N-acetylcysteine attenuates iodine contrast agent-induced nephropathy in 5/6-nephrectomized rats.

AIMS: In the present study we tested the efficacy of N-acetylcysteine (NAC) to minimize nephrotoxic effects of iodine contrast agents in intact rats as well as in 5/6-nephrectomized (5/6-Nx) rats. METHODS: Rats were allocated to a group of intact rats (n = 42) and a group of 5/6-Nx rats (n = 42). After 1 month of recovery from surgery, 5/6-Nx rats and intact (sham-operated) animals received either 6 ml/kg body weight (b.w.) meglumine ioxithalamate (Telebrix 350) or 6 ml/kg b.w. iohexol (Omnipaque 350) intravenously with or without pretreatment with 100 mg/kg b.w. NAC. Plasma and urinary concentrations of creatinine, sodium and protein in 24-hour urine collections were determined prior to and on days 1, 3 and 7 after drug administration. RESULTS: In intact animals, contrast agents caused no significant changes in kidney function throughout the duration of the experiment. In contrast, significant increases in plasma creatinine levels and decreases in creatinine clearance were induced by both contrast agents in 5/6-Nx rats. These changes were significantly attenuated by NAC pretreatment. CONCLUSION: The results of the present study demonstrate that iodine contrast agent-induced nephropathy in 5/6-Nx rats is significantly attenuated by intravenous pretreatment with NAC.

Isovolumic loading of the failing heart by intraventricular placement of a spring expander attenuates cardiac atrophy after heterotopic heart transplantation.

Cardiac atrophy is the most common complication of prolonged application of the left ventricle (LV) assist device (LVAD) in patients with advanced heart failure (HF). Our aim was to evaluate the course of unloading-induced cardiac atrophy in rats with failing hearts, and to examine if increased isovolumic loading obtained by intraventricular implantation of an especially designed spring expander would attenuate this process. Heterotopic abdominal heart transplantation (HTx) was used as a rat model of heart unloading. HF was induced by volume overload achieved by creation of the aorto-caval fistula (ACF). The degree of cardiac atrophy was assessed as the weight ratio of the heterotopically transplanted heart (HW) to the control heart. Isovolumic loading was increased by intraventricular implantation of a stainless steel three-branch spring expander. The course of cardiac atrophy was evaluated on days 7, 14, 21, and 28 after HTx Seven days unloading by HTx in failing hearts sufficed to substantially decrease the HW (-59 ± 3%), the decrease progressed when measured on days 14, 21, and 28 after HTx Implantation of the spring expander significantly reduced the decreases in whole HW at all the time points (-39 ± 3 compared with -59 ± 3, -52 ± 2 compared with -69 ± 3, -51 ± 2 compared with -71 ± 2, and -44 ± 2 compared with -71 ± 3%, respectively; P<0.05 in each case). We conclude that the enhanced isovolumic heart loading obtained by implantation of the spring expander attenuates the development of unloading-induced cardiac atrophy in the failing rat heart.

Prevention of contrast agent-induced renal impairment in patients with chronic renal insufficiency and heart disease by high-dose intravenous N-acetylcysteine: a pilot-ministudy.

BACKGROUND: Contrast-induced nephropathy is a relatively common complication occurring after various procedures requiring contrast agent injection, especially in patients with pre-existing renal failure. AIM: This pilot study was designed to assess the effects of a high intravenous dose of N-acetylcysteine (NAC) on plasma creatinine concentration. METHODS: Twenty patients with pre-existing renal insufficiency were given NAC at a dose of 100 mg/kg. No contrast agent was given to 10 patients (Group A), whereas 10 patients received contrast at the time of coronary angiography (Group B). Changes in plasma creatinine were assessed at 3 hours and one day following NAC administration. RESULTS: In Group B, NAC prevented creatinine increase: baseline levels were 210.98+/-77.33 micromol/L, 200.26+/-71.94 micromol/L (NS) after 3 hours, and 203.80+/-83.94 micromol/L 24 hours later (NS). The following was seen in Group A patients: 201.21+/-42.28 micromol/L, 190.31+/-42.74 micromol/L (p<0.01), and 170.08+/-45.53 micromol/L (p<0.01), respectively. CONCLUSION: The results of this study confirm the effectiveness of NAC in prevention of contrast agent-induced renal impairment. In addition, we demonstrated the beneficial effects of NAC on renal function in patients who were not exposed to contrast agent. This pilot study should provide the basis for more comprehensive research and, also, for safe clinical practice.

Clinical manifestations of infective endocarditis in relation to infectious agents: An 8-year retrospective study.

AIM: To compare clinical complications and outcomes of infective endocarditis (IE) episodes caused by Staphylococcus aureus (S. aureus) and other most frequent aetiological agents (streptococci, enterococci, coagulase-negative staphylococci, and culture-negative IE). METHODS: A total of 117 IE episodes assessed by all internal medicine services of a major teaching institution in the Czech Republic over an eight-year period were identified. RESULTS: We found that S. aureus IE episodes (n = 36) were significantly more associated with systemic embolism (41.7% vs 18.5%, P = 0.01), severe sepsis/septic shock (33.3% vs 3.7%, P < 0.0001), and in-hospital mortality (33% vs 12.3%, P = 0.01). No differences in local, structural, and/or functional complications (cardiac abscess formation, impaired integrity of the valvular apparatus, conduction disturbances, or incidence of heart failure) were observed between studied groups. Long-term survival estimates were significantly improved in patients with IE caused by agents other than S. aureus (13.78 median years vs 5.48 median years, P=0.03). CONCLUSIONS: IE episodes caused by S. aureus are associated with both increased short-term and long-term mortality. Of all the studied parameters, only systemic embolism and severe sepsis/septic shock predicted in-hospital mortality.

N-acetylcysteine in acute cardiology: 10 years later: what do we know and what would we like to know?!

N-acetylcysteine (NAC) is known in a variety of branches of medicine. This paper addresses in detail the action of NAC as it is emerging from research and clinical trials over the past decade in cardiology, giving rise to new concepts. The result is a process resembling creation of a mosaic from individual pieces. Also, the role of NAC in acute cardiology, during acute reperfusion in particular, is defined.

Not all statins are alike: induced rhabdomyolysis on changing from one statin to another one.

A 59-year-old woman underwent orthotopic heart transplantation 4 years earlier. At the time of transplantation, she was receiving pravastatin at a dose of 20 mg per day; she tolerated subsequent combination with immunosuppression (cyclosporine A, prednisone, mycophenolate mofetil) very well throughout the 4 years. After switching from pravastatin to simvastatin, she developed severe muscular weakness and laboratory evidence of muscle break down. Biochemical markers of rhabdomyolysis did not subside until after repeat hemodialysis and normalized after 2 months in conjunction with improved renal function. Clinical improvement was not apparent until after 5 months.

Bone marrow suppression and associated consequences in patients after heart transplantation: A 6-year retrospective review.

AIMS: To evaluate the incidence of bone marrow suppression and consequences of MMF dose adjustment in patients within the first year after heart transplantation. METHODS: Group I (n=47) was treated with a regimen currently used in patients after heart transplantation (mycophenolatemofetil - MMF, valganciclovir - VGC and trimethoprim/sulfamethoxazole - TMP-SMX). Group II (n=47) received only MMF of potentially myelotoxic medications. The myelotoxic effect and need for dose modification were assessed. The incidence of rejections and infectious episodes associated with MMF adjustment were analyzed during the first 12 months in Group I. RESULTS: There was a significantly greater proportion of patients with leukopenia (leukocyte count < 4 x 10^9/L) at 3 months after orthotopic heart transplantation in Group I compared with Group II (19.1% vs 2.1%; P = 0.02). The difference in lymphopenia (lymphocyte count < 0.8 x 10^9/L) at 3 months follow-up was highly significant (38.3 % vs 6.4 %; P = 0.0002). MMF was modified due to bone marrow suppression or severe infection in 63.8% patients in Group I and in only 8.5% of patients in Group II (P < 0.001). Reducing or stopping MMF was not associated with increased rejections. In Group I, at least 1 episode of higher degree cellular or humoral rejection occurred in 35% of patients with the standard MMF dosage compared with only 26% in patients with modified MMF (P = 0.0534). CONCLUSIONS: Addition of VGC+TMP-SMX to current immunosuppressive medication regimen in patients after heart transplantation is associated with significant lymphocytopenia and leukopenia. Importantly, modification of immunosuppressive prophylaxis (reducing or stopping MMF) leads to normalization of blood count without increased incidence of rejections.

Twin valve caval stent for functional replacement of incompetent tricuspid valve: a feasibility animal study.

OBJECTIVE: To evaluate feasibility of a twin valve caval stent (TVCS) for functional replacement of an incompetent tricuspid valve (TV) in an acute animal study. METHODS: One swine and three sheep were used in the study. TVCS placement was tested in a swine with a normal TV. TVCS function was tested in three sheep with TV regurgitation created by papillary muscle avulsion. Cardiac angiograms and pressure measurements were used to evaluate TVCS function. Two sheep were studied after fluid overload. RESULTS: TVCS was percutaneously placed properly at the central portions of the superior vena cava (SVC) and inferior vena cava (IVC) in the swine. Papillary muscle avulsion in three sheep caused significant tricuspid regurgitation with massive reflux into the right atrium (RA) and partial reflux into the SVC and IVC. TVCS placement eliminated reflux into the SVC and IVC. After fluid overload, there was enlargement of the right ventricle and RA and significant increase in right ventricle, RA, SVC, and IVC pressures, but no reflux into the IVC and SVC. CONCLUSION: The results of this feasibility study justify detailed evaluation of TVCS insertion for functional chronic replacement of incompetent TV.

Need for new materials, biofunctionalization and non-surgical heart valve technology.

Transition from non-surgical heart valve defects repair from bench to bedside is a reality. Some biological material-based designs for transcatheter aortic valve implantation are ready for use. Their drawback, however is their unknown functional as well as structural durability. Moreover, research on new non-biological materials is essential to replace classical animal-derived sources of human heart valve prostheses.

A new cone-shaped aortic valve prosthesis for orthotopic position: an experimental study in Swine.

The aim of this experimental study was to evaluate a newly designed cone-shaped aortic valve prosthesis (CAVP) for one-step transcatheter placement in an orthotopic position. The study was conducted in 15 swine using either the transcarotid (11 animals) or the transfemoral (4 animals) artery approach. A 12- or 13-Fr sheath was inserted via arterial cutdown. The CAVP was deployed under fluoroscopic control and its struts, by design, induced significant native valve insufficiency. CAVP function was evaluated by aortography and aortic pressure curve tracing. In 11 of 15 swine the CAVP was properly deployed and functioned well throughout the scheduled period of 2-3 h. In three swine the CAVPs were placed lower than intended, however, they were functional even in the left ventricular outflow tract position. One swine expired due to inadvertent low CAVP placement that caused both aortic regurgitation and immobilization of the anterior mitral valve leaflet by the valve struts. We conclude that this design of CAVP is relatively easy to deploy, works well throughout a short time period (2-3 h), and, moreover, seems to be reliable even in a lower-than-orthotopic position (e.g., infra-annulary space). Longer-term studies are needed for its further evaluation.

Potential use of a combined extractor in intravascular procedures.

Extraction techniques are gaining increasing attention in proportion to the increasing range of endovascular procedures. The choice of the instrumentarium depends, among other things, on whether the object to be extracted is a foreign body (most often a catheter) with or without a free end. This communication offers our experience with a combined extractor of our own manufacture allowing both central and lateral grasping techniques. The technique of catheterization is illustrated in one case.

Catheter-based modification of heart valve diseases: from experimental to clinical application.

Efforts to modify cardiac valve defects using catheter-based techniques are increasing at the present time. We present observations on cardiac valve morphology and disease and review the progress being made to address valve defects with these innovative methods. Some new procedures developed through animal experimentation have already been put to use in clinical practice, but the newness of these techniques and the small number of cases in which they have been applied to date precludes an evaluation of their long-term durability. Although at the present time cardiac surgery remains the standard for treating most cases of valve disease, in certain situations a catheter-based treatment might provide a reasonable alternative, even if only temporary, especially for individuals with serious disease who are not suitable candidates for surgery.

Percutaneous transcatheter one-step mechanical aortic disc valve prosthesis implantation: a preliminary feasibility study in swine.

PURPOSE: To evaluate the feasibility of one-step implantation of a new type of stent-based mechanical aortic disc valve prosthesis (MADVP) above and across the native aortic valve and its short-term function in swine with both functional and dysfunctional native valves. METHODS: The MADVP consisted of a folding disc valve made of silicone elastomer attached to either a nitinol Z-stent (Z model) or a nitinol cross-braided stent (SX model). Implantation of 10 MADVPs (6 Z and 4 SX models) was attempted in 10 swine: 4 (2 Z and 2 SX models) with a functional native valve and 6 (4 Z and 2 SX models) with aortic regurgitation induced either by intentional valve injury or by MADVP placement across the native valve. MADVP function was observed for up to 3 hr after implantation. RESULTS: MADVP implantation was successful in 9 swine. One animal died of induced massive regurgitation prior to implantation. Four MADVPs implanted above functioning native valves exhibited good function. In 5 swine with regurgitation, MADVP implantation corrected the induced native valve dysfunction and the device's continuous good function was observed in 4 animals. One MADVP (SX model) placed across native valve gradually migrated into the left ventricle. CONCLUSION: The tested MADVP can be implanted above and across the native valve in a one-step procedure and can replace the function of the regurgitating native valve. Further technical development and testing are warranted, preferably with a manufactured MADVP.

Percutaneous extraction of a fractured permanent pacemaker lead with no free end.

From various points of view abandoned or displaced permanent pacemaker leads should be extracted in indicated cases using a broad spectrum of catheter-based techniques. We describe a relatively easy extraction procedure of almost the whole pacemaker lead, which broke near the pulse generator and migrated into right-heart chambers; so both ends were indwelling. The described procedure was undertaken using a simple homemade nitinol-based extractor.

Catheter-based untying of a knot on an electrode catheter.

This case report describes an unusual complication: a knot formed on an electrode catheter, which became entangled in a pelvic vein and could not be withdrawn. The case was managed by a new catheter technique allowing the knot to be untied and subsequently removing it via the insertion site without the need for surgical intervention.

Percutaneous extraction of a severed and frayed permanent pacing lead.

From the point of view of established practice, redundant permanent pacing leads have been abandoned or extracted using various catheter-based procedures. An unusual complication was caused by failed surgical lead extraction resulting in electrode severing and wire unbraiding with subsequent induction of electric interaction between the metallic, noninsulated part of the lead fragment and the defibrillating electrode. This interaction was sensed and detected by the ICD system. A modified catheter-based extraction procedure is described.