Spontaneous dissection of the LAD mimicking inferior myocardial infarction.

The case presented here is intended to raise awareness of two uncommon coronary angiographic findings in the clinical context of acute coronary syndrome. The prevalence of patients presenting with spontaneous coronary dissection as the underlying cause of an ST-elevation myocardial infarction is low. It is typically found in women, often occurring during the peripartum period. There is some debate as to whether spontaneous dissection could also be managed conservatively without coronary intervention. As for spontaneous dissection, knowledge of a culprit lesion within the distal left anterior descending artery (LAD) causing inferior ST elevation (wrap around of the LAD) is not prevalent. Patient characteristics and treatment options are discussed on the basis of the recent literature on both clinical entities.

Postcardiac injury syndrome following radiofrequeny ablation of atrial flutter.

We report the case of a 64-year-old woman who was admitted to our hospital for radiofrequency ablation of isthmus-dependent counterclockwise atrial flutter. Following an initially uncomplicated right atrial linear isthmus ablation that was associated with conversion of atrial flutter to sinus rhythm and evidence of complete isthmus block, the patient developed a small pericardial effusion, a marked and recurrent left-sided pleural effusion, and had significantly elevated inflammatory markers. After an extensive diagnostic work-up which excluded infectious, malignant and thromboembolic causes of the effusions, a diagnosis of postcardiac injury syndrome was made and the patient was treated with oral corticosteroids and nonsteroidal anti-inflammatory drugs. Over a treatment period of 2 months there was complete resolution of the pericardial and left-sided pleural effusions and normalization of inflammatory markers. Postcardiac injury syndrome is a rare complication of radiofrequency ablation that is characterized by signs of pericardial, pleural and pulmonary parenchymal inflammation.

Acquired right coronary artery fistula draining to the right ventricle: angiographic documentation of first appearance following reperfusion after acute myocardial infarction, with subsequent spontaneous closure.

Most coronary artery fistulae are congenital in origin but have been reported to be acquired as complications of chest trauma, coronary angioplasty, or rupture of a coronary artery aneurysm. This is the first angiographic documentation of a coronary fistula acquired after myocardial infarction that subsequently closed spontaneously during follow up.

Intralobar lung sequestration with systemic coronary arterial supply.

Pulmonary sequestration is a rare anomaly. An accurate pre-operative evaluation of its vascular supply is essential for the surgeon's operative approach. We describe here an intrapulmonary sequestration with vascular arterial supply via the left circumflex and the right coronary artery. This case demonstrates that if aortography is unrevealing, then a coronary source should be considered in the preoperative search for the arterial supply to a pulmonary sequestration. Moreover, pulmonary sequestration should be listed in the differential diagnosis of aberrant coronary arteries.

Specific impairment of human platelet P2Y(AC) ADP receptor-mediated signaling by the antiplatelet drug clopidogrel.

Clopidogrel is an effective new antiplatelet agent useful for the treatment of ischemic cerebrovascular, cardiac, and peripheral arterial disease. However, the mechanism of clopidogrel action is not well understood, although it is known to inhibit ADP-evoked platelet aggregation. In the current study, the effect of clopidogrel on recently identified human platelet ADP receptors and their signaling pathways was investigated by using platelets from clopidogrel-treated subjects, 6 healthy volunteers (2 females and 4 males) who received 75 mg of clopidogrel daily for 7 days. Blood was taken and various platelet receptor signaling pathways were analyzed before treatment, after 7 days of medication, and 4 weeks after treatment had ceased. Platelet tests included the analysis of aggregation, rapid calcium influx, calcium mobilization from intracellular stores, adenylyl cyclase, and phosphorylation of vasodilator-stimulated phosphoprotein (VASP). The data indicate that clopidogrel does not affect those platelet ADP receptors coupled to cation influx (P2X1 ADP receptors) or calcium mobilization (P2Y1 ADP receptors). In contrast, clopidogrel treatment specifically impairs the ADP receptor coupled to G(i)/adenylyl cyclase (P2Y(AC) ADP receptors). Clopidogrel abolishes the inhibitory P2Y(AC) receptor-mediated ADP effects on prostaglandin E(1)-stimulated, cAMP-dependent phosphorylation of VASP without affecting epinephrine, thrombin, and thromboxane signaling. VASP phosphorylation is known to be closely correlated with the inhibition of platelet and fibrinogen receptor (glycoprotein IIb/IIIa) activation. Therefore, inhibition of the platelet P2Y(AC) ADP receptor and its intracellular signaling, including decreased VASP phosphorylation, is suggested as a molecular mechanism of clopidogrel action.

Ligand specificity and ticlopidine effects distinguish three human platelet ADP receptors.

Human platelets express adenosine 5'-diphosphate (ADP)-specific purinoceptors of the P2X and P2Y receptor superfamily, but their structure, diversity, and precise pharmacological profile is not well understood. Here, functional assays with intact platelets and well-characterized nucleotide derivatives were performed in order to characterize the ligand specificity of these platelet-specific purinoceptors. For the signalling pathways investigated (aggregation, rapid Ca2+-influx, desensitization of Ca2+-influx, Ca2+-mobilization, inhibition of adenylyl cyclase), significant differences in ligand specificity were demonstrated. ADP activated all purinoceptors of human platelets, while adenosine 5'-triphosphate (ATP) was a weak agonist for the P2X receptor and an antagonist for the P2Y receptors. The ADP-receptor pathway-antagonist ticlopidine inhibited ADP-evoked aggregation and adenylyl cyclase inhibition but did not affect platelet purinoceptors associated with Ca2+-influx and Ca2+-mobilization. These results indicate the presence of three distinct ADP-selective purinoceptors on human platelets.

[Elective coronary implantation of a newly developed stent without conventional anticoagulation]. / Elektive koronare Implantation eines neu entwickelten Stents ohne klassische Antikoagulation.

OBJECTIVE: To assess in an open prospective study the angiographic and clinical results of the elective implantation of the recently developed AVE micro-stent (Applied Vascular Engineering, Santa Rosa, CA, USA), in combination with dual antiaggregation treatment. PATIENTS AND METHODS: Between January and December 1995 AVE micro-stents were implanted into 128 vessels in 121 patients (20 women, 101 men; mean age 60.7 +/- 9.5 [34-84] years) with symptomatic coronary heart disease (CHD). Indication for the primary implantation of the stent type was a complex morphology of the stenosis with unfavourable short- and long-term prognosis. The stent consists of a 4 mm long tubular highly flexible segment made of 0.008 inch wire and can be advanced even into tortuous vessels. After balloon dilatation of the stenosis the stent was advanced into the vessel wall at a pressure of 10-12 bar, followed by further dilatation at 16-18 bar. Conventional long-term anticoagulation was dispensed with, patients only receiving antiaggregation medication: 500 mg ticlopidine and 100 mg aspirin daily for 6 weeks. RESULTS: The primary success rate of stent implantation was 99% (121 of 122). Neither acute nor subacute thromboses were revealed during hospital stay nor was there any emergency bypass operation or early repeat balloon angioplasty. There were no abnormal bleedings. CONCLUSION: Stenoses which are unsuitable for conventional balloon angioplasty can be reliably treated with the AVE microstent. Optimal high-pressure dilatation in combination with dual antiaggregation treatment will prevent stent thrombosis and bleeding complications.

Platelet-vessel wall interactions, focal adhesions, and the mechanism of action of endothelial factors.

Endothelial cells produce a variety of vasoactive substances including prostacyclin (PGI2) and endothelium-derived relaxing factor (EDRF/NO) which are potent inhibitors of platelet adhesion/aggregation and vascular smooth muscle cell contraction/proliferation. PGI2 and EDRF elevate cAMP or cGMP, respectively, in vascular cells and other targets. The intracellular effects of cAMP and cGMP in vascular smooth muscle cells and platelets are primarily mediated by the family of cAMP- and cGMP-dependent protein kinases and their substrates. Important effector systems include enzymes, channels and regulatory proteins responsible for the regulation of intracellular Ca++. Other evidence suggests that VASP, a focal adhesion protein phosphorylated in platelets and smooth muscle cells in response to PGI2 and EDRF, is important for the regulation of integrins and cell-matrix interactions.

[Noninvasive quantification of aortic and mitral insufficiency. Comparison of dynamic magnetic resonance imaging and Doppler color echocardiography]. / Nicht-invasive Quantifizierung von Aorten- und Mitralinsuffizienz. Vergleich zwischen dynamischer Magnetresonanztomographie und Farbdopplerechokardiographie.

The degree of valvular regurgitation was measured by dynamic magnetic resonance imaging (MRI) and colour-Doppler echocardiography (CDE) in 23 patients (14 men, 9 women; mean age 53 [19-75] years) with aortic (n = 13) or mitral (n = 10) regurgitation. Quantification by MRI was from a section corresponding to the four-chamber view. In aortic regurgitation, maximal regurgitant jet area (JA), ratio of JA to left-ventricular area (JA/LVA) were measured, while in mitral regurgitation, the ratio of JA to left atrial area (JA/LAA) was measured, as well as jet volume (JV) and the ratio of JV to the corresponding volume of the receiving chamber (JV/LVV or JV/LVA). The results were compared with corresponding measurement obtained by CDE in the four-chamber view. The degree of regurgitation was graded as small if JA/LVA or JA/LAA, respectively, was less than 0.2, moderate if 0.2-0.4, and marked if more than 0.4. In the patients with aortic regurgitation the correlation between the two methods was r = 0.91 regarding the jet area, 0.93 regarding JA/LVA and 0.92 regarding JV/LVV and JA/LVA. For mitral regurgitation the r values were 0.93 for JA, 0.89 for JA/LAA, and 0.85 for JV/LAV to JA/LAA. The grading of aortic regurgitation by MRI and CDE agreed in 12 of 13 patients (92%), and in nine of ten (90%) with mitral regurgitation (deviation by one degree of severity in each). These data indicate that quantification of aortic and mitral regurgitation gives similar results with MRI and CDE: thus, MRI is an equal substitute to CDE in patients with inadequate conditions for sonography.

[Acute pancreatitis and stomach wall necrosis caused by cholesterol embolisms]. / Akute Pankreatitis und Magenwandnekrose durch Cholesterinembolie.

A 60-year-old man was hospitalized because of a sudden onset of severe pain in the epigastrium and haematemesis. Acute pancreatitis was diagnosed on the basis of an increased serum amylase concentration (642 U/l). Abdominal ultrasound and computed tomography demonstrated a necrotic zone with central liquefaction in the tail of the pancreas adjoining the stomach wall. Gastroscopy revealed as source of the bleeding an extensive mucosal necrosis at the greater curvature of the stomach. At laparotomy, partial resection of the pancreas, gastrectomy and splenectomy were performed. Histological examination of the resected specimens showed multiple cholesterol emboli in the small arteries of the pancreas and the gastric submucosa.

[Primary coronary stent implantation in complex morphology of stenosis or unsatisfactory results of angioplasty]. / Primäre koronare Stent-Implantation bei komplexer Stenosemorphologie oder ungenügendem Angioplastieergebnis.

Early and late results of coronary angioplasty are influenced by the morphology of the coronary artery stenosis. Primary implantation of a balloon-expandable Palmaz-Schatz stent was indicated in 37 patients (31 men and 6 women; mean age 57 +/- 2 years) with symptomatic coronary heart disease and complex morphology of the stenosis. Intracoronary stents were successfully placed in 30 of 37 patients, without complications in all but one. This patient developed a thrombotic occlusion of the vessel 3 days after the procedure which, despite high-dosage thrombolysis treatment, resulted in an anterior wall myocardial infarction. A repeat angiography has since been performed (3-7 months after the procedure) in 25 of the 29 patients with a complication-free course. In 19 of the 25 patients the site of implantation was smooth, while a silent re-occlusion had occurred in one after successful recanalization of a chronic occlusion. Two patients had a subtotal restenosis (12% angiographic restenosis rate). These data indicate that intracoronary stent implantation improves the morphological results after balloon dilatation and reduces the restenosis rate.

Endothelial cell-dependent phosphorylation of a platelet protein mediated by cAMP- and cGMP-elevating factors.

We reported previously that a 46/50-kDa membrane-associated vasodilator-stimulated phosphoprotein (VASP) is phosphorylated in intact human platelets in response to both cGMP- and cAMP-elevating vasodilator drugs and presented evidence that this is mediated by cGMP- and cAMP-dependent protein kinases, respectively. VASP was recently purified and an antibody against it was developed which detects a phosphorylation-induced mobility change of VASP in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (Halbrügge, M., Friedrich, C., Eigenthaler, M., Schanzenbächer, P., and Walter, U. (1990) J. Biol. Chem. 265, 3088-3093). We have now used these methods for the quantitative analysis of VASP phosphorylation during coincubations of human endothelial cells and human platelets. Endothelial cell-derived factors caused the rapid, stoichiometric, and reversible phosphorylation of platelet VASP during these coincubations. Other experiments indicated that the endothelium-derived factors which stimulate VASP phosphorylation are prostacyclin and endothelium-derived relaxing factor whose effects are mediated by cAMP/cAMP-dependent protein kinase and cGMP/cGMP-dependent protein kinase, respectively. The results suggest that VASP phosphorylation is an important component of the inhibitory effects of prostacyclin and endothelium-derived relaxing factor on platelet activation and that VASP phosphorylation is a useful biochemical marker for the interaction of endothelial cells and platelets.

Comparison of vasodilatory prostaglandins with respect to cAMP-mediated phosphorylation of a target substrate in intact human platelets.

The recent purification of a vasodilator-stimulated phosphoprotein (VASP) from human platelets and the development of a specific antiserum against VASP made it possible to study the quantitative effects of cAMP-elevating prostaglandins on cAMP-mediated phosphorylation of VASP in intact human platelets. Prostacyclin (PG-I2), prostaglandin-E1 (PG-E1) and the stable prostacyclinanalog Iloprost, all agents used for the treatment of peripheral vascular disease, induced rapid, stoichiometric and reversible phosphorylation of VASP in human platelets mediated by the cAMP-dependent protein kinase. However, there were substantial differences between these three cAMP-elevating prostaglandins with respect to their effects on extent, duration and reversibility of VASP phosphorylation. Maximal VASP phosphorylation was induced both by PG-I2 and Iloprost, but the PG-I2 effect was only of short duration in comparison to that of Iloprost. The extent of PG-E1-induced VASP phosphorylation was less than that observed with PG-I2 and Iloprost. In endothelial cell-platelet coincubations, an endothelial cell-derived, indomethacin-sensitive factor caused a rapid elevation of platelet cAMP level and VASP phosphorylation. These results provided direct evidence that human endothelial cells are capable of producing biologically active quantities of cAMP-elevating prostaglandins sufficient to induce stoichiometric cAMP-mediated protein phosphorylation in human platelets. VASP-phosphorylation induced by PG-I2 and PG-E1 was completely reversible after removal of the prostaglandins whereas this was only partially the case with Iloprost. In addition, evidence is presented that the prostaglandin-regulated adenylate cyclase system but not the cAMP-mediated protein phosphorylation desensitizes in human platelets after prolonged treatment with cAMP-elevating prostaglandins. VASP phosphorylation is proposed as a marker for quantitating aspects of vessel wall-platelet interaction.

[Effects of high and low doses of acetylsalicylic acid on the restenosis rate after initially successful coronary angioplasty]. / Wirkung hoher und niedriger Dosen Acetylsalicylsäure auf die Re-Stenosierungsrate nach primär erfolgreicher koronarer Angioplastie.

A comparison was made in 79 patients (63 men, 16 women: mean age 52 +/- 9 years) of the effect of high and low doses of aspirin on restenosis rate during the first six months after originally successful percutaneous transluminal coronary angioplasty (PTCA), 39 patients (group 1) received 1000 mg aspirin daily, while 40 (group 2) received 100 mg daily. All patients took 1000 mg aspirin as loading dose on the day before PTCA, and additionally calcium antagonists and slow-release nitrates in the post-PTCA period. Both groups were comparable with respect of localization of the dilated coronary artery stenosis and the morphological changes after dilatation. Intimal lesions after PTCA were demonstrated in 9 patients of group 1 and 10 of group 2. Within six months clinically significant restenosis had occurred in 8 patients of group 1 and 7 of group 2. 33 patients in group 2 and 31 in group 1 were free of symptoms and had no ischaemic reaction on the exercise ECG six months after the initial successful PTCA. These results demonstrate that high aspirin dosage does not reduce the restenosis rate more than low dosage.

[Congenital aneurysm of the membranous interventricular septum]. / Angeborenes Aneurysma des membranösen interventrikulären Septums.

In a 50-year-old patient with complex ventricular arrhythmia (monotopic ventricular extrasystoles in bigeminy and triplet form), coronary angiography with ventriculography revealed an aneurysm of about 2-3 cm diameter that bulged visibly into the right ventricle during the systole. Electrophysiology was able to localise the earliest excitation during the ventricular extrasystoles at the septal border of the aneurysm. Hence, the congenital aneurysm was definitely identified as the source of the arrhythmia. Surgery or drug therapy were not indicated since there was no haemodynamically effective ventricular tachycardia in the patient who was largely free from complaints.