Evaluation of a QRS scoring system for estimating myocardial infarct size. II. Correlation with quantitative anatomic findings for anterior infarcts

The ability of an independently developed QRS point score to estimate the size of infarcts predominantly within the anterior third of the left ventricle was evaluated by quantitative pathologic-electrocardiographic correlation. The study was limited to 21 patients with a single infarct documented by postmortem examination, for whom an appropriately timed standard 12 lead electrocardiogram was available that did not exhibit signs of left or right ventricular hypertrophy, left or right bundle branch block or anterior or posterior fascicular block. At necropsy the heart was cut into five to seven slices. The location and size of the infarct was quantitated by computer-assisted planimetry of the slices.The electrocardiogram of 19 (90 percent) of the patients exhibited either a Q wave or an R wave of no more than 20 ms in lead V₂. The infarct in the two patients without this electrocardiographic finding was small, occupying 2 and 3 percent of the left ventricle, respectively. The percent infarction of the left ventricle correlated with the QRS point score (r = 0.80). Thus in patients without complicating factors in the electrocardiogram and with a single infarct, the electrocardiogram provides a marker for infarction in the anterior third of the left ventricle and permits estimation of infarct size.     

Immediate response of 5-methoxytryptophol in the circulation to hypoglycaemic stress induced by insulin.

Pineal indoles have been shown to affect the release of anterior pituitary hormones but details of the interrelationships are lacking. Using a new gas chromatography-mass spectrometry (g.c.-m.s.) assay the concentration of 5-methoxytryptophol (ML) was measured in plasma samples obtained from 16 children undergoing investigation of pituitary function for delayed growth. All the children received an insulin tolerance test (ITT) to study their endocrine response to stress. Some children received luteinizing hormone releasing hormone (LH-RH) and/or thyrotrophin releasing hormone (TRH). The change in concentration of ML during an ITT was similar to the change in concentration of blood sugar; a drop at 20 min followed by a rise at 30 min. This was not significantly altered by the administration of LH-RH or TRH, nor was there a different pattern of response in children who were deficient in growth hormone as opposed to those with idiopathic delayed growth. The fall in concentration of ML with stress may mediate the increased secretion of pituitary hormones. Alternatively, the pineal gland may respond directly to insulin.     

Primary tumor cells of myeloma patients induce interleukin-6 secretion in long-term bone marrow cultures

Long-term bone marrow cultures (LTBMC) from patients with multiple myeloma (MM) and normal donors were analyzed for immunophenotype and cytokine production. Both LTBMC adherent cells from myeloma and normal donor origin expressed CD10, CD13, the adhesion molecules CD44, CD54, vascular cell adhesion molecule 1, very late antigen 2 (VLA-2), and VLA- 5, and were positive for extracellular matrix components fibronectin, laminin, and collagen types 3 and 4. LTBMC from myeloma patients and normal donors spontaneously secreted interleukin-6 (IL-6). However, levels of IL-6 correlated with the stage of disease; highest levels of IL-6 were found in LTBMC from patients with active myeloma. To identify the origin of IL-6 production, LTBMC from MM patients and normal donors were cocultured with BM-derived myeloma cells and cells from myeloma cell lines. IL-6 was induced by plasma cell lines that adhered to LTBMC such as ARH-77 and RPMI-8226, but not by nonadhering cell lines U266 and FRAVEL. Myeloma cells strongly stimulated IL-6 secretion in cocultures with LTBMC adherent cells from normal donors and myeloma patients. When direct cellular contact between LTBMC and plasma cells was prevented by tissue-culture inserts, no IL-6 production was induced. This implies that intimate cell-cell contact is a prerequisite for IL-6 induction. Binding of purified myeloma cells to LTBMC adherent cells was partly inhibited by monoclonal antibodies against adhesion molecules VLA-4, CD44, and lymphocyte function-associated antigen 1 (LFA-1) present on the plasma cell. Antibodies against VLA-4, CD29, and LFA-1 also inhibited the induced IL-6 secretion in plasma cell-LTBMC cocultures. In situ hybridization studies performed before and after coculture with plasma cells indicated that LTBMC adherent cells produce the IL-6. These results suggest that the high levels of IL-6 found in LTBMC of MM patients with active disease are a reflection of their previous contact with tumor cells in vivo. These results provide a new perspective on tumor growth in MM and emphasize the importance of plasma cell-LTBMC interaction in the pathophysiology of MM.     

Histochemical demonstration of desialation and desulphation of normal and inflammatory bowel disease rectal mucus by faecal extracts.

Experiments were carried out to assess the susceptibility of normal and inflammatory bowel disease rectal mucus to desulphation and desialation by faecal extracts and by bacterial sialidase. The effects were assessed histochemically using a combined high iron diamine (HID) and alcian blue (AB) stain for sulphomucins and sialomucins. Rectal mucus in biopsies from controls (irritable bowel syndrome) and patients with ulcerative colitis or Crohn's disease was resistant to desialation by Clostridium perfringens sialidase, but susceptible to desialation and desulphation by bacteria-free extracts of normal faeces. Periodic acid-Schiff (PAS) staining of adjacent sections similarly treated showed retention of neutral mucus. One faecal extract selectively desulphated all 42 biopsies, causing the goblet cells to change from HID positive to AB positive, suggesting that most, or all HID positive cells also contain sialomucins. This alters the interpretation of previous histochemical studies. Faecal extracts from patients with active ulcerative colitis (n = 6) had desialating and desulphating effects similar to faecal extracts from normal subjects (n = 6). Ulcerative colitis (n = 21), Crohn's disease (n = 18), and control (irritable bowel syndrome) (n = 17) rectal biopsies all showed similar susceptibility to desulphation by a pooled normal faecal extract, but rectal biopsies from patients with Crohn's disease proved more resistant to desialation than control or ulcerative colitis biopsies (p less than 0.02). These studies imply that colonic mucus undergoes continual desulphation and desialation in vivo as a result of faecal enzyme activity that is probably mainly of bacterial origin. Altered susceptibility of colonic mucus to this may be important in the pathogenesis of colonic disease.     

Effect of known history of heart disease on survival outcomes after out‐of‐hospital cardiac arrests

Objective

We aimed to investigate the effect of known heart disease on post‐out‐of‐hospital cardiac arrest (OHCA) survival outcomes, and its association with factors influencing survival.

Methods

This was an observational, retrospective study involving an OHCA database from seven Asian countries in 2009–2012. Heart disease was defined as a documented diagnosis of coronary artery disease or congenital heart disease. Patients with non‐traumatic arrests for whom resuscitation was attempted and with known medical histories were included. Differences in demographics, arrest characteristics and survival between patients with and without known heart disease were analysed. Multivariate logistic regression was performed to identify factors influencing survival to discharge.

Results

Of 19 044 eligible patients, 5687 had known heart disease. They were older (77 vs 72 years) and had more comorbidities like diabetes (40.9 vs 21.8%), hypertension (60.6 vs 36.0%) and previous stroke (15.2 vs 10.1%). However, they were not more likely to receive bystander cardiopulmonary resuscitation (P = 0.205) or automated external defibrillation (P = 0.980). On univariate analysis, known heart disease was associated with increased survival (unadjusted odds ratio 1.16, 95% confidence interval 1.03–1.30). However, on multivariate analysis, heart disease predicted poorer survival (adjusted odds ratio 0.76, 95% confidence interval 0.58–1.00). Other factors influencing survival corresponded with previous reports.

Conclusions

Known heart disease independently predicted poorer post‐OHCA survival. This study may provide information to guide future prospective studies specifically looking at family education for patients with heart disease and the effect on OHCA outcomes.     

Dual endothelin‐1 receptor antagonism attenuates platelet‐mediated derangements of blood coagulation in Eisenmenger syndrome

Essentials

• Eisenmenger syndrome is characterised by thrombotic and hemorrhagic risks of unclear aetiology.
• Calibrated automated thrombography was used to assess these coagulation derangements.
• Platelet activity supported abnormalities in procoagulant and anticoagulant pathway function.
• Endothelin‐1 antagonism appeared to ameliorate these derangements.

Summary

Aims

The mechanisms underlying the competing thrombotic and hemorrhagic risks in Eisenmenger syndrome are poorly understood. We aimed to characterize derangements of blood coagulation and to assess the effect of dual endothelin‐1 receptor antagonism in modulating hemostasis in this rare disorder.

Methods

In a 10‐month recruitment period at a tertiary cardiology referral center, during which time there were over 14 000 outpatient consultations, consecutive subjects with Eisenmenger syndrome being considered for macitentan therapy (n = 9) and healthy volunteers (n = 9) were recruited. Plasma thrombin generation in platelet‐rich and platelet‐poor plasma was assessed by calibrated automated thrombography prior to and following therapy.

Results

Median peak plasma thrombin generation was higher in platelet‐rich plasma obtained from Eisenmenger syndrome subjects relative to controls (median peak thrombin [25th–75th percentile]: 228.3 [206.5–258.6] nm vs. 169.9 [164.3–215.8] nm ), suggesting a critical mechanistic role for platelets in supporting abnormal hypercoagulability in Eisenmenger syndrome. Abnormal enhanced sensitivity to the anticoagulant activity of activated protein C was also observed in platelet‐rich plasma in Eisenmenger syndrome, suggesting that derangements of platelet activity may influence the activity of anticoagulant pathways in a manner that might promote bleeding in this disease state. Following 6 months of macitentan therapy, attenuations in the derangements in both procoagulant and anticoagulant pathways were observed.

Conclusions

Abnormal platelet activity contributes to derangements in procoagulant and anticoagulant pathways in Eisenmenger syndrome. Therapies targeting the underlying vascular pathology appear to ameliorate these derangements and may represent a novel strategy for the management of the competing prothrombotic and hemorrhagic tendencies in this disorder.

     

Mechanism of complement activation after coronary artery occlusion: evidence that myocardial ischemia in dogs causes release of constituents of myocardial subcellular origin that complex with human C1q in vivo

To evaluate whether ischemic myocardium releases molecules that react with the first component of complement, we studied cardiac lymph from eight dogs before and at intervals after coronary artery occlusion and reperfusion. Before occlusion, the dogs were injected intravenously with radiolabeled human C1q. Labeled C1q could be detected in the cardiac lymph within minutes following injection. Rabbit antisera, prepared against substances precipitated from postreprefusion cardiac lymph by anti-human C1q, also reacted with specific constituents of isolated cardiac sarcoplasmic reticulum and mitochondria. To evaluate whether mitochondria are the source of these C1q-binding proteins, we isolated intramyofibrillar and subsarcolemmal mitochondria from canine heart and incubated sonicates of these with purified C1q, immobilized on nitrocellulose. Molecules bound to the immobilized C1q were removed with 0.1% sodium dodecyl sulfate, fractionated under reducing conditions by polyacrylamide gel electrophoresis, and transferred electrophoretically to nitrocellulose paper. Antisera prepared against postreperfusion lymph reacted with a 31,000-32,000-dalton protein in these nitrocellulose paper replicas. Since this protein originates from mitochondria, binds to C1q, and is recognized by antibodies made against postreperfusion lymph, this protein is likely to be one of the subcellular constituents that, upon release from ischemic cells, activates the complement cascade. To evaluate the clinical relevance of these observations, we tested sera from 53 patients obtained 48-72 hours after hospitalization for suspected myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)