bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intravenous nitroglycerin infusion inhibits cyclic blood flow responses caused by periodic platelet thrombus formation in stenosed canine coronary arteries.
Authors: Folts J D , Stamler J , Loscalzo J 
Published: June 2012

BACKGROUND
Nitroglycerin and other clinically relevant organic nitrate derivatives have been shown to inhibit platelet aggregation in vitro. This antithrombotic effect of nitrates is potentiated by reduced thiol. To determine the potential relevance of this mechanism of action in vivo, we examined the effect of intravenous nitroglycerin infusion on periodic platelet thrombus formation in a canine model of coronary artery stenosis.

METHODS AND RESULTS
We used a canine model of coronary artery stenosis associated with cyclic reductions in coronary blood flow that have been shown to depend on periodic platelet thrombus formation. We quantified the frequency of cycles per 40-minute observation period and monitored the effect of a continuous infusion of intravenous nitroglycerin on the cycle frequency. The administration of 10-15 micrograms/kg/min nitroglycerin reduced cyclic platelet thrombus formation significantly and did so without a significant change in coronary artery blood flow. Pretreatment with the reduced thiol, N-acetylcysteine (100 mg/kg during 30 minutes), led to inhibition of cyclic platelet thrombus formation by intravenous nitroglycerin at doses that alone had no such effect (5 micrograms/kg/min).

CONCLUSION
These data suggest that one mechanism by which intravenous nitroglycerin improves ischemia in acute coronary artery disease syndromes may be by inhibition of platelet thrombus formation and may highlight the potential importance of reduced thiol in this mechanism.
Racial (black-white) differences in serum lipoprotein (a) distribution and its relation to parental myocardial infarction in children. Bogalusa Heart Study.
Authors: Srinivasan S R , Dahlen G H , Jarpa R A , Webber L S , Berenson G S 
Published: June 2012

BACKGROUND
The value of lipoprotein (a) [Lp(a)] in the prediction of coronary artery disease risk very early in life remains to be established in different racial groups.

METHODS AND RESULTS
Serum Lp(a) distribution and its relation to parental histories of myocardial infarction were examined in 2,438 children (8-17 years old) from a biracial community. Parental myocardial infarction was used as a surrogate measure of future risk of disease in the offspring. Lp(a) levels averaged 1.7-fold higher in blacks than in whites (p less than 0.0001). A small but significant sex difference (females greater than males, p less than 0.05) was seen in both races. Race was the only independent variable that contributed appreciably (9%) to the variability of Lp(a) in serum. White children with parental myocardial infarction (n = 90) had increased levels of Lp(a) compared with those without parental myocardial infarction (22.4 versus 17.1 mg/dl, p less than 0.01). Furthermore, among white children, the prevalence of parental myocardial infarction was higher in those with Lp(a) levels of more than 25 mg/dl than in those with values of 25 mg/dl or less (9.5% versus 5.4%, p less than 0.01). In contrast, the relation of Lp(a) to parental myocardial infarction was not seen in black children. No associations were observed between parental myocardial infarction and serum levels of any of the lipids or lipoprotein cholesterol classes in children of either race.

CONCLUSIONS
Serum Lp(a) levels may prove valuable in the assessment of coronary artery disease risk early in life among white populations. These findings also emphasize the need to evaluate the atherogenic potential of Lp(a) in different racial groups.
Canine myocardial creatine kinase isoenzymes after chronic coronary artery occlusion.
Authors: Sharkey S W , Murakami M M , Smith S A , Apple F S 
Published: June 2012

BACKGROUND
Creatine kinase (CK) exists as three cytosolic isoenzymes, CK-MM, CK-MB, and CK-BB, and one mitochondrial isoenzyme. Animal and human observations suggest that the CK-MB content of myocardium is dynamic and may increase in response to ischemia, but the response of the myocardial CK system to chronic coronary artery occlusion is not well-defined.

METHODS AND RESULTS
We measured serial changes in myocardial total CK, percent CK-MB, and percent CK-BB before and 3 weeks after coronary artery occlusion in 17 pentobarbital-anesthetized dogs. Tissue biopsies were obtained from the left anterior descending (LAD) coronary artery myocardium, the right coronary artery (RCA) myocardium, and the circumflex coronary artery myocardium at baseline and 3 weeks after LAD occlusion (n = 6), RCA occlusion (n = 5), and no coronary artery occlusion (n = 6). Tissue samples were assayed for total CK, percent CK-MB, and percent CK-BB. Samples were also examined by electron microscopy for evidence of ischemic myopathy. Total myocardial CK activity did not change over 3 weeks. Percent CK-MB increased significantly in the tissue supplied by the occluded artery (4.1-fold in dogs with LAD occlusion and 6.7-fold in dogs with RCA occlusion). Percent CK-BB did not change. Dogs with LAD occlusion had ultrastructural evidence of myopathic fibers interspersed with normal fibers in the LAD myocardium. Dogs with RCA occlusion had no ultrastructural evidence of myopathic fibers in the RCA myocardium.

CONCLUSIONS
Chronic coronary artery occlusion causes a pronounced change in the canine myocardial CK system that is limited to the tissue supplied by the occluded coronary artery. These biochemical alterations do not correlate with any cellular ultrastructural changes. Myocardial CK-MB content is dynamic, varies geographically within the heart, and increases rapidly after coronary artery occlusion.
Effect of ST segment measurement point on performance of standard and heart rate-adjusted ST segment criteria for the identification of coronary artery disease.
Authors: Okin P M , Bergman G , Kligfield P 
Published: June 2012

BACKGROUND
Recent reports critical of the performance of heart rate-adjusted indexes of ST depression during exercise electrocardiography have used J-point rather than ST segment measurements. However, no standard exists for the optimal time after the J-point at which to measure ST segment deviation.

METHODS AND RESULTS
To assess the effect of ST segment measurement position on performance of standard exercise electrocardiographic criteria, the delta ST segment/heart rate (delta ST/HR) index, and the ST segment/heart rate (ST/HR) slope for the detection of coronary artery disease, the exercise electrocardiograms of 50 clinically normal subjects and 80 patients with known or likely coronary disease were analyzed using ST depression measured at both the J-point and at 60 msec after the J-point (J + 60). A positive exercise electrocardiogram by standard criteria, defined as 0.1 mV or more of additional horizontal or downsloping ST depression at end exercise, had a specificity of 96% when ST depression was measured at either the J-point or J + 60. There was no difference in sensitivity of standard electrocardiographic criteria at J + 60 and J point (both 59%, p = NS). However, at matched specificity of 96%, the delta ST/HR index and ST/HR slope calculated using ST depression at J + 60 were significantly more sensitive (90% and 93%) than when calculated using J-point depression (64% and 61%, each p less than 0.001). Comparison of areas under respective receiver operating characteristic curves confirmed the superior performance of J + 60 as opposed to J-point measurements for both the delta ST/HR index (0.98 versus 0.89, p = 0.006) and the ST/HR slope (0.96 versus 0.87, p = 0.007) and also demonstrated modestly improved overall test performance for standard electrocardiographic criteria using J + 60 measurements (0.88 versus 0.82, p = 0.001).

CONCLUSIONS
Use of J-point measurements significantly degrades performance of heart rate-adjusted indexes of ST depression but has less effect on standard criteria.
Left ventricular thrombus in anterior acute myocardial infarction after thrombolysis. A GISSI-2 connected study.
Authors: Vecchio C , Chiarella F , Lupi G , Bellotti P , Domenicucci S 
Published: June 2012

BACKGROUND
Streptokinase reduces the incidence of left ventricular thrombosis after acute myocardial infarction. However, it is unknown whether a similar effect can be obtained with different thrombolytic agents and whether subcutaneous calcium heparin can have an additional efficacy.

METHODS AND RESULTS
To compare the effects of two different thrombolytic agents combined or not with heparin on the incidence and features of left ventricular thrombi and their related embolic events, we performed a GISSI-2 ancillary echocardiographic study (the first echocardiogram obtained within 48 hours of symptoms onset and the second before hospital discharge) that enrolled 180 consecutive patients (mean age, 63 +/- 11 years, 142 men) with a first anterior acute myocardial infarction. Patients were randomized into four groups of treatment: recombinant tissue-type plasminogen activator (rt-PA) (n = 47), rt-PA plus heparin (n = 45), streptokinase (n = 39), and streptokinase plus heparin (n = 49). Left ventricular thrombosis was observed in 51 of 180 patients (28%). No significant differences were found concerning the incidence of thrombi in the four treatment groups. Mural shape of left ventricular thrombi was found more frequently than the protruding shape (71% versus 29% at the first examination, 64% versus 36% at the second), particularly in heparin-treated patients (93% versus 7% at first examination, 70% versus 30% at the second). Only one embolic event (0.5%) occurred during the hospitalization.

CONCLUSIONS
We conclude that 1) the rate of left ventricular thrombi does not differ in patients with acute myocardial infarction treated either with streptokinase or rt-PA, 2) subcutaneous heparin, when begun 12 hours after intravenous thrombolysis, does not appear to further reduce the occurrence of thrombi but seems to influence the shape of left ventricular thrombi, and 3) during the predischarge period, embolic events are rare in patients treated by thrombolysis.
Clinical implications of late proven patency after successful coronary angioplasty.
Authors: Weintraub W S , Ghazzal Z M , Cohen C L , Douglas J S , Liberman H , Morris D C , King S B 
Published: June 2012

BACKGROUND
The introduction of percutaneous transluminal coronary angioplasty (PTCA) has changed the pattern of intervention in coronary artery disease. However, the long-term results in patients undergoing successful, elective, native-vessel PTCA are not yet fully characterized. Because the healing and subsequent proliferative response after angioplasty are time related, it was the purpose of the present study to determine the long-term outcome in patients whose dilated arteries have been demonstrated to be patent 4-12 months after successful, uncomplicated PTCA.

METHODS AND RESULTS
The patients were grouped on the basis of the 4-12 month catheterization into those whose vessels were angiographically "normal" or had luminal irregularities only at the PTCA sites (396 patients), those whose vessels also had luminal irregularities elsewhere with or without PTCA site luminal irregularities (680 patients), and those with significant obstructive disease (more than 50% diameter narrowing) at sites other than the PTCA sites (426 patients). Of 1,502 such patients, long-term follow-up was available in 1,491. At the time of the original angioplasty, the normal patients had a 1.8% incidence of multivessel disease; luminal irregularity patients, 9.4%; and obstructive disease patients, 58.7%. At angiographic restudy, 16.4% of the obstructive disease patients continued to have multivessel disease. The patients were followed for the events of death, myocardial infarction, coronary surgery, and repeat PTCA. The 6-year survival rate was 95%; cardiac survival, 96%; and freedom from all events, 65%. The strongest correlate of events during follow-up was the angiographic status of the undilated segments. At 6 years, freedom from cardiac events was noted in 77% of the normal group, 61% of the luminal irregularity group, and 55% of the obstructive disease group. Diabetes and hypertension were also independent correlates of events.

CONCLUSIONS
Results from the present study show that associated disease in undilated segments is a strong predictor of late events in patients after successful, uncomplicated, reatenosis-free PTCA. However, the need for further revascularization was frequent even in patients without obstructive disease. Completeness of revascularization is appropriate when possible, and limiting progression of coronary disease at sites remote from those dilated should improve on these late results.
Expression of perforin in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3.
Authors: Seko Y , Shinkai Y , Kawasaki A , Yagita H , Okumura K , Takaku F , Yazaki Y 
Published: June 2012

BACKGROUND
Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of viral myocarditis.

METHODS AND RESULTS
Using a murine model of acute myocarditis caused by coxsackievirus B3, we analyzed the phenotypes and morphology of the infiltrating cells in the hearts by immunofluorescence and electron microscopy. We also examined the expression of a cytolytic factor, perforin, in the infiltrating cells by immunoperoxidase and in situ hybridization. We found that the dominant population of the infiltrating cells were asialo GM1 positive, were negative for T-cell markers, and had electron-dense cytoplasmic granules, which is consistent with a morphology of large granular lymphocytes. Perforin was found in the cytoplasmic granules of the infiltrating cells expressing perforin messenger RNA. These findings provide for the first time the direct evidence that the first wave of cell infiltration in hearts mainly consists of killer cells and strongly suggests that perforin plays, in part, an important role in myocardial cell damage involved in acute viral myocarditis. T-helper cells and cytotoxic T lymphocytes made up the second wave of cell infiltration.

CONCLUSIONS
As we previously reported, the expression of major histocompatibility complex class I antigen on cardiac myocytes induced by the infiltrating cells, such as killer cells, may facilitate the interaction between cardiac myocytes and cytotoxic T lymphocytes, and may lead to further myocardial cell damage in a later phase.
Role of oxygen-derived free radicals in myocardial edema and ischemia in coronary microvascular embolization.
Authors: Hori M , Gotoh K , Kitakaze M , Iwai K , Iwakura K , Sato H , Koretsune Y , Inoue M , Kitabatake A , Kamada T 
Published: June 2012

BACKGROUND
Oxygen-derived free radicals are thought to injure the ischemic heart during coronary microvascular embolization.

METHODS AND RESULTS
To test this idea, microspheres (15 microns in diameter) were repetitively administered into the left anterior descending coronary artery to cause microvascular embolization in dogs. Myocardial contractile and metabolic dysfunctions were significantly attenuated after treatments with recombinant human superoxide dismutase, an acyl derivative of ascorbic acid (CV3611, 2-O-octadecylascorbic acid), and xanthine oxidase inhibitor (allopurinol). The free radical scavengers and inhibitor enhanced the coronary hyperemic flow response during embolization, and the total number of microspheres causing maximal embolization was increased by these drugs. When 8-phenyltheophylline was additionally administered with superoxide dismutase, these beneficial effects were abolished, indicating that coronary effects of these drugs may be due to increased release of adenosine during coronary microvascular embolization.

CONCLUSIONS
We conclude that oxygen radicals worsen the ischemic injury in coronary microembolization.
Effects of vascular runoff on myointimal hyperplasia after mechanical balloon or thermal laser arterial injury in dogs.
Authors: Hehrlein C , Chuang C H , Tuntelder J R , Tatsis G P , Littmann L , Svenson R H 
Published: June 2012

BACKGROUND
Clinical evidence suggests that poor vascular runoff reduces the long-term success rate of femoral angioplasty procedures. The purpose of this experimental study was to examine myointimal hyperplasia of dog femoral arteries after balloon denudation, thermal laser arterial injury, or sham operation in normal and reduced vascular runoff conditions.

METHODS AND RESULTS
Before mechanical balloon injury or transluminal heated laser probe motion, the peripheral vascular runoff of dogs was reduced by ligating the femoral artery below its three distal side branches, decreasing the femoral flow rate from 114 +/- 9 to 52 +/- 5 ml/min (mean +/- SEM). Endothelial denudation with a predominantly intact elastic internal membrane and circumferential structural changes in the media were noted by light microscopy 1 hour after balloon injury. Focal completely necrotic lesions of intima and media were found 1 hour after thermal laser arterial injury. After 8 weeks, the maximal thickness of neointima plus media of the site of previous intervention was greater after balloon injury (0.45 +/- 0.03 mm) and thermal laser injury (0.54 +/- 0.03 mm) than after sham operation (0.40 +/- 0.01 mm; p less than 0.001) in normal runoff dogs. Reduced vascular runoff augmented myointimal hyperplasia both in the balloon-injured and thermally damaged arteries; the wall thickness increased from 0.45 +/- 0.03 to 0.93 +/- 0.10 mm and from 0.54 +/- 0.03 to 0.65 +/- 0.05 mm, respectively (p less than 0.001). The neointimal and medial wall area of the balloon-injured arteries contributed 48% to the area encompassed by the external elastic membrane compared with an 81% portion when vascular runoff was reduced (p less than 0.01). A 47% neointimal and medial wall area was found in thermally injured arteries with normal runoff compared with 63% after runoff reduction (p less than 0.05).

CONCLUSION
This study suggests that hemodynamic factors associated with poor vascular runoff play an important role in extending myointimal hyperplasia independent of method and severity of the arterial injury during angioplasty.
Comparative effects of APSAC and rt-PA on infarct size and left ventricular function in acute myocardial infarction. A multicenter randomized study.
Authors: Bassand J P , Cassagnes J , Machecourt J , Lusson J R , Anguenot T , Wolf J E , Maublant J , Bertrand B , Schiele F 
Published: June 2012

BACKGROUND
Recombinant tissue-type plasminogen activator (rt-PA or alteplase) and anisoylated plasminogen streptokinase activator complex (APSAC or anistreplase) have been demonstrated to limit infarct size significantly and to preserve left ventricular function when injected soon after acute myocardial infarction. However, as yet, the efficacy and safety of these two thrombolytic agents have not been directly compared in one trial; this was the aim of this study.

METHODS AND RESULTS
One hundred eighty-three patients suffering from a first acute myocardial infarction were randomly allocated to either APSAC (30 units over 5 minutes) or single-chain rt-PA (100 mg over a 3-hour period) within 4 hours of the onset of symptoms. Global and regional left ventricular function were assessed from contrast angiography an average of 5.3 +/- 2.3 days after initial therapy. Radionuclide angiography and thallium-201 single-photon emission computerized tomography were performed before hospital discharge. Infarct size was assessed by single-photon emission computerized tomography and expressed in percentage of the total myocardial volume. Ninety patients received APSAC and 93 received rt-PA within a mean period of 172 +/- 52 minutes after the onset of symptoms. The two groups were similar in age, location of the acute myocardial infarction, Killip class, and time of randomization. The patency rate of the infarct-related artery was 72% in the APSAC group and 76% in the rt-PA group (NS). Initial and predischarge left ventricular ejection fraction as well as infarct size were similar in both therapeutic groups (0.50 +/- 0.14 versus 0.52 +/- 0.12 for initial and 0.48 +/- 0.10 versus 0.47 +/- 0.10 for predischarge ejection fraction, 11 +/- 7% versus 9 +/- 7% for infarct size, respectively, for APSAC- and rt-PA-treated patients). Bleeding complications requiring blood transfusion occurred in one APSAC patient and in two rt-PA patients. One patient in the rt-PA group died of a massive intracranial hemorrhage. At the end of the 3-week follow-up period, five APSAC patients (5.5%) and seven rt-PA patients (7.5%) had died.

CONCLUSIONS
The early infusion of APSAC or rt-PA in acute myocardial infarction produced a similar patency rate, limitation of infarct size, and preservation of left ventricular systolic function with an equivalent rate of bleeding complications.
Light and electron microscopic localization of brain natriuretic peptide in relation to atrial natriuretic peptide in porcine atrium. Immunohistocytochemical study using specific monoclonal antibodies.
Authors: Hasegawa K , Fujiwara H , Itoh H , Nakao K , Fujiwara T , Imura H , Kawai C 
Published: June 2012

BACKGROUND
Although first isolated from the porcine brain, brain natriuretic peptide (BNP) is also found in the heart, particularly in the atria.

METHODS AND RESULTS
We examined the immunocytochemical localization of BNP in relation to atrial natriuretic peptide (ANP) in five porcine atria using highly specific monoclonal antibodies. With the use of an indirect immunoperoxidase method, serial sections examined by light microscopy showed foci of multihormonal myocytes containing both ANP and BNP localized in the subendocardium. Monohormonal myocytes containing ANP only were observed in the subepicardium and part of the subendocardium. The staining intensity of ANP and BNP showed a transmural gradient from the subendocardium to the subepicardium. At the electron microscopic level, double immunocytochemistry using a two-face immunogold-staining method revealed two types of granules: Type 1 is a monohormonal granule containing ANP alone, and type 2 is a multihormonal granule containing both ANP and BNP. Although most atrial myocytes contained both, type 1 granules were frequently observed in the epicardial side, and type 2 granules were frequently observed in the endocardial side. We observed a few type 2 granules even in the light microscopically monohormonal myocytes.

CONCLUSIONS
These data suggest that the atrial myocyte population comprises single, multipotential cells able to synthesize both natriuretic peptides in varying proportions. The atrial transmural gradient of BNP and ANP may be related to responses to wall stress.