Hans-Henrik Kimose - Academia.edu (original) (raw)
Papers by Hans-Henrik Kimose
Journal of clinical & laboratory immunology, 1988
A microplate-adapted polyclonal IgM-rheumatoid factor enzyme-linked immunosorbent assay (pIgM-RF ... more A microplate-adapted polyclonal IgM-rheumatoid factor enzyme-linked immunosorbent assay (pIgM-RF ELISA) for the detection of circulating immune complexes (cIC) is presented. The assay involves the competitive binding of cIC and horseradish peroxidase conjugated aggregated human IgG (HRP-AHG) to solid-phase bound polyclonal IgM-RF (pIgM-RF). Aggregated human IgG (AHG) inhibited the binding of HRP-AHG to pIgM-RF in a dose-dependent way. The detection limit of the assay was about 125 ng AHG/ml diluted serum. The coefficients of variation for the assay varied from 5.0 to 14.7% for intra-assay runs and from 4.5 to 13.8% for inter-assay runs. The levels of cIC in sera from 29 patients with systemic lupus erythematosus (SLE), 85 untreated patients with breast cancer and 105 blood bank donors were studied by the pIgM-RF ELISA. Increased levels of cIC were demonstrated in 41.4% of the SLE group, in 8.2% of the breast cancer group, and in 1.9% of the normal control group. The difference in cI...
Acta chirurgica Scandinavica
Major surgery is associated with fall in the concentration of inorganic phosphate in serum, as is... more Major surgery is associated with fall in the concentration of inorganic phosphate in serum, as is intravenous infusion of glucose. Hypophosphatemia during different forms of postoperative dextrose administration was evaluated in patients who had undergone colorectal surgery. They were randomized to two groups. All patients received standardized intravenous fluids on the first 3 postoperative days, but one group had constant infusion of a solution containing glucose (4%), sodium (40 mmol/l) and potassium (20 mmol/l) throughout the observation period, while the other group had a 5-hour infusion of 10% glucose daily, with potassium and sodium solution in between. The amounts of administered glucose and electrolytes were the same in both groups. The serum phosphate levels were significantly lower in the group with constant glucose infusion, due to intergroup difference in renal handling of phosphate. Significantly less phosphate was reabsorbed in the proximal tubules when glucose was gi...
The Cardiothoracic Surgeon
Background The long saphenous vein is one of the most used conduits for coronary artery bypass gr... more Background The long saphenous vein is one of the most used conduits for coronary artery bypass graft surgery. The aim of this study was to assess the existing evidence regarding the effects of preoperative ultrasound mapping of the long saphenous vein with special attention to leg wound complications in patients undergoing elective coronary artery bypass graft surgery. Main text A systematic literature search was conducted in PubMed, Cochrane, and Embase databases. Extraction of relevant data was performed including study characteristics, patient characteristics, and all reported outcomes. The Cochrane Risk of Bias tool was used to evaluate the risk of bias of the included studies. The primary outcome measure was leg wound infections. Of 4514 papers screened in this systematic review, 36 papers underwent full-text assessment with final inclusion of 5 studies; 3 observational studies, and 2 randomized trials. The two randomized controlled trials showed no effects of preoperative ultr...
The Thoracic and Cardiovascular Surgeon, 1993
Metabolic adaptation of the ischemic human heart includes release of lactate, augmented uptake of... more Metabolic adaptation of the ischemic human heart includes release of lactate, augmented uptake of glucose and glutamate, together with increased release of citrate and alanine. In the present study exchanges of these metabolites were examined in relation to left ventricular function (LVF) in pig hearts during reperfusion after hypothermic cardioplegic-induced global ischemia and storage. Three groups of pig hearts were studied. Group I consisted of 11 hearts subjected to 9 minutes of warm ischemia prior to cold chemical cardioplegia with Bretschneider's cardioplegic solution (CCC), and hypothermic storage (HS), for a total of 180 minutes. Groups II and III, 8 hearts in each, were subjected to 90 and 180 minutes of CCC and HS, without precardioplegic warm ischemia. All hearts were reperfused in an isolated blood-perfused Langendorff model. Myocardial oxygen uptake and LVF were two-fold depressed in Group I compared to Groups II and III during the first 25 minutes of reperfusion. An increased uptake of glucose (p < 0.05) and augmented release of lactate (p < 0.01) and citrate (p < 0.001) were found during the reperfusion period in the hearts subjected to precardioplegic warm ischemia, indicating an increased total ischemic burden compared to Groups II and III. No significant changes in LVF or myocardial metabolism were noted between Groups II and III during reperfusion. In all three heart groups a substantial release or loss of glutamate was found at start of reperfusion, although in the preischemic state prior to cardioplegia pig hearts were found to extract glutamate from the circulation to an extent similar to that of the human heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Scandinavian Cardiovascular Journal
European Journal of Cardio-Thoracic Surgery, 1997
Objective: Patients with mechanical heart valves require lifelong oral anticoagulant treatment wh... more Objective: Patients with mechanical heart valves require lifelong oral anticoagulant treatment which entails frequent blood sampling and dosage adjustment. The purpose of this study was to investigate the feasibility of letting heart valve operated patients manage blood specimen analysis and dosage adjustment themselves. Methods: A total of 21 patients were enrolled in the study and followed for at least 9 months postoperatively. Immediately after the heart valve operation they were trained in operating a CoaguChek ® international normal ratio (INR) monitor to analyze capillary whole blood samples. Subsequently training in dosage adjustment was accomplished and all patients were considered fully capable of self management after 30 weeks. In the training period, parallel laboratory INR measurements were made at 3-4 week intervals for reference. A control group of 20 patients was matched, respectively, to the study group. The INR target range was 2.0-3.0. Results: Out of the 21 study patients 19 continued self management beyond 9 months. The median INR value obtained with the monitor was within therapeutic target range for all study patients and only 15 out of 20 control patients were within this range. The mean systematic deviation between laboratory and CoaguChek ® INR was 7.8% but each patient had a constant characteristic deviation from − 11 to +21%.The study patients were within therapeutic target range 77% of the time compared with 53% for the control patients. Conclusions: Self management of oral anticoagulation is feasible for selected patients and constitutes a significant service improvement compared with conventional management. The CoaguChek ® monitor seems sufficiently accurate and reliable for self testing and the treatment quality is comparable or even better than conventional management. Assessment of the rate of bleeding and thrombo-embolic events shall be settled in studies comprising larger number of patients.
European Journal of Cardio-Thoracic Surgery, 2016
OBJECTIVES: This study compares the durability and risk of reoperation in patients undergoing aor... more OBJECTIVES: This study compares the durability and risk of reoperation in patients undergoing aortic valve replacement (AVR) with either a Mitroflow or a Carpentier-Edwards (CE) pericardial bioprosthesis. Since AVR with bioprosthetic valves has increased progressively in recent years as compared to mechanical valves, especially in patients aged 60-70 years, there has been renewed interest in the long-term durability of current pericardial bioprostheses. METHODS: We compared 440 AVR with Mitroflow valves with 1953 AVR with CE pericardial valves implanted from 1999 to 2014 with regard to reoperation, reoperation for structural valve deterioration (SVD) and all-cause mortality. RESULTS: Ten-year freedom from explant of any cause was higher for CE Perimount (98 ± 0.7%) than for Mitroflow (95 ± 1.4%, P < 0.01). Reasons for explant for CE Perimount were SVD (n = 2), endocarditis (n = 8) and paraprosthetic leak (n = 10). The reasons for explant for Mitroflow were SVD (n = 11), endocarditis (n = 3) SVD and pericarditis (n = 1) and paraprosthetic leak (n = 2). Ten-year freedom from explant due to SVD was higher for CE Perimount (100%) than for Mitroflow (96%) (P < 0.01). In small aortic annuli (bioprosthesis size 19-21 mm), freedom from SVD at 10 years for CE Perimount and Mitroflow was 100 versus 96%, respectively. By multivariate analysis, it was found that bioprosthesis size was not a risk factor for SVD. The choice of valve type could not be demonstrated to influence long-term survival. CONCLUSIONS: The Mitroflow pericardial bioprosthesis provides less than optimal mid-and long-term durability compared with the CE Perimount pericardial valve, especially for small aortic diameter implants (19 and 21 mm). This study hereby confirms the existence of a real risk of valvular deterioration of the Mitroflow valve that might compromise the prognosis of the patients.
European Surgical Research, 1990
Circulation, 2012
Posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is cardio... more Posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is cardioprotective but its role in cardioprotection by remote ischemic preconditioning (rIPC) and the reduced efficacy of rIPC in type 2 diabetes mellitus is unknown Hypothesis: The remote stimulus mediating and the target organ response eliciting the cardioprotective effect of rIPC in non-diabetic and diabetic myocardium activates O-GlcNAcylation. Methods and Results: The cardioprotective capacity and influence on myocardial O-GlcNAc levels of plasma dialysate from 8 healthy volunteers and 8 type 2 diabetic patients drawn before and after rIPC, were tested on human isolated atrial trabeculae subjected to ischemia-reperfusion injury. Dialysate from healthy volunteers exposed to rIPC improved post ischemic hemodynamic recovery (40±6% vs 16±2%; p<0.01) and increased myocardial O-GlcNAc levels (Figure 1a, left columns). Similar observations were made with dialysate from diabetic patients before ...
Journal of Cardiothoracic and Vascular Anesthesia
Interactive CardioVascular and Thoracic Surgery, 2014
Objectives: The study compares the durability and risk of reoperation in patients undergoing isol... more Objectives: The study compares the durability and risk of reoperation in patients undergoing isolated aortic valve replacement (AVR) with either the Mitroflow or the Carpentier-Edwards Perimount pericardial bioprosthesis. Methods: Registry data from 1999 to 2014 on 440 AVR with Mitroflow and 1953 AVR with Perimount bioprostheses were examined. From 2001 to 2007 the Mitroflow prosthesis was used in patients with small aortic annuli (prosthesis size 19 and 21). The total (mean) patient years was 2615 (5.9) years for Mitroflow and 7864 (4.0) years for Perimount. Results: Ten-year freedom from explant of any cause was higher for Perimount [97.9% (97.0-98.9%)] than for Mitroflow [94.9% (90.9-97.2%)] (P < 0.001). Reasons for explant for Perimount were structural valve deterioration (SVD) (n = 2), endocarditis (n = 8), and paraprosthetic leak and other (n = 10) and for Mitroflow were SVD (n = 12), endocarditis (n = 4) and paraprosthetic leak (n = 2). For bioprosthesis sizes 19-21 mm freedom from reoperation for SVD at 10 years for Perimount and Mitroflow was 100% vs 95.3% (91.2-97.5%), respectively (P < 0.001). Independently of bioprosthesis size the Mitroflow was a risk factor for reoperation for SVD [HR = 7.9 (1.8-35.6), P < 0.007]. By multivariate statistical analysis there was a tendency towards better 10-year survival after AVR with Perimount compared to Mitroflow [42.3% (38.5-46.1%) vs 32.8% (27.3-38.3%), P= 0.07]. Conclusion: The Mitroflow provides less than optimal midterm durability compared to the Perimount bioprosthesis. The increased risk of SVD for the Mitroflow bioprosthesis might compromise the long-term prognosis of the patients.
European Surgical Research, 1990
Magnetic Resonance in Medicine
Magnetic Resonance in Medicine
Scientific Reports
Ischemia reperfusion (IR) injury may be attenuated through succinate dehydrogenase (SDH) inhibiti... more Ischemia reperfusion (IR) injury may be attenuated through succinate dehydrogenase (SDH) inhibition by dimethyl malonate (DiMAL). Whether SDH inhibition yields protection in diabetic individuals and translates into human cardiac tissue remain unknown. In isolated perfused hearts from 24 weeks old male Zucker diabetic fatty (ZDF) and age matched non-diabetic control rats and atrial trabeculae from patients with and without diabetes, we compared infarct size, contractile force recovery and mitochondrial function. The cardioprotective effect of a 10 minutes DiMAL administration prior to global ischemia and ischemic preconditioning (IPC) was evaluated. In non-diabetic hearts exposed to IR, DiMAL 0.1 mM reduced infarct size compared to IR (55 ± 7% vs. 69 ± 6%, p < 0.05). Mitochondrial respiration was reduced by DiMAL 0.6 mM compared to sham and DiMAL 0.1 mM (p < 0.05). In diabetic hearts an increased concentration of DiMAL (0.6 mM) was required for protection compared to IR (64 ± 13% vs. 79 ± 8%, p < 0.05). Mitochondrial function remained unchanged. In trabeculae from humans without diabetes, IPC and DiMAL improved contractile force recovery compared to IR (43 ± 12% and 43 ± 13% vs. 23 ± 13%, p < 0.05) but in patients with diabetes only IPC provided protection compared to IR (51 ± 15% vs. 21 ± 8%, p < 0.05). Neither IPC nor DiMAL modulated mitochondrial respiration in patients. Cardioprotection by SDH inhibition is possible in human tissue, but depends on diabetes status. The narrow therapeutic range and discrepancy in respiration between experimental and human studies may limit clinical translation.
Pulmonary Circulation
Prostacyclins are vasodilatory agents used in the treatment of pulmonary arterial hypertension. T... more Prostacyclins are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostacyclins on right heart function are still not clarified. The aim of this study was to investigate the possible direct inotropic properties of clinical available prostacyclin mimetics in the normal and the pressure-overloaded human right atrium. Trabeculae from the right atrium were collected during surgery from chronic thromboembolic pulmonary hypertension (CTEPH) patients with pressureoverloaded right hearts, undergoing pulmonary thromboendarterectomy (n ¼ 10) and from patients with normal right hearts operated by valve replacement or coronary bypass surgery (n ¼ 9). The trabeculae were placed in an organ bath, continuously paced at 1 Hz. They were subjected to increasing concentrations of iloprost, treprostinil, epoprostenol, or MRE-269, followed by isoprenaline to elicit a reference inotropic response. The force of contraction was measured continuously. The expression of prostanoid receptors was explored through quantitative polymerase chain reaction (qPCR). Iloprost, treprostinil, epoprostenol, or MRE-269 did not alter force of contraction in any of the trabeculae. Isoprenaline showed a direct inotropic response in both trabeculae from the pressure-overloaded right atrium and from the normal right atrium. Control experiments on ventricular trabeculae from the pig failed to show an inotropic response to the prostacyclin mimetics. qPCR demonstrated varying expression of the different prostanoid receptors in the human atrium. In conclusion, prostacyclin mimetics did not increase the force of contraction of human atrial trabeculae from the normal or the pressure-overloaded right heart. These data suggest that prostacyclin mimetics have no direct inotropic effects in the human right atrium.
Interactive CardioVascular and Thoracic Surgery
OBJECTIVES: In cardiac surgery, postoperative bleeding remains a frequent complication with vario... more OBJECTIVES: In cardiac surgery, postoperative bleeding remains a frequent complication with various possible adverse outcomes. Re-exploration due to bleeding is frequent in this type of patient. Sternal wound infection is an infrequent but serious and devastating complication. Whether re-exploration due to bleeding significantly affects the incidence of sternal wound infection is uncertain. There is no consensus on allowed severity of bleeding and timing of intervention. METHODS: A retrospective, observational cohort study of 15 350 consecutive patients who underwent cardiac surgical procedures from 1 April 2006 through 31 December 2013 in 3 different university hospitals in Denmark was performed. Re-exploration due to postoperative bleeding occurred in 873 patients. To adjust for possible confounders, propensity score matching and logistic regression analyses were performed based on the centre, EuroSCORE I/II factors, extracorporeal circulation time, drugs affecting bleeding and coagulation, postoperative bleeding and units of blood transfusions. Patients were matched into 2 groups of 779 patients each for further analysis. The shortterm outcomes were sternum infection, 30-day mortality and acute renal failure needing dialysis. The long-term outcome was the number of deaths 6 months after surgery. RESULTS: The incidence of re-exploration was 5.7%. In the raw data, sternal infection was higher in the re-exploration group (2.4% vs 1.4; P = 0.020). After propensity score matching, no differences in sternal infection or other measured outcomes were found between the groups, either by crude or adjusted analyses. CONCLUSIONS: Our study indicates that re-exploration is not associated with a higher frequency of severe postoperative complications. Probably the time of intervention for bleeding is important.
Scandinavian Journal of Gastroenterology, Oct 1, 1990
During 25 years, 708 patients with primary malignant tumours of the thoracic oesophagus (n = 376)... more During 25 years, 708 patients with primary malignant tumours of the thoracic oesophagus (n = 376) or cardia (n = 332) were referred to our department. Two hundred and forty-nine patients had squamous cell carcinoma and 425 adenocarcinoma. The other 34 tumours, which were primarily classified as undifferentiated carcinoma, malignant carcinoid or non-epithelial, were re-evaluated by means of a second microscopic histologic examination and immunohistologic investigation. This showed primary malignant non-epithelial tumours in seven patients (0.99%): two malignant melanomas, one leiomyosarcoma, one malignant fibrous histiocytoma in the oesophagus (1.06%), two malignant lymphomas, and one malignant melanoma in the cardia (0.90%). All but two of the patients with non-epithelial malignant tumours were 67 years of age or older, and oesophagogastrectomy was performed in all. All tumours were 5 cm or more in diameter (median, 8 cm). Distant metastases were found in three cases. Five died of postoperative complications, one of cancer recurrence 7 months after the operation, and one of an unrelated cause without cancer recurrence 16 months postoperatively. Except for two of the melanomas, the diagnosis was not established until histologic examination of the surgical specimen was performed and, for the third melanoma and the malignant fibrous histiocytoma, not until the present re-evaluation. The characteristics of these seven tumours are discussed, and the importance of obtaining a correct diagnosis from endoscopic biopsy specimens is emphasized.
Cardiac valve replacement was performed on 76 patients with acute or subacute native infective en... more Cardiac valve replacement was performed on 76 patients with acute or subacute native infective endocarditis. The 30-day mortality/5-year survival (%/% +/- SE) was 18/67 +/- 7, after aortic valve replacement (n = 50), 6/82 +/- 10 in the mitral group (n = 18) and 38/63 +/- 17 after double valve replacement (n = 8): NS/NS. In patients with destruction and/or abscess of the anulus (DESAB), which was commonest in the aortic group, the corresponding figures were 31/48 +/- 10, compared with 10/81 +/- 6 in the other patients (p less than 0.05/less than 0.01). Atrioventricular block and complete bundle branch block were commoner in the former group. When the time from onset of fever to operation was 1-6 months (n = 50), the 5-year survival was 79 +/- 6% compared with 51 +/- 10% (p less than 0.05) when that time was less than 1 month (n = 14) or greater than 6 months (n = 12). Logistic regression analysis showed NYHA class III-IV and DESAB to be independent risk factors in 30-day mortality, which was 3.8% when neither, and 46.2% when both of these factors were present (p less than 0.01). Cox regression analysis identified NYHA class IV (p less than 0.0001), calcified mitral valve or anulus (p = 0.001), DESAB (p = 0.01), male gender (p = 0.02), supraventricular arrhythmia (p = 0.04) and vegetations on the diseased valve (p = 0.05) as independent determinants of overall long-term mortality. Patients with none (n = 6), any one (n = 16), any two (n = 28), any three (n = 20), any four (n = 6) or any five (n = 2) of these risk factors (none had 6) had respective 30-day/5-year survival rates (% +/- SE) of 100/100, 94 +/- 6/94 +/- 6, 89 +/- 6/85 +/- 7, 75 +/- 10/43 +/- 13, 67 +/- 9/17 +/- 15 (at 1 year) and 0/0 (p less than 0.0001). Identification of independent risk factors permitted stratification of the patients into subgroups with prognosis ranging from 100% 5-year survival to 0% 30-day survival. Surgical treatment of native infective endocarditis should be undertaken before cardiac disability is advanced or infective destruction of the anulus, notably of the aortic valve, becomes evident.
Journal of clinical & laboratory immunology, 1988
A microplate-adapted polyclonal IgM-rheumatoid factor enzyme-linked immunosorbent assay (pIgM-RF ... more A microplate-adapted polyclonal IgM-rheumatoid factor enzyme-linked immunosorbent assay (pIgM-RF ELISA) for the detection of circulating immune complexes (cIC) is presented. The assay involves the competitive binding of cIC and horseradish peroxidase conjugated aggregated human IgG (HRP-AHG) to solid-phase bound polyclonal IgM-RF (pIgM-RF). Aggregated human IgG (AHG) inhibited the binding of HRP-AHG to pIgM-RF in a dose-dependent way. The detection limit of the assay was about 125 ng AHG/ml diluted serum. The coefficients of variation for the assay varied from 5.0 to 14.7% for intra-assay runs and from 4.5 to 13.8% for inter-assay runs. The levels of cIC in sera from 29 patients with systemic lupus erythematosus (SLE), 85 untreated patients with breast cancer and 105 blood bank donors were studied by the pIgM-RF ELISA. Increased levels of cIC were demonstrated in 41.4% of the SLE group, in 8.2% of the breast cancer group, and in 1.9% of the normal control group. The difference in cI...
Acta chirurgica Scandinavica
Major surgery is associated with fall in the concentration of inorganic phosphate in serum, as is... more Major surgery is associated with fall in the concentration of inorganic phosphate in serum, as is intravenous infusion of glucose. Hypophosphatemia during different forms of postoperative dextrose administration was evaluated in patients who had undergone colorectal surgery. They were randomized to two groups. All patients received standardized intravenous fluids on the first 3 postoperative days, but one group had constant infusion of a solution containing glucose (4%), sodium (40 mmol/l) and potassium (20 mmol/l) throughout the observation period, while the other group had a 5-hour infusion of 10% glucose daily, with potassium and sodium solution in between. The amounts of administered glucose and electrolytes were the same in both groups. The serum phosphate levels were significantly lower in the group with constant glucose infusion, due to intergroup difference in renal handling of phosphate. Significantly less phosphate was reabsorbed in the proximal tubules when glucose was gi...
The Cardiothoracic Surgeon
Background The long saphenous vein is one of the most used conduits for coronary artery bypass gr... more Background The long saphenous vein is one of the most used conduits for coronary artery bypass graft surgery. The aim of this study was to assess the existing evidence regarding the effects of preoperative ultrasound mapping of the long saphenous vein with special attention to leg wound complications in patients undergoing elective coronary artery bypass graft surgery. Main text A systematic literature search was conducted in PubMed, Cochrane, and Embase databases. Extraction of relevant data was performed including study characteristics, patient characteristics, and all reported outcomes. The Cochrane Risk of Bias tool was used to evaluate the risk of bias of the included studies. The primary outcome measure was leg wound infections. Of 4514 papers screened in this systematic review, 36 papers underwent full-text assessment with final inclusion of 5 studies; 3 observational studies, and 2 randomized trials. The two randomized controlled trials showed no effects of preoperative ultr...
The Thoracic and Cardiovascular Surgeon, 1993
Metabolic adaptation of the ischemic human heart includes release of lactate, augmented uptake of... more Metabolic adaptation of the ischemic human heart includes release of lactate, augmented uptake of glucose and glutamate, together with increased release of citrate and alanine. In the present study exchanges of these metabolites were examined in relation to left ventricular function (LVF) in pig hearts during reperfusion after hypothermic cardioplegic-induced global ischemia and storage. Three groups of pig hearts were studied. Group I consisted of 11 hearts subjected to 9 minutes of warm ischemia prior to cold chemical cardioplegia with Bretschneider's cardioplegic solution (CCC), and hypothermic storage (HS), for a total of 180 minutes. Groups II and III, 8 hearts in each, were subjected to 90 and 180 minutes of CCC and HS, without precardioplegic warm ischemia. All hearts were reperfused in an isolated blood-perfused Langendorff model. Myocardial oxygen uptake and LVF were two-fold depressed in Group I compared to Groups II and III during the first 25 minutes of reperfusion. An increased uptake of glucose (p < 0.05) and augmented release of lactate (p < 0.01) and citrate (p < 0.001) were found during the reperfusion period in the hearts subjected to precardioplegic warm ischemia, indicating an increased total ischemic burden compared to Groups II and III. No significant changes in LVF or myocardial metabolism were noted between Groups II and III during reperfusion. In all three heart groups a substantial release or loss of glutamate was found at start of reperfusion, although in the preischemic state prior to cardioplegia pig hearts were found to extract glutamate from the circulation to an extent similar to that of the human heart.(ABSTRACT TRUNCATED AT 250 WORDS)
Scandinavian Cardiovascular Journal
European Journal of Cardio-Thoracic Surgery, 1997
Objective: Patients with mechanical heart valves require lifelong oral anticoagulant treatment wh... more Objective: Patients with mechanical heart valves require lifelong oral anticoagulant treatment which entails frequent blood sampling and dosage adjustment. The purpose of this study was to investigate the feasibility of letting heart valve operated patients manage blood specimen analysis and dosage adjustment themselves. Methods: A total of 21 patients were enrolled in the study and followed for at least 9 months postoperatively. Immediately after the heart valve operation they were trained in operating a CoaguChek ® international normal ratio (INR) monitor to analyze capillary whole blood samples. Subsequently training in dosage adjustment was accomplished and all patients were considered fully capable of self management after 30 weeks. In the training period, parallel laboratory INR measurements were made at 3-4 week intervals for reference. A control group of 20 patients was matched, respectively, to the study group. The INR target range was 2.0-3.0. Results: Out of the 21 study patients 19 continued self management beyond 9 months. The median INR value obtained with the monitor was within therapeutic target range for all study patients and only 15 out of 20 control patients were within this range. The mean systematic deviation between laboratory and CoaguChek ® INR was 7.8% but each patient had a constant characteristic deviation from − 11 to +21%.The study patients were within therapeutic target range 77% of the time compared with 53% for the control patients. Conclusions: Self management of oral anticoagulation is feasible for selected patients and constitutes a significant service improvement compared with conventional management. The CoaguChek ® monitor seems sufficiently accurate and reliable for self testing and the treatment quality is comparable or even better than conventional management. Assessment of the rate of bleeding and thrombo-embolic events shall be settled in studies comprising larger number of patients.
European Journal of Cardio-Thoracic Surgery, 2016
OBJECTIVES: This study compares the durability and risk of reoperation in patients undergoing aor... more OBJECTIVES: This study compares the durability and risk of reoperation in patients undergoing aortic valve replacement (AVR) with either a Mitroflow or a Carpentier-Edwards (CE) pericardial bioprosthesis. Since AVR with bioprosthetic valves has increased progressively in recent years as compared to mechanical valves, especially in patients aged 60-70 years, there has been renewed interest in the long-term durability of current pericardial bioprostheses. METHODS: We compared 440 AVR with Mitroflow valves with 1953 AVR with CE pericardial valves implanted from 1999 to 2014 with regard to reoperation, reoperation for structural valve deterioration (SVD) and all-cause mortality. RESULTS: Ten-year freedom from explant of any cause was higher for CE Perimount (98 ± 0.7%) than for Mitroflow (95 ± 1.4%, P < 0.01). Reasons for explant for CE Perimount were SVD (n = 2), endocarditis (n = 8) and paraprosthetic leak (n = 10). The reasons for explant for Mitroflow were SVD (n = 11), endocarditis (n = 3) SVD and pericarditis (n = 1) and paraprosthetic leak (n = 2). Ten-year freedom from explant due to SVD was higher for CE Perimount (100%) than for Mitroflow (96%) (P < 0.01). In small aortic annuli (bioprosthesis size 19-21 mm), freedom from SVD at 10 years for CE Perimount and Mitroflow was 100 versus 96%, respectively. By multivariate analysis, it was found that bioprosthesis size was not a risk factor for SVD. The choice of valve type could not be demonstrated to influence long-term survival. CONCLUSIONS: The Mitroflow pericardial bioprosthesis provides less than optimal mid-and long-term durability compared with the CE Perimount pericardial valve, especially for small aortic diameter implants (19 and 21 mm). This study hereby confirms the existence of a real risk of valvular deterioration of the Mitroflow valve that might compromise the prognosis of the patients.
European Surgical Research, 1990
Circulation, 2012
Posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is cardio... more Posttranslational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) is cardioprotective but its role in cardioprotection by remote ischemic preconditioning (rIPC) and the reduced efficacy of rIPC in type 2 diabetes mellitus is unknown Hypothesis: The remote stimulus mediating and the target organ response eliciting the cardioprotective effect of rIPC in non-diabetic and diabetic myocardium activates O-GlcNAcylation. Methods and Results: The cardioprotective capacity and influence on myocardial O-GlcNAc levels of plasma dialysate from 8 healthy volunteers and 8 type 2 diabetic patients drawn before and after rIPC, were tested on human isolated atrial trabeculae subjected to ischemia-reperfusion injury. Dialysate from healthy volunteers exposed to rIPC improved post ischemic hemodynamic recovery (40±6% vs 16±2%; p<0.01) and increased myocardial O-GlcNAc levels (Figure 1a, left columns). Similar observations were made with dialysate from diabetic patients before ...
Journal of Cardiothoracic and Vascular Anesthesia
Interactive CardioVascular and Thoracic Surgery, 2014
Objectives: The study compares the durability and risk of reoperation in patients undergoing isol... more Objectives: The study compares the durability and risk of reoperation in patients undergoing isolated aortic valve replacement (AVR) with either the Mitroflow or the Carpentier-Edwards Perimount pericardial bioprosthesis. Methods: Registry data from 1999 to 2014 on 440 AVR with Mitroflow and 1953 AVR with Perimount bioprostheses were examined. From 2001 to 2007 the Mitroflow prosthesis was used in patients with small aortic annuli (prosthesis size 19 and 21). The total (mean) patient years was 2615 (5.9) years for Mitroflow and 7864 (4.0) years for Perimount. Results: Ten-year freedom from explant of any cause was higher for Perimount [97.9% (97.0-98.9%)] than for Mitroflow [94.9% (90.9-97.2%)] (P < 0.001). Reasons for explant for Perimount were structural valve deterioration (SVD) (n = 2), endocarditis (n = 8), and paraprosthetic leak and other (n = 10) and for Mitroflow were SVD (n = 12), endocarditis (n = 4) and paraprosthetic leak (n = 2). For bioprosthesis sizes 19-21 mm freedom from reoperation for SVD at 10 years for Perimount and Mitroflow was 100% vs 95.3% (91.2-97.5%), respectively (P < 0.001). Independently of bioprosthesis size the Mitroflow was a risk factor for reoperation for SVD [HR = 7.9 (1.8-35.6), P < 0.007]. By multivariate statistical analysis there was a tendency towards better 10-year survival after AVR with Perimount compared to Mitroflow [42.3% (38.5-46.1%) vs 32.8% (27.3-38.3%), P= 0.07]. Conclusion: The Mitroflow provides less than optimal midterm durability compared to the Perimount bioprosthesis. The increased risk of SVD for the Mitroflow bioprosthesis might compromise the long-term prognosis of the patients.
European Surgical Research, 1990
Magnetic Resonance in Medicine
Magnetic Resonance in Medicine
Scientific Reports
Ischemia reperfusion (IR) injury may be attenuated through succinate dehydrogenase (SDH) inhibiti... more Ischemia reperfusion (IR) injury may be attenuated through succinate dehydrogenase (SDH) inhibition by dimethyl malonate (DiMAL). Whether SDH inhibition yields protection in diabetic individuals and translates into human cardiac tissue remain unknown. In isolated perfused hearts from 24 weeks old male Zucker diabetic fatty (ZDF) and age matched non-diabetic control rats and atrial trabeculae from patients with and without diabetes, we compared infarct size, contractile force recovery and mitochondrial function. The cardioprotective effect of a 10 minutes DiMAL administration prior to global ischemia and ischemic preconditioning (IPC) was evaluated. In non-diabetic hearts exposed to IR, DiMAL 0.1 mM reduced infarct size compared to IR (55 ± 7% vs. 69 ± 6%, p < 0.05). Mitochondrial respiration was reduced by DiMAL 0.6 mM compared to sham and DiMAL 0.1 mM (p < 0.05). In diabetic hearts an increased concentration of DiMAL (0.6 mM) was required for protection compared to IR (64 ± 13% vs. 79 ± 8%, p < 0.05). Mitochondrial function remained unchanged. In trabeculae from humans without diabetes, IPC and DiMAL improved contractile force recovery compared to IR (43 ± 12% and 43 ± 13% vs. 23 ± 13%, p < 0.05) but in patients with diabetes only IPC provided protection compared to IR (51 ± 15% vs. 21 ± 8%, p < 0.05). Neither IPC nor DiMAL modulated mitochondrial respiration in patients. Cardioprotection by SDH inhibition is possible in human tissue, but depends on diabetes status. The narrow therapeutic range and discrepancy in respiration between experimental and human studies may limit clinical translation.
Pulmonary Circulation
Prostacyclins are vasodilatory agents used in the treatment of pulmonary arterial hypertension. T... more Prostacyclins are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostacyclins on right heart function are still not clarified. The aim of this study was to investigate the possible direct inotropic properties of clinical available prostacyclin mimetics in the normal and the pressure-overloaded human right atrium. Trabeculae from the right atrium were collected during surgery from chronic thromboembolic pulmonary hypertension (CTEPH) patients with pressureoverloaded right hearts, undergoing pulmonary thromboendarterectomy (n ¼ 10) and from patients with normal right hearts operated by valve replacement or coronary bypass surgery (n ¼ 9). The trabeculae were placed in an organ bath, continuously paced at 1 Hz. They were subjected to increasing concentrations of iloprost, treprostinil, epoprostenol, or MRE-269, followed by isoprenaline to elicit a reference inotropic response. The force of contraction was measured continuously. The expression of prostanoid receptors was explored through quantitative polymerase chain reaction (qPCR). Iloprost, treprostinil, epoprostenol, or MRE-269 did not alter force of contraction in any of the trabeculae. Isoprenaline showed a direct inotropic response in both trabeculae from the pressure-overloaded right atrium and from the normal right atrium. Control experiments on ventricular trabeculae from the pig failed to show an inotropic response to the prostacyclin mimetics. qPCR demonstrated varying expression of the different prostanoid receptors in the human atrium. In conclusion, prostacyclin mimetics did not increase the force of contraction of human atrial trabeculae from the normal or the pressure-overloaded right heart. These data suggest that prostacyclin mimetics have no direct inotropic effects in the human right atrium.
Interactive CardioVascular and Thoracic Surgery
OBJECTIVES: In cardiac surgery, postoperative bleeding remains a frequent complication with vario... more OBJECTIVES: In cardiac surgery, postoperative bleeding remains a frequent complication with various possible adverse outcomes. Re-exploration due to bleeding is frequent in this type of patient. Sternal wound infection is an infrequent but serious and devastating complication. Whether re-exploration due to bleeding significantly affects the incidence of sternal wound infection is uncertain. There is no consensus on allowed severity of bleeding and timing of intervention. METHODS: A retrospective, observational cohort study of 15 350 consecutive patients who underwent cardiac surgical procedures from 1 April 2006 through 31 December 2013 in 3 different university hospitals in Denmark was performed. Re-exploration due to postoperative bleeding occurred in 873 patients. To adjust for possible confounders, propensity score matching and logistic regression analyses were performed based on the centre, EuroSCORE I/II factors, extracorporeal circulation time, drugs affecting bleeding and coagulation, postoperative bleeding and units of blood transfusions. Patients were matched into 2 groups of 779 patients each for further analysis. The shortterm outcomes were sternum infection, 30-day mortality and acute renal failure needing dialysis. The long-term outcome was the number of deaths 6 months after surgery. RESULTS: The incidence of re-exploration was 5.7%. In the raw data, sternal infection was higher in the re-exploration group (2.4% vs 1.4; P = 0.020). After propensity score matching, no differences in sternal infection or other measured outcomes were found between the groups, either by crude or adjusted analyses. CONCLUSIONS: Our study indicates that re-exploration is not associated with a higher frequency of severe postoperative complications. Probably the time of intervention for bleeding is important.
Scandinavian Journal of Gastroenterology, Oct 1, 1990
During 25 years, 708 patients with primary malignant tumours of the thoracic oesophagus (n = 376)... more During 25 years, 708 patients with primary malignant tumours of the thoracic oesophagus (n = 376) or cardia (n = 332) were referred to our department. Two hundred and forty-nine patients had squamous cell carcinoma and 425 adenocarcinoma. The other 34 tumours, which were primarily classified as undifferentiated carcinoma, malignant carcinoid or non-epithelial, were re-evaluated by means of a second microscopic histologic examination and immunohistologic investigation. This showed primary malignant non-epithelial tumours in seven patients (0.99%): two malignant melanomas, one leiomyosarcoma, one malignant fibrous histiocytoma in the oesophagus (1.06%), two malignant lymphomas, and one malignant melanoma in the cardia (0.90%). All but two of the patients with non-epithelial malignant tumours were 67 years of age or older, and oesophagogastrectomy was performed in all. All tumours were 5 cm or more in diameter (median, 8 cm). Distant metastases were found in three cases. Five died of postoperative complications, one of cancer recurrence 7 months after the operation, and one of an unrelated cause without cancer recurrence 16 months postoperatively. Except for two of the melanomas, the diagnosis was not established until histologic examination of the surgical specimen was performed and, for the third melanoma and the malignant fibrous histiocytoma, not until the present re-evaluation. The characteristics of these seven tumours are discussed, and the importance of obtaining a correct diagnosis from endoscopic biopsy specimens is emphasized.
Cardiac valve replacement was performed on 76 patients with acute or subacute native infective en... more Cardiac valve replacement was performed on 76 patients with acute or subacute native infective endocarditis. The 30-day mortality/5-year survival (%/% +/- SE) was 18/67 +/- 7, after aortic valve replacement (n = 50), 6/82 +/- 10 in the mitral group (n = 18) and 38/63 +/- 17 after double valve replacement (n = 8): NS/NS. In patients with destruction and/or abscess of the anulus (DESAB), which was commonest in the aortic group, the corresponding figures were 31/48 +/- 10, compared with 10/81 +/- 6 in the other patients (p less than 0.05/less than 0.01). Atrioventricular block and complete bundle branch block were commoner in the former group. When the time from onset of fever to operation was 1-6 months (n = 50), the 5-year survival was 79 +/- 6% compared with 51 +/- 10% (p less than 0.05) when that time was less than 1 month (n = 14) or greater than 6 months (n = 12). Logistic regression analysis showed NYHA class III-IV and DESAB to be independent risk factors in 30-day mortality, which was 3.8% when neither, and 46.2% when both of these factors were present (p less than 0.01). Cox regression analysis identified NYHA class IV (p less than 0.0001), calcified mitral valve or anulus (p = 0.001), DESAB (p = 0.01), male gender (p = 0.02), supraventricular arrhythmia (p = 0.04) and vegetations on the diseased valve (p = 0.05) as independent determinants of overall long-term mortality. Patients with none (n = 6), any one (n = 16), any two (n = 28), any three (n = 20), any four (n = 6) or any five (n = 2) of these risk factors (none had 6) had respective 30-day/5-year survival rates (% +/- SE) of 100/100, 94 +/- 6/94 +/- 6, 89 +/- 6/85 +/- 7, 75 +/- 10/43 +/- 13, 67 +/- 9/17 +/- 15 (at 1 year) and 0/0 (p less than 0.0001). Identification of independent risk factors permitted stratification of the patients into subgroups with prognosis ranging from 100% 5-year survival to 0% 30-day survival. Surgical treatment of native infective endocarditis should be undertaken before cardiac disability is advanced or infective destruction of the anulus, notably of the aortic valve, becomes evident.