Silicalite-1, an adsorbent for 2-, 3-, and 4-chlorophenols.

The adsorption of the three chlorophenol isomers, ortho, meta and para, by silicalite-1 has been studied at 30 °C, below the solubility (at the same temperature) in water. Large differences, up to 30 times, have been observed between the adsorption of the para- vs. the ortho-isomer. The difference of behavior observed between the isomers is assigned to the tendency to self-organization of the para-isomer. It seems probable that the adsorption sites are at the intersection channels. From a technical point of view, silicalite-1 seems a competitive adsorbent for p-chlorophenol.

Divergence between respirometry and physicochemical methods in the fractionation of the chemical oxygen demand in municipal wastewater.

For activated sludge modeling purposes, the methods used to evaluate the readily biodegradable chemical oxygen demand (RBCOD) in the influents are by biological or via physicochemical assays. However, there has not been sufficient wide comparison between these methods. The main goal of this study was to investigate the performance of the main chemical oxygen demand (COD) fractionation protocols, considering a representative wastewater in the context of tropical and developing countries. Different physicochemical characterization procedures, respirometric tests, and chemical analyses were performed. The fate of the soluble COD in the aeration tanks was studied. The results of the study showed that a marked difference may exist, in municipal wastewaters, between the estimates of the RBCOD fractions measured by respirometry and by any of the physicochemical methods. The evaluated influent showed a rather large fraction of COD that was passing the filters without being rapidly biodegradable, but which was removed quickly by enmeshment in the bioflocs. The consequences of such divergences and behavior are discussed.

[The severity of rheumatoid arthritis as a timely predictor of instability in the asymptomatic cervical spine]. / La severidad de la artritis reumatoide como predictor oportuno de inestabilidad de la columna cervical asintomática.

INTRODUCTION: Cervical spine involvement is common in patients with RA, risk factors such as disease activity may be related to asymptomatic cervical instability. OBJECTIVE: To determine the associated factors for asymptomatic cervical spine instability in patients with rheumatoid arthritis. MATERIAL AND METHODS: Case and control study from the external spine and rheumatology consultation of a level II trauma center to identify all patients diagnosed with rheumatoid arthritis (RA) and asymptomatic cervical instability. With simple X-rays of the cervical spine, carrying out radiographic measurements, the diagnosis of cervical instability was performed, risk factors such as the presence of rheumatoid factor (FR), previous articular surgeries, elevations of the C-reactive protein (PCR) values were evaluated. The severity and activity of the disease measured in the activity index of 28 articulations (DAS 28) in addition to the index of activity of the simplified disease (SDAI). RESULTS: We assessed 32 patients, nine patients (28.1%) met the criteria for instability of the anterior cervical spine atlantoaxial subluxation (SAAa) (100%), also one patient with SAAa presented vertical subluxation (SV), risk factors more relevant: DAS 28 with an OR = 3.54, SDA with an OR = 2.34 and finally the PCR 1.0 its OR = 2.88. CONCLUSION: The risk factors associated opportunely in our population are the severity of the activity of the disease that we can see in the DAS and SDAI when applied in patients and PCR 1.0.

INTRODUCCIÓN: La afectación de la columna cervical es común en pacientes con artritis reumatoide (AR), factores de riesgo como la actividad de la enfermedad puede estar relacionada con inestabilidad cervical asintomática. OBJETIVO: Determinar los factores asociados a la inestabilidad de la columna cervical asintomáticos en pacientes con artritis reumatoide. MATERIAL Y MÉTODOS: Estudio de casos y controles provenientes de la consulta externa de reumatología y columna de un centro de trauma de nivel II para identificar a todos los pacientes diagnosticados con AR e inestabilidad cervical asintomáticos. Con radiografías simples de la columna cervical que hacen mediciones radiográficas, se realizó el diagnóstico de inestabilidad cervical, se evaluaron los factores de riesgo como la presencia de factor reumatoide (FR), cirugías articulares previas, las elevaciones de los valores de proteína C reactiva (PCR), la severidad y actividad de la enfermedad medida en el índice de actividad de la enfermedad de 28 articulaciones (DAS 28), además del índice de actividad de la enfermedad simplificada (SDAI). RESULTADOS: Se evaluaron 32 pacientes, nueve (28.1%) cumplieron con los criterios para inestabilidad de la columna cervical con subluxación atlantoaxial anterior (SAAa) (100%), también un paciente con SAAa presentaba subluxación vertical (SV), los factores de riesgo más relevantes: el DAS 28 con un OR = 3.54, SDA con un OR = 2.34 y por último el PCR 1.0 su OR = 2.88. CONCLUSIÓN: Los factores de riesgo asociados oportunamente en nuestra población son la severidad de la actividad de la enfermedad que podemos observar en el DAS y SDAI al aplicarlos en los pacientes y PCR 1.0.

Platelet activation during myocardial ischaemia: a contributory arrhythmogenic mechanism.

Experimental and clinical observations of the involvement of platelets in the pathophysiology of myocardial ischaemia indicate the importance of interactions between these formed elements and the heart. The aim of this review is to outline evidence linking platelet activation, myocardial ischaemia and infarction, and to present evidence for a link between platelet activation, arrhythmogenesis and sudden death. A brief review of platelet physiology and pharmacology is provided, with a review of the cardiac electrophysiological effects of ischaemia and the electrophysiological effects of platelet-derived substances. The concept that platelet activation during myocardial ischaemia is a contributory arrhythmogenic mechanism is discussed.

The effects of diadenosine polyphosphates on the cardiovascular system.

Diadenosine polyphosphates are members of a group of dinucleoside polyphosphates that are ubiquitous, naturally occurring molecules. They form a recently identified class of compounds derived from ATP and consist of two adenosine molecules bridged by up to six phosphate groups. These compounds are stored in high concentrations in platelet dense granules and are released when platelets become activated. Some of the compounds promote platelet aggregation, while others are inhibitory. Possible roles as neurotransmitters, extracellular signalling molecules or 'alarmones' secreted by cells in response to physiologically stressful stimuli have been postulated. Recent studies suggest a role for these compounds in atrial and synaptic neurotransmission. Studies using isolated mesenteric arteries indicate an important role of phosphate chain length in determining whether diadenosine polyphosphates produce vasodilation or vasoconstriction, but in the coronary circulation, diadenosine polyphosphates generally produce vasodilation via mechanisms thought to involve release of NO or prostacyclin (PGI2). They produce cardiac electrophysiological effects by altering ventricular refractoriness at submicromolar concentrations and reduce heart rate. Mechanisms involving KATP channels have been proposed in addition to the involvement of P1- and P2-purinergic receptors and the specific diadenosine polyphosphate receptor identified on isolated cardiac myocytes. Clinical evidence suggests a role for diadenosine polyphosphates in hypertensive patients and those with the Chédiak-Higashi syndrome. This review outlines the effects of these compounds on the cardiovascular system and considers their potential involvement in mediating the pathophysiological effects associated with platelet activation during myocardial ischaemia.

Hypertrophy causes delayed conduction in human and guinea pig myocardium: accentuation during ischaemic perfusion.

OBJECTIVE: The aim was to investigate why cardiac hypertrophy causes increased vulnerability to arrhythmias during myocardial ischaemia. METHODS: The electrophysiological basis for this increased vulnerability was studied in isolated perfused guinea pig hearts obtained 50 and 150 d after aortic constriction, and in sham operated controls. Cellular electrophysiology, conduction, and refractory periods were examined during control perfusion and during low flow (coronary flow reduced to 10% of control) and zero flow ischaemia. ECGs in patients with left ventricular hypertrophy and in controls matched for age and heart rate were also studied. RESULTS: Aortic constriction increased heart weight:body weight ratio by 33% at 50 d and by 69% at 150 d. Action potentials were unchanged in hypertrophied hearts. Significant conduction delay occurred in 150 d hypertrophied hearts [conduction time index 23(SEM 4) ms v 18(3) ms, p < 0.001; QRS width 40(1) ms v 35(1) ms, p < 0.01], but not in 50 d hypertrophied hearts. Conduction delay was also present in humans with left ventricular hypertrophy [QRS width 96(13) ms v 87(8) ms, p < 0.01]. Although the QTc interval was increased in humans, at 422(23) ms v 411(17) ms in controls, p < 0.05, this could be explained by the increased QRS duration. During ischaemia, ventricular arrhythmias tended to occur earlier in hypertrophied hearts. Hypertrophy was also associated with a greater increase in conduction delay. Ischaemia reduced action potential duration and refractory periods; the reduction in action potential duration was attenuated by hypertrophy (p < 0.01), although the reverse was apparent during low flow ischaemia at 50 d. CONCLUSIONS: Delayed conduction is an important feature of severe cardiac hypertrophy in guinea pigs and man. Hypertrophy is associated with accentuated conduction delay and altered repolarisation during ischaemia.

Myocardial ischaemia induces platelet activation with adverse electrophysiological and arrhythmogenic effects.

OBJECTIVE: The aim was to investigate how platelet activation during myocardial ischaemia can induce electrophysiological and arrhythmogenic effects, and examine the involvement of different platelet membrane receptors in producing these effects. METHODS: Transmembrane action potentials and electrograms were recorded from isolated, Langendorff perfused guinea pig hearts during normal perfusion, global myocardial ischaemia, and reperfusion during infusion of human platelets. Platelet reactivity was altered by treating platelets with forskolin, aspirin, the platelet activating factor (PAF) receptor antagonist BN 52021, the thromboxane A2 (TP) receptor antagonist GR 32191B, and the alpha 2 adrenoceptor antagonist yohimbine. Myocardial catecholamine depletion was induced by treatment with 6-hydroxydopamine. RESULTS: Platelet infusion had no electrophysiological effects during normal perfusion, but during ischaemia it enhanced the reduction in action potential duration at 95% repolarisation [APD95, 110(SEM 3) ms v 121(5) ms, p < 0.05, at 15 min] and increased the incidence of ventricular arrhythmias (from 56% to 94%, p = 0.04) compared to hearts receiving buffer but no platelets. The reductions in APD95 and the arrhythmogenic effects were attenuated when forskolin treated, aspirin treated or GR 32191B treated platelets were infused (VF: 50% v 94%, p = 0.03; 50% v 94%, p = 0.02; 22% v 94%, p < 0.001, respectively). Similar results were obtained when normal platelets were infused into catecholamine depleted hearts (VF: 60% v 94%, p = 0.0549). These differences were associated with inhibited aggregatory responses to thrombin (for forskolin treated platelets) and the thromboxane mimetic U44069 (for GR 32191B treated platelets). Yohimbine was antiarrhythmic in the presence and absence of platelets, suggesting direct myocardial effects, but BN 52021 had no antiarrhythmic effects. CONCLUSIONS: Myocardial ischaemia causes platelet activation resulting in electrophysiological and arrhythmogenic effects. PAF receptor antagonism does not prevent these effects, but inhibition of platelet reactivity, platelet thromboxane receptor antagonism, and myocardial catecholamine depletion are effective. These findings suggest that the arrhythmogenic effects of platelet activation during myocardial ischaemia are principally mediated by a thromboxane dependent mechanism, while catecholamine release has a contributory role.

Nitric oxide and prostacyclin modulate the alterations in cardiac action potential duration mediated by platelets during ischaemia.

OBJECTIVE: To investigate the effects of alterations of nitric oxide (NO) and prostacyclin (PGI2) availability on platelet-mediated electrophysiological effects during myocardial ischaemia. METHODS: Transmembrane action potentials and electrograms were recorded from isolated, Langendorff-perfused guinea-pig hearts during normal perfusion, global myocardial ischaemia and reperfusion during infusion of washed human platelets. Experiments were performed in the presence of 100 microM NG-nitro-L-arginine methyl ester (L-NAME), 30 microM L-arginine, 10 microM haemoglobin, 100 microM sodium nitroprusside and 2.3 nM iloprost, or using hearts obtained from DL-lysine monoacetylsalicylate (Aspisol, 50 mg.kg-1 i.p.)-treated animals. RESULTS: Perfusion with L-NAME and haemoglobin increased perfusion pressure by 33% (P = 0.0017) and 23% (P = 0.0026) while sodium nitroprusside and iloprost reduced it (17%, P = 0.0004, and 24%, P = 0.0006). In the absence of platelets, these compounds had no effect on arrhythmogenesis, but in the presence of platelets L-NAME reduced the onset time of ventricular tachycardia during ischaemia from 19.4 (s.e.m. 2.0) min to 12.9 (2.1) min, P = 0.04 and accentuated the ischaemia-induced reduction of action potential duration at 95% repolarization (APD95): 95(6) vs. 115(5) ms, P < 0.05 at 25 min. Sodium nitroprusside in the presence of platelets attenuated the ischaemia-induced reduction in APD95, while iloprost in the presence of platelets was antiarrhythmic (ventricular fibrillation 25 vs. 75%, P = 0.04) and attenuated the reduction in APD95 during ischaemia 115(4) vs. 94(4) ms, P < 0.05 at 20 min. Infusion of platelets into hearts obtained from DL-lysine-monoacetylsalicylate-treated guinea-pigs accentuated the ischaemia-induced reduction in APD95 (94(4) vs. 119(7) ms, P < 0.05 at 20 min) and this was reversed by sodium nitroprusside (117(7) ms, P < 0.05 at 20 min). L-NAME and haemoglobin had no effect on the aggregatory responses of the platelets to 5 microM ADP and 4 micrograms.ml-1 collagen, while sodium nitroprusside and iloprost ablated the responses to ADP and reduced the responses to collagen (maximum height of the aggregatory response reduced by 75 and 84%, respectively, both P = 0.03.) CONCLUSIONS: Inhibition of NO and PGI2 synthesis exacerbates the reduction in cardiac action potential duration associated with platelet activation during ischaemia, while provision of exogenous NO and PGI2 attenuates the reduction in cardiac action potential duration. Provision of exogenous NO and PGI2 (as iloprost) was associated with inhibition of platelet reactivity.

Capillary filtration is reduced in lungs adapted to chronic heart failure: morphological and haemodynamic correlates.

OBJECTIVE: To determine pulmonary capillary filtration in experimental chronic heart failure and to investigate some morphological and haemodynamic mechanisms that could account for reduced filtration in lungs adapted to chronic heart failure. METHODS: We studied pulmonary capillary filtration, vascular resistances and morphology in lungs from guinea-pigs adapted to chronic heart failure. Heart failure was induced by banding of the ascending aorta (n=66) or sham control operation (n=78) in guinea-pigs which were studied at 150+/-8 days post-operation. RESULTS: Reduced cardiac output, increased systemic vascular resistance and LV end diastolic pressure and increased LV and RV weight:body weight ratio (all P<0.05) indicated chronic heart failure at 5 months following aortic banding in guinea-pigs. Lung weight was increased (61%, P<0.05) in heart failure compared with controls, but lung water content was reduced (5.5%, P<0.05), a reversal of the pattern seen acutely. Studies in isolated perfused lungs demonstrated a reduced capillary filtration coefficient (0. 018+/-0.003 vs. 0.003+/-0.002 ml min(-1)mmHg(-1)g(-1), P<0.001), increased arterial (61%) and venous resistance (50%) in heart failure lungs, P<0.05. Wall thickness:lumen ratio was increased in small (<250 microm) pulmonary arterioles (0.15+/-0.02 vs. 0.08+/-0. 01) and venules (0.06+/-0.005 vs. 0.04+/-0.002) in heart failure, P<0.01. Alveolar septal volume fractions (35.2+/-5.1 vs. 23.1+/-2.7) and septal:air-space volume ratios (60.5+/-13.6 vs. 31.9+/-5.3) were also increased in heart failure, P<0.05. CONCLUSIONS: Pulmonary adaptation to chronic heart failure is associated with vascular and alveolar remodelling that contributes to increased vascular resistance and reduced capillary filtration. These changes are likely to be important in mediating resistance to pulmonary oedema in chronic heart failure.

Electrophysiological and antiarrhythmic effects of UK 52,046-27 during ischaemia and reperfusion in the guinea-pig heart.

1. We studied the antiarrhythmic and electrophysiological effects of UK 52,046-27 (10(-8) M and 5 x 10(-8) M), a highly selective alpha 1-adrenoceptor antagonist, during global ischaemia (flow reduced to 10% of control for 30 min) and reperfusion, in isolated, buffer-perfused hearts of guinea-pigs. 2. The compound had few electrophysiological effects during normal perfusion, although action potential amplitude and Vmax were reduced with 10(-8) M (by 9% and 22%) and refractory period was increased with 5 x 10(-8) M (by 13%) compared to control hearts. 3. Perfusion with 5 x 10(-8) M UK 52,046-27 reduced the incidence of ventricular tachycardia during ischaemia from 67% to 25%, and during reperfusion reduced the incidence of ventricular tachycardia (from 83% to 17%) and ventricular fibrillation (from 67% to 8%). 4. The compound prolonged significantly action potential duration and refractory period during ischaemia and reperfusion. Vmax was reduced to a greater extent during reperfusion in the treated hearts, while greater increases in QRS width and stimulation threshold occurred during ischaemia in the treated group. 5. These results confirm that blockade of the alpha 1-adrenoceptor subpopulation during myocardial ischaemia and reperfusion decreases the incidence of arrhythmias and alters cellular electrophysiology during ischaemia and reperfusion.

Electrophysiological and arrhythmogenic effects of platelet activating factor during normal perfusion, myocardial ischaemia and reperfusion in the guinea-pig.

1. Platelet activating factor (PAF) is often used to study the effects of platelet activation. While direct myocardial electrophysiological effects of PAF have been described in superfused myocardial tissue, little is known about its actions on the whole heart. 2. The cellular electrophysiological and arrhythmogenic effects of PAF (10(-11)M, 10(-10)M and 10(-9)M) were studied during normal perfusion, global myocardial ischaemia and reperfusion in Langendorff-perfused guinea-pig hearts at 32 degrees C. 3. PAF (10(-9)M) increased the incidence of ventricular fibrillation during ischaemia and reduced action potential duration (APD) during normal perfusion and early myocardial ischaemia (10(-9)M and 10(-10)M). PAF also reduced refractory period (RP) during normal perfusion (10(-9)M) and early ischaemia (10(-9)M and 10(-10)M). PAF prevented recovery of APD (10(-9)M) and RP (10(-9)M and 10(-10)M) during reperfusion. PAF at a concentration of 10(-11)M had no electrophysiological effects. 4. PAF (10(-9)M) increased the QRS width of the electrocardiogram during late ischaemia while 10(-10)M PAF raised pacing threshold during late ischaemia. 5. Perfusion pressure was increased, and developed tension decreased by 10(-9)M PAF. 6. These results demonstrate that PAF has direct myocardial electrophysiological effects in the whole heart which occur during normal perfusion and are capable of augmenting the effects of myocardial ischaemia, but are independent of the presence of platelets.

Changes in extracellular pH and myocardial ischaemia alter the cardiac effects of diadenosine tetraphosphate and pentaphosphate.

1. The structural conformation of diadenosine tetraphosphate (Ap(4)A) and pentaphosphate (Ap(5)A) has been reported to alter as pH is reduced. As such, it is possible that the cardiac effects of Ap(4)A and Ap(5)A vary during acidosis and myocardial ischaemia due to changes in ligand structure, receptor proteins or intracellular signalling. 2. We investigated whether the cardiac electrophysiological and coronary vasomotor effects of Ap(4)A and Ap(5)A are preserved under conditions of extracellular acidosis (pH 6.5) and alkalosis (pH 8.5) and whether Ap(4)A has any electrophysiological or antiarrhythmic effects during ischaemia. 3. Transmembrane right ventricular action potentials, refractory periods and coronary perfusion pressure were recorded from isolated, Langendorff-perfused guinea-pig hearts under constant flow conditions. The effects of 1 nM and 1 microM Ap(4)A and Ap(5)A were studied at pH 7.4, 6.5 and 8.5. The effects of 1 microM Ap(4)A were studied during global low-flow ischaemia and reperfusion. 4. At pH 7.4, Ap(4)A and Ap(5)A increased action potential duration (APD(95)) and refractory period (RP) and reduced coronary perfusion pressure. The electrophysiological effects were absent at pH 6.5 while the reductions in perfusion pressure were attenuated. At pH 8.5, Ap(4)A increased RP but the effects of Ap(4)A and Ap(5)A on perfusion pressure were attenuated. During ischaemia, Ap(4)A had no antiarrhythmic or electrophysiological effects. 5. These data demonstrate the importance of extracellular pH in influencing the effects of Ap(4)A and Ap(5)A on the heart and indicate that any potentially cardioprotective effects of these compounds during normal perfusion at physiological pH are absent during ischaemia.

Effects of the PAF antagonists BN50726 and BN50739 on arrhythmogenesis and extent of necrosis during myocardial ischaemia/reperfusion in rabbits.

1. The effects of two novel platelet activating factor (PAF) antagonists BN50726 and BN50739 on arrhythmias, haemodynamics and extent of necrosis during myocardial ischaemia and reperfusion were investigated in anaesthetized rabbits subjected to coronary artery ligation. 2. BN50739 reduced heart rate prior to coronary artery occlusion (P < 0.005) but had no other significant haemodynamic effects at this time. BN50739 and BN50726 did not significantly alter heart rate or blood pressure during 30 min of ischaemia or 30 min of reperfusion, compared to control hearts. 3. BN50739 and BN50726 had no effect on the incidence of arrhythmias during ischaemia. BN50726 significantly reduced the incidence of reperfusion ventricular fibrillation compared to controls (0% v 40%, P < 0.05), and improved survival (80% v 39%, P < 0.05). Similar trends were observed with BN50739. 4. BN50726 reduced the extent of necrosis compared to control hearts (18 +/- 2% v 30 +/- 3%, P < 0.01). A similar trend was observed with BN50739. 5. These results demonstrate that PAF antagonism with BN50726 attenuates reperfusion-induced arrhythmias and preserves myocardium in the early phase of ischaemia, independently of haemodynamic effects.

Investigation of mechanisms that mediate reactive hyperaemia in guinea-pig hearts: role of K(ATP) channels, adenosine, nitric oxide and prostaglandins.

1. Reactive hyperaemia is a transient vasodilatation following a brief ischaemic period. ATP-dependent K(+) (K(ATP)) channels may be important in mediating this response, however it is unclear whether mitochondrial K(ATP) channels contribute to this in the heart. 2. We examined the involvement of K(ATP) channels and the relative role of mitochondrial channels as mediators of coronary reactive hyperaemia and compared them to mechanisms involving NO, prostaglandins and adenosine in the guinea-pig isolated heart. 3. Reactive hyperaemic vasodilatation (peak vasodilator response and flow debt repayment) were assessed after global zero-flow ischaemia (5 -- 120 s) in the presence of nitro-L-arginine methyl ester (L-NAME, 10(-5) M, n=9), 8-phenyltheophylline (8-PT, 10(-6) M, n=12) and indomethacin (10(-5) M, n=12). 4. Glibenclamide (10(-6) M, n=12) a non-selective K(ATP) channel inhibitor and 5-hydroxy-decanoic acid (5-HD, 10(-4) M, n=10) a selective mitochondrial K(ATP) channel inhibitor were also used. The specificity of the effects of glibenclamide and 5-HD (n=6 each) were confirmed using pinacidil (38 nmol -- 10 micromol) and diazoxide (42 nmol -- 2 micromol). Glibenclamide was most effective in blocking the hyperaemic response (by 87%, P<0.001) although 5-HD and 8-PT also had a marked effect (40% inhibition, P<0.001 and 32%, P<0.001, respectively). L-NAME and indomethacin had little effect. 5. Perfusion with L-NAME and glibenclamide significantly reduced baseline coronary flow (22%, P<0.01 and 33%, P<0.01) while 8-PT, indomethacin and 5-HD had no effect. 6. K(ATP) channels are the major mediators of the coronary reactive hyperaemic response in the guinea-pig. Although mitochondrial K(ATP) channels contribute, they appear less important than sarcolemmal channels.

Effects of cicletanine on haemodynamics, arrhythmias and extent of necrosis during coronary ligation in rabbits.

1. The effects of cicletanine on arrhythmias, haemodynamics and extent of necrosis during myocardial ischaemia were investigated in rabbits subjected to coronary ligation. 2. Cicletanine increased cardiac output prior to coronary occlusion (P < 0.01) but had no other significant haemodynamic effects at this time and did not significantly alter heart rate, blood pressure or cardiac output during 30 min of ischaemia or 30 min of reperfusion. 3. Ventricular fibrillation and mortality were greater in control (65% and 60% respectively) than treated animals (15.4% and 15.4%, P < 0.01). 4. The extent of myocardial necrosis expressed as a percentage of the area at risk was also reduced by cicletanine from 61 +/- 8% in controls to 37 +/- 6% (P < 0.05). 5. These findings indicate that cicletanine attenuates arrhythmias and preserves myocardium in the early phase of ischaemia and this effect appears to be independent of an established antihypertensive action.

Tedisamil (Solvay).

Tedisamil, a potassium channel blocker (class III anti-arrhythmic agent)from Solvay, is in phase II trials for the potential treatment of atrial fibrillation [342434]. The drug had completed phase III trials for angina pectoris [342434], [177648], and although an NDA dossier for angina pectoris in refractory patients was ready for filing with the US FDA, Solvay has decided to pursue the broader indication of atrial fibrillation instead [342434]. Tedisamil is bradycardic without producing a negative inotropic effect. In a canine model of exercise-induced angina, myocardial function was maintained. In rat, rabbit, canine and simian hearts, there was a marked prolongation of action potential, due to tedisamil's modulating effects on potassium channels. Diastolic arterial pressure was not influenced [276934]. Tedisamil also rapidly terminated sustained atrial fibrillation and prevented its reinitiation in a canine model of the condition [315378]. The class III antiarrhythmic effect of tedisamil is related predominantly to the strong blocking effect of the drug on the rapid component of the delayed rectifier potassium current [334806].

Coronary microangiography in the guinea pig, rabbit and ferret.

Using improved methods, we have developed a microangiographic technique for studying the coronary circulation in Langendorff perfused guinea pig, rabbit and ferret hearts. Striking anatomical differences were observed between these species. In the guinea pig, the interventricular septum was supplied by a large septal artery which always arose from the right coronary artery, whereas in the rabbit and ferret, the septal artery was smaller and originated from the left coronary artery. The circumflex artery was more prominent than the right coronary artery in the ferret and guinea pig, whereas the reverse pertained in the rabbit. Extensive apical collateral connections were observed between terminal branches of the left anterior descending, left ventricular branches and the septal artery in the guinea pig, while collaterals were usually absent in the rabbit and ferret. These species differences in the myocardial blood supply have wide ranging implications regarding the choice of small animals for cardiac research.

Platelet-mediated alterations in cardiac cellular electrophysiology.

Recent clinical and experimental evidence indicates that platelet activation contributes to the arrhythmogenic effects of myocardial ischaemia, but little is known about the electrophysiological effects produced by controlled platelet activation under conditions of normal perfusion and how these might relate to effects during ischaemia. To investigate this, we studied changes in cardiac cellular electrophysiology and arrhythmogenesis during infusion of platelets [10(8)/ml] in isolated, perfused guinea-pig hearts during normal perfusion and global myocardial ischaemia. Hearts were studied in four groups: group A (n = 4) receiving frozen/thawed (activated) platelets; group B (n = 4) receiving normal platelets in the presence of 10(-9) M platelet activating factor (PAF); group C (n = 9) receiving buffer only during normal perfusion and myocardial ischaemia; group D (n = 9) receiving platelets during normal perfusion and myocardial ischaemia. Infusion of platelets (group D) had no effects during normal perfusion, but activated platelets (group A) decreased action potential duration (APD) from 165 +/- 1 ms to 138 +/- 5 ms (mean +/- SE) at 15 min of normal perfusion (P less than 0.02) and produced ventricular fibrillation (VF) in 3/4 at 21 +/- 1 min. Infusion of platelets in the presence of PAF (group B) produced similar reductions of APD during normal perfusion and VF in 2/4. During ischaemia, platelets (group D) increased the incidence of VF (100% vs 56% group C, P less than 0.05) and enhanced the ischaemia-induced reductions in APD (107 +/- 3 ms vs 121 +/- 5 ms (group C) P less than 0.05 at 15 min).(ABSTRACT TRUNCATED AT 250 WORDS)