Reserve-driven flow control for extracorporeal life support: proof of principle.

Extracorporeal life support systems lack volume-buffering capacity. Therefore, any decrease in venous intravascular volume available for drainage may result in acutely reduced support flow. We recently developed a method to quantify drainable volume and now conceived a reserve-driven pump control strategy, which is different from existing pressure or flow servo control schemes. Here, we give an outline of the algorithm and present animal experimental data showing proof of principle. With an acute reduction in circulatory volume (10-15%), pump flow immediately dropped from 4.1 to 1.9 l/min. Our pump control algorithm was able to restore bypass flow to 3.2 l/min (about 80% of the original level) and, thereby, reduced the duration of the low-flow condition. This demonstrates that a reserve-driven pump control strategy, based on the continuous monitoring of drainable volume, may maintain extracorporeal circulatory support flow, despite serious changes in filling conditions.

Epicardial left ventricular lead placement for cardiac resynchronization therapy: optimal pace site selection with pressure-volume loops.

OBJECTIVES: Patients in heart failure with left bundle branch block benefit from cardiac resynchronization therapy. Usually the left ventricular pacing lead is placed by coronary sinus catheterization; however, this procedure is not always successful, and patients may be referred for surgical epicardial lead placement. The objective of this study was to develop a method to guide epicardial lead placement in cardiac resynchronization therapy. METHODS: Eleven patients in heart failure who were eligible for cardiac resynchronization therapy were referred for surgery because of failed coronary sinus left ventricular lead implantation. Minithoracotomy or thoracoscopy was performed, and a temporary epicardial electrode was used for biventricular pacing at various sites on the left ventricle. Pressure-volume loops with the conductance catheter were used to select the best site for each individual patient. RESULTS: Relative to the baseline situation, biventricular pacing with an optimal left ventricular lead position significantly increased stroke volume (+39%, P =.01), maximal left ventricular pressure derivative (+20%, P =.02), ejection fraction (+30%, P =.007), and stroke work (+66%, P =.006) and reduced end-systolic volume (-6%, P =.04). In contrast, biventricular pacing at a suboptimal site did not significantly change left ventricular function and even worsened it in some cases. CONCLUSIONS: To optimize cardiac resynchronization therapy with epicardial leads, mapping to determine the best pace site is a prerequisite. Pressure-volume loops offer real-time guidance for targeting epicardial lead placement during minimal invasive surgery.

Transmural gradients of cardiac myofiber shortening in aortic valve stenosis patients using MRI tagging.

Aortic valve stenosis impairs subendocardial perfusion with a risk of irreversible subendocardial tissue damage. A likely precursor of damage is subendocardial contractile dysfunction, expressed by the parameter TransDif, which is defined as epicardial minus endocardial myofiber shortening, normalized to the mean value. With the use of magnetic resonance tagging in two short-axis slices of the left ventricle (LV), TransDif was derived from LV torsion and contraction during ejection. TransDif was determined in healthy volunteers (control, n = 9) and in patients with aortic valve stenosis before (AVSten, n = 9) and 3 mo after valve replacement (AVRepl, n = 7). In the control group, TransDif was 0.00 +/- 0.14 (mean +/- SD). In the AVSten group, TransDif increased to 0.96 +/- 0.62, suggesting impairment of subendocardial myofiber shortening. In the AVRepl group, TransDif decreased to 0.37 +/- 0.20 but was still elevated. In eight of nine AVSten patients, the TransDif value was elevated individually (P < 0.001), suggesting that the noninvasively determined parameter TransDif may provide important information in planning of treatment of aortic valve stenosis.

Three-dimensional electromechanical mapping: imaging in the operating room of the future.

BACKGROUND: Three-dimensional electromechanical mapping has previously been shown to be a clinically important tool for cardiac imaging and intervention. We hypothesized that this technology may be beneficial as an intraoperative modality for assessing cardiac hemodynamics and viability during cardiac surgery. We report here the use of this technology as an imaging modality for intraoperative cardiac surgery. METHODS: The tip of a locatable catheter connected to an endocardial mapping and navigating system is accurately localized while simultaneously recording local electrical and mechanical functions. Thus the three-dimensional geometry of the beating cardiac chamber is reconstructed in real time. The system was tested on 6 goats that underwent acute dynamic cardiomyoplasty and on 5 dogs that underwent left anterior descending (LAD) coronary artery ligation. RESULTS: The electromechanical mapping system provided an accurate three-dimensional reconstruction of the beating left ventricle during cardiomyoplasty. After the wrapping procedure, significant end-diastolic area reduction was noted in the base and mid parts of the heart (948 +/- 194 mm2 vs 1245 +/- 33 mm2, p = 0.021; and 779 +/- 200 mm2 vs 1011 +/- 80 mm2, p = 0.016). The area of the cross-section of the apex did not change during the operation. Acute infarcted tissue was characterized 3 days after LAD ligation by concomitant deterioration in both electrical and mechanical function. CONCLUSIONS: By providing both a clear view of the anatomical changes that occur during cardiac surgery, and an accurate assessment of tissue viability, electroanatomic mapping may serve as an important adjunct tool for imaging and analysis of the heart during cardiac surgery

Hemodynamic evaluation of descending aortomyoplasty versus intra-aortic balloon pump performed in normal animals: an acute study.

OBJECTIVE: Aortomyoplasty is a surgical procedure that aims to induce hemodynamic benefits similar to those of the intra-aortic-balloon-pump (IABP). The objective of this study was to compare the coronary blood flow augmentation and afterload reduction produced by IABP and descending aortomyoplasty counterpulsation. METHODS: From a series of fifteen mongrel dogs (18-35 kg), eight underwent acute descending aortomyoplasty and seven had IABP application. Left anterior descending (LAD) coronary artery blood flow was measured using a Doppler flow probe. Left ventricular pressure in addition to aortic pressures both proximal and distal to either the aortomyoplasty site or the IABP position were monitored continuously. All experiments were acute and performed in normal hearts. RESULTS: Descending aortomyoplasty induced a 27% increase in the LAD blood flow integral during assisted beats (14.0+/-6 ml/min integral compared to 10.8+/-4 ml/min integral in unassisted beats [P<0.001]). This was comparable to an 18% rise in the LAD blood flow integral during IABP counterpulsation (from 8.6+/-3 ml/min to 10.2+/-4 ml/min [P<0.001]). Conversely, while IABP counterpulsation reduced the left ventricular afterload by 16% (from 102+/-23 mmHg to 86+/-26 mmHg [P<0.001]), descending aortomyoplasty did not result in afterload reduction. CONCLUSIONS: Descending aortomyoplasty produces coronary blood flow augmentation comparable to that achieved by the IABP. This may be important for end-stage ischemic patients. However, afterload reduction achieved by the IABP was not reproduced during descending aortomyoplasty counterpulsation. The surgical technique of descending aortomyoplasty should be modified to attain afterload reduction, thus improving treatment for congestive heart failure patients.

Right ventricular support for off-pump coronary artery bypass grafting studied with bi-ventricular pressure--volume loops in sheep.

OBJECTIVES: Tilting the heart during off-pump coronary artery bypass grafting (OPCABG) causes a strong decrease in cardiac output. It is hypothesized that this decrease is caused by reduced right ventricular filling and that right ventricular support is thus the best way to restore cardiac output. Simultaneous left and right ventricular pressure-volume loops were used to test this hypothesis. METHODS: In seven sheep, the heart was tilted with the use of an Octopus device. After unsupported tilting, a novel right ventricular support, the Enabler, was activated at a pulsatile flow of 1.6 l/min. Pressure-volume loops of both ventricles were obtained using conductance catheters, and cardiac output was monitored with an aortic flow probe. RESULTS: Tilting reduced cardiac output by 31% (4.4--3.1 l/min, P=0.001) and right ventricular end-diastolic volume by 44% (86--51 ml, P=0.005), while right ventricular end-diastolic pressure did not decrease. Left ventricular systolic pressure was not significantly reduced upon tilting and even increased in two animals. During Enabler right ventricular support, the cardiac output remained 23% lower than pre-tilting values (3.4 vs. 4.4 l/min, P=0.001). CONCLUSIONS: Restricted right ventricular filling is the primary cause of the strong decrease in cardiac output during tilting. The Enabler right ventricular support can currently not restore cardiac output to pre-tilting values, mainly caused by its limited output and a decrease in right ventricular output upon Enabler activation. Constant monitoring of cardiac output is crucial during (unsupported or supported) tilting as blood pressure alone may not reflect the extent of the reduction in cardiac function.

Performance of a polyurethane vascular prosthesis carrying a dipyridamole (Persantin) coating on its lumenal surface.

A porous polyurethane vascular prosthesis with an internal diameter of 5 mm was studied. The graft carries a coating of immobilized dipyridamole (Persantin(R)) on the surface of its lumen. Dipyridamole is a potent nontoxic inhibitor of platelet activation/aggregation, and also a strong inhibitor of vascular smooth muscle cell proliferation. The polyurethane material is also known as Chronoflex(R), and already finds use as a vascular access graft. The coated vascular graft was studied in vitro (hemocompatibility, interaction with blood platelets and cultured endothelial cells), as well as in two established in vivo models. In the first in vivo study, coated grafts were implanted in goats, as a bypass of the carotid artery (four animals, eight grafts, length of the graft was approximately 12 cm). Four uncoated grafts were used as controls in otherwise identical experiments. In the second in vivo experiment, eight sheep were used. Each animal received one coated and one uncoated prosthesis as an interposition graft in the carotid artery (length of the graft was 4 cm). The in vitro experiments revealed that the dipyridamole coating has three beneficial effects: reduced thrombogenicity, reduced adherence of blood platelets, and accommodation of a confluent monolayer of endothelial cells. The goat experiments showed patency of the coated grafts in three of the eight cases. The sheep experiments were not useful for the evaluation of the dipyridamole coating because deterioration of the polyurethane material was observed. The in vivo results indicate that the dipyridamole coating may positively influence the patency rate, probably because the coating promotes the growth of an endothelial cell lining. The sheep data show, however, that the limited stability of the Chronoflex(R) material precludes its issue for the construction of permanent small-bore vascular grafts.

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.

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.

Acute descending aortomyoplasty induces coronary blood flow augmentation.

BACKGROUND: Aortomyoplasty is a procedure aimed to improve cardiac output in patients suffering from heart failure. Stimulation of the latissimus dorsi muscle around the aorta produces hemodynamic effects similar to those of the intraaortic balloon pump. These may be maintained without the accompanying complications or the need for anticoagulation. The objective of this study was to test the acute effects of aortomyoplasty on coronary artery blood flow. METHODS: Eight mongrel dogs (18 to 30 kg) underwent acute descending aortomyoplasty. Several stimulation protocols were applied after wrapping of the latissimus dorsi muscle around the aorta in different surgical configurations. The left anterior descending coronary blood flow was measured using a transonic Doppler flow probe. Left ventricular and aortic pressures, proximal and distal to the aortomyoplasty site, were monitored continuously. RESULTS: Significant aortic diastolic pressure augmentation was expressed both as an increase in peak values, from 110 +/- 24 mm Hg to 120 +/- 24 mm Hg (p < 0.001) and as an increase in the diastolic integral, from 64 +/- 23 mm Hg x s to 84 +/- 37 mm Hg x s (p < 0.001). Concomitantly, peak left anterior descending coronary blood flow increased from 26 +/- 10 mL/min to 32 +/- 12 mL/min (p < 0.001). This was associated with an increase in the diastolic flow integral from 11 +/- 4 mL to 14 +/- 6 mL (p < 0.001). CONCLUSIONS: Descending aortomyoplasty induces significant augmentation of coronary blood flow. Optimal timing of muscle stimulation is important in achieving the best assist. This procedure may prove beneficial for end-stage ischemic patients.

Metallic wires with an adherent lubricious and blood-compatible polymeric coating and their use in the manufacture of novel slippery-when-wet guidewires: possible applications related to controlled local drug delivery.

A new procedure was developed for the controlled application of adherent hydrophilic and biocompatible coatings onto the surface of "endless" metallic wires. Use of copolymers of 1-vinyl-2-pyrrolidinone and alkylmethacrylates provided coatings with excellent adherence and lubricity, and markedly low thrombogenicity. Coated wires could be spiralized without damaging the coating; the resulting coils are potentially useful as lubricious guidewires for use in, for example, interventional cardiology or urology. This study demonstrates that the lubricity of the coating is dependent on the composition (hydrophilicity) of the coating biomaterial, as well as on the thickness of the coating. Furthermore, the results imply that the adherence of the hydrophilic coating is essentially due to entanglement of the binder polymer chains and the hydrophilic copolymer chains. Moreover, the idea to use the hydrophilic coating on the wire as a temporary depot for controlled local drug delivery was explored. The coating was loaded with the dye rhodamine, and release of the dye upon immersion of the coated wire in water was studied. This work revealed that release of the drug is dependent on the composition of the coating. The potential utility of such wires with a drug-charged coating for controlled local drug delivery is discussed briefly.

The enabler right ventricular circulatory support system for beating heart coronary artery bypass graft surgery.

BACKGROUND: Beating heart coronary artery bypass graft surgery of the left anterior descending, diagonal, and right coronary artery can be performed safely with the Octopus Stabilization System. However, tilting of the heart, which is necessary to reach the obtuse marginal and distal right coronary arteries, causes hemodynamic instability. This study was performed to investigate the possible role of the Enabler right ventricular circulatory support system in counteracting this instability. METHODS: In 8 sheep, the Enabler cannula was introduced via the jugular vein and positioned with the inlet valve in the right atrium and outlet valve in the pulmonary artery. The Octopus was used to expose the inferior wall and the posterior wall of the left ventricle. The hemodynamic effects of this tilting with and without Enabler right ventricular support were recorded, including Pressure Volume (PV) loops measured by conductance catheters in both ventricles. RESULTS: Tilting caused a reduction in stroke volume (inferior 31%, posterior 17%) and Enabler activation increased stroke volume (inferior 13%, posterior 31%). CONCLUSIONS: Tilting the heart has severe hemodynamic consequences that can be partially counteracted by the use of the Enabler for right ventricle support.

Ex vivo testing of heparin-coated extracorporeal circuits: bovine experiments.

In this study the intrinsic thrombogenicity of the extracorporeal circuits and the benefit of heparin-bonded circuits in an extracorporeal life support system without full systemic heparinization and with minimal interference of the so called material-independent factors was tested in four calves. In two circuits (group A) all blood-contacting surfaces were coated with end-point-attached heparin and the other two were non-coated (group B). Under standardized conditions the calves were perfused at a blood flow rate of 2 L/min. After only one bolus injection of heparin (250 IU/kg body weight) before cannulation, plasma heparin activity rapidly decreased in both groups: half life of about 55 minutes. This decrease of the heparin activity was accompanied by a fall of the activated clotting time (ACT) level to baseline values. The experiments using a heparin-coated circuit, had a runtime of more than 360 minutes, whereas the experiments using a non-coated circuit had to be terminated after a runtime of 255 minutes, because massive fibrin formation was noticed in the circuit. This formation was accompanied by a rapid increase in the line pressure, measured just before the inlet of the oxygenator. The macroscopic inspections after terminating the experiments and rinsing the circuit showed a clean circuit in group A. The fibrinopeptide A (FPA) level increased faster during perfusion with the non-coated circuit than in the heparin coated circuit. Lung histopathological examinations of the lungs of the animals in group A showed no fibrin deposition, whereas most of the blood vessels of the lung preparations of the animals in group B were partially or completely occluded with fibrin. These results suggest that heparin-bonding greatly reduces the thrombogenicity of the extracorporeal circuit, and therefore it can reduce the need for systemic heparinization in an extracorporeal life support system.

Structural alterations in the latissimus dorsi muscles in three patients more than 2 years after a cardiomyoplasty procedure.

AIMS: The long-term effects of the use of the latissimus dorsi muscle for dynamic cardiomyoplasty were studied. Skeletal muscle fast fatiguable type II fibres are transformed to highly fatigue-resistant type I fibres in animal models, and is assumed to occur in men. However, it is not known whether this same transformation occurs in patients with chronic heart failure. METHODS AND RESULTS: Three patients who underwent a cardiomyoplasty procedure (pre-operative NYHA class IV) were studied. The left latissimus dorsi muscle was stimulated, according to routine clinical protocol, with 30 Hz bursts in a 2:1 ratio to cardiac activation. The patients died more than 2 years after surgery and five autopsy samples were obtained at defined places in the wrapped muscle. In the proximal part of the latissimus dorsi muscle, the type I fibres comprised 68-80% in all three patients, whereas peroperatively type I fibres comprised 17-30% indicating significant but not complete transformation. Transformation in the latissimus dorsi muscle as a whole appeared to be inhomogeneous, with type I fibres ranging from 10-80%. An extensive amount of muscle fibre appeared to be replaced by fatty tissue (10%-50%). This occurred at random and resulted in complete loss of muscle structure. A significant increase in the density of small arteries was observed in the latissimus dorsi after transformation. CONCLUSIONS: In these patients, muscle fibre type transformation was not as complete as that observed in animal experiments, and was accompanied by loss of muscle viability. The stimulation current in the latissimus dorsi muscle appeared not to be the direct cause of local tissue lipomatosis or collagen deposition.

Sustained local drug delivery from a radiopaque implanted reservoir.

A new polymeric biomaterial that contains covalently bound iodine, and is therefore radiopaque, was used to construct a sustained local drug-delivery device. A polymeric wall was designed to be porous (i.e., passage of low-molecular-weight molecules across the wall is possible), self-healing, and biocompatible. Once implanted, the sphere cavity can be filled and refilled with a concentrated solution of a (cytostatic) drug, which is subsequently released by slow diffusion into the tissue region surrounding the sphere. This principle of sustained local drug delivery is shown by a series of in vitro experiments on the release of 5-fluorouracil, and in vivo animal experiments, using x-ray fluoroscopic and scintigraphic techniques.

Distal embolization during thrombectomy with use of the hydrolyser (hydrodynamic thrombectomy catheter): in vitro testing.

PURPOSE: To evaluate distal embolization while using the Hydrolyser (hydrodynamic thrombectomy catheter) with special attention to the severity of the stenosis and temporary distal or proximal flow obstruction. MATERIALS AND METHODS: The Hydrolyser procedure was assessed in plastic tubes (5-8 mm) with a 70% or 90% diameter stenosis with or without temporary distal flow obstruction and a 72-hour-old clot proximal to the stenosis. The weight of the embolized particles was established after passage through filters of 1,000, 500, 100, and 10 microm. To evaluate the influence of the absolute inner diameter of the stenosis 1.0-, 2.1-, and 3.0-mm stenoses were compared in 10-mm tubes. RESULTS: Thrombus removal was greater than 99.9% in all but one of the cases in the 5-8-mm tubes. Embolization with a weight of more than 1 mg was only found in tubes with a relative stenosis of 70% and a stenosis inner diameter of greater than 1.5 mm. There was a positive relationship between inner diameter of the stenosis and the amount of distal embolization. In the presence of a proximal or distal temporary flow obstruction during thrombectomy, no distal embolization greater than 1 mg was found. CONCLUSION: In this in vitro study, the Hydrolyser thrombectomy device demonstrated minimal distal embolization. The amount of distal embolization that did occur was related to the absolute stenosis diameter and could be prevented by a severe distal stenosis and/or a temporary proximal or distal flow obstruction.

Left ventricular pressure-volume relationships before and after cardiomyoplasty in patients with heart failure.

BACKGROUND: The aim of this study was to elucidate whether beneficial effects of cardiomyoplasty (CMP) in patients with dilated cardiomyopathy are the result of a decrease in existing ventricular dilatation or a prevention of further dilatation. METHODS AND RESULTS: Combined micromanometer-conductance catheters were used to evaluate left ventricular pressure-volume relationships in six patients with dilated cardiomyopathy before and at 6 and 12 months after CMP. Acute changes in preload and afterload were induced by a standardized leg-tilting intervention and a bolus infusion of nitroglycerin. After CMP, end-diastolic volume (EDV) decreased from 138+/-10 to 103+/-18 mL/m2 (P<.01) at 6 months and to 83+/-17 mL/m2 (P<.01) at 12 months. End-diastolic pressure (EDP) decreased from 20.2+/-6.4 to 13.9+/-7.7 mm Hg (P<.01) at 6 months after CMP. Peak ejection rate and ejection fraction increased at 6 months after CMP from 594+/-214 to 799+/-214 mL/s (P<.05) and from 26.6+/-4.7% to 40.1+/-8.3% (P<.05), respectively. Peak dP/dt decreased at 12 months after CMP from -842+/-142 to -712+/-168 mm Hg/s (P<.05). Leg-tilting before CMP increased EDP from 20.2+/-6.4 to 25.6+/-5.2 mm Hg (P<.01), end-systolic pressure (ESP) from 118+/-17 to 122+/-17 mm Hg (P<.05), and tau from 50.8+/-2.8 to 53.8+/-2.3 ms (P<.05). Six months after CMP, leg-tilting also increased EDV from 103+/-18 to 110+/-22 mL/m2 (P<.05) and ESV from 62+/-14 to 66+/-14 mL/m2 (P<.05). Before CMP, nitroglycerin decreased EDP from 20.2+/-6.4 to 10.4+/-3.8 mm Hg (P<.01), ESP from 118+/-17 to 96+/-11 mm Hg (P<.05), ESV from 100+/-11 to 89+/-7 mL/m2 (P<.05), and tau from 50.8+/-2.8 to 44.5+/-3.7 ms (P<.05). Six months after CMP, nitroglycerin decreased EDP, ESP, and tau to similar values. CONCLUSIONS: Our findings show that up to 1 year after CMP, marked decreases in left ventricular volume are present. Our measurements suggest that CMP actively reduced the dilated ventricle but did not prevent a higher EDV on an increased venous return. The latissimus dorsi muscle wrap contraction results in better synchronization of contraction and more rapid emptying of the left ventricle.

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.

In vivo tissue compatibility of two radio-opaque polymeric biomaterials.

Polymeric biomaterials featuring intrinsic radio-opacity continue to attract considerable scientific attention. This work focusses on two polymers that contain covalently bound iodine, rendering the materials radio-opaque. The first material is hard, transparent and glass-like, and consists of methyl methacrylate, 2-(2'-iodobenzoyl)-ethyl methacrylate (1) and 2-hydroxyethyl methacrylate (HEMA), in the molar ratio 65:20:15, respectively. The second material is a cross-linked hydrophilic network, consisting of HEMA and 1, in the molar ratio 80:20, respectively. Both materials were characterized by means of different physico-chemical techniques, including magic-angle-spinning solid state NMR spectroscopy, infrared spectroscopy and differential scanning calorimetry. Moreover, both materials were implanted subcutaneously in rats for 24 days. Upon explanation and histological examination, it appeared that both materials were well tolerated. No tissue necrosis, abscess formation or inflammation were observed. The samples were found to be surrounded by a vascularized capsule consisting of connective tissue cells. The results reveal excellent tissue compatibility for both materials. This is an important observation, since tissue compatibility is absolutely necessary for the applications which are foreseen for this type of radio-opaque biomaterials.

A versatile three-iodine molecular building block leading to new radiopaque polymeric biomaterials.

A methacrylic monomer containing three iodine atoms, 2- [2',3',5'-triiodobenzoyl]-ethyl methacrylate (compound 1), was prepared in pure form. Compound 1 can be reacted with other methacrylates, such as methyl methacrylate (MMA), and 2-hydroxyethyl methacrylate (HEMA) with high conversion. Typically, less than 0.5% of free monomer is left after polymerization. For example, compound 1 was reacted with MMA and HEMA in the molar ratio 7:73:20, respectively. This yielded a terpolymer with Tg = 86 degrees C, Mw = 47,000 g/ mol and Mn = 22,800 g/mol. This material was characterized by various physicochemical techniques, including gel permeation chromatography, differential scanning calorimetry, thermogravimetric analysis, and nuclear magnetic resonance (NMR) spectroscopy (1H at 400 MHz, DMSO-d6 solution). In addition the material was found to exhibit low surface thrombogenicity in vitro and a low propensity to activate contacting blood platelets. Furthermore it was found that the terpolymer is markedly radiopaque: even thin objects (< 0.5 mm) could be easily visualized using X-ray fluoroscopic techniques as are routinely used in the clinic, e.g., during coronary angiography. The combined results obtained with the present terpolymer (particularly its in vitro hemocompatibility and its radiopacity) leads to the suggestion that this type of polymer could be used as cardiovascular biomaterials, for instance for the construction of a new type of endovascular stents. These would be expected to show improved biocompatibility if compared with metallic stents which are currently used, for instance in conjunction with percutaneous transluminal coronary angioplasty (PTCA). A stent prototype, constructed from the present radiopaque terpolymer, is shown and discussed briefly.