of this study was to evaluate the short-term effects of partial left ventriculectomy (PLV) on left ventricular (LV) pressure-volume (P-V) loops, wall stress, and the synchrony of LV segmental volume motions in patients with dilated cardiomyopathy. BACKGROUND Surgical LV volume reduction is under investigation as an alternative for, or bridge to, heart transplantation for patients with end-stage dilated cardiomyopathy. METHODS We measured P-V loops in eight patients with dilated cardiomyopathy before, during and two to five days after PLV. The conductance catheter technique was used to measure LV volume instantaneously. RESULTS The PLV reduced end-diastolic volume (EDV) acutely from 141+/-27 to 68+/-16 ml/m2 (p < 0.001) and to 65+/-6 ml/m2 (p < 0.001) at two to five days postoperation (post-op). Cardiac index (CI) increased from 1.5+/-0.5 to 2.6+/-0.6 l/min/m2 (p < 0.002) and was 1.8+/-0.3 l/min/m2 (NS) at two to five days post-op. The LV ejection fraction (EF) increased from 15+/-8% to 35+/-6% (p < 0.001) and to 26+/-3% (p < 0.003) at two to five days post-op. Tau decreased from 54+/-8 to 38+/-6 ms (p < 0.05) and was 38+/-5 ms (NS) at two to five days post-op. Peak wall stress decreased from 254+/-85 to 157+/-49 mm Hg (p < 0.001) and to 184+/-40 mm Hg (p < 0.003) two to five days post-op. The synchrony of LV segmental volume changes increased from 68+/-6% before PLV to 80+/-7% after surgery (p < 0.01) and was 73+/-4% (NS) at two to five days post-op. The LV synchrony index and CI showed a significant (p < 0.0001) correlation. CONCLUSIONS The acute decrease in LV volume in heart-failure patients following PLV resulted at short-term in unchanged SV, increases in LVEF, and decreases in peak wall stress. The increase in LV synchrony with PLV suggests that the transition to a more uniform LV contraction and relaxation pattern might be a rationale of the working mechanism of PLV.

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 patients 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.

In vivo evaluation of the Hydrolyser hydrodynamic thrombectomy catheter.

PURPOSE The authors evaluated a 7-F double-lumen thrombectomy catheter (Hydrolyser) in vivo. MATERIALS AND METHODS To evaluate efficacy, thrombectomy was performed 1, 4, or 8 days after local denudation in peripheral arteries (n = 18) and veins (n = 29) of nine goats. To evaluate safety, the reaction of the vessel wall to a functioning and nonfunctioning Hydrolyser catheter was evaluated in the peripheral arteries and veins of three goats 10 days after the procedure. RESULTS Reopening was achieved in all vessels with residual thrombus in 11% of arteries (two of 18) and 55% of veins (16 of 29). Slight intimal thickening was observed, but no difference was seen between the passage of a functioning versus nonfunctioning catheter. CONCLUSIONS The Hydrolyser device can remove intravascular thrombus up to 8 days after induction. There was no difference in vessel wall reaction after the passage of a functioning and nonfunctioning catheter.

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.

Late hemodynamic results after cardiomyoplasty in congestive heart failure

Between November 1989 and September 1990, a cardiomyoplasty procedure was performed in 12 male patients with a mean age of 59 years. All patients were in New York Heart Association class III. Reinforcement cardiomyoplasty was isolated in 4 patients and associated with a cardiac procedure in 8. There were no perioperative deaths. Failure of cardiomyoplasty occurred in 5 patients because of recurrence of disabling congestive heart failure: 3 patients died late, and 2 had heart transplantation. The actuarial survival rate was 83% at 1 year and 73% at 2 years. Hemodynamic studies were done preoperatively in all patients, at 6 months postoperatively in 11 patients, at 1 year in 8, and at 2 years in 7. At the 2-year follow-up, 6 of the 7 survivors who did not have transplantation were functionally improved with reduced medical treatment. The following indices improved significantly at the 2-year evaluation compared with baseline: exercise capacity (63 +/- 13 W versus 83 +/- 17 W); left ventricular (LV) end-diastolic pressure (20 +/- 7 mm Hg versus 11 +/- 5 mm Hg); and angiographic LV ejection fraction (0.25 +/- 0.09 versus 0.40 +/- 0.15). Pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac index remained unchanged. Four patients underwent beat-to-beat analysis of LV function at 2 years; during skeletal muscle stimulation, stroke volume increased by 7% to 35% and LV end-systolic pressure, by 5% to 9%. In the 5 patients with failed cardiomyoplasty, mean pulmonary artery pressure and LV end-diastolic volume were higher preoperatively than in the 7 survivors.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of arterial wall reaction after passage of the Hydrolyser device versus a thrombectomy balloon in an animal model

PURPOSE This study was designed to compare the reaction of the vessel wall after application of the Hydrolyser hydrodynamic thrombectomy device to the reaction after use of a balloon thrombectomy catheter. The influence of the vessel inner diameter on vessel wall reaction was evaluated after passage of the Hydrolyser. MATERIALS AND METHODS After measurement of the vessel inner diameter with intravascular ultrasound (US), 102 segments of femoral and carotid arteries of goats were treated with one of the following four procedures: passage of the intravascular US catheter alone; passage of the Hydrolyser without or with an activated jet; or passage of an inflated thrombectomy balloon. Histologic evaluation was performed after 3 weeks. RESULTS Intimal thickening (more than five cell layers of neointima) 3 weeks after treatment occurred more frequently after passage of the balloon than after any of the other procedures (P < .001). For vessels with a diameter of 3-4 mm, 4-5mm, or more than 5 mm, no significant difference in vessel wall reaction was observed following Hydrolyser passage. CONCLUSION In this model, passage of the Hydrolyser device resulted in less intimal reaction compared with the thrombectomy balloon.

New biocompatible polymer surface coating for stents results in a low neointimal response

Clinical studies indicate a more pronounced endothelial response after stent implantation than after balloon inflation. This might be related to the metal surface of the stent, and therefore it is speculated that coating of the stent might partially prevent hyperplasia. One coated and one noncoated Palmaz-Schatz stent were implanted in two separate coronary arteries of seven pigs. The coating was composed of methylmethacrylate (MMA) (hydrophobic, 70 mol %) and 2-hydroxyethyl methacrylate (HEMA) (hydrophilic 30 mol %). After sacrifice (3 weeks), cross sections were made of the stented areas. Vessel wall reaction was calculated both independently and dependently of local vessel wall injury due to the stent struts. Overall, vessel wall reaction of the coated stents was lower than that of the noncoated stents. The degree of hyperplasia was linearly related to the degree of stent-induced vessel wall injury. Analyses of all the struts showed that significantly less hyperplasia occurred in the coated versus noncoated stents. In this porcine coronary artery model, the MMA/HEMA stent coating resulted in significantly reduced vessel wall response. However, it remains to be determined whether this favorable outcome will also be present in humans.

Cardiomyoplasty as an isolated procedure to treat refractory heart failure

OBJECTIVE Cardiomyoplasty represents a controversial therapy for chronic heart failure. The aim of this study is to review our experience of such a surgical procedure as an isolate approach to treat refractory left ventricular dysfunction. METHODS Twenty-two patients were considered candidates for cardiomyoplasty because of chronic heart failure. Mean age was 58.7 +/- 5.3 (range 48-71 years), 19 patients were male and 3 were female. Ischemic or idiopathic etiology was present in 11 cases, respectively. Traditional as well as innovative techniques were used to assess hemodynamic function. Pre-operative hemodynamic profile included mean left ventricular ejection fraction of 20 +/- 5.8% (9-28%), absence of severe right ventricular failure, and mean left ventricular end-diastolic diameter of 75.5 +/- 7.4 mm (range 61-92 m). All patients were in New York Heart Association Class III or Intermittent IV despite conventional medical therapy. RESULTS There was no intra-operative death. No additional surgery was performed. Left latissimus dorsi (LD) muscle was used in 20 cases, and right LD in two patients. Early mortality occurred in one patient (low cardiac output syndrome), whereas late mortality in five patients (three sudden deaths, one lung cancer, one heart failure). Mean follow-up is 20.7 +/- 16.7 months (3-51 months). Actuarial survival at 4 years is 70%. Cardiac index increased at 6 months (3.08 +/- 0.5 l/min per m2, P = 0.04), but no other significant changes were observed in the long term (3.03 +/- 0.7 l/min per m2, 3 +/- 0.7 l/min per m2, and 2.85 +/- 0.7 l/min per m2, at 12, 24 and 36 months, respectively). Ejection fraction improved at 6 and 12 months (29.1 +/- 1.03%, P = 0.0017; and 27.3 +/- 5.6%, P = 0.0091, respectively), while no substantial augmentation was documented at 2 and 3 years (25.6 +/- 2.5% and 25.1 +/- 4.0%, respectively). Left ventricular end-diastolic diameter was markedly reduced at 6 (73.2 +/- 8.0 mm, P = 0.0176), 12 (69.4 +/- 8.5 mm, P = 0.002) and 24 months (71.1 +/- 7.0 mm, P = 0.011), and was then stable (74.0 +/- 9.1 mm, P = 0.47) at 36 months. Postoperative pressure/volume loop evaluation showed some improvement of hemodynamic function from skeletal muscle assistance. Acute pulmonary edema episodes, as well as number of hospitalizations, were considerably reduced following cardiomyoplasty. CONCLUSIONS In our experience, cardiomyoplasty was shown to exert moderate beneficial influence on left ventricular performance, to significantly reduce cardiac dilatation and to promote the stabilization of the disease course.