Early and transient release of leukocyte pentraxin 3 during acute myocardial infarction

Pentraxin 3 (PTX3) plays cardioprotective and anti-atherogenic roles in murine models. PTX3 blood levels raise during early acute myocardial infarction (AMI). Neutrophils from healthy subjects physiologically contain PTX3 in secondary (also called specific) granules. In this study, we report that circulating neutrophils release preformed PTX3 in the early phase of AMI (within 6 h from the onset of clinical symptoms). Depletion of intracellular PTX3 correlates with increased plasma levels and with platelet-neutrophil heterotypic aggregates. Neutrophil PTX3 returns to normal values 48 h after the onset of symptoms; concentration does not vary in matched healthy controls or in patients with chronic stable angina. In vitro, recognition of activated P-selectin(+) platelets causes the formation of neutrophil-platelet heteroaggregates and the release of neutrophil PTX3. Purified or membrane-bound P-selectin triggers PTX3 release from resting neutrophils. Released PTX3 binds to activated platelets in vitro. Moreover, PTX3 binds to a substantial fraction of platelets from patients in the circulating blood. PTX3-bound activated platelets have a reduced ability to 1) form heterotypic aggregates with neutrophils and monocytes; 2) activate neutrophils, as evaluated assessing the upregulation of leukocyte β(2) integrins; 3) aggregate with other platelets; and 4) bind to fibrinogen. Our results suggest that neutrophils early release prestored PTX3 in patients undergoing AMI. PTX3 binds to activated circulating platelets and dampens their proinflammatory and prothrombotic action, thus possibly contributing to its cardioprotective effects.     

Improved myocardial performance induced by clofibrate during reperfusion after acute myocardial infarction

The increase of cellular fatty acids appears to be one of the causes of the myocardial injury during ischemia and reperfusion. This study was designed to examine whether a hypolipidemic drug such as clofibrate can reduce the myocardial injury during ischemia and reperfusion. Clofibrate was fed to experimental pigs for 9 days. Isolated in situ hearts from both experimental and control pigs were subjected to 60 min of regional ischemia induced by occluding the left anterior descending coronary artery, followed by 60 min of global ischemia by hypothermic cardioplegic arrest and 60 min of reperfusion. The clofibrate feeding resulted in the better cardiac performance as judged by increased coronary blood flow, improved left ventricular function, and reduced myocardial injury as judged by creatine kinase release. Although the clofibrate-fed animals contained higher levels of thiobarbituric reactive materials, the free fatty acid levels of plasma and myocardium were much lower compared with control animals. The clofibrate feeding was also associated with increased peroxisomal catalase and beta-oxidation of fatty acids. These results suggest that decreased levels of free fatty acids in the plasma and the myocardium and increased catalase activity induced by antilipolytic therapy appear to provide beneficial effects to the myocardium during ischemia and reperfusion.     

Biphasic and monophasic pattern of brain natriuretic peptide release in acute myocardial infarction

This study evaluated brain natriuretic peptide (BNP) release in acute myocardial infarction (AMI), absolute values as well as pattern of its release. There are two different patterns of BNP release in AMI; monophasic pattern--concentration in the first measurement is higher than in the second one, and biphasic pattern--concentration in the first measurement is lower than in the second one. We observed significance of biphasic and monophasic pattern of BNP release related to diagnostic and prognostic value. We included in this prospective observational study total of 75 AMI patients, 52 males and 23 females, average age of 62.3 +/- 10.9 years with range of 42 to 79 years. BNP was measured and pattern of its release was evaluated. In AMI group BNP levels were significantly higher than in controls (462.88 pg/mL vs. 35.36 pg/mL, p < 0.001). We found statistically significant real negative correlation (p < 0.05) between BNP concentration and left ventricle ejection fraction (LVEF) with high correlation coefficient (r = -0.684). BNP concentrations were significantly higher among patients in Killip class II and III compared to Killip class I; Killip class I BNP = 226.18 pg/mL vs. Killip class II 622.51 pg/mL vs. Killip class III 1530.28 pg/mL, p < 0.001. BNP concentrations were significantly higher in patients with; (i) myocardial infarction vs. controls; (BNP 835.80 pg/mL vs. 243.03 pg/mL); (ii) in pts with positive major adverse cardiac events (MACE) vs. negative MACE (BNP 779.08 pg/mL vs. 242.28 pg/mL, p < 0.001); (iii) in pts with positive compared to negative left ventricle (LV) remodelling (BNP 840.77 pg/mL vs. 341.41 pg/mL, p < 0.001). Group with biphasic pattern of BNP release had significantly higher BNP concentration compared to monophasic pattern group. In biphasic pattern group we found significant presence of lower LVEF, Killip class II and III, LV remodelling and MACE. We found that BNP is strong marker of adverse cardiac events in patients presenting with a myocardial infarction. In our AMI group we found significant elevation of BNP and it is suspected that second peak secretion is not only due to systolic dysfunction and subsequent remodeling of LV but also due to impact of ischaemia. Patients with biphasic pattern probably have worse prognosis due to severe coronary heart disease. Besides its diagnostic role as a simple blood marker of systolic function, BNP is also important prognostic marker who helps making clinical decision about early invasive vs. conservative management.     

Left ventricular catecholamines during acute myocardial infarction in the dog

To determine whether changes in left ventricular catecholamine content occur during the first 30 to 90 min of acute myocardial infarction, myocardial catecholamine (radioenzymatic assay) over the interval was studied in the dog. In nine pentobarbital-anesthetized opened-chest dogs without coronary ligation, myocardial catecholamine at 2.5 h after pentobarbital (i) consisted mainly of norepinephrine (87% total catecholamine), (ii) showed a base to apex gradient in norepinephrine (1.44 +/- 0.10 vs. 1.03 +/- 0.10 micrograms/g, p less than 0.05) and dopamine (0.20 +/- 0.03 vs. 0.12 +/- 0.02 micrograms/g, p less than 0.05) but not epinephrine (0.017 vs. 0.016 micrograms/g), and (iii) showed no difference in norepinephrine, dopamine, or epinephrine across basal, mid, and apical left ventricular transverse planes spanning the vascular territories of the two coronary arteries. In 18 pentobarbital-anesthetized dogs with coronary ligation, (i) norepinephrine, measured in 14 regions across the mid left ventricle after 90 min ischemia in four dogs, was less in the ischemic center of the occluded bed than normal myocardium (1.01 +/- 0.04 vs. 1.29 +/- 0.04 micrograms/g, p less than 0.05), and (ii) norepinephrine was unchanged in normal myocardium of 14 dogs at 30, 60, 90 min, and 48 h but decreased in ischemic myocardium by 31% at 60 min (0.89 +/- 0.10 vs. 1.29 +/- 0.08 micrograms/g, p less than 0.025) and 79% at 48 h (0.27 +/- 0.04 vs. 1.26 +/- 0.08 micrograms/g, p less than 0.001). Thus, norepinephrine depletion from ischemic but not normal myocardium is detectable by 60 min during acute myocardial infarction.     

Increased expression of calcium-sensing receptors in atherosclerosis confers hypersensitivity to acute myocardial infarction in rats

Acute myocardial infarction (AMI) is a leading cause of death worldwide. Most cases of AMI result from coronary atherosclerosis (AS). The pathogenic mechanisms underlying AS lesions and AMI are incompletely understood. Calcium-sensing receptors (CaSR) belong to a family of G-protein-coupled receptors. We previously discovered that CaSR was expressed in the heart tissue of adult rats. CaSR may contribute to AMI in AS. We initially established a rat model of AS by injection of vitamin D(3) and feeding with a high-fat diet. Isoproterenol (ISO) was used to induce AMI. The MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), cardiac troponin T (cTnT), tetrazolium chloride staining, and cardiac function parameters were selected as indicators of myocardial damage or necrosis. Cardiac apoptosis was analyzed by transferase dUTP nick-end labeling (TUNEL) assay. Expression of CaSR, Bcl-2, Bax, caspase-3, p-ERK1/2, p-JNK, and p-p38 were determined by Western blot analysis. Compared with the control group, levels of cTnT, CK-MB, and LDH; number of TUNEL-positive cells; and expression of CaSR, Bax, caspase-3, p-ERK1/2, p-JNK and p-p38, were significantly increased, whereas cardiac function and expression of Bcl-2 were decreased markedly in isoproterenol (ISO)-treated group (C/ISO) and AS groups. These changes were significant in the AS/ISO group than in the C/ISO group or AS group. The upregulation of CaSR during AS formation renders hypersensitivity to AMI. Activation of the pro-apoptotic mitochondria pathway and JNK-p38 MAPK pathway triggered by increased expression of CaSR may be one of molecular mechanisms underlying AMI in AS.     

Computational modeling of acute myocardial infarction

Myocardial infarction, commonly known as heart attack, is caused by reduced blood supply and damages the heart muscle because of a lack of oxygen. Myocardial infarction initiates a cascade of biochemical and mechanical events. In the early stages, cardiomyocytes death, wall thinning, collagen degradation, and ventricular dilation are the immediate consequences of myocardial infarction. In the later stages, collagenous scar formation in the infarcted zone and hypertrophy of the non-infarcted zone are auto-regulatory mechanisms to partly correct for these events. Here we propose a computational model for the short-term adaptation after myocardial infarction using the continuum theory of multiplicative growth. Our model captures the effects of cell death initiating wall thinning, and collagen degradation initiating ventricular dilation. Our simulations agree well with clinical observations in early myocardial infarction. They represent a first step toward simulating the progression of myocardial infarction with the ultimate goal to predict the propensity toward heart failure as a function of infarct intensity, location, and size.     

Trichinosis presenting as acute myocardial infarction

A 20-year-old male patient is presented as a case of trichinous myocarditis with clinical symptoms and electrocardiographic evidence of an acute inferior myocardial infarction. He recovered rapidly and completely without any specific therapy. This seems to be a distinct rarity, having never been previously reported, but is of importance because of the almost uniformly excellent prognosis in this condition in contradistinction to that of a bona fide myocardial infarction occurring at this age.     

Weather fronts and acute myocardial infarction

Some methodological aspects are discussed of the investigation of acute infarct myocarditis (AIM) in relation to weather fronts. Results of a new method of analysis are given. Data were analysed from about the hour of the onset of symptoms, and led to the diagnosis of AIM either immediately or within a few hours or days (3019 cases observed over 4.5 years during 1982–1986 in Plzen, Czechoslovakia). Weather classification was based on three factors (the type of the foregoing front, the type of the subsequent front, the time section of the time interval demarcated by the passage of the surfaces of the fronts). AIM occurrence increased in particular types of weather fronts: (i) by 30% during 7–12 h after a warm front, if the time span between fronts exceeded 24 h; (ii) by 10% in time at least 36 h distant from the foregoing cold or occlusion front and from the succeeding warm or occlusion front; (iii) by 20% during 0–2 h before the passage of the front, provided the foregoing front was not warm and the interval between fronts exceeded 5 h. AIM occurrence decreased by 15%–20% for time span between fronts > 24 h at times 6–11, 6–23 and 6–35 h before a coming warm or occlusion front (for interfrontal intervals 25–48, 49–72 and possibly > 72 h), and also at 12–23 and possibly 12–35 h before a cold front (for intervals 49–72 and possibly > 72 h), if the foregoing front was cold or an occlusion front.     

Thrombolytic therapy for acute myocardial infarction

A retrospective analysis of 4,094 deliveries among Navajo Indian women was carried out to determine the prevalence of gestational diabetes mellitus and diabetes antedating pregnancy. Three data sources--a local prenatal registry, a delivery room log, and hospital discharge records--were evaluated for their usefulness as surveillance systems for gestational diabetes. In all, 177 cases of gestational diabetes and 13 cases of preexisting diabetes were identified, giving a prevalence of maternal diabetes in pregnancy of 4.6%. When women with preexisting diabetes or documented gestational diabetes during a previous pregnancy were excluded, the prevalence of gestational diabetes during the study period was 3.4%. Although each data source used separately failed to identify 20% to 40% of diabetic pregnancies, more than 97% of cases were identified using a combination of the prenatal registry and the delivery log.