Göran Matejka

Human endothelial cells produce orosomucoid, an important component of the capillary barrier

The serum protein orosomucoid (α1-acid glycoprotein) is needed to maintain the high capillary permselectivity required for normal homeostasis. It is not known how the protein executes its action, but it seems to contribute to the charge barrier. Moreover, recent studies suggest that the endothelial glycocalyx is essential for the charge barrier. The main site of orosomucoid synthesis is the liver, but we wanted to explore the possibility that orosomucoid was synthesized in endothelial cells. Primary cultures of human microvascular endothelial cells (HMVEC) from dermal tissue were established. Human liver cells were used as positive controls, and total RNA was prepared from both cell types. Reverse transcription-polymerase chain reaction (RT-PCR) was performed and demonstrated orosomucoid expression. After RT-PCR, the identities of the PCR products were confirmed by sequencing. RNase protection assay performed on total RNA from the HMVEC confirmed the results from the RT-PCR, i.e., orosomucoid mRNA is expressed by endothelial cells. Synthesis of orosomucoid in both liver and endothelial cells was demonstrated by immunoprecipitation. In conclusion, endothelial cells normally produce orosomucoid, which is essential for capillary charge selectivity. We suggest that orosomucoid exerts its effect by interacting with other components of the endothelial glycocalyx.The serum protein orosomucoid (alpha1-acid glycoprotein) is needed to maintain the high capillary permselectivity required for normal homeostasis. It is not known how the protein executes its action, but it seems to contribute to the charge barrier. Moreover, recent studies suggest that the endothelial glycocalyx is essential for the charge barrier. The main site of orosomucoid synthesis is the liver, but we wanted to explore the possibility that orosomucoid was synthesized in endothelial cells. Primary cultures of human microvascular endothelial cells (HMVEC) from dermal tissue were established. Human liver cells were used as positive controls, and total RNA was prepared from both cell types. Reverse transcription-polymerase chain reaction (RT-PCR) was performed and demonstrated orosomucoid expression. After RT-PCR, the identities of the PCR products were confirmed by sequencing. RNase protection assay performed on total RNA from the HMVEC confirmed the results from the RT-PCR, i.e., orosomucoid mRNA is expressed by endothelial cells. Synthesis of orosomucoid in both liver and endothelial cells was demonstrated by immunoprecipitation. In conclusion, endothelial cells normally produce orosomucoid, which is essential for capillary charge selectivity. We suggest that orosomucoid exerts its effect by interacting with other components of the endothelial glycocalyx.

Impairment of Cardiac Function and Bioenergetics in Adult Transgenic Mice Overexpressing the Bovine Growth Hormone Gene1

Cardiovascular abnormalities represent the major cause of death in patients with acromegaly. We evaluated cardiac structure, function, and energy status in adult transgenic mice overexpressing bovine GH (bGH) gene. Female transgenic mice expressing bGH gene (n = 11) 8 months old and aged matched controls (n = 11) were used. They were studied with two-dimensional guided M-mode and Doppler echocardiography. The animals (n = 6) for each group were examined with 31P magnetic resonance spectroscopy to determine the cardiac energy status. Transgenic mice had a significantly higher body weight (BW), 53.2+/-2.4 vs. 34.6+/-3.7 g (P < 0.0001) and hypertrophy of left ventricle (LV) compared with normal controls: LV mass/BW 5.6+/-1.6 vs. 2.7+/-0.2 mg/g, P < 0.01. Several indexes of systolic function were depressed in transgenic animals compared with controls mice such as shortening fraction 25+/-3.0% vs. 39.9+/-3.1%; ejection fraction, 57+/-9 vs. 77+/-5; mean velocity of circumferential shortening, 4.5+/-0.8 vs. 7.0+/-1.1 circ/sec, p < 0.01. Creatine phosphate-to-ATP ratio was significantly lower in bGH overexpressing mice (1.3+/-0.08 vs. 2.1+/-0.23 in controls, P < 0.05). Ultrastructural examination of the hearts from transgenic mice revealed substantial changes of mitochondria. This study provides new insight into possible mechanisms behind the deteriorating effects of long exposure to high level of GH on heart function.

Unfractionated heparin administration in patients treated with bivalirudin during primary percutaneous coronary intervention is associated lower mortality and target lesion thrombosis: a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)

Background Bivalirudin reduces bleeding events and is associated with a lower mortality than the combination of unfractionated heparin (UFH) and glycoprotein IIb/IIIa inhibitor during primary percutaneous coronary intervention (PCI). However, the effect of adding UFH in patients with ST elevation myocardial infarction (STEMI) treated with bivalirudin during primary PCI is unknown. Methods Patients enrolled in the national Swedish Coronary Angiography and Angioplasty Registry who underwent primary PCI due to STEMI with bivalirudin as anticoagulant were evaluated. Patients were divided into two groups: those treated with bivalirudin only and those treated with bivalirudin plus a bolus dose of UFH. Results 2996 patients were included in the study: 1928 (64%) received only bivalirudin and 1068 (36%) received bivalirudin plus a bolus dose of UFH. The primary combined endpoint of death or target lesion thrombosis at 30 days occurred more often in the bivalirudin group (11.3% vs 6.5%, OR 0.55, 95% CI 0.41 to 0.72, p<0.001). This difference remained significant after adjustment (HR 0.64, 95% CI 0.44 to 0.95, p=0.03). Death at 30 days and definite target lesion thrombosis at 30 days did not differ between the two groups after adjustment (9.2% vs 5.1%, adjusted HR 0.66, 95% CI 0.42 to 1.03, p=0.07 and 2.3% vs 1.5%, adjusted HR 0.59, 95% CI 0.27 to 1.33, p=0.21, respectively). Conclusion An additional bolus dose of UFH is associated with a lower rate of death or definite target lesion thrombosis at 30 days in patients undergoing primary PCI with bivalirudin as anticoagulant.

Stress-Induced Cardiomyopathy in Sweden: Evidence for Different Ethnic Predisposition and Altered Cardio-Circulatory Status

Background: In this paper, we report about new insights regarding clinical course, long-term outcome, ethnic/genetic predisposition and cardio-circulatory status in the large stress-induced cardiomyopathy (SIC) cohort from Sweden. Methods and Results: We have included 115 consecutive SIC patients between January 2005 and January 2010 at Sahlgrenska University Hospital in Gothenburg. Hemodynamic status and sympathetic nerve activity were evaluated and compared with those of healthy controls. Mean age was 64, and 14% were males. Thirty-day and 3-year mortality was 6 and 10%, respectively. Eleven percent had ischemic heart disease, 3% developed thromboembolic complications, 6% had cardiac arrest and 14% developed cardiogenic shock. The great majority of SIC patients (93%) were ethnic Swedes. In three families, several close relatives developed SIC. Fourteen percent developed two or more episodes of SIC. Hemodynamic evaluation has shown subnormal systemic vascular resistance, 22% lower sympathetic activity and preserved cardiac output in SIC patients. Conclusions: SIC affects both men and women of different ages and is associated with significant short- and long-term mortality. There is a strong signal for the presence of ethnic/genetic predisposition to develop SIC. Sympathetic activity and systemic vascular resistance are lower in SIC patients, suggesting that SIC is a cardio-circulatory phenomenon.

Chronic Total Occlusions in Sweden - A Report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR)

Introduction Evidence for the current guidelines for the treatment of patients with chronic total occlusions (CTO) in coronary arteries is limited. In this study we identified all CTO patients registered in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and studied the prevalence, patient characteristics and treatment decisions for CTO in Sweden. Methods and Results Between January 2005 and January 2012, 276,931 procedures (coronary angiography or percutaneous coronary intervention) were performed in 215,836 patients registered in SCAAR. We identified all patients who had 100% luminal diameter stenosis known or assumed to be ≥3 months old. After exclusion of patients with previous coronary artery bypass graft (CABG) surgery or coronary occlusions due to acute coronary syndrome, we identified 16,818 CTO patients. A CTO was present in 10.9% of all coronary angiographies and in 16.0% of patients with coronary artery disease. The majority of CTO patients were treated conservatively and PCI of CTO accounted for only 5.8% of all PCI procedures. CTO patients with diabetes and multivessel disease were more likely to be referred to CABG. Conclusion CTO is a common finding in Swedish patients undergoing coronary angiography but the number of CTO procedures in Sweden is low. Patients with CTO are a high-risk subgroup of patients with coronary artery disease. SCAAR has the largest register of CTO patients and therefore may be valuable for studies of clinical importance of CTO and optimal treatment for CTO patients.

Clinical and Procedural Characteristics Associated With Higher Radiation Exposure During Percutaneous Coronary Interventions and Coronary Angiography

Background—We aim to study the clinical and procedural characteristics associated with higher radiation exposure in patients undergoing percutaneous coronary interventions (PCIs) and coronary angiography. Methods and Results—Our present study included all coronary angiography and PCI procedures in 5 PCI centers in the Western part of Sweden, between January 1, 2008, and January 19, 2012. The radiation exposure and clinical data were collected prospectively in these 5 PCI centers in Sweden as part of the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). A prediction model was made for the radiation exposure (dose–area product) expressed in Gy·cm2. A total of 20 669 procedures were included in the present study, consisting of 9850 PCI and 10 819 coronary angiography procedures. In multivariable analyses, body mass index (&bgr;=1.04; confidence interval [CI], 1.04–1.04; P<0.001); history of coronary artery bypass graft surgery (&bgr;=1.32; CI, 1.28–1.32; P<0.001); 2, 3, or 4 treated lesions (2 treated lesions: &bgr;=1.95; CI, 1.84–2.03; P<0.001; 3 treated lesions: &bgr;=2.34; CI, 2.16–2.53; P<0.001; and 4 treated lesions: &bgr;=2.83; CI, 2.53–3.16; P<0.001); and chronic total occlusion lesions (&bgr;=1.39; CI, 1.31–1.48; P<0.001) were associated with the highest radiation exposure. After adjusting for procedural complexity, radial access route was not associated with increased radiation exposure (&bgr;=1.00; CI, 0.98–1.03; P=0.67). Conclusions—In the largest study population to assess radiation exposure, we found that high body mass index, history of coronary artery bypass graft surgery, number of treated lesions, and chronic total occlusions were associated with the highest patient radiation exposure. Radial access site was not associated with higher radiation exposure when compared with femoral approach.

17-year trends in incidence and prognosis of cardiogenic shock in patients with acute myocardial infarction in western Sweden

BACKGROUND Cardiogenic shock remains the leading cause of in hospital death in acute myocardial infarction (AMI) and is associated with a mortality rate of approximately 50%. Here we investigated the 17-year trends in incidence and prognosis of AMI-induced cardiogenic shock in Västra Götaland in western Sweden, an area with approximately 1.6 million inhabitants. The study period includes the transition from thrombolysis to primary percutaneous coronary intervention (PCI) as the region-wide therapy of choice for patients with ST-elevation myocardial infarction (STEMI). METHODS Data on patients hospitalized in cardiac care units in Västra Götaland, Sweden between 1995 and 2013 were obtained from the Swedish Websystem for Enhancement of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). We determined the incidence of cardiogenic shock among patients diagnosed with AMI and the risk of death associated with developing cardiogenic shock. We fitted logistic regression models to study which factors predicted post-AMI cardiogenic shock. Analyses were performed on complete case data as well as after multiple imputation of missing data. RESULTS Incidence of cardiogenic shock as a complication of AMI declined in western Sweden in the past decade, from 14% in 1995 to 4% in 2012. The risk of dying once cardiogenic shock had developed increased during the study period (p<0.01). Patients presenting with STEMI were more likely to develop cardiogenic shock than patients presenting with non STEMI (p<0.001). CONCLUSIONS The incidence of cardiogenic shock has declined but cardiogenic shock carries a worse prognosis today than in 1995.

Primary Percutaneous Coronary Interventions in Nonagenarians

The optimal treatment of very elderly patients with ST elevation myocardial infarction (STEMI) is not yet defined. The aim of this study is to present the feasibility and safety of primary percutaneous coronary interventions (PCI) in nonagenarians.

Radial vs. femoral approach for primary percutaneous coronary intervention in octogenarians

BACKGROUND The transradial approach is associated with fewer bleeding complications during percutaneous coronary interventions (PCIs) but is more technically challenging and associated with prolonged times during intervention. The aim of this study is to retrospectively compare the results of radial vs. femoral approach in patients >or=80 years old undergoing primary or rescue PCI. METHODS Between January 2002 and December 2007, 354 interventions were performed in our institution with the indication of primary or rescue PCI in patients over 80 years old, without history of previous bypass operation or cardiogenic shock on presentation. Thirteen patients required a change of the approach during the procedure and were not enrolled in the final analysis. Forty (12%) interventions were performed through the transradial approach and 301 (88%) through the femoral approach. In-hospital major adverse cerebral and cardiac events and access site bleeding complications as well as 30- and 365-day mortality, procedural times, and contrast volume were evaluated. RESULTS The two groups had similar clinical characteristics, with the exception of serum creatinine that was higher in the transfemoral approach group. There were no differences in procedural times and clinical outcomes, although the transfemoral group had numerically more access site bleeding complications (12/301 vs. 0/40, P=.41). The transradial approach had a higher conversion rate compared with the transfemoral approach (18.3% vs. 1.3%, P<.001). CONCLUSION The transradial approach is feasible and safe in the octogenarians undergoing primary and rescue PCI, but it is associated with a high conversion rate to another approach.

Levosimendan neither improves nor worsens mortality in patients with cardiogenic shock due to ST-elevation myocardial infarction

Background: The aim of this study was to evaluate the effect of levosimendan on mortality in cardiogenic shock (CS) after ST elevation myocardial infarction (STEMI). Methods and results: Data were obtained prospectively from the SCAAR (Swedish Coronary Angiography and Angioplasty Register) and the RIKS-HIA (Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) about 94 consecutive patients with CS due to STEMI. Patients were classified into levosimendan-mandatory and levosimendan-contraindicated cohorts. Inotropic support with levosimendan was mandatory in all patients between January 2004 and December 2005 (n = 46). After the SURVIVE and REVIVE II studies were presented, levosimendan was considered contraindicated and was not used in consecutive patients between December 2005 and December 2006 (n = 48). The cohorts were similar with respect to pre-treatment characteristics and concomitant medications. There was no difference in the incidence of new-onset atrial fibrillation, in-hospital cardiac arrest and length of stay at the coronary care unit. There was no difference in adjusted mortality at 30 days and at one year. Conclusion: The use of levosimendan neither improves nor worsens mortality in patients with CS due to STEMI. Well-designed randomized clinical trials are needed to define the role of inotropic therapy in the treatment of CS.