Andreas Hannekum

Reliability of a new algorithm for continuous cardiac output determination by pulse-contour analysis during hemodynamic instability.

Objective The method of determining continuous cardiac output (CO) with beat-to-beat pulse-contour analysis calibrated by transthoracic thermodilution is gaining much wider clinical acceptance. However, some questions have been raised regarding the reliability of this method during periods of profound hemodynamic instability. We validated the original calculation of pulse-contour analysis and a new, improved algorithm against thermodilution-derived measurements of CO in patients with changes of CO >20%. Design Comparative study. Setting Cardiac surgical intensive care unit of a university hospital. Patients Twenty-four patients after cardiac surgery who experienced changes of CO >±20% during their postoperative course. Interventions CO was measured by transthoracic thermodilution and pulse-contour analysis (PiCCO, PULSION Medical Systems, Munich, Germany) at serial intervals every 60 mins during study periods of 8–44 hrs. During this time, no recalibration of the pulse-contour computer was performed. Measurements and Main Results A total of 517 simultaneous measurements of thermodilution CO and pulse-contour CO measured by the two different algorithms were compared by regression, structural regression, and Bland-Altman analyses. Mean change of CO was 40% ± 27% (range, 20% to 139%), range of systemic vascular resistance was 450–2360 dyne·sec/cm5. Correlation of the original pulse-contour algorithm to thermodilution CO was r = .76, with p = .027; bias was 0.08 L/min, with 1.8 L/min single sd. Correlation of the improved pulse-contour algorithm to thermodilution CO was r = .88, with p = .0001; bias was 0.2 L/min, with 1.2 L/min single sd. Mean CO by the new pulse-contour algorithm did not differ significantly from CO by thermodilution during the study period. The difference between the methods was not influenced by variations of heart rate or arterial pressure. Conclusions CO measurement by arterial pulse-contour analysis based on a new, improved algorithm is reliable, even in patients with profound changes of CO and during periods of hemodynamic instability.

Endocarditis after nipple piercing in a patient with a bicuspid aortic valve

Piercing the skin for cosmetic reasons can be dangerous in young adults who have previously undergone surgery for congenital defects of the heart. We report the case of a 24-year-old man in whom coarctation of the aorta had been corrected 15 years earlier. Two months after piercing his left nipple without antibiotic prophylaxis, he developed a local mastitis, followed by bacterial endocarditits that required replacement of the aortic valve.

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)

The expression of heat shock protein 60 in myocardium of patients with chronic atrial fibrillation

Objective Cardiomyocytes respond to stress with the expression of different heat shock proteins (HSP). HSP60 is induced by various stress factors. The aim of this study was to investigate the expression of HSP60 in human atrial fibrillation (AF). Method Right atrial samples from 14 patients undergoing elective cardiac surgery were excised and immediately frozen in liquid nitrogen. Eight patients had chronic AF and six patients were in sinus rhythm. The HSP60 protein level was determined by SDS-PAGE, Western blot and quantified by optical densitometry according to the immunoreactive bands of actin. Results In myocardial samples from patients with chronic AF, we found a more than 2.5-fold increase in HSP60 expression compared to atrial myocardium of patients in sinus rhythm. Conclusion This result indicates an up regulation of HSP60 in response to chronic atrial fibrillation

New aspects concerning the regulation of the postoperative 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.

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.

Ca2+-activated K+ channels in human smooth muscle cells of coronary atherosclerotic plaques and coronary media segments

The behavior of Ca2+-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 was 216.4±16.7pS (n=6) in SMCP and 199.9±6.7pS (n=6) in SMCM in symmetrical 140 mMK+ solutions. Using outside-out patches, external perfusion with 500 μM 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=0.0542±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 Ca2+-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.

Modulation of Ca2+-activated K+ channels in human vascular cells by insulin and basic fibroblast growth factor.

Insulin and basic fibroblast growth factor (bFGF) play an important role in the pathogenesis of atherosclerosis and have been shown to have vasodilatory effects. Since modulation of vascular ion channels determines membrane potential and thereby influences essential Ca2+-dependent intracellular pathways, we have investigated the effect of insulin and bFGF on Ca2+-activated K+ channels (BKCa) in human umbilical vein endothelial cells (HUVEC) and smooth muscle cells. The latter were obtained from either atherosclerotic plaques (SMCP) or from media segments (SMCM) of human coronary arteries. Using the patch-clamp technique, insulin (100 microU/ml) caused a significant increase in BKCa open-state probability in SMCP and HUVEC, whereas no significant changes were observed in SMCM. Basic FGF (30 ng/ml) revealed a significant increase in BKCa activity in HUVEC and a significant decrease in the BKCa open-state probability in SMCP, but caused no changes in SMCM. Thus, growth factors modulate vascular BKCa in a cell-type specific manner, which may be of importance concerning vasoactive and atherogenic effects of growth factors.

Leaflet escape in a TEKNA and an original duromedics bileaflet valve

We report a case of leaflet escape in an Edwards-TEKNA bileaflet valve, in the mitral position. The examination findings of the explanted valve are compared with a similar case of leaflet escape in an original Edward-Duromedics prosthesis. Based on our findings alone, it is not certain whether the TEKNA valve continues to have a higher risk for fracture.

Expression of mortalin in patients with chronic atrial fibrillation

Abstract.Background:In myocardium of patients with chronic atrial fibrillation (AF) the expression of the mitochondrial heat shock proteins HSP60 and HSP10 is increased. They are responsible for folding and translocation of proteins inside the mitochondria. Import of these proteins is accomplished by mortalin. The aim of our study was to investigate if the expression of the heat shock protein mortalin is also increased in patients with AF.Methods:Right atrial samples from 18 patients undergoing elective cardiac surgery were excised and immediately frozen in liquid nitrogen: 8 patients had chronic AF (≥ 3 month) and 10 patients were in sinus rhythm (SR). Mortalin was determined by SDS-PAGE, Western blot and quantified by optical densitometry.Results:In myocardial samples from patients with chronic AF we found a more than 2-fold increase in mortalin expression.Conclusions:The increased expression of mortalin may represent an adaptive heat shock response to restore cellular homeostasis.