eHealth technology use and eHealth literacy after percutaneous coronary intervention.

AIMS: Electronic health (eHealth) sources have great potential to improve patients' access to health information for self-management of secondary prevention after percutaneous coronary intervention (PCI). It remains unclear, however, whether patients are health-related digitally active and whether they have sufficient eHealth literacy. This study aimed to determine the extent to which patients after PCI are health-related digitally active at baseline, 2 and 6 months after PCI, and to determine the association between patients' eHealth literacy and their health-related digital activity. METHODS AND RESULTS: This multicentre cohort study included patients at three large referral PCI centres in Norway (n = 1970). Data were collected from medical records, national registries, and patients' self-reports. The eHealth Literacy Scale (eHEALS) assessed patients' eHealth literacy. At baseline, 67% had used the internet to find health information. The mean eHEALS score was 25.71 (standard deviation 6.22), illustrating a lower level of eHealth literacy. There were substantial associations between eHealth literacy and use of the internet to find health information [coefficient 10.90, 95% confidence interval (CI) 8.05-14.57]. At the 2-month follow-up, there were substantial associations between baseline eHealth literacy and use of the internet to find information about health, prevention, illness, or treatment [odds ratio (OR) 1.19, 95% CI 1.14-1.24] and use of health applications (OR 1.15, 95% CI 1.08-1.22). CONCLUSION: This study provides evidence that patients' level of eHealth literacy after PCI is associated to how patients use, and can make use of, eHealth technology for health information. REGISTRATION: ClinicalTrials.gov (NCT03810612).

Percutaneous left ventricular assist device can prevent acute cerebral ischaemia during ventricular fibrillation.

AIMS: A percutaneous left ventricular assist device has been shown to be able to perfuse cardiac and cerebral tissues during cardiac arrest and may be a useful supplement to current methods in resuscitation. We wished to assess device-assisted circulation during cardiac arrest with microspheres injections and continuous end-tidal CO(2) monitoring, and used cerebral microdialysis to detect ischaemia in the brain. METHODS: 12 anaesthetised pigs had microdialysis and pressure catheters implanted via craniotomy. The percutaneous assist device was deployed transfemorally. Ventricular fibrillation was induced by angioplasty-balloon occlusion of the left coronary artery. Cerebral microdialysis samples representing 0-20 and 20-40 min of cardiac arrest with assisted circulation were analysed for markers of cerebral injury (glucose, pyruvate, lactate, and glycerol). RESULTS: Microdialysis showed no ischaemic changes after 20 min of cardiac arrest (P=NS to Baseline for glucose, glycerol, lactate, pyruvate and lactate/pyruvate ratio) in subjects with maintained end-tidal CO(2) values above 1.3 kPa (10 mmHg). After 40 min only lactate showed a significant change compared to Baseline (P<0.05). Microspheres flow to the brain was 57% and myocardial flow was 72% compared to Baseline after 15 min (P<0.05). After 45 min flow declined to 22% and 40% of Baseline, respectively (P=NS vs. 15 min). CONCLUSIONS: A percutaneous left ventricular assist device may prevent ischaemic cerebral injury during cardiac arrest for a limited time. Cerebral injury and tissue perfusion were indicated by end-tidal CO(2).

Ribosome distribution in normal and infarcted rat hearts.

Distribution of ribosomes throughout the myocardium of normal and infarcted rat hearts was studied by immunofluorescence and laser confocal scanning microscopy. In addition, sections were labelled with peroxidase or immunogold particles for electron microscopic examination. Ligation of the proximal free left coronary artery produced severe myocardial ischaemia, and after 6 days of ligation most of the left ventricular wall was necrotic and partially replaced by granulation tissue. Immunofluorescence microscopy revealed the presence of ribosomes throughout the non-necrotic myocardium. Some cardiac muscle cells located in subendocardial areas and in the border areas surrounding the infarct were particularly intensely stained. Cells constituting the granulation tissue frequently exhibited strong ribosomal immunostaining. Within longitudinally sectioned cardiac muscle cells, ribosomes were organized in strands oriented along the long axis of the cell as well as in a cross-striated pattern. By double labelling of muscle cells with antibodies against ribosomes and Z-line-associated proteins (desmin or alpha-actinin), it was shown that the cross-striated bands of anti-ribosomal staining coincided with the I-bands along the myofibrils. Immunoelectron microscopy confirmed a wide distribution of ribosomes throughout the intermyofibrillar and subsarcolemmal sarcoplasm, and some labelling was also observed within the I-band. The present results indicate that ribosomes are distributed in a characteristic pattern throughout the sarcoplasm of cardiac muscle cells in association with the myofibrils. Furthermore, it is suggested that within viable cardiac muscle cells located adjacent to the infarct, protein synthesis is increased; this might be an important factor in regional development of compensatory hypertrophy of the surviving cardiac muscle cells.

Cholesterol induced lipid accumulation in myocardial cells of rats.

OBJECTIVE: The aim was to investigate whether cholesterol feeding of rats for only 10 d would result in lipid accumulation in myocardial cells and a change in the peroxisomal beta oxidation in the heart compared to the hearts of rats on standard feeds. METHODS: Eight rats received a cholesterol diet (2%) and eight rats received a standard diet for 10 d. Lipids were measured in serum, liver, and heart. Palmitoyl-CoA hydrolase and fatty acyl-CoA oxidase were determined in total homogenate of hearts. The fractional volume of lipid droplets in myocardial cells was calculated from micrographs at a magnification of x9600 obtained by electron microscopy. RESULTS: The fractional volume of lipid droplets in the cardiomyocytes increased from 0.109(SEM 0.019)% to 0.259(0.037)%, (p < 0.003), as a result of cholesterol feeding. Cholesterol and triglycerides in the heart measured by biochemical methods increased by 13% and 24%, respectively. There was no difference in palmitoyl-CoA hydrolase or fatty acyl-CoA oxidase in the hearts of the cholesterol fed group compared to the control group, suggesting an unaltered peroxisomal beta oxidation of fatty acids in the myocardium. The serum triglycerides and serum phospholipids were reduced in the cholesterol fed rats (p < 0.05 and p < 0.001, respectively). Rats fed cholesterol diet showed a reduced ratio of HDL cholesterol to total cholesterol in serum, together with an increased liver weight and relative liver weight compared to the control rats. The addition of cholesterol to the diet increased liver cholesterol to 21.0(1.6) mumol.g-1 wet weight compared to 5.87(0.93) mumol.g-1 in the controls on standard diet (p < 0.0001). Cholesterol feeding had no effect on the hepatic level of phospholipids, but the liver triglycerides tended to increase from 23.3(9.5) mumol.g-1 wet weight to 53.3(6.3) mumol.g-1. CONCLUSIONS: Lipid accumulation in the myocardial cells was shown by morphometry after 10 d of cholesterol feeding, without any visible damage to the tissue.

Fibronectin and laminin in transverse tubules of cardiac myocytes studied by laser confocal microscopy and immunocytochemistry.

The distribution of two non-collagenous glycoproteins of high molecular weight, fibronectin (FN) and laminin (LMN), was investigated in myocardial cells from the ventricle of rats, and from biopsies collected from the auricle of patients undergoing a coronary bypass operation. In order to elucidate the expression of FN and LMN across cells, non-invasive serial sectioning has been carried out by laser scanning confocal microscopy of frozen, immunostained tissue sections. In addition, immunoelectron microscopy was used to study the distribution of these antigens at higher magnifications. These studies show that FN is part of the basement membrane of the surface sarcolemma of both ventricular and atrial cells, in addition to being an abundant protein of the extracellular matrix (ECM). Along transverse tubular(TT)-membranes, FN was only detected in tubules exceeding 200 nm in diameter. Even here, the intensity of labelling varied greatly and was generally low. By contrast, a heavy investment of LMN was organized in the basal lamina along the surface sarcolemma and along ramifications of the entire TT-system in ventricular heart muscle cells. In this way, the network of TT-membrane systems of working heart muscle cells provides a supply of LMN to all depths of the myocardial fibre. In human atrial muscle cells, a regular TT-system appears to be absent. Instead occasional, deep sarcolemmal invaginations occur with diameters of 300-500 nm, the surfaces of which are also invested with LMN. The significance of the present findings has been discussed, with special reference to LMN as a possible component of a series of proteins involved in transmembrane communication between the ECM and the sarcoplasm.

Intracellular free magnesium concentration: relevance to cardiovascular medicine.

There is a growing awareness of the role hypomagnesemia plays in cardiovascular medicine. Recent experimental studies have also provided a new understanding og how Mg2+ ions influence various ion channels and transport mechanisms. Yet, the pathophysiological mechanisms that may be responsible for various phenomena associated with hypomagnesemia, have not been clarified. This is partly due to that there, until recently, has been a lack of convenient and reliable methods for measuring cytosolic free Mg2+ concentration. It is the hope that newly developed techniques for measuring the cytosolic free Mg2+ concentration will prove useful in this respect.

Tissue protection by verapamil in the calcium paradox.

The effect of verapamil (+/- 2 mumol/l verapamil) on calcium paradox injuries, as well as on hearts subjected to calcium-free perfusion alone, was studied in isolated perfused rat hearts. Three different protocols for calcium depletion (5 min) were followed: 5 or 45 ml of nominally calcium-free solution (1 or 9 ml/min), or 45 ml of nominally calcium-free solution to which 20 mumol/l CaCl2 was added. Ultrastructural analyses showed that verapamil protects against cellular injuries upon readmission of calcium to hearts subjected to partial calcium depletion (5 ml calcium-free solution, or 45 ml to which 20 mumol/l CaCl2 was added) by reducing the number of affected cells. No protection was found after more extensive calcium washout. However, in all groups examined, we found an inverse relationship between the number of injured cells and ATP content. Verapamil protected against contracture development and reduced the increase in tissue calcium content observed after readmission of calcium to hearts perfused with 5 ml calcium free solution, whereas no significant effect of verapamil on tissue calcium content was found in hearts perfused with 45 ml nominally calcium-free solution. In hearts studied after calcium-free perfusion no effect of verapamil treatment on the separation of the intercalated disc was found. The protective effect of verapamil could not be explained by differences in calcium or cAMP levels after calcium-free perfusion.

Early morphologic changes in cat heart muscle cells after acute coronary artery occlusion.

The left descending coronary artery (LAD) was occluded in 16 open-chest cats for 10, 20, 40, or 60 minutes (four cats in each group). In addition, four sham-operated cats served as controls. Specimens for electron microscopy were obtained from the normal and ischemic zones, guided by in vivo injection of fluorescein, and verified by blood flow measurements with microspheres. The ultrastructure of 2,400 heart muscle cells and nuclei was studied. Fractional volumes of main cell components, mitochondrial surface density, and mitochondrial surface: volume ratio were calculated in 480 micrographs. After 10 minutes of ischemia we observed signs of sarcolemmal fragility, mitochondrial swelling, and lipid droplet accumulation. After 20 minutes of ischemia sarcolemmal fragmentation, chromatin clumping or margination and a maximal cytoplasmic edema were evident. The fractional volume of mitochondria was equally increased in ischemic zones of all groups. In both normal and ischemic zones there was a tendency toward smaller fractional volumes of lipid droplets during ischemia. In the normal zone there was mild cytoplasmic edema and slight mitochondrial swelling 10 minutes after occlusion as compared with the sham group. The present study demonstrates that a large proportion of cardiac myocytes undergoes severe damage within 20 minutes of coronary occlusion.

Mitochondrial calcium in hearts subjected to lipid peroxidation with contracture development.

In the present study we have investigated isolated rat hearts perfused with oxygen radicals generated by xanthine oxidase and hypoxanthine. The influence of verapamil (1 mg.1(-1] pretreatment on oxygen radical-induced contracture development and decrease in contractility was examined. In addition, we have measured mitochondrial calcium and magnesium levels in control hearts and hearts perfused with oxygen radicals with and without addition of superoxide dismutase (SOD) and catalase. The presence of oxygen radical-induced lipid peroxidation was confirmed by the increased level of conjugated diens in lipid extracts from oxygen radical-perfused hearts. Verapamil prevented contracture development in hearts perfused with oxygen radicals. Diastolic pressure measured with a left ventricle balloon was at the end of the experiments. 18 +/- 3 mm Hg (mean +/- SEM) with verapamil and 66 +/- 9 mm Hg without (p less than 0.001). Perfusion with oxygen radicals resulted in a reduction in mitochondrial calcium from 14.63 +/- 0.93 to 8.26 +/- 0.61 nmol.mg-1 (p less than 0.001) which was partly reversed by superoxide dismutase and catalase. Mitochondrial magnesium levels were unchanged in all groups.

Cytosolic free magnesium concentration in cultured chick heart cells.

Cytosolic free magnesium (Mgi) was measured in embryonic chick heart cells loaded with one of two newly developed 19F nuclear magnetic reasonance (NMR)-sensitive magnesium chelators, 4-methyl,5-fluoro-2-aminophenol-N,N,O-triacetate (MF-APTRA) and 5-fluoro-2-aminophenol-N,N,O-triacetate (5F-APTRA). The cells, embedded in strands of collagen, were superfused at a rate that allowed for solution changes in 2 min. In this preparation 19F- and 31P-NMR spectra were stable for at least 3.5 h. Because Na-coupled Mg countertransport may be a possible mechanism of Mg transport, in some experiments extracellular Na was reduced to 1 mM (choline substituted). This manipulation caused a 2.5-fold increase in Mgi from the basal level of 0.56 mM. A significant proportion of this increase in Mgi could be secondary to an increase in Cai that occurs with low extracellular Na (Nao) perfusion (Nai-Cao exchange). Perfusing cells with nominally Ca-free, 1 mM Na salt solution substantially attenuated the increase in Mgi that occurred with Ca present (1.25 mM) in the low Na (1 mM) solution. Furthermore, perfusion with 1 mM Na, Mg-free salt solution caused a 1.5-fold increase in Mgi, which cannot be attributable to Nai-Mgo exchange. Therefore attempts to describe the regulation of Mgi in heart cells must differentiate between the effects of Nai-Mgo exchange and competition for binding sites that are secondary to stimulation of ion gradient-coupled mechanisms.

Lifestyle and mortality among Norwegian men.

Information on six different habits (cigarette smoking, physical activity, frequency of alcohol and of fruit/vegetable consumption, and daily bread and potato consumption) was obtained by two postal surveys (1964 and 1967) among Norwegian men. The answers were related to mortality among 10,187 respondents ages 35-74 years at the start of the follow-up period (1967-1978). Analyses, stratified by age, place of residence, marital status, and socioeconomic group, showed an association between the six variables and observed/expected deaths, as well as odds ratio estimates. A health practice score, obtained by adding the number of favorable habits, showed a strong inverse relationship with total mortality as well as deaths from cancer, cardiovascular diseases, and other causes. Odds ratio estimates for men with only favorable habits vs those with at most one such habit, were 0.31 for total mortality, 0.44 for cancer, and 0.36 for cardiovascular mortality. Separate analyses among current smokers and nonsmokers showed a particularly strong association between the five other habits and mortality from cardiovascular disease.

Effects of verapamil on intracellular lipid accumulation in cat hearts with 3 h of regional-ischaemia.

In the regionally ischaemic heart lipid droplet accumulation is found in the ischaemic area and is most pronounced in the periphery. The purpose of the present study is to explore the potential effects of the calcium-channel-blocker verapamil on this accumulation. The drug is known to reduce the intensity of myocardial ischaemic injury. The myocardial ultrastructure was studied in anaesthetized open chest cats with 3 h of coronary artery occlusion. Biopsies were taken from the ischaemic, border and normally perfused myocardium defined in vivo injections of fluorescein and verified by blood flow measurements using radiolabelled microspheres. Arterial concentration of non esterified fatty acids (NEFA) was measured during the ischaemic period. A higher accumulation of lipid droplets was found in the central ischaemic myocardium of verapamil-treated cats than in control animals (p less than 0.05). The normally perfused and borderline areas were unaffected by verapamil as far as lipid accumulation was concerned and showed the same pattern as in the untreated group. The increased accumulation of lipid droplets in the ischaemic myocardium, after treatment with verapamil, may reflect a preserved metabolic activity in the ischaemic tissue or result from a higher supply of fatty acids due to increased perfusion of the central ischaemic tissue.

Morphological changes across the border zone of cat hearts subjected to regional ischaemia.

The left anterior descending coronary artery (LAD) was ligated for 3 h in six open chest cats. Six biopsies for electron microscopy were collected from the normal, the ischaemic and the border zones as defined by in vivo injection of fluorescein and as verified by blood flow measurements. Across the fluorescein demarcation line, we collected 3 mm long border zone biopsies, extending 1.5 mm in both the normal and the ischaemic direction. Starting from the normal end twenty subsequent areas (165 microns apart) were studied. By examining a total number of 5280 myocytes we observed an abrupt increase in the number of cells with sarcolemmal fragmentation. This point called border line is accompanied by an abrupt increase in the number of cells with chromatin clumping or margination, and of cells which are mainly necrotic with a massive cytoplasmic oedema. Morphometric analysis of 576 micrographs indicates a border zone on both sides of the border line. The border zone is characterized by a larger fractional volume of mitochondria (extending 1.5-2.0 mm in the normal direction) and by a larger lipid droplet accumulation (extending 1.2 mm or less in the normal direction) than seen in the ischaemic zone. These changes are in the normal part of the border zone accompanied with a moderate cytoplasmic oedema and a fragile sarcolemma with focal disruptions.

Effects of verapamil and timolol on cellular morphometric changes in cat hearts with regional ischaemia.

In twenty-one anaesthetized open chest cats the left anterior descending coronary artery (LAD) was occluded for three hours. Seven cats were pretreated with a bolus injection of Verapamil, followed by a continuous infusion of Verapamil during the ischaemic period. Seven cats were pretreated with a bolus injection of Timolol to a heart rate reduction of 20 beats/min or more and seven cats were given saline. In the latter two groups the cats received a continuous infusion of saline during the period of coronary occlusion. Biopsies were taken from the mid-myocardium of the normal, border and ischaemic zones, as defined by fluorescein staining, and verified by blood flow measurements with radiolabelled microspheres. Standard point counting techniques were used for calculations of fractional volumes of mitochondria, cytoplasm and myofibrils as well as of mitochondrial surface density and surface to volume ratio. We observed a cytoplasmic oedema in the border and ischaemic zones, that was not altered by medical treatment. In the border zone of the control cats there is greater mitochondrial swelling than in the ischaemic zone. This particular swelling is not seen in the treatment groups. However, in the normal and border zones of the verapamil group the mitochondria are smaller when compared with the respective zones in the two other groups, but increases relatively more in size in the border and ischaemic zones. Furthermore, we measured the water content, sarcomere length and per cent heavily damaged cells. These variables were not altered by Verapamil or Timolol in any zone when compared with the respective zones in the control group.

Cellular morphometric changes in cat hearts subjected to three hours of regional ischaemia.

The left anterior descending coronary artery (LAD) was occluded for three hours in seven anaesthetized open chest cats. Seven cats served as sham operated controls. Biopsies were collected from the mid-myocardium of the normal, border and ischaemic zones as defined by fluorescein staining and verified by blood flow measurements with radiolabelled microspheres. In the sham operated hearts the biopsies were taken from the mid-myocardium of the lateral wall of the left ventricle. Fractional volumes of mitochondria, myofibrils and remaining cytoplasm as well as data on the outer mitochondrial membrane were obtained by standard point counting techniques. In the LAD occluded hearts we observed a morphologically distinct lateral border zone characterized by a greater swelling of the mitochondria than in the ischaemic zone. However, in this group a more marked oedema of the cytoplasm and a greater percentage of heavily damaged cells were observed in the ischaemic than in the border zone. The ischaemic zone also had the largest water content. Furthermore, cytoplasmic oedema occurred in the normal zone of the LAD occluded cats when compared with the sham operated controls. This indicates that LAD occlusion also affects the normally perfused parts of the heart.

Myocardial cAMP and calcium levels in the calcium paradox.

In a graded model (minimal, subtotal, total) of the calcium paradox phenomenon induced by a progressive increase in the flow rate and volume (5 ml, 10 ml, 45 ml) of calcium-free perfusion (5 min) the severity of tissue injury on calcium repletion was related to a potential elevation of cAMP during calcium depletion. In the subtotal and total models of the calcium paradox a 50% increase was found for tissue cAMP after calcium-free perfusion, but no such rise could be associated with the minimal calcium paradox. In the study tissue injury, as assessed by whole tissue and mitochondrial accumulation of calcium and by myocardial leakage of creatine kinase, could only partly be related to cAMP changes. It is concluded that calcium-free coronary perfusion induces a complex series of events favouring excessive calcium entry, only one of which may be related to a change in cAMP.

The calcium paradox phenomenon: a flow rate and volume response study of calcium-free perfusion.

A dose-response study concerning the importance of the flow rate (0.5 to 12 ml/min) and volume (2.5 to 60 ml) of calcium-free coronary perfusion (duration 5 min) in the induction of a calcium paradox on reperfusion (duration 15 min) with calcium-containing medium has been performed in the isolated rat heart (37 degrees C). On the basis of enzymatic, physiological, and metabolic assessments three different levels of tissue injury were identified: a minimal paradox at 1.0 ml/min or 5 ml, a subtotal paradox at 2 ml/min or 10 ml and a total paradox at 9 ml/min or 45 ml. Ultrastructural examination revealed that cellular injury following calcium repletion was always severe, and that an increase in the flow rate and volume of calcium-free perfusion increased the number of severely injured cells. During calcium-free perfusion the external lamina largely remained intact over the surface coat of the sarcolemma, but variable degrees of separation of intercalated discs were observed. It is concluded that the calcium paradox model of myocardial injury presents a rather sharp threshold related to the flow rate or volume of calcium-free coronary perfusion and that on trespassing this threshold there is a narrow zone characterized by a decreasing number of viable cells. Furthermore, the study indicates that a separation of the external lamina from the surface coat of the sarcolemma is not a prerequisite for the induction of a calcium paradox, and that cell injury may occur in the presence of intact intercalated discs.

Ultrastructural studies of intercalated disc separations in the rat heart during the calcium paradox.

The ultrastructure of intercalated disc separations were studied in isolated rat hearts subjected to 5 min of coronary perfusion with small volumes of a calcium-free solution (i.e., 10.0 ml, 5.0 ml, and 2.5 ml). The same groups of hearts were studied after 15 min of calcium repletion. A semiquantitative examination shows that after calcium depletion 20%-45% of the intercalated discs (ID) were separated in the 2.5-ml group, 50%-75% in the 5.0-ml group, and 75%-90% in the 10.0-ml group. Readmission of calcium did not give any significant changes in the percentage of ID dehiscence in the two lowest volume groups, which indicates that ID separation has been irreversible during the first 15 min of calcium repletion. A semiquantitative analysis has also been performed of the percentages of severely damaged cells at each of the three volume groups after calcium repletion. It appears that in the two lowest volume groups, the percentage of widened discs tend to exceed the percentage of severely injured cells after calcium readmission. This suggests that ID separation not necessarily implies severe injuries to the implicated cells during calcium repletion. After calcium-free perfusion, cellular edema, cytoplasmic disintegration, and plasmalemmal fragmentation were present in the interdigitating cellular projections of the dissociated ID. Similar injuries did also occasionally occur outside the ID, usually situated in close proximity to a capillary.

Propranolol induced lipid accumulation and mitochondrial granularity in myocardial cells.

The ultrastructure of the left ventricular wall was studied in mice given intraperitoneal injections of propranolol (5 mg or 20 mg.kg-1 b.w. twice a day for 48 h with an additional dose 3 h before death), and in saline injected controls. Injections of propranolol increase the number of lipid droplets in areas of the myocardium. Fractional volume of lipid droplets in myocardial cells determined using quantitative stereological techniques, showed an increase of 280% and 544% in the group receiving the lowest and highest doses respectively. Injections of propranolol were also followed by an increased granularity of the mitochondria.