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Biomedical subjects

A Hannekum

Publications and source records attributed to A Hannekum.

At least 37 records · Page 2Linked to original sources
PubMed1998

Intermediate follow up of the TEKNA bileaflet valve.

BACKGROUND AND AIM OF THE STUDY: The study aim was to collect intermediate clinical data on the TEKNA bileaflet valve. METHODS: This nine-center clinical study involved 884 patients implanted between June 1990 and October 1993. The population consisted of 522 (59.0%) males and 362 (41.0%) females. Mean age at implant was 59.1 +/- 11.8 years (range: 14.7 to 88.4 years). Indication for valve replacement was dependent on the position: stenosis was the predominant reason in the aortic position; regurgitation was more pronounced for the mitral position. A total of 261 (29.5%) patients underwent concomitant procedures. Mean follow up is 2.7 +/- 1.2 years; total follow up is 2386.1 patient-years (pt-yr). RESULTS: Total operative (< or = 30 days postoperative) mortality rate was 3.7%; seven patients (0.8%) died due to valve-related causes. Total postoperative (> 30 days postoperative) mortality rate was 2.5%/pt-yr and included a valve-related mortality rate of 1.1%/pt-yr. The following valve-related complication rates (%/pt-yr) were reported for the long-term postoperative period: thromboembolism 0.6; valve thrombosis 0.3; bleeding events 1.5; non-structural deterioration 0.6; and endocarditis 0.4. No structural valve deterioration was reported. Actuarial freedom at four years was: overall survival rate 86.9 +/- 1.4%; valve-related survival rate 94.7 +/- 1.0%; freedom from thromboembolism 96.8 +/- 0.9%; valve thrombosis 99.3 +/- 0.3%; endocarditis 98.5 +/- 0.5%; bleeding events 94.3 +/- 1.0%; and non-structural deterioration 98.2 +/- 0.6%. CONCLUSIONS: The data indicate that observed mortality is due mainly to non-valve-related disorders. Risk of thromboembolic and bleeding events was low (0.9%/pt-yr and 1.5%/pt-yr, respectively). We conclude that this valve is safe and efficacious for use.

Actuarial Analysis↗
PubMed1997

Ca(2+)-activated K+ channels in human smooth muscle cells of coronary atherosclerotic plaques and coronary media segments.

The behavior of Ca(2+)-activated K+ channels of large conductance (BKCa) in smooth muscle cells, which were obtained from atherosclerotic plaque material (SMCP) and from media segments (SMCM) of human coronary arteries, were compared using the patch-clamp technique. Voltage-clamp protocols in cell-attached patches revealed the characteristic voltage-dependent activation of BKCa in both cell groups. Single-channel conduction as 216.4 +/- 16.7 pS (n = 6) in SMCP and 199.9 +/- 6.7 pS (n = 6) in SMCM in symmetrical 140 mM K+ solutions. Using outside-out patches, external perfusion with 500 microM tetraethylammonium ions caused a typical "flickery block" of the unitary current. The selective BKCa channel inhibitor iberiotoxin (50 nM) effectively blocked BKCa, channel activity. Comparing BKCa open-state probabilities (P0) at +80 mV in cell-attached patches, a highly significant difference between SMCP (P0 = 0.1438 +/- 0.1301; n = 15) and SMCM (P0 = 0.0093 +/- 0.0044; n = 15; Kruskal-Wallis test, p < 0.001) was found. In contrast to this finding, there was no significant difference in the open-state probability of BKCa, between SMCP (P0 = 0.542 +/- 0.0237; n = 9) and SMCM (P0 = 0.0472 +/- 0.0218; n = 10; p = n.s.) using inside-out patches. The results show an interesting difference in the behavior of large conductance Ca(2+)-activated K+ channel in SMCP compared to SMCM with a significantly higher channel activity in human smooth muscle cells obtained from coronary atherosclerotic plaque material. This finding may indicate an important functional role of BKCa channels in the development of atherosclerosis.

Calcium↗
PubMed1997

Damage to arterial and venous endothelial cells in bypass grafts induced by several solutions used in bypass surgery.

The purpose of our study was to evaluate the cytotoxicity of incubation solutions used in heart surgery to endothelial cells. The endothelial layer of human saphenous veins (HSV) and bovine internal mammary arteries (BMA) and veins (BMV) were studied after a two-hour storage interval and compared with control vessel segments prepared immediately after harvesting. To visualize the endothelial cell damage, specimens were stained with a silver nitrate technique. The surface covered by light-microscopically intact endothelial cells was computed in percent. In the control HSV segments 70.8 +/- 4.6% of the endothelium were found to be morphologically intact. The results for stored HSV segments were 50.0 +/- 4.2% (Bretschneider's solution), 14.8 +/- 4.5% (physiological saline), 0.45 +/- 0.1% (physiological saline with heparin), 16.7 +/- 4.7% (Ringer's lactate) and 37.2 +/- 5.3% (heparinized blood). Comparable values obtained with BMA specimens were 98.3 +/- 0.7% (controls), 78.1 +/- 4.7% (Bretschneider's solution), 39.2 +/- 3.3% (physiological saline), 8.4 +/- 2.0% (physiological saline with heparin), 11.3 +/- 1.7% (Ringer's lactate) and 67.8 +/- 6.2% (heparinized blood). A similar trend was found with BMV segments: 85.2 +/- 4.7% (controls), 75.6 +/- 6.0% (Bretschneider's solution), 49.5 +/- 8.9% (physiological saline), 5.95 +/- 0.7% (physiological saline with heparin), 6.2 +/- 0.7% (Ringer's lactate) and 54.3 +/- 5.1% (heparinized blood). In conclusion, Bretschneider's solution proved to be superior for storage of bypass grafts in comparison to all other tested solutions in this series.

Animals↗
PubMed1997

Sex steroids in cardiopulmonary bypass.

BACKGROUND: Sex steroids have immunomodulatory effects. No data exist on alterations of sex steroids during cardiopulmonary bypass (CPB). Cardiac surgery with CPB releases an immunological response with complement and cytokine activation. RESULTS: Plasma estradiol and progesterone levels before and immediately after CPB were measured in 11 patients. During CPB, mean estradiol levels decreased from 29 to 15 pg/ml and progesterone levels rose from 0.13 to 0.90 ng/ml. These changes were statistically significant. CONCLUSIONS: These are the first preliminary results evaluating plasma levels of sex steroids during CPB. Whether alterations in estradiol and progesterone levels influence complement and cytokine activation during bypass or vice versa is currently being investigated.

Journal Article↗
PubMed1996

Increased endothelin release by cultured human smooth muscle cells from atherosclerotic coronary arteries.

OBJECTIVES: Endothelin, a 21-amino acid peptide initially purified from the medium of cultured endothelial cells, is a potent vasoconstrictor exerting its effects predominantly in a paracrine or autocrine manner. Recent data indicate that endothelin is also synthesized by cultured vascular smooth muscle cells and that endothelin is an effective stimulator of smooth muscle cell proliferation. This study aimed to investigate the endothelin release of cultured human smooth muscle cells, isolated from coronary plaques and from normal coronary tunica media, and to determine circulating endothelin concentrations in patients with coronary artery disease compared to control subjects. METHODS: Coronary plaque material was extracted by thrombendarterectomy during aorto-coronary bypass grafting (n = 19). Segments of normal coronary arteries were obtained at autopsy (n = 33). Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells with antibodies against smooth muscle alpha-actin. Venous blood samples were drawn from patients with coronary artery disease undergoing cardiac catheterization (n = 32) and from control subjects (n = 38). Endothelin concentrations in culture medium and in plasma samples were measured by radioimmunoassay after Sep Pak C18 extraction. RESULTS: Cultured smooth muscle cells, isolated from coronary plaques, released a significantly (P < 0.001) higher amount of immunoreactive endothelin into the culture medium (39.2 +/- 3.9 pg/10(4) cells, mean +/- s.e.m., 31 supernatant samples) than smooth muscle cells from normal coronary tunica media (3.9 +/- 0.8 pg/10(4) cells, 28 samples). Circulating endothelin concentrations were slightly elevated (P < 0.01) in patients with coronary artery disease (3.8 +/- 0.2 pg/ml) compared to control subjects (3.0 +/- 0.2 pg/ml). CONCLUSIONS: These data suggest that the endothelin production is markedly increased in smooth muscle cells of coronary atherosclerotic plaques. The enhanced endothelin release may stimulate smooth muscle cell proliferation in a paracrine or autocrine manner and thus may contribute to the development or progression of coronary artery disease.

Cells, Cultured↗
PubMed1996

[Initial clinical experiences with indirect myocardial revascularization--free skeletal muscle transplantation for induction of epimyocardial neovascularization].

Patients with multiple and peripherial coronary stenosis are not suitable for direct coronary artery surgery. For these patients a new surgical myocardial revascularization was developed. This new surgery was adopted on 5 patients from May 1993 through May 1995. The operation consisted in the grafting of a free skeletal muscle flap onto the anterior wall of the heart (musculus-latissimus-dorsi). The flap artery was implanted into the aorta, the venous flow was directed into the right atrium. All patients were about 3 weeks after the intervention free from angina. The postoperative bicycle ergometry showed no signs of ischemic ST-segment changes, meanwhile the preoperative ergometry evinced signs of ischemic ST-segment changes in almost all patients. Angiographically a patent anastomosis of the flap artery implanted into the aorta was found as well as a good contrast of the graft. Thus, "indirect myocardial revascularization" may be a surgical alternative treatment for patients suffering from therapy refractory ischemic heart disease.

Aged↗
PubMed1995

New aspects concerning the regulation of the post-operative acute phase reaction during cardiac surgery.

During a cardio-pulmonary bypass, as well as post-operatively, high levels of endotoxin, interleukin-6 (Il-6) and C-reactive protein (CRP) were measured in 30 patients. A significant increase in endotoxin plasma level occurred during surgery, culminating in a peak during reperfusion. Plasma levels of endotoxin continued to be slightly raised until the fifth day after surgery, whereas those of Il-6 rose at the time the operation came to an end and were at their highest 6 h later. CRP levels were also high, post-operatively, and were markedly raised on day 2. A definite, statistically significant correlation between the plasma levels of endotoxin and Il-6 during the operation was established, leading us to conclude that the endotoxin liberated during cardiac surgery acts as the main trigger in the release of Il-6 and thus induces the post-operative acute phase reaction. There was no evidence of a correlation between CRP and endotoxin or Il-6 plasma levels.

Acute-Phase Reaction↗
PubMed1995

Aprotinin in elective primary bypass surgery. Graft patency and clinical efficacy.

The proteinase inhibitor aprotinin is used in open heart surgery to reduce intraoperative and postoperative blood loss and transfusion requirements. To investigate a possible influence on graft patency, a randomized double-blind group comparison study was carried out in male patients elected for primary bypass surgery. One hundred ten (55/55) patients received either placebo treatment or aprotinin according to the Hammersmith scheme (2 Mio KIU as loading dose before sternotomy, followed by an infusion of 0.5 Mio KIU/h until the end of surgery; 2 Mio KIU added to the priming volume additionally). Graft patency was evaluated by angiography in 44 aprotinin and 35 placebo patients between the 18th and 35th days postoperatively. There was no difference in the overall graft occlusion: in the aprotinin group 89.5% (111/124) grafts were found patent compared to 87.2% (89/102) in the placebo group. Of the aprotinin patients 72.7% (32/44) and 71.4% (25/35) of the placebo patients had all grafts patent. Venous grafts were occluded in 16% (7/44) of aprotinin patients and in 29% (10/35) of placebo patients. On the other hand 5/27 patients in the aprotinin group vs 0/27 in the placebo group had occluded internal mammary artery (IMA) grafts (P = 0.0511%). Graft occlusions were not accompanied by signs of myocardial infarction in any case. Fifty-one patients in the aprotinin group and 47 patients in the placebo group were valid for parameters of clinical efficacy: blood loss within 6 h postoperatively was reduced by 58.5% in the aprotinin group (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Effect of chronic nicotine delivery on the proliferation rate of endothelial and smooth muscle cells in experimentally induced vascular wall plaques.

To study the effect of nicotine, cholesterol feeding, and their combination on endothelial and smooth muscle cells in vascular wall plaques an experimental method was established which allows the immunohistochemical detection and quantification of the fractions of endothelial and smooth muscle cells in DNA synthesis under the effect of these stimuli. For this purpose standardized fibromuscular plaques were produced by electrostimulation in the common carotid arteries of rabbits. The animals received either nicotine via implanted osmotic minipumps or a cholesterol diet or both. Plaque size was determined at the end of the experiments after 7 or 14 days as well as the fraction of endothelial and smooth muscle cells in DNA synthesis during exposure to bromodeoxyuridine (BrdU). The BrdU labeling index of endothelial cells clearly increased under chronic nicotine administration for either 7 days or 14 days compared to controls. The combination of nicotine and cholesterol diet led to a more significant increase. In contrast, the BrdU labeling index of smooth muscle cells was not increased under nicotine delivery. The combination of nicotine and cholesterol, however, led to a significant increase of the BrdU labeling index of smooth muscle cells in the plaques compared to cholesterol feeding. Measurement of the plaque size revealed no difference between controls and nicotine-treated animals after 14 days of nicotine delivery, whereas the combination of cholesterol and nicotine produced increased plaque formation compared to a group of animals which received a cholesterol diet alone.

Analysis of Variance↗
PubMed1994

Characterization of the sodium currents in isolated human cardiocytes.

The whole-cell recording technique was used to register Na+ currents from 403 atrial cardiocytes isolated from 80 human biopsies. With intracellular [Na+] ([Na+]i) raised to 70 mM, and at physiological extracellular [Na+] ([Na+]e, 145 mM) and room temperature, the Na+ currents were small enough for the error of the voltage clamp not to exceed 2 mV (series resistances 0.4-2 M omega). The threshold potential of the Na+ current was -64.0 +/- 7.7 mV. The peak amplitude was at -30.0 +/- 6.2 mV. The time course of fast inactivation was satisfactorily described with a single exponential. The time constant of inactivation was 2.0 ms at -55 mV and asymptotically approached 0.2 ms at positive membrane potentials. The steady-state inactivation curve was well fitted by a single Boltzmann distribution. Increasing the prepulse duration from 32 to 512 ms shifted the inflexion point of the curve from -61.7 +/- 6.4 to -72.2 +/- 2.6 mV. The time course of slow inactivation was also well described by a single exponential, the time constant ranging from 76.1 +/- 29.3 ms at -115 mV to 18.6 +/- 7.8 ms at -55 mV. Fitting the time course of recovery from inactivation required two time constants. At a recovery potential of -135 mV these were 1.6 +/- 0.2 and 8.6 +/- 2.9 ms and 15.9 +/- 9.4 and 53.2 +/- 33.3 ms at -95 mV. A 50% block of the Na+ currents was achieved by tetrodotoxin at 10 microM. It is concluded that the properties of human cardiac Na+ channels are similar to those of the juvenile Na+ channels of human skeletal muscle.

Heart Atria↗
PubMed1994

A new experimental approach for monitoring postoperative bypass patency after coronary artery bypass grafting.

Little information is known concerning hemodynamic parameters of bypass grafts after open heart surgery during the postoperative period. As there is no easy to use bedside-method for monitoring, we developed a new implantable Doppler probe to measure blood flow velocity with a 20 MHz pulsed Doppler system. The accuracy of this method was proved in a circulatory model and in animal studies. Our conclusion is that the implantable pulsed Doppler system is a sensitive method for monitoring small vessel hemodynamics.

Animals↗
PubMed1994

Indirect myocardial revascularization--an experimental study in the dog.

It has been shown in previous studies that grafting a free skeletal muscle flap onto the heart of the dog produces myocardial revascularization. In order to evaluate the functional aspect of these neovessels, an Ameroid constrictor was implanted into the LADs (left anterior descending coronary artery) of five dogs. At the same time, the free muscle flap was grafted onto the anterior wall of the heart. The arterial anastomosis was achieved with the internal mammary artery. Venous flow was drained into the right atrium. About 12 months later, the regional myocardial blood flow was evaluated adopting the radioactive microsphere technique. This was carried out with the LAD occluded by the Ameroid constrictor and the circumflex artery (CX) open (control conditions). Then the CX was occluded in order to exclude collateral blood flow. Afterwards another occlusion of the CX was performed ("preconditioning") to produce maximal opening of the anatomical collaterals. It was found that regional myocardial blood flow was unchanged in the antero-lateral parts of the hearts despite complete occlusion of the coronaries supplying this area. In the parts supplied by the CX, though, flow was minimal. "Preconditioning" positively influenced the perfusion of this region only in the epicardial parts. Histologically large sinusoid-like blood conductors connected the graft and the heart. Thus, grafting a free skeletal muscle flap onto the heart in the dog produces functional myocardial revascularization in the dog.

Anastomosis, Surgical↗
PubMed1994

Effects of vasoactive drugs on postoperative coronary bypass flow: a new technique.

OBJECTIVE: This study aimed to investigate the influence of vasoactive drugs, including a calcium channel blocker, nitroglycerine, and a beta-blocker, often used after coronary artery bypass grafting (CABG). Measurements were taken using a new, completely implantable, mini-Doppler system. The probes were implanted during CABG, led outside through the thoracic wall, and removed 3 days after the operation by a simple pull. RESULTS: The mean Doppler flow increased dramatically in the calcium channel blocker and the nitroglycerine groups (P = 0.002) and decreased slightly in the beta-blocker group (P = 0.015). Mean arterial pressure decreased significantly in all three groups. Heart rate decreased in the beta-blocker group (P = 0.002). Changes in the other hemodynamic variables measured were not significant; there were no changes in the control group. Doppler sonographic monitoring of bypass diameters did not show any changes. CONCLUSION: This is the first study to measure the influence of vasoactive drugs directly and online after CABG. From our experience of more than 40 implantations, we conclude that our method is easy to use and reliable and will help improve the therapeutic regimen for patients after CABG.

Aged↗
PubMed1993

Free skeletal muscle transplantation to an infarction area: an experimental study in the dog.

In plastic surgery, free skeletal muscle flaps are used for treatment of non-healing injuries like chronic osteitis or radiation ulcers. We wanted to evaluate if the neoangiogenesis induced by these flaps can also constitute a method for revascularization in ischemic heart disease. In diffuse small vessel coronary heart disease, patients are not suitable for bypass surgery because it is impossible to create a microanastomosis with the coronary artery. As an alternative, a free striated muscle flap, transplanted onto the heart, can constitute a source of neovessels. With the induction of extra-intracardial collaterals that develop within 4 weeks after transplantation of the flap, a new surgical approach may be offered to those patients. Our experimental work was performed with 20 dogs. In these, a myocardial infarction of the anterior wall was selectively produced using the Judkins-technique (Radiology 89: 815-824, 1967) for injection of Sephadex-microspheres. Four weeks later a free pectoralis muscle flap was transplanted onto the anterior wall of the heart. Arterial blood supply was achieved with an anastomosis with the internal mammary artery. The venous flow was directed into the right atrium. Four to eight weeks after surgery, the patency of the anastomosis was studied by angiography, showing patency in almost all surviving animals. Histological examination of the hearts revealed a prominent vascular network penetrating into the underlying myocardium. Corrosion cast preparations, as well as a postmortem angiography, showed even further penetration of the neovessels into the uninjured parts of the myocardium. Thus, myocardial revascularization may be achieved by transplantation of a skeletal muscle onto the heart.

Anastomosis, Surgical↗
PubMed1993

[Monitoring aortocoronary bypass. A new experimental approach].

Only few data are known concerning haemodynamic parameters and pathomechanisms of small vessels and bypass grafts. No easy-to-use bedside method exists for monitoring. We developed a miniaturised implantable Doppler probe linked to a 20 MHz pulsed Doppler system. In a circulation model and in animal studies we can show the accuracy of this method. We conclude that the implantable pulsed Doppler system is a sensitive method for monitoring the haemodynamics of small vessels.

Animals↗
PubMed1993

Patient selection for ICD treatment and peri-operative mortality.

In view of the reported high risks resulting from the implantation of a cardioverter (ICD) and our own experience, we retrospectively evaluated the patients who received an ICD at our institution, so as to predict factors that could lead to a high peri-operative risk. The patients were divided into three groups according to their diagnoses and the surgical procedure. Group I: 10 patients with non-ischaemic cardiomyopathy, age 53.9 +/- 14.0 years, ejection fraction (EF) 33.1 +/- 11.8; group II:13 patients with coronary artery disease (CAD), diffuse arteriosclerosis, age 60.0 +/- 6.8 years, EF 31.4 +/- 9.1%; group III:12 patients, age 61.9 +/- 9.4 years, EF 41.2 +/- 8.6, CAD, concomitant bypass grafting. In cases of cardiomyopathy, cardiac complications (30%) were reversible by adequate drug therapy. However, five patients in group II (38.5%) died from cardiac complications, mainly frequent arrhythmias and subsequent pump failure. In group III no peri-operative complications occurred. Therefore the high mortality (overall 13.2%) in our series was exclusively due to patients suffering from severe CAD and unsuitable for revascularization. Considering the high risk after ICD placement, primary heart transplantation might be the better procedure in younger patients with end-stage CAD.

Adult↗
PubMed1993

The in-vitro effect of antineoplastic agents on proliferative activity and cytoskeletal components of plaque-derived smooth-muscle cells from human coronary arteries.

BACKGROUND: Restenosis after successful percutaneous transluminal coronary angioplasty remains the major clinical problem limiting the long-term efficacy of the treatment. Recent advances in the understanding of the biology of restenosis indicate that its cause is predominantly a multifactorial stimulation of smooth-muscle cell proliferation. The aim of this study was to investigate the in-vitro effect of antineoplastic agents on smooth-muscle cells isolated from human coronary plaque material. METHODS: Atherosclerotic tissue from coronary arteries was extracted from 15 patients of both sexes by thrombendarterectomy. Cells were isolated using enzymatic disaggregation and identified to be smooth-muscle cells with fluorescent antibodies for smooth-muscle-specific alpha-actin. The antineoplastic agents cytarabine (500-0.005 micrograms/ml), doxorubicin (50-0.0005 micrograms/ml), and vincristine (10-0.0001 micrograms/ml) were added to the cultures. Six days after seeding, the cells were trypsinized and then counted. RESULTS: All three antineoplastic agents had a strong dose-dependent antiproliferative effect on cultured smooth-muscle cells. After the application of cytostatic agents, cells either became rounded or underwent complete lysis. Cytoskeletal elements, such as actin, microtubules, and vimentin, were largely altered. CONCLUSION: This investigation examined the potential role of antineoplastic therapy in the prevention of restenosis after coronary angioplasty. The development of new intravascular delivery systems, such as coated stents, may open the way for local antiproliferative strategies in interventional cardiology.

Aged↗