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Biomedical subjects

G Alloatti

Publications and source records attributed to G Alloatti.

At least 37 records · Page 2Linked to original sources
PubMed1991

Prostaglandin I2 (PGI2) enhances calcium current in guinea-pig ventricular heart cells.

In the present study we have investigated the electrophysiological effects of two prostaglandins, PGI2 (prostacyclin) and PGE1, in ventricular cells enzymatically isolated from adult guinea pigs, using the whole cell patch-clamp technique. PGI2 (tested in the range 1 nM-10 microM) had marked effects on both action potential and calcium current. The action potential duration and the plateau voltage were enhanced, without any significant modification of the other electrical parameters. In this preparation PGI2 increased the calcium current in a concentration-dependent manner, by up to 60% over the control value (at 10 microM), whereas PGE1 (tested in the range 1 nM-10 microM) had practically no effect on the calcium current. Pretreatment with 10 microM acetylcholine markedly reduced the effect of PGI2 (10 microM). No further increase in the calcium current was induced by PGI2 (5 microM) when the cell was internally perfused with 50 microM cAMP. These data indicate that the positive inotropic effect exerted by PGI2 on cardiac preparations is probably due to enhancement in the calcium current via a cAMP-dependent phosphorylation of the calcium channel.

Acetylcholine↗
PubMed1991

The mechanical and electrical effects of rhinoceros viper (Bitis nasicornis) venom on the isolated perfused guinea pig heart and atrial preparations.

The mechanical and electrical effects of the venom of Bitis nasicornis were studied on the guinea-pig Langendorff and left atrial myocardium preparations. While Langendorff preparations were treated with individual doses of 0.1, 0.6 and 1.4 mg, isolated left atria were treated using concentrations of 2.0, 20 and 200 micrograms/ml of venom in the perfusion solution. In the Langendorff preparation, transient increases in left ventricular systolic pressure (LVSP) and heart rate (HR) were seen after 0.1 mg of venom. When 0.6 mg of venom was given, the increases were followed by decreases, while 1.4 mg doses simply induced decreases in LVSP and HR. After both 0.6 and 1.4 mg doses the decreases were accompanied by increases in left ventricular diastolic pressure. In addition to these mechanical effects, transient increases in HR with atrio-ventricular blocks, ventricular extrasystoles and tachycardia were observed after each dose. In the left atrium the 2 micrograms/ml venom concentration produced an increase, followed by a decrease, in the maximum tension developed, which was only seen to decrease with higher concentrations of 20 and 200 micrograms/ml of venom. A dose dependent significant reduction in the action potential duration was observed for the doses of 0.6 and 1.4 mg in the ventricle and for all three concentrations in the atrium.

Action Potentials↗
PubMed1991

The haemodynamic effect of Bitis nasicornis (rhinoceros horned viper) venom.

1. Intravenous venom (0.0625 mg/kg) in the dog caused an immediate increase in coronary blood flow due to a fall in coronary vascular resistance (CVR). 2. Subsequently, total peripheral resistance (TPR) fell causing a significant reduction in aortic blood pressure (ABP). 3. CVR and TPR returned to normal after 20 min but ABP did not recover completely. 4. The failure of ABP to recover was due to decreased stroke volume and cardiac output (CO). 5. Animals died after four doubling doses of venom following irreversible reductions in CO, ABP and coronary flow.

Animals↗
PubMed1991

The mechanical effects of rhinoceros horned viper (Bitis nasicornis) venom on the isolated perfused guinea-pig heart.

In the guinea-pig Langendorff heart preparation, addition of 0.1 mg Bitis nasicornis venom to the perfusion solution caused transient increases in heart rate (HR) and left ventricular systolic pressure (LVSP) with peak increases at 2 min. With higher doses (0.6 and 1.4 mg), these increases were followed by the return of HR to normal, significant decreases in LVSP below control values and marked increases in left ventricular diastolic pressure. Histaminergic blockade with ranitidine reduced the positive responses. The results suggest that a venom component, possibly acting on intracellular calcium movement, could be responsible for both positive and negative effects.

Animals↗
PubMed1990

Prostacyclin inhibits the platelet-dependent effects of platelet-activating factor in the rabbit isolated heart.

In a previous study we showed that platelet-activating factor (PAF) is released in the coronary effluent early after reperfusion of ischemic, isolated rabbit heart. The amounts released were sufficient to induce intracoronary platelet activation and release of secondary mediators, suggesting a relevant contribution of this mediator to the cardiac dysfunction during reperfusion. We examined the modulatory effect of prostaglandin I2 (PGI2) on the cardiac alterations caused by infusion of PAF and autologous platelets in rabbit isolated heart. The intra-coronary infusion of PAF (10 ng-1 microgram) in the presence of autologous platelets induced marked alterations in the electrical and mechanical activities in rabbit heart, characterized by a transient positive inotropic effect (mean +/- SD = 113 +/- 6.1% of the control at 10 ng, 116 +/- 11.6% at 1 microgram), followed by a decrease in coronary flow (76 +/- 6.5 and 57 +/- 8.1%), contractile force (88 +/- 2.5 and 56 +/- 10.6%), and action potential duration (APD, 87 +/- 2.5 and 83 +/- 4.9%), and by conduction arrhythmias (75 and 100% of cases). The infusion of adenosine (1 x 10(-5) M) to increase coronary flow maximally abolished PAF and platelet-dependent reduction in coronary flow (CF) and contractile force, as well as conduction arrhythmias, but not the early transient positive inotropic effect. The alterations induced by platelets and PAF infusion were not affected by treatment of hearts with aspirin (3 x 10(-4) M), indicating that endogenous PGI2 generation did not affect the platelet-dependent response of the rabbit heart to PAF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1990

Role of platelet-activating factor in the reperfusion injury of rabbit ischemic heart.

This study shows that the administration of the PAF receptor antagonist SDZ 63.675 (5 mg/kg body weight) before reperfusion significantly reduced the hematologic and hemodynamic alterations, as well as the size of necrotic area in rabbits subjected to 40 minutes of coronary occlusion and reperfusion. Pretreatment with SDZ 63.675 prevented the reduction of platelet counts in the blood obtained from the right ventricle (86.6 +/- 2.8% of the control preischemia value) and the transient bradycardia (85.0 +/- 2.8%), the systemic hypotension (58.0 +/- 2.8%), and the increase in right ventricular pressure (125.0 +/- 3.6%) that were evident in the first minutes of reperfusion in untreated control rabbits. Two as well as 24 hours after reperfusion, the infarct size, judged by staining with tetrazolium, was significantly reduced in rabbits treated with SDZ 63.675 (infarct size in control animals, 66.0 +/- 2.9% and 63.46 +/- 2.09% of the risk region at 2 or 24 hours, respectively, compared with 38.9 +/- 5.2% and 37.11 +/- 2.44% of the risk region at 2 and 24 hours in rabbits treated with SDZ 63.675). This result was confirmed by histologic examination of cardiac tissue 24 hours after reperfusion. In addition, SDZ 63.675 markedly reduced the accumulation of 111In-oxine-labeled platelets that occurs 15 minutes after reperfusion in the central ischemic area of the heart and in the lungs. These results suggest that PAF plays a role in the evolution of myocardial injury observed during reperfusion.

Animals↗
PubMed1989

Identification of a new epitope of the 4F2/44D7 molecular complex present on sarcolemma and isolated cardiac fibers.

The murine monoclonal antibody (mAb) CB43, raised against the K-562 erythroleukemia line, reacts with monocytes, tissue macrophages, thymocytes and with all the human lines tested but not with resting lymphocytes, large granular lymphocytes, granulocytes and erythrocytes. However, activated lymphocytes and natural killer cells express the CB43 antigen. Embryonic and fetal fibroblasts are positive, while adult fibroblasts are negative. Proximal convoluted tubules in kidney, epithelial cells in esophagus and breast, and sarcolemma in skeletal muscle are reactive with mAb CB43. This antibody can also bind to isolated guinea pig cardiac myocytes, and, furthermore, can induce a transient inotropic effect on isolated atria. The reactivity with different cell and tissue types and the functional effects of the CB43 mAb were reminiscent of the 4F2/44D7 antibodies, shown previously to block Na+/Ca2+ exchange in heart and skeletal muscle. Co-immunoprecipitation studies with CB43 and 44D7 mAb, using radiolabeled Daudi cells, revealed co-migration of polypeptides of 87 and 38 kDa. However, the epitope recognized by CB43 is not present on the human heavy chain which bears the 44D7/4F2 epitope as demonstrated by the lack of reactivity of CB43 mAb with mouse L cells transfected with the 4F2 heavy chain gene. Thus, CB43 represents a newly described epitope present on the human light chain or dependent on the conformation of the human dimer.

Adult↗
PubMed1989

Cyclic GMP regulates the Ca-channel current in guinea pig ventricular myocytes.

The effect of intracellular perfusion with cyclic GMP (cGMP) on Ca current (Ica) was investigated in Cs-loaded isolated cells from guinea pig ventricle using the whole-cell patch-clamp technique and a perfused patch pipette. cGMP (5 microM) strongly reduced Ica which had been elevated by intracellular perfusion with 50 microM of either cyclic AMP (cAMP) or its hydrolysis-resistant analog 8-Bromo-cAMP. In addition, cGMP prevented the stimulation of Ica by IBMX, a phosphodiesterase inhibitor. The membrane permeant cGMP analog 8-Bromo-cGMP (100 microM), when applied outside the cell, also antagonized the stimulatory effect of IBMX on Ica. It is concluded that cGMP inhibits Ica in guinea pig ventricular cells by a mechanism different from the activation of a cGMP-stimulated phosphodiesterase recently found in frog ventricular cells.

Animals↗
PubMed1989

Release of platelet-activating factor from ischemic-reperfused rabbit heart.

This study shows that platelet-activating factor (PAF) is released in significant amounts (10.9 +/- 12.8 ng/min) during the initial reperfusion of the ischemic-isolated rabbit heart. When reperfusion was performed in the presence of autologous rabbit platelets, the electrical and mechanical alterations characteristic of this phase were significantly worsened. These alterations were antagonized by pretreatment of rabbit platelets with a PAF receptor antagonist (SDZ 63-675), suggesting a contribution of PAF released during reperfusion in the cardiac dysfunction. To discriminate whether the effect of PAF was platelet dependent, infusion of PAF (10-40 ng) was performed in nonischemic rabbit hearts perfused with or without autologous platelets. Although the effect of PAF per se was minimal, in the presence of platelets PAF induced a biphasic effect characterized by a transient positive inotropism followed by a dose-dependent decrease in coronary flow, negative inotropism, reduction of action potential duration, and conduction arrhythmias. These effects were abolished by pretreatment of platelets with SDZ 63-675, suggesting a PAF receptor-mediated platelet activation. In addition, a relative contribution of histamine, thromboxanes, and leukotrienes released from activated platelets was inferred by experiments performed with pyrilamine and cimetidine, imidazole, and FPL 55712, respectively.

Animals↗
PubMed1988

Potassium and calcium currents and action potentials in mouse Balb/c 3T3 fibroblasts.

The electrical properties of Balb/c 3T3 mouse fibroblasts were studied with the whole-cell patch clamp technique. In current clamp mode a resting potential of -75.5 +/- 2.1 mV was recorded. In voltage clamp mode an inward current was also observed at potentials negative to Vm. This current crossed the 0-current axis at a voltage near Vm, and rectified at more positive potentials; the degree of rectification was dependent on [K+]o. At potentials positive to -30 mV a transient inward current was observed, showing a peak amplitude of -193 +/- 36 pA at +10 mV; the current amplitude was dependent on voltage and [Ca2+]o, it was strongly increased by 20 mM BaCl2 and abolished by 2 microM verapamil and 1 microM nifedipine. These cells, in response to depolarizing stimuli, develop slow action potentials, probably supported by the Ca2+ current.

Action Potentials↗
PubMed1988

Histamine modulates calcium current in guinea pig ventricular myocytes.

In the present work we have examined the effects of histamine on electrophysiological parameters of isolated cardiocytes acutely dissociated from adult guinea pigs. The whole cell patch clamp technique was used to examine action potential and currents. Stable recordings of calcium current (average peak amplitude of 563 +/- 256 pA per cell, n = 83) were obtained. Application of histamine (5 nM-10 microM) resulted in marked modification of action potentials and calcium current. Calcium current was enhanced by histamine in a concentration-dependent manner (half-maximal dose, 10 nM) up to 315% of the control level. Action potentials were prolonged by small doses of histamine whereas larger doses caused voltage instabilities and spontaneous arrhythmic bursts. Histamine effects were reduced by cimetidine and ranitidine (1 microM), two H2-receptor antagonists. After the calcium current was increased by intracellular perfusion of micromolar cyclic AMP saturating doses of histamine had no effect. Micromolar concentrations of acetylcholine rapidly antagonized the histamine effect. The latter results indicate that the response to histamine is based on H2-receptor-mediated activation of adenylate cyclase and cyclic AMP regulation of phosphorylation of calcium channel.

Acetylcholine↗
PubMed1987

The pattern of cardiovascular alterations induced by infusion of platelet-activating factor in rabbit is modified by pretreatment with H1-H2 receptor antagonists but not by cyclooxygenase inhibition.

The intravenous infusion of platelet activating factor (PAF) (0.8 micrograms/kg b.w.) induced ECG and hemodynamic alterations characterized by the following sequential three phases. Phase I (15 sec) consisted of a transient bradycardia with reduction in left ventricular pressure (LVPs), mean arterial pressure (MAP) and cardiac output (CO). Phase II developed within 30 sec and consisted of a rise in cardiac frequency, increase in LVPs, MAP and total peripheral resistances (TPR), which were associated with a decrease in CO. Finally, phase III, that occurred about 90 sec after PAF infusion, was characterized by marked ECG changes (ST segment depression and conduction arrhythmias), a decrease in LVPs and MAP, as well as a rise in TPR and in right atrial pressure (RAP). All these alterations were reversible within 30-60 min. Pretreatment with promethazine and cimetidine, as H1 and H2 histamine receptor antagonists, markedly prevented the development of phase II, namely the rise in cardiac frequency, LVPs, MAP and TPR, but did not significantly modify phase I and III. In contrast, pretreatment with indomethacin, an inhibitor of cyclooxygenase, moderatively attenuated, but did not abolish, the three phases of cardiovascular changes induced by PAF infusion.

Animals↗
PubMed1987

Protective effect of verapamil on the cardiac and circulatory alterations induced by platelet-activating factor.

The role of calcium channels in the mediation of the cardiovascular effects of synthetic (1-O-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) platelet-activating factor (PAF) was studied in vivo in the rabbit and in vitro in the coronary-perfused isolated heart and papillary muscle of the guinea pig following pretreatment with verapamil, a calcium antagonist. In the rabbit, verapamil (0.3 mg/kg) abrogated the ECG changes, and reduced all the hemodynamic alterations caused by PAF (0.8 microgram/kg). Verapamil (20 nmol) reduced both the electrical and mechanical alterations observed in the isolated heart and papillary muscle after the infusion of PAF (0.2 nmol). These results suggest that the transmembranal calcium channels play a crucial role in the mechanism by which PAF acts on the cardiovascular tissues.

Animals↗
PubMed1986

The effects of Gaboon viper (Bitis gabonica) venom on the electrical and mechanical activity of the guinea-pig myocardium.

The effects of Bitis gabonica venom were tested on guinea-pig heart, using both Langendorff preparations and isolated atrial strips or papillary muscles. In the self-paced whole heart, a single passage of 50 micrograms of venom per ml produced in sequence: irregularities of the A-V conduction and decrease of the contractile strength, progressive failure to relax and systolic arrest of the heart. Pretreatment with atropine reduced but did not abolish these effects. Venom recycled through the heart was effective at a much lower dose. The relationship between resting membrane potential and [K+]o was unaffected by envenomation, suggesting that the action of the venom cannot be ascribed to a loss of ionic selectivity of the cell membrane. The peak amplitude of action potentials declined in papillary muscle exposed to venom at physiological [K+]o, while in atrial cells it was affected only at higher [K+]o. Maximum upstroke rate of the action potential vs. resting potential at different [K+]o gave a sigmoid relationship, characterized by a higher upper asymptote as compared to controls, and by a shift of the curve towards more negative voltage values. A marked shortening of the action potential duration, paralleled by a decrease in time to peak tension, was recorded as well. 'Slow' action potentials, elicited in 20 mM K+ solution, were completely abolished within 10 min of perfusion with venom. These results are consistent with the hypothesis that the venom interacts with both transmembrane Ca2+ inflow and Ca2+ binding at the external side of the cell membrane. A transient positive inotropic effect induced by the venom was observed in papillary muscle and in atropinized atrium. This effect was abolished by previous administration of reserpine to the animal or by addition of propranolol to the perfusing solution, suggesting a venom-induced release of both adrenergic and cholinergic transmitters from nerve endings within the cardiac tissue.

Action Potentials↗
PubMed1986

In vitro contractile effect of platelet-activating factor on guinea-pig myometrium.

Platelet-activating factor (PAF) evoked myometrial contractions in two different patterns, depending on whether spontaneous activity was present. In spontaneously active myometrial strips (58%), both PAF and oxytocin enhanced the amplitude of myometrial contractions. In quiescent myometrial strips, PAF induced contractions characterized by a prompt development of tension, a plateau, and a final, rapid relaxation. In 54% of these strips, PAF-induced contraction was followed by rhythmic activity. PAF contractile response was dependent upon the concentration (0.1-100 nM); the minimal effective concentration of PAF was 0.1 nM and the EC50 was 1 nM. The response to oxytocin (0.01-10 mU/ml), assumed as reference stimulus, was characterized by a prompt development of tension, which was followed by a sustained, slow contraction and relaxation. PAF response was almost completely dependent on cyclooxygenase and partially on lipoxygenase pathways, as inferred from studies with indomethacin and FPL 55712, respectively. A receptor mediated mechanism of PAF action was suggested by specific desensitization of the myometrium to a second challenge with an equimolar concentration of PAF (but not with oxytocin) and the blocking effect of CV 3988, a specific PAF receptor antagonist.

Animals↗
PubMed1986

Effect of platelet-activating factor (PAF) on human cardiac muscle.

The effect of platelet activating factor (PAF) on three mechanical [maximal mechanical tension (Pmax); time to peak tension; maximal rate of rise of tension (+dP/dt)] and four electrical [action potential duration (APD); resting membrane potential; overshoot; maximum rate of depolarization] parameters of cardiac function was studied on fragments of isolated human cardiac papillary muscle. 20 specimens of small tissue fragments excised from the left ventricle by open heart surgery were challenged with various doses of synthetic PAF (10(-10)-10(-6) M). PAF, but not its biologically inactive 2-lyso-derivative (lyso-PAF), induced a biphasic dose-dependent effect, characterized by a transient positive effect on inotropism (increased Pmax, +dP/dt) and of APD, followed by a marked, prolonged negative effect on both inotropism (decreased Pmax, time to peak tension, +dP/dt) and APD. No changes in resting membrane potential, overshoot and maximum rate of depolarization were detected after PAF challenge. Propranolol (2 X 10(-7) M) completely prevented the positive inotropic effect suggesting a stimulation of beta-receptors, possibly exerted by endogenous catecholamines. Indomethacin (1 X 10(-4) M) did not modify the initial positive effect, but markedly reduced the subsequent negative effect induced by PAF on inotropism. These findings are consistent with the interpretation that the effect of PAF on the inotropism is related to liberation of cyclooxygenase-derived metabolites.

Action Potentials↗
PubMed1986

Platelet-activating factor contracts human myometrium in vitro.

The myometrial contractile responses to synthetic 1-0-octadecyl-2-acetyl-sn-glyceryl-3-phosphorylcholine (platelet-activating factor, PAF) and to oxytocin were evaluated in vitro on uterine (lower segment) strips obtained from pregnant women at term (39th week), undergoing elective cesarean section. Contractility was measured isometrically in an isolated organ bath using a superfusion technique. PAF in a concentration range between 5 and 100 nM as well as oxytocin (0.1-10 mU/ml) induced a dose-dependent contraction which could be categorized in two patterns, depending on whether spontaneous activity was present. In resting strips, oxytocin induced a prompt (0.5-1 min) development of active tension, followed by a prolonged (6-18 min), slow contraction and a final relaxation. However, at variance with oxytocin, PAF-induced contractions were rhythmic (3-8/hr), and characterized by a prompt (0.5-2 min) development of tension, followed by a brief (0.5-2 min) plateau, and a final, rapid relaxation. In spontaneously active strips, both stimuli induced a marked potentiation of the contractile activity. PAF response was dependent on both cyclooxygenase- and lipoxygenase-derived products as inferred from the abrogating effects of indomethacin and FPL 55712. A receptor-mediated mechanism of action was inferred from the occurrence of specific desensitization to PAF (but not to oxytocin), and from the blocking effect of CV 3988, a specific PAF receptor antagonist. The present study indicates that PAF stimulates the contraction of human myometrium in vitro and suggests that this mediator may have a role in labor.

Adult↗