Are predictors for myocardial infarction the same for women and men when evaluated prior to hospital admission?

AIM: To describe predictors of myocardial infarction prior to hospital admission in women and men among patients with a suspected acute coronary syndrome without ST-elevation. DESIGN: Prospective observational study in Stockholm and Göteborg, Sweden. RESULTS: Of 433 patients who did fulfill the inclusion criteria 45% were women. Fewer women (17%) than men (26%) developed acute myocardial infarction (AMI) (p=0.054), particularly among patients with initial ST-depression, in whom AMI was developed in 22% of women and 54% of men (p = 0.001). Predictors for infarct development in women were: a history of AMI and advanced age. Among men they were: initial ST-depression or a Q-wave on ECG and elevation of biochemical markers (both recorded on admission of the ambulance crew). There was a significant interaction between gender and the influence of ST-depression on the risk for development of myocardial infarction (p < 0.05). CONCLUSION: Among patients transported with ambulance due to a suspected acute coronary syndrome and no ST-elevation fewer women than men seem to develop AMI particularly among patients with ST-depression. These results suggest that early prediction of myocardial infarction might differ between women and men with acute chest pain.

Percutaneous cooling of ischemic myocardium by hypothermic retroperfusion of autologous arterial blood: effects on regional myocardial temperature distribution and infarct size.

The effects of synchronized coronary venous retroperfusion of cooled autologous arterial blood on regional myocardial temperature distribution and infarct size were studied in open chest dogs with 3.5 h of left anterior descending coronary artery occlusion. After 30 min of occlusion, the dogs were randomly assigned to one of three groups: 1) untreated control group (n = 5), 2) normothermic retroperfusion group (infusion temperature 32 degrees C) (n = 7), and 3) hypothermic retroperfusion group (infusion temperature 15 degrees C) (n = 7). Regional myocardial temperatures were measured by using needle-tipped thermistors stabbed in the 1) anterior wall distal to the occlusion site, 2) anterior wall proximal to the occlusion site, 3) left lateral wall, 4) posterior wall, and 5) right ventricular free wall. Rectal and pulmonary artery temperatures were also measured. In the hypothermic retroperfusion group, the anterior wall temperature decreased rapidly by 5 degrees C at 15 min of retroperfusion (p less than 0.05 vs. normothermic retroperfusion or untreated control groups), whereas the temperature at other sites decreased with a linear trend over time. Myocardial temperatures in the ischemic area (distal anterior wall) were generally lower than those in the other sites during the first 60 min of hypothermic retroperfusion and the largest intramyocardial temperature difference (3.6 degrees C) was found at 15 min after retroperfusion. Infarct size expressed as a percent of the risk area was significantly smaller in the hypothermic retroperfusion group (6.2 +/- 3.3%) than in the control (64.9 +/- 14%) or normothermic retroperfusion groups (24.1 +/- 6.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary venous retroinfusion of deferoxamine reduces infarct size in pigs.

The efficacy of coronary venous retroinfusion of the iron chelator deferoxamine was studied in 24 pentobarbital-anesthetized open chest pigs with a 60 min occlusion of the left anterior descending coronary artery followed by 3 h of reperfusion. Eight retrogradely treated pigs were given 10 mg/kg body weight of deferoxamine by way of the anterior interventricular vein and eight systemically treated pigs received the same doses of deferoxamine intravenously. Drug infusions lasted for 5 min, beginning 15 min before reperfusion. Eight control pigs received systemic intravenous saline solution. Myocardial area at risk and necrotic area were assessed by the monastral blue dye and the triphenyltetrazolium chloride staining method, respectively. There were no significant differences in hemodynamics or regional myocardial function (sonomicrometry) among the groups. Infarct size expressed as percent of risk area was 73.9 +/- 13.5% in the control group, 70.6 +/- 16.4% in the systemically treated group and 48.5 +/- 21.4% (p less than 0.05) in the retrogradely treated group. In conclusion, deferoxamine significantly reduced infarct size after coronary occlusion only when given regionally by way of the coronary vein. Because there was no significant hemodynamic effect caused by deferoxamine infusion, it is suggested that this drug prevents postischemic reperfusion injury by a direct cardioprotective effect.

Synchronized coronary venous retroperfusion for support and salvage of ischemic myocardium during elective and failed angioplasty.

To determine the safety and efficacy of synchronized coronary venous retroperfusion during brief periods of ischemia, 30 patients undergoing angioplasty of the left anterior descending coronary artery were studied. Each patient underwent a minimum of two angioplasty balloon inflations. Alternate dilations were supported with retroperfusion; the unsupported inflations served as the control inflations. Synchronized retroperfusion was performed by pumping autologous femoral artery blood by means of an electrocardiogram-triggered retroperfusion pump into the great cardiac vein through a triple lumen 8.5F balloon-tipped retroperfusion catheter inserted percutaneously from the right internal jugular vein. Clinical symptoms, hemodynamics and two-dimensional echocardiographic wall motion abnormalities were analyzed. Retroperfusion was associated with a lower angina severity score (0.8 +/- 1 vs. 1.2 +/- 1) and delay in onset of angina (53 +/- 31 vs. 37 +/- 14 s; p less than 0.05) compared with the control inflations. The magnitude of ST segment change was 0.11 +/- 0.14 mV with retroperfusion and 0.16 +/- 0.17 mV without treatment (p less than 0.05). The severity of left ventricular wall motion abnormality was also significantly (p less than 0.01) reduced with retroperfusion compared with control (0.7 +/- 1.4 [hypokinesia] vs. -0.3 +/- 1.6 [dyskinesia]). There were no significant changes in hemodynamics, except in mean coronary venous pressure, which increased from 8 +/- 3 mm Hg at baseline to 13 +/- 6 mm Hg with retroperfusion. Four patients required prolonged retroperfusion for treatment of angioplasty-induced complications. The mean retroperfusion duration in these patients was 4 +/- 2 h (range 2 to 7). In the three patients who underwent emergency bypass surgery, the coronary sinus was directly visualized during surgery and found to be without significant injury. There were no major complications. Minor adverse effects were transient atrial fibrillation (n = 2), jugular venous catheter insertion site hematomas (n = 4) and atrial wall staining (n = 1), all of which subsided spontaneously. Thus, retroperfusion significantly reduced and delayed the onset of coronary angioplasty-induced myocardial ischemia and provided effective supportive therapy for failed and complicated angioplasty.

Coronary venous drug infusion in the ischaemic-reperfused isolated rat heart.

OBJECTIVES: Coronary venous retroinfusion (CVR) has been used experimentally in large animals for selective drug delivery into ischaemic myocardium. It would be an advantage if CVR could also be used in isolated perfused rat heart models. The aim of the present paper is to develop a regional ischaemic model in the isolated perfused rat heart combined with CVR. METHOD: Pharmacokinetic study: The spatial distribution of retrogradely infused felodipine (used as a tracer) during regional myocardial ischaemia was investigated. Following occlusion of the left coronary artery, felodipine was administered over a period of 5 min by CVR. Ischaemia-reperfusion study: Following 30 min of stabilisation, 14 rat hearts were subjected to 60 min of regional ischaemia followed by 60 min of reperfusion. Felodipine (0.7 nmol/kg, n = 7) or vehicle (n = 7) was administered by means of CVR. The infusion was given during the last 5 min of ischaemia at a rate of 0.6 ml/min. RESULTS: Pharmacokinetic study: By means of CVR, the compound was distributed specifically into the ischaemic myocardium. The highest tissue concentration was obtained when the coronary vein was occluded during CVR. The maximal concentration in the ischaemic myocardium was 20-70 times that in the non-ischaemic areas. A transmyocardial gradient was noted with higher drug concentration in the subepicardial zone. Ischaemia-reperfusion study: At the end of reperfusion, the recovery of coronary flow, left ventricular developed pressure and double product (DP; LVDP x HR) was 101 +/- 7% (mean +/- s.e.m.), 99 +/- 8% and 98 +/- 4% of the pre-ischaemic values, respectively. This was significantly different from the vehicle group (78 +/- 5, P < 0.05, 74+/- 6, P < 0.01 and 78 +/- 3, P < 0.05). CONCLUSION: CVR could easily be accomplished in the isolated perfused rat heart. The drug was specifically delivered into the ischaemic myocardium. Felodipine exerted a myocardioprotective effect in isolated rat hearts subjected to 60 min of regional ischaemia followed by 60 min of reperfusion.

Axonal growth cones in the developing amphibian spinal cord.

Axonal growth cones in the spinal cord of embryonic and larval Xenopus (stages 24-48) were filled with the anatomical tracer horseradish peroxidase (HRP). Growth cones of lateral and ventral marginal zones, including those of descending spinal and supraspinal pathways, were labeled by application of tracer to the caudal medulla or to one of several levels of the spinal cord. Central axons of sensory neurons were filled via their peripheral processes. Growth cone configuration varied widely but fell into five general categories: complex with both filopodia and veils, filopodia only, lamellipodia only, clavate, and fusiform. Several general patterns emerged from the distribution of these various configurations. Growth cones of younger animals generally were more complex than those of older ones. Growth cones closer to the leading edge of descending fiber bundles were more elaborate than those that followed. Growth cones of the dorsolateral fascicle, which carries ascending central processes of Rohon-Beard and sensory ganglion neurons, were very simple and followed a straight course rostrally, whereas those of descending axons of the lateral fiber areas were more complex and sometimes spread over almost the entire lateral marginal zone. Growth cones of Rohon-Beard central ascending axons were fusiform or clavate, while those of sensory ganglion axons showed several fine filopodia at their tips. Growth cones of both types of sensory axons change configuration as they approached the hindbrain, becoming more complex. This study demonstrates that the configurations of growth cones belonging to the same axonal pathway vary with age and with position along their routes, and that growth cones of different neuron classes exhibit characteristic ranges of morphological variation.

Developing descending neurons of the early Xenopus tail spinal cord in the caudal spinal cord of early Xenopus.

The enzyme horseradish peroxidase (HRP) was used to describe and identify neurons, axons of which initiate the earliest descending pathways of the tail spinal cord of Xenopus embryos and larvae. Spinal cords were pierced at different rostrocaudal levels with fine insect pins coated with HRP. The resulting pattern of cellular labeling indicated that primitive sensory (Rohon-Beard) axons were at the lead of developing descending tracts followed by axons of primary motor neurons. Axons of these two neuron types travel in widely separated fascicles located dorso- and ventro-laterally, respectively. Subsequently, axons of several morphologically distinct intersegmental interneurons establish several additional fascicles positioned dorsal to the descending motor axons. Descending supraspinal axons appear only later. The distinctive morphological characteristics of each of the early descending cell types are illustrated along with some stages in their early differentiation. These observations establish the temporal pattern by which new axons are added to descending pathways beginning with the simplest level of the amphibian spinal cord and determine the identity of neurons to which axons at early stages in this sequence belong.

Cellular and subcellular distribution of HNK-1 immunoreactivity in the neural tube of Xenopus.

The HNK-1 antigen, a carbohydrate moiety bound to many cell adhesion and recognition molecules, is implicated in cell-cell and cell-substrate interactions during neural development. HNK-1 immunoreactivity (HNK1-IR) appears on neurons of the Xenopus neural tube very early in their development (Nordlander, Devel. Brain Res., 50:147-153, 1989). The distribution and onset of expression of the HNK-1 epitope on and within individual neurons is examined in this study. HNK-1 labels developing neurons and their processes, and focal areas of other structures which are directly contacted by neurons, such as neuroepithelial cell surfaces, basal lamina, and culture surfaces. HNK1-IR first appears in the Golgi apparatus and subsequently on the cell surface and in streams of punctate material directed toward the site of axon initiation and into the developing axon and its growth cone. The entire neuron is coated with a thin (20-30 nm) surface layer of HNK1-IR. In addition, the surface is dotted with small (100-250 nm) boluses of HNK1-IR material. Such boluses also occur within cytoplasmic vesicles, and extracellularly on basal lamina and culture substrata in proximity to neurons or their processes. The subcellar distribution of HNK1-IR in this tissue is compatible with a role for the HNK-1 epitope in axonal outgrowth and guidance.

Motoneurons of the tail of young Xenopus tadpoles.

The purpose of this study was to identify, characterize, and follow the morphogenesis of motoneurons innervating tail myotomes of Xenopus during early and middle larval stages (33-48). Application of horseradish peroxidase to a single myotome results in a column of labeled motor cells extending over four spinal segments. By midlarval stages two morphologically distinct cell types were recognizable in this column-primary and secondary motoneurons. Primary motoneurons occupied the more rostral and secondary motoneurons the more caudal portions of the column with some overlap of the two populations. Primary neurons developed earlier, were larger, and displayed thicker axons and proximal dendrites. Secondary neurons, in contrast, were smaller, more variable in configuration and dendritic distribution, and displayed thinner axons and dendrites. Development of the labeled motor column during the period observed involved the addition of more labeled neurons, principally secondary cells, and the enlargement of individual cell somata with the progressive elaboration of more and longer dendrites into the developing lateral fasciculus.

The role of ependyma in regeneration of the spinal cord in the urodele amphibian tail.

The new spinal cord formed during tail regeneration in the newt first develops as a caudal extension of the ependymal tube. Neuroblasts and neuroglia subsequently differentiate from cells of the ependymal tube in a proximal-caudal sweep. Descending axons from the cord rostral to the lesion and from newly differentiating neurons travel in channels which are present prior to the ingrowth of axons. The present study confirms previous observations from our laboratory and presents details of the ultrastructural relations of axons and ependymal processes within the cord. The ependymal cell surface facing channels typically forms numerous digitor sheet-like protuberances which extend into the channel lumen. As axons enter the channels in increasing numbers these protuberances partially subdivide the axons into smaller groupings, even occasionally segregating individual axons. At levels where fibers have not yet entered or have most recently entered the ependymal channesl two specializations appear on the ependymal plasmalemma facing the channels and their axons: coated membranes and hemidesmosome-like structures. At more mature levels, where many fibers have already entered the channels, axons in contact with ependymal processes sometimes show synapse-lide vesicle accumulations with associated membrane densities. Coated membranes and hemidesmosome-like structures are lacking at these levels. Our observations suggest that ependymal processes, in addition to providing substrate and direction for regenerating spinal cord axons, may also furnish or exchange more specific information at the morphologically identifiable specializations described above.

Distribution of ultrastructural tracers in crustacean axons.

Ruthenium red and horseradish peroxidase were used to compare the uptake of exogenous molecules into crayfish motor axons and their sheaths in severed and intact peripheral nerves. Both tracers penetrated the axonal sheath and were subsequently seen lining small vesicles and tubules in the axoplasm. Tracer appeared to enter the axon via pinocytotic vesicles. There were no perceptible quantitative or qualitative differences in ruthenium red uptake between intact and severed axons. However, counts of tracer-filled vesicles in axons exposed to peroxidase showed that at least three times as much tracer penetrated the severed as opposed to the intact axons.

Growth cones and axon trajectories of a sensory pathway in the amphibian spinal cord.

Central axons of sensory ganglion (SG) neurons of the Xenopus tail enter the spinal cord via the ventral roots and travel dorsally and rostrally following a diagonal course within the lateral marginal zone (LMZ) to reach the dorsolateral fasciculus (DLF) (Nordlander et al.: Brain Res., 440:391-395, 1988). Axons are dispersed as they cross the cord. At the DLF they turn and travel together rostrally, sharing the fascicle with axons of primary sensory neurons (Rohon-Beard cells) already present in the tract. In this paper we analyze the growth patterns of the central projections of SG axons in the tail by using HRP applied to proximal branches of tail spinal nerves. Growth cones of the diagonal route are variable in configuration, often bearing processes that spread within the LMZ. Once the DLF, growth cones change shape, becoming distinctly linear. While growth cones navigating the diagonal part of the route never contact or fasciculate with other diagonal SG axons, SG growth cones and axons of the DLF are more closely associated with their fellows. Measurements of the slopes of SG axons in the diagonal route indicated a limited range with a mean of 23 degrees with respect to the cord axis. On the basis of these observations, we conclude that 1) navigational patterns for growth cones of this pathway differ for the diagonal versus the DLF part of its course, and 2) fasciculation is not a mechanism used by SG axons to reach the DLF, but that instead, each axon is able to find its way independently.

Axonal guidance during embryogenesis and regeneration in the spinal cord of the newt: the blueprint hypothesis of neuronal pathway patterning.

In our previous studies on studies on spinal cord regeneration in the adult lizard and the newt, we observed that the radial processes of the regenerating ependyma form between them channels which are subsequently invaded by growing neurites. In the present study we compare embryogenesis of the newt spinal cord with regeneration in the adult. Except for minor differences, we observed that the germinal neuroepithelium of the embryo and larva patterns the longitudinal neural tracts in a similar manner. With these facts in mind we propose the blueprint hypothesis which asserts that inherent in the primitive germinal neuroepithelium and its derivative primitive glia is the pattern of the primary neuronal pathways which is expressed in neurogenesis as formed channels or spaces between the processes of the epithelial cells, the surfaces of which contain trace pathways which the growing neurites follow toward their destination. The trace pathways are envisoned as mechanical-chemical itineraries which the neurities follow according to their individual affinities. The hypothesis is compared to extant theories and the limitations in central nervous regeneration of vertebrates is compared.

Development of early brainstem projections to the tail spinal cord of Xenopus.

Horseradish peroxidase (HRP) was used to determine the sequence in which axons from different brain neurons reach the tail spinal cord during embryonic and early larval development of Xenopus laevis. Brainstem cells of several classes project to the tail at these stages: mesencephalic reticulospinal neurons of the nucleus of the medial longitudinal fasciculus, a variety of other reticulospinal neurons, vestibulospinal neurons, and a group of median basal cells which may be raphe neurons. Among the reticulospinal neurons the paired Mauthner cells are the most prominent. They and caudally situated reticular neurons are the first to label with HRP applied to the tail spinal cord (stage 37). Vestibulospinal and other reticular neurons begin to label next (stage 39), followed by mesencephalic and then median basal neurons (stage 41). Except for the Mauthner cells, the number of labeled cells belonging to each neuron class increases gradually as development proceeds.

An ultrastructural examination of early ventral root formation in amphibia.

The morphology of early interactions between neural tube and myotome in the amphibian embryo and tail regenerate was examined using the electron microscope. Two types of contacts were observed. At the most primitive level where the myotome was yet unsegmented, multiple adhesive-type contacts linked neural tube and myotome. In newly segmented areas early ventral roots were recognizable as small bundles of one to five axons extending the short distance to the myotome. There was only one bundle per segment and in addition to axons, each bundle always contained one or more primitive glial cell processes which accompanied axons as they left the cord. At points of root exit primitive glial processes appeared to funnel axons into the root. The cytoarchitecture of the cord and the new roots suggested that the primitive glia may play a role in pathfinding for motor axons as they leave the cord and extend toward their targets.

Cardioversion of atrial fibrillation and its effect on right ventricular function as assessed by tricuspid annular motion.

In patients with atrial fibrillation, the reduced right ventricular function determined by tricuspid annular motion before cardioversion returns to normal 1 month after successful cardioversion to sinus rhythm. The simplicity of recording the tricuspid annular motion provides an easy opportunity to assess right ventricular function following electroconversion of atrial fibrillation to sinus rhythm.

Cardiac effects of treatment with quinidine and digoxin, alone and in combination.

Systolic time intervals (QS2-I and LVET-I) and echocardiographically determined ejection fraction and velocity of circumferential fiber shortening were recorded in 10 healthy volunteers as measures of inotropic effect during maintenance treatment with 4 consecutive drug regimens: (1) quinidine, 1,200 mg/day; (2) digoxin, average dose 0.31 mg/day; (3) the combination of (1) and (2); and (4) digoxin alone (average dose 0.65 mg/day) to provide the same steady-state serum concentration of digoxin as during the period with combination of digoxin and quinidine. The steady-state serum concentration of digoxin during the low-dose regimen increased from 0.72 +/- 0.15 (mean +/- standard deviation [SD]) to 1.63 +/- 0.28 nmol/liter when quinidine was added. With the high dose of digoxin alone, the serum digoxin level reached 1.68 +/- 0.50 nmol/liter. Skeletal muscle digoxin concentrations during these periods were 27.7 +/- 8.3, 48.7 +/- 16.2, and 51.6 +/- 23.6 nmol/kg of dry weight, respectively. The skeletal muscle to serum concentration ratio of digoxin decreased significantly during quinidine treatment. Systolic time intervals were significantly prolonged by quinidine alone and shortened by digoxin alone, the latter effect being dose-dependent. Subtracting the effect of quinidine itself, the induced increase in digoxin level caused a significant increase in inotropic effect. When these corrected values were compared with those attained during the period with the same steady-state digoxin concentration but in the absence of quinidine, no significant differences were found. Echocardiographically measured ejection fraction and velocity of circumferential fiber shortening showed trends for similar drug effects, as did the systolic time intervals. This study, performed under steady-state conditions, demonstrates that the quinidine-induced increase in steady-state serum digoxin concentration will, with due consideration to quinidine's own pharmacodynamic properties, be accompanied by increased cardiac effects. This indicates that quinidine is not interfering with active receptor sites in the heart for digoxin.

Results of atrioventricular synchronous pacing with optimized delay in patients with severe congestive heart failure.

To verify that atrioventricular (AV) synchronous pacing (DDD) with short AV delay improves the condition of patients with severe congestive heart failure, we implanted DDD pacemakers in 10 patients with severe heart failure (New York Heart Association [NYHA] class III to IV). One day after pacemaker implantation, the AV delay was optimized by Doppler echocardiographic measurements over the aortic outflow tract. Patients were evaluated regarding NYHA class, stroke volume, cardiac output, ejection fraction, and quality of life at 1, 3, and 6 months after pacemaker implantation. Although the optimized AV delay was associated with short-term improvement in stroke volume and cardiac output (baseline stroke volume = 22 +/- 7 ml, day 1 = 28 +/- 12 ml; p = 0.03: baseline cardiac output = 1.9 +/- 0.6 L/min, day 1 = 2.2 +/- 1.1 L/min; p = 0.10), the mean stroke volume, cardiac output, NYHA class, and ejection fraction did not change significantly after 1, 3, and 6 months of pacing compared with baseline values. Three patients improved in NYHA class during the follow-up. A consistent improvement in stroke volume, cardiac output, NYHA class, and ejection fraction was observed in only 1 patient. In conclusion, we found no beneficial effects of AV-synchronous pacing with optimized AV delay in patients with severe heart failure.

Use of nitrates in the treatment of unstable and variant angina.

Unstable angina is a clinical syndrome that includes patients with new onset of angina, a change in a previous stable pattern, or the development of chest pain at rest. Generally, more than 90% of patients with this syndrome have significant fixed atherosclerotic coronary artery disease. Other complex, interacting pathophysiological mechanisms may include coronary vasoconstriction, plaque rupture and thrombosis. Therapeutic strategies aim at either reduction of myocardial oxygen demand or restoration of coronary blood flow. Both alternatives have been suggested as treatment of choice. However, as long as the pathophysiological mechanism(s) is unknown in the individual case, the treatment will mainly be empirical or based on results from clinical trials of heterogeneous groups of patients with unstable angina with probably varying aetiology. The results from such studies indicate that some strategies may be of value, but others may even be harmful in treatment of patients with this unstable syndrome. In this situation nitrates seem to be a safe drug which may be used in most forms of irrespective of the underlying pathophysiological mechanism(s).

The high-risk unstable angina patient. An approach to treatment.

Unstable angina, an intermediate stage in acute coronary ischaemic syndromes, accounts for about 50% of all admissions to the coronary care units in the United States today. It may progress to myocardial infarction in 15% of cases in the first 2 days, and the in-hospital mortality rate is 5%. The pathological hallmark of this syndrome, confirmed by angioscopy, is fissure of the atherosclerotic plaque within the coronary artery, leading to platelet adhesion and aggregation and fibrin-platelet thrombus formation, which may accelerate progression of the stenotic lesion. Management of unstable angina is aimed at ameliorating symptoms and reducing ischaemia, improving ventricular function, preventing recurrent ischaemia, myocardial infarction and death, and lastly, containing progression of the underlying coronary artery disease. Acute management includes bedrest, aspirin, heparin, nitroglycerin (glyceryl trinitrate) infusion and beta-blockers and calcium channel blockers in selected cases. After the patient is clinically stabilised, provocative tests and angiography may be performed, to be followed by angioplasty or bypass surgery, if necessary. In cases that are refractory to optimal medical therapy, interventions should be performed on a more emergent basis. Long term management includes aspirin and beta-blockers, if there is prior infarction, and control of the conventional risk factors.