[Pulmonary embolectomy for acute massive pulmonary thromboembolism after failure of thrombolytic therapy].

Acute massive pulmonary thromboembolism (PTE) is associated with an exceptionally high mortality rate and results in death if not diagnosed early and treated properly. We observed 3 cases of acute massive PTE. One of the patients had undergone a surgery for femoral neck fracture. Ten days postoperatively, she developed severe dyspnea with hypoxia, and computed tomography (CT) pulmonary angiography confirmed the PTE diagnosis. She then had cardiac arrest when catheter examination. Although emergency surgical thrombectomy was successful with good postoperative hemodynamic stability and oxygenation, the patient did not recover from the unconsciousness caused by preoperative ischemic brain damage. Subsequently, she died 6 months after surgery. Of the 3 patients, 2 suffered from right ventricular dysfunction without hemodynamic instability. They underwent open thrombectomy after the failure of conservative treatment with a systemic injection of urokinase. Both patients demonstrated a good clinical course and were discharged from hospital in a good general condition 22 and 28 days postoperatively. Herein, we review the current literature on PTE treatment. We concluded that an aggressive surgical intervention might be preferred to thrombolytic therapy for PTE patients with massive thrombosis and progressive right ventricular dysfunction.

Transesophageal echocardiography for detection of mitral regurgitation due to papillary muscle rupture or dysfunction associated with acute myocardial infarction: a report of five cases.

Severe mitral regurgitation was associated with cardiogenic shock in five (0.8%) of 623 patients with acute myocardial infarction who were urgently admitted to the authors' hospitals between 1994 and 1996. The infarct was located in the inferior wall in four patients and in the inferoposterior wall in one patient. Severe mitral valve regurgitation occurred concurrently with cardiogenic shock between one and six days after the onset of myocardial infarction. A mitral regurgitant murmur was not audible in four of five patients. Similarly, mitral regurgitant Doppler signals were not detected in four patients by transthoracic echocardiographic examination, while transesophageal echocardiographic examination detected mitral regurgitant signals clearly in all patients. Thus, when cardiogenic shock is unexpectedly associated with inferior or inferoposterior wall acute myocardial infarction, severe mitral regurgitation should be suspected, even when a mitral regurgitant murmur is not audible. Furthermore, mitral regurgitant flow signals may not always be detected by transthoracic echocardiography. Thus, examination for mitral regurgitation by transesophageal echocardiography should be considered.

[Newly developed technology for intravenous contrast echocardiography].

Until now we have not been able to employ a contrast enhancer for ultrasonic echocardiography at the everyday clinical level because the agent itself, composed of microbubbles, was too easily dispersed or even destroyed by several factors. However, contrast echocardiography has made a great leap forward with major developments on two fronts; the application of some new intravenous contrast enhancers, and newly developed machine technology permitting second harmonic imaging, intermittent or triggered imaging, pulse inversion harmonic imaging, and so on. New contrast enhancing agents are proving durability enough to permit greatly enhanced imaging for more than several minutes after injection. Recent new echocontrast specific imaging allows real-time visualizing of myocardial perfusion and assessment of myocardial function.

Peripheral arterial coil embolization for hepatic arteriovenous malformation in Osler-Weber-Rendu disease; useful for controlling high output heart failure, but harmful to the liver.

A 55-year-old Japanese housewife, who had Osler-Weber-Rendu disease, was admitted to our hospital because of frequent epistaxis and worsening exertional dyspnea. The computed tomography and hepatic arteriography revealed large hepatic arteriovenous malformation, which was considered to be the leading cause of her high output heart failure. Two series of hepatic arterial coil embolization procedures were performed to reduce hepatic shunt flow. They temporarily improved her cardiac condition, but gradually induced progressive hepatic failure due to intrahepatic cholangitis. Hepatic dysfunction restricted her quality of life and lead to a fatal clinical course one year after the second coil embolization.

[A case report: surgical treatment of hypertrophic obstructive cardiomyopathy with acute hemodynamic deterioration due to chordae rupture of the mitral valve].

A 70-year-old woman was found to have new heart systolic murmur and was transferred to our hospital for the treatment of high fever and dyspnea. The chest X ray showed cardiomegaly (CTR 63%) and marked pulmonary congestion. The UCG revealed that there was no evidence of infective endocarditis, but there was hypertrophic obstructive cardiomyopathy with the left ventricular pressure gradient of 90 mmHg accompanied by mitral regurgitation (grade 3/4). Two weeks after the admission, mitral regurgitation progressed due to chordae rupture confirmed by UCG. Transaortic subvalvular myectomy and mitral valve replacement were underwent. Post-operative electrocardiogram demonstrated right and left anterior bandle branch block. Eleven months after the operation left ventricular outflow pressure gradient was not detected by echocardiogram and she has been in I/IV NYHA functional class.

[A case of papillary muscle rupture associated with acute inferior myocardial infarction].

A sixty-year-old man was admitted to our hospital due to prolonged left anterior chest oppression and hypotention. The electrocardiogram revealed acute inferior myocardial infarction, confirmed by the coronary angiography which showed occluded right coronary artery (RCA) at the segment 4AV. The intra-coronary pro-urokinase infusion and coronary angioplasty successfully revascularized the occluded 4AV segment. Although the 4AV segment perfused small area, he developed severe pulmonary edema on the second hospital day. A transesophageal echocardiography revealed severe mitral regurgitation due to posterior mitral valve prolapse by the ruptured tendineae with a mobile mass. The damaged mitral valve was replaced by the prosthetic mechanical valve (SJM 25M), resulted in stable hemodynamic state. He discharged one month after the operation.

Left ventricular thrombosis following coronary artery bypass grafting in a patient with nephrotic syndrome: report of a case.

We present herein the case of a 63-year-old man with nephrotic syndrome who developed an apical infarction 4 days after undergoing coronary artery bypass grafting. Echocardiography done 2 weeks postoperatively revealed a left ventricular thrombus which was successfully removed. He has no further thrombotic events since anticoagulant therapy was initiated.

2-Phenylethoxy-9-methyladenine: an adenosine receptor antagonist that discriminates between A2 adenosine receptors in the aorta and the coronary vessels from the guinea pig.

Substituting a methyl group for the ribose moiety of N6-substituted adenosines that are selective agonists at the adenosine A1 receptor creates antagonists that are A1-selective. Inasmuch as 2-phenylethoxyadenosine is a selective agonist for the adenosine A2 receptor, 2-phenylethoxy-9-methyl-adenine (PEMA) was synthesized and tested as a potential adenosine A2 receptor antagonist. In guinea pig hearts, PEMA antagonized with the same potency (pKB approximately 6.1) the A1-mediated negative dromotropic and inotropic actions and the A2-mediated coronary vasoactivity of the nonselective adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA). PEMA at concentrations up to 30 microM did not antagonize the NECA-induced relaxations in guinea pig aortic rings. At concentrations exceeding 10 microM, PEMA caused xanthine-insensitive relaxations of both the aorta and the coronary vessels. Pharmacological resultant analysis revealed A2 receptor antagonism by PEMA in the guinea pig aorta (pKB = 5.2). The nonselective adenosine receptor antagonist 8-p-sulfophenyl-theophylline antagonized NECA responses in all four assays with equal potency (pKB approximately 5.7). Thus, PEMA does not discriminate between A2 receptors in the coronary vessels and A1 receptors in the atria of the guinea pig, but it is 10-fold more potent at antagonizing the A2 receptor in coronaries than the A2 receptors in the aorta. The data suggest that the A2 receptors in the coronary vasculature may be of the A2a subtype, whereas those in the aorta may be of the A2b subtype.

2-(N'-alkylidenehydrazino)adenosines: potent and selective coronary vasodilators.

The reaction of aliphatic aldehydes and ketones with 2-hydrazinoadenosine under relatively mild conditions (at room temperature or in refluxing methanol) formed 2-(N'-alkylidenehydrazino)-adenosines, 5-22, in good yields. Two kinds of adenosine receptors regulate cardiac and coronary physiology. In supraventricular tissues an A1AR coupled to muscarinic K channels mediates the negative chronotropic, dromotropic, and inotropic actions of adenosine, and an inhibitory A1AR coupled to adenylate cyclase mediates the "antiadrenergic" action of adenosine. One or more kinds of A2 receptors mediate coronary vasodilation. Bioassays employing a guinea pig heart Langendorff preparation showed that 5-22 weakly retard impulse conduction through the AV node (negative dromotropic effect), but several analogues were very active coronary vasodilators. The coronary vasoactivity of the (n-alkylidene- and of the (isoalkylidenehydrazino)adenosines paralleled the length of the alkyl chain, the EC50s of the of the most active n-pentylidene (8) and isopentylidene (18) congeners being 1 nM. The EC50s of the cyclohexylmethylene (9), cyclohexylethylidene (10), and cyclohex-3-enylmethylene (12), analogues were likewise < 1 nM, but the cyclohex-1-enylmethylene congener 12 was 10 times less active than 9. The unselective adenosine receptor antagonist 8-(p-sulfophenyl)theophylline (0.1 mM) raised the EC50s of the negative dromotropic effects of 8, 9, and 18 by 5-28-fold and the EC50s of coronary vasodilation of 22-90-fold. Catalytic reduction of 9 increased the hydrophobicity and changed the UV spectrum, suggesting reduction of the --CH = N-- bond. The product darkened on exposure to air and so was not characterized further. A new method for preparing 2',3',5'-tri-O-acetyl-2,6-dichloropurine riboside, a precursor in the synthesis of 2-hydrazinoadenosine, consists of the addition of tert-butyl nitrite to a mixture of 2',3',5'-tri-O-acetyl-6-chloroguanosine and CuCl in CHCl3 saturated with Cl2.

Nitric oxide modulates coronary autoregulation in the guinea pig.

A guinea pig heart Langendorff preparation was used in the present study to test the hypothesis that the coronary endothelium modulates coronary autoregulation through the production of nitric oxide (NO). Pacing at 250 beats per minute and venting the left ventricle to ensure that the hearts did no external work were performed in an attempt to reduce the metabolic stimulus to coronary vasomotion and keep it constant. We measured the responses of coronary flow and oxygen metabolism to stepwise changes of the perfusion pressure over the range between 18 and 85 mm Hg. The hearts exhibited autoregulation between 25 and 55 mm Hg and active vasodilation at perfusion pressures above that range. Perfusion with 100 microM NG-nitro-L-arginine (NNLA), an inhibitor of NO synthase, decreased coronary flow over the entire range of perfusion pressures and abolished active vasodilation over 65 mm Hg, thus widening the autoregulatory range. The administration of 200 microM L-arginine, but not D-arginine, reversed the action of NNLA. Inhibition of the cyclooxygenase pathway by 10 microM indomethacin did not affect autoregulation. Perfusion with 1 nM arginine vasopressin, a direct smooth muscle constrictor, lowered coronary flow rate to the same extent as NNLA at 55 mm Hg but did not prevent the pressure-dependent increase in flow above that pressure. These observations suggest that 1) the coronary endothelium actively modulates coronary autoregulation through the production of NO but not prostanoids, 2) mechanical stress (shear stress and/or stretching secondary to vasodilation) may be the stimulus to NO production, especially above the autoregulatory range, and 3) autoregulatory tone is likely to be myogenic in origin rather than mediated by extrinsic vasoconstrictors.

2-aralkoxyadenosines: potent and selective agonists at the coronary artery A2 adenosine receptor.

A Langendorff guinea pig heart preparation served for the assay of agonist potency of a series of 26 2-aralkoxyadenosines at the A1 and A2 receptors of, respectively, the atrioventricular node (conduction block) and coronary arteries (vasodilation). All of the analogues are weak agonists at the A1 receptor, requiring concentrations greater than 9 microM to cause second degree heart block. At the A2 receptor 2-phenethoxyadenosine is the most potent of the 2-phenylalkyladenosines. The activity of ring-substituted (F, Cl, CH3, and OCH3) 2-phenethoxyadenosines increases ortho less than meta less than para. The EC50s of coronary vasoactivity of several para-substituted analogues are in the subnanomolar range. The most potent analogue, 2-[2-(4-methylphenyl)ethoxy]adenosine 19, has an EC50 for coronary vasodilation of 190 pM and an A1/A2 selectivity ratio of 44,000. Aryl groups such as thienyl, indoloyl, or naphthyl also support A2 agonist activity. Although 2-oxoadenosine is 3 times more vasoactive than 2-aminoadenosine, the activities of the phenyl derivatives are markedly different; 2-phenoxyadenosine is 23 times weaker than 2-(phenylamino)adenosine (CV-1808).

2-Alkoxyadenosines: potent and selective agonists at the coronary artery A2 adenosine receptor.

A Langendorff guinea pig heart preparation served for the assay of agonist activity of a series of 24 2-alkoxyadenosines at the A1 and A2 adenosine receptors of, respectively, the atrioventricular node (conduction block) and coronary arteries (vasodilation). Activities are low at the A1 receptor and do not show a clear relationship to the size or hydrophobicity of the C-2 substituent. All the analogues are more potent at the A2 receptor, activity varying directly with the size and hydrophobicity of the alkyl group. The most potent analogue in this series, 2-(2-cyclohexylethoxy)adenosine has an EC50 of 1 nM for coronary vasodilation and is 8700-fold selective for the A2 receptor.

Cardiovascular actions of adenosines, but not adenosine receptors, differ in rat and guinea pig.

This study compared the structure-activity relationships of 16 analogues at the A1 and A2 adenosine receptors (A1AR, A2AR) of rat and guinea pig. Radioligand binding studies revealed no marked differences in the affinities of each analogue at the A1AR of brain cortex or the A2AR of brain striatum. Bioassay employing Langendorff heart preparations showed that the guinea pig is more sensitive than the rat to A1AR-mediated slowing of conduction through the atrioventricular node and, in some instances, to A2AR-mediated coronary vasodilation. That difference could reflect factors such as receptor density or efficacy of coupling to effector systems.

Reactive hyperaemic flow characteristics of the right coronary artery compared to the left anterior descending coronary artery in the open-chest dog.

Reactive hyperaemia, the cardiovascular response to transient occlusion of a vessel, was examined and compared in the right coronary artery (RCA) and the left anterior descending coronary artery (LAD) in the same heart of an open-chest dog. First, to study the relationship between reactive hyperaemia and occlusion time in the RCA and LAD, respective flows were measured and reactive hyperaemia was induced with different occlusion times. Occlusion time required for half the maximum peak percentage reactive hyperaemic flow (%PRH), t 1/2, for the RCA was approximately twice that of the LAD: 11.4 +/- 2.3 s versus 5.9 +/- 1.4 s. Maximum %PRH of the RCA was significantly greater than that of the LAD while the percentage repayment of the RCA was lower than that of the LAD. Augmentation of right ventricular oxygen consumption shortened t 1/2 and increased percentage repayment significantly. Second, to determine "critical pressure", which was defined as the perfusion pressure below which reactive hyperaemia was abolished completely, the RCA and LAD were perfused through a shunt from the carotid artery, perfusion pressure was varied in the range of 100 to 20 mmHg and reactive hyperaemia was induced. Critical pressure in the RCA was significantly lower than in the LAD: 32.2 +/- 5.7 mmHg versus 41.5 +/- 5.0 mmHg. These results suggest that the RCA has a greater flow reserve than the LAD. These results were consistent with the difference of oxygen metabolism between the right and left ventricles. The difference of oxygen metabolism between the two ventricles would, at least partly, account for these results.

Autoregulation by the right coronary artery in dogs with open chests; comparison with the left coronary artery.

Experiments were conducted to study autoregulatory responses of the right and left coronary arteries in dogs with open chests. The right and left circumflex coronary artery were cannulated and perfused with blood from the femoral artery via a pressurized reservoir. The perfusion pressure was varied in steps over a wide range and coronary blood flow rates were measured. Both the right and left coronary arteries exhibited autoregulation but the pressure at the end of the autoregulatory range was lower in the right (39.8 +/- 9.1 mm Hg) than in the left circumflex coronary artery (57.6 +/- 14.5 mm Hg). The slope of the pressure-flow relationship in the autoregulatory range was less steep in the right than the left circumflex coronary artery. The closed-loop gain when the perfusion pressure was less than 100 mm Hg was greater in the right than in the left circumflex coronary artery. Increases in the right ventricular afterload produced by pulmonary artery constriction decreased the closed-loop gain, shifted the auto-regulatory range upward and to the right, and made the slope steeper. These results indicate that more effective autoregulation is carried out by the right than the left circumflex coronary artery.

Coronary flow reserve and oxygen metabolism of the right ventricle.

The flow reserve of the right coronary artery (RCA) and myocardial oxygen extraction are important tractors in any investigation of the mechanisms of impaired right ventricular function. The present study induced brief coronary occlusions and examined the effect on right coronary blood flow in normal dogs, and the effect on myocardial oxygen metabolism in dogs with right ventricular hypertrophy (RVH). Right coronary flow reserve, represented by occlusion duration causing a half maximum dilatation (T1/2), was greater in the RCA than in the left anterior descending coronary artery of normal dogs; 11.4 +/- 2.3 sec vs 5.9 +/- 1.4 sec. Myocardial oxygen extraction ratio (EO2) of the right ventricle (RV), 51.3 +/- 1.6%, was significantly (p less than 0.05) lower than the index of the left ventricle (LV), 60.6 +/- 1.0%, and the extraction of the RV increased significantly in association with an increase of myocardial oxygen demand. In dogs with RVH caused by chronic banding of the pulmonary artery, this dominant oxygen reserve was lost: the EO2 of the hypertrophied RV was high compared with the EO2 of the normal RV (57.3 +/- 3.4% vs 51.3 +/- 1.6%, p less than 0.05), and no further increase in EO2 was observed in the hypertrophied RV in response to the elevation of the myocardial oxygen requirement. Oxygen usage per 100g of the RV for a certain level of overall RV work, rate-pressure product, was significantly (p less than 0.02) lower in the hypertrophied RV (0.00054 mlO2/beat.mmHg) than in the normal RV (0.0012 mlO2/beat.mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement of reduced coronary vasodilatory response during reactive hyperemia by diltiazem.

This study was performed to reconfirm transiently-reduced vasodilatory responses of the coronary artery in the reactive hyperemic period, and also to study whether an increase in calcium influx into the coronary smooth muscle accounts for the reduced coronary vasodilatory responses. Blood flow in the circumflex coronary artery was measured with an electromagnetic flow transducer in anesthetized open-chest dogs. Two successive occlusions for 3 to 7 s performed in pairs with a brief interval were accompanied by decreasing reactive hyperemia: the maximum reduction of reactive hyperemia appeared when the occlusion period was around 5 s with a 5-s interval. Around 5 s after the release of occlusion, excess arterial inflow almost equaled the blood flow debt incurred during the first occlusion. Pretreatment with diltiazem (150 micrograms/kg), a calcium entry blocker, significantly attenuated the reduction of coronary vasodilatory responses, but glyceryl trinitrate (nitroglycerin) did not affect the phenomenon of coronary reactivity. The results suggest that excess accumulation of calcium in the smooth muscle of small coronary arteries occurred during an early period of post-occlusion hyperemia, which resulted in a reduced vasodilatory reactivity of the vessels to the second ischemic stimulus.

Forskolin potentiates myocardial reactive hyperaemia in the open chest dog: the contribution of adenylate cyclase.

Forskolin, a diterpene, directly stimulates adenylate cyclase and also potentiates receptor mediated stimulation of this enzyme by many stimulatory agonists. We exploited the potentiating effect of forskolin to test the hypothesis that activation of adenylate cyclase contributes to myocardial reactive hyperaemia, especially by release of adenosine at the time of brief coronary occlusions. In 10 open chest dogs, intracoronary forskolin infusions which produced plasma concentrations between 0.22 and 0.34 mumol.litre-1 slightly increased coronary blood flow and had no effect on haemodynamics or myocardial metabolism. Under these conditions, though peak reactive hyperaemic flow rates were not affected, forskolin infusions reversibly potentiated repayments of flow debt by 28, 25 and 27% following coronary occlusions of 15 s, 20 s and 30 s, respectively (p less than 0.05). In another seven dogs, after observations of the effects of forskolin (0.16-0.26 mumol), 10 mumol of 8-phenyltheophylline, a potent adenosine antagonist, was infused simultaneously with forskolin into the coronary arteries. Forskolin increased debt repayments by about 23-27% following 15 s, 20 s and 30 s occlusions, but with simultaneous 8-phenyltheophylline, forskolin induced increments in the debt repayments were reduced significantly (p less than 0.05). These results indicate that adenylate cyclase contributes to myocardial reactive hyperaemia, and adenosine has a significant role as metabolic regulator of reactive hyperaemia through activation of adenylate cyclase.

Effect of heart rate and myocardial contractile force on coronary resistance.

The effect of the heart rate and myocardial contractile force on the extravascular resistance to blood flow of the left anterior descending coronary artery (LAD) was evaluated in 15 mongrel dogs anesthetized with sodium pentobarbital. The LAD was maximally dilated by intracoronary infusion of adenosine, which precluded the influence of vasomotor tone. Increases in the heart rate and myocardial contractile force decreased coronary blood flow in the absence of a change in coronary perfusion pressure. The changes in mean coronary resistance showed a significant linear relationship to changes in developed tension. The changes in coronary resistance caused by varying the heart rate and contractile force were so small that a normal coronary vascular tree could easily compensate for the increase in resistance. However, it is supposed that with critical stenosis of the vascular tree even a small increase in resistance might cause deleterious effects on coronary blood flow.

The QRS complex of the standard 12-lead electrocardiogram in septal myocardial infarction.

Interventricular septal involvement in myocardial infarction is suggested by the findings of a QS deflection in lead V1 and/or absence of the Q wave in leads I and V6, using the standard 12-lead electrocardiogram (ECG). However, these findings were not sufficiently established for the criteria of septal infarction, because several factors including anatomic position of the heart, changes of intraventricular conduction, and condition of the lung would affect the QRS complex in the leads. In this study, we analyzed the ECGs of anterior myocardial infarction with (group A) and without (group B) involvement of the first septal coronary artery. The R wave in V1 was absent in 64.7% of group A and 60.0% of group B. The Q wave was absent in 35.3% in lead I and 64.7% in lead V6 of group A, while in group B the Q wave in leads I and V6 were not observed in 60.0% and 40.0%, respectively. The prevalence rates of the R wave and the Q wave in these leads were not significantly different between the two groups. Left ventriculography revealed that the prevalence rate of the R wave in V1, and the Q wave in I and V6 was not significantly different, regardless of the presence or absence of impaired septal motion. Experimental study in anesthetized dogs confirmed the difficulty in clarifying acute septal ischemia by changes in the QRS complex. These results indicate that septal myocardial infarction is hardly detectable with changes in the QRS complex of the standard 12-lead electrocardiogram.