Intracoronary Administration of Streptokinase in a Canine Model: Disturbances in Thromboxane A2-Prostacyclin Balance

Gj, Becker; Dl, Kreipke; Rw, Holden; Rg, Dreesen; Ryder, Kenneth W.; Petersen, B; Ap, Evan; Pj, Bendick; Td, Franklin; Ec, Klatte

doi:10.1097/00004424-198603000-00003

Cited by 3 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This large washout of thromboxane metabolites upon thrombolysis has been confirmed in dogs using intracoronary administration of streptokinase. 30 It is therefore likely that inhibition of thromboxane synthesis with an appropriate thromboxane synthetase inhibitor, or the blockade of thromboxane receptors with a potent thromboxane-receptor antagonist would prevent the untoward effects of TXA 2 in the coronary vasculature occurring during ischemia and establishment of a reperfused coronary vessel or vessels. Our results indicate that CGS-13080 totally blocked the rise in plasma TXB 2 concentration upon reperfusion, and that t-PA did not act as a thromboxane synthetase inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Potentiation of myocardial salvage by tissue type plasminogen activator in combination with a thromboxane synthetase inhibitor in ischemic cat myocardium.

Lefer

Mentley

Sun

1988

Circulation Research

View full text Add to dashboard Cite

We studied the effects of a thrombolytic agent (t-PA) and a thromboxane synthetase inhibitor (CGS-13080) in a model of myocardial ischemia and reperfusion. Occlusion of the left anterior descending coronary artery for 2 hours followed by 4 hours of reperfusion in anesthetized cats results in a large washout of creatine kinase into the blood (32 ±7 lU/mg protein) and an area of necrotic tissue comprising 52±5% of the area at risk and 9±0.6% of the left ventricle. Intravenous administration of t-PA (500 IU/kg • min) for 30 minutes alone at reperfusion or infusion of CGS-13080 (500 figlkg • hr) had no effect on washout of creatine kinase or extent of necrotic tissue development. Administration of the same doses of both t-PA and CGS-13080 together markedly attenuated creatine kinase release to 10 ± 2 IU/mg protein (p<0.01) and reduced the area of necrotic tissue to 9 ± 2% of the area at risk and only 1.3 ± 0.3% of the left ventricle (/?<0.001). No significant sustained effects of these agents were observed on mean arterial blood pressure, heart rate, or the pressure rate index in these experiments. Thus, t-PA and CGS-13080 exert synergistic effects hi preserving myocardial integrity in cats subjected to acute myocardial ischemia followed by reperfusion. The mechanism of this beneficial effect does not appear to be via reduced myocardial oxygen demand, increased myocardial oxygen supply, or enhanced inhibition of thromboxane A 2 formation. The mechanism of this anti-ischemic effect is not clear but may involve a metabolic or a cytoprotective effect. (Circulation Research

show abstract

Section: Discussionmentioning

confidence: 99%

Potentiation of myocardial salvage by tissue type plasminogen activator in combination with a thromboxane synthetase inhibitor in ischemic cat myocardium.

Lefer

Mentley

Sun

1988

Circulation Research

View full text Add to dashboard Cite

show abstract

The proton-controlled fluorescence of aminomethyltetraphenylporphyrin–tin(IV) derivatives

Grigg¹,

Norbert²

1992

J. Chem. Soc., Chem. Commun.

View full text Add to dashboard Cite

The fluorescence quantum yield of the aminomethyltetraphenylporphyrin-tin(iv) compound, la-h is strongly influenced by pH in a bimodal manner owing to photoinduced electron transfer and axial ligand exchange processes. ~ Ion-controlled fluorescence in the visible region, especially 'on-off' switching, is of interest not only for ion sensing in the life sciences,2 but also for the construction of molecular optoelectronic devices.3 The use of porphyrin derivatives in photodynamic therapy4 and their intracellular location by fluorescence imaging,5 combined with the fact that intracellular pH is significantly different in normal and tumour cells,6 provided the impetus to the present work.The aminomethyltetraphenylporphyrin-tin(1v) series 1 was designed so that photoinduced electron transfer7 would take place from the amino group to the porphyrin moiety, resulting in fluorescence quenching. However, when the amino group is protonated fluorescence becomes an important deexcitation pathway. A related intermolecular situation is known.* Application of the Weller equation9 shows that the photoinduced electron transfer process is thermodynamically feasible (Table 1). The syntheses of la-h are summarised in Scheme 1.The fluorescence quantum yield (@)-pH profiles (Fig. 1) of 1 are bimodal, being composed of two sigmoidal curves of opposite gradients, and are due to two separate processes. The segment with the negative gradient is assignable to the photoinduced electron transfer process. The other is attributed to an axial ligand exchange process on the tin(1v) centre. The results (Table 1, Fig. 1) show that significant protoninduced fluorescence changes are exhibited by all members of the series la-h without alteration of fluorescence band position or vibrational fine structure of fluorescence. The pKa2 values determined by fluorescence titration and the use of eqn. (1) on the sigmoidal segment of the @-pH profile with negative gradient correlate well with the pKa,model values for the corresponding 'parent' methylamines, as demonstrated by the constant ApK, values in Table 1. Thus the sigmoidal segment results from protonation equilibria of the amino group in la-h. Furthermore, this correlation suggests a constant steric hindrance to solvation16 of the protonated amino group by the bulky porphyrin moiety across the series. It is also notable that the pKa2 values determined fluorimetrically are in close agreement with those obtained by the analysis, via eqn. (2), of the small pH-dependent alterations of the UV-VIS absorption spectrum for each member of series 1. This demonstrates the unusual result that the pKa2 values obtained by excited state experiments are thermodynamic (equilibrated) values. 17 This arises from the spatial isolation of the amino group from the photoantenna porphyrin moiety by the methylene spacer unit. The @max values are essentially constant across the series la-h and are identical to the value for the parent compound 2. The @min2 values correlate with the thermodynamic driving force for photoinduced el...

show abstract

Inhibition of vascular endothelial cell prostacyclin synthesis by plasmin

Schafer

Rodríguez

Loscalzo

et al. 1989

Blood

View full text Add to dashboard Cite

Vascular endothelial cells (EC) play an active role in the synthesis and assembly of components of the fibrinolytic system and the generation of the major fibrinolytic protease plasmin. However, the reciprocal effects of plasmin on EC function have not been previously examined. We have studied the actions of plasmin on the production of prostacyclin (PGI2) by cultured human umbilical vein (HUVEC) and bovine aortic (BAEC) endothelial cells. Plasmin causes little or no direct stimulation of PGI2 formation by EC. Preincubation of EC with plasmin, however, produces a time- and concentration-dependent inhibition of ionophore A23187-, thrombin-, and histamine-induced PGI2 synthesis; a smaller inhibitory effect on arachidonate- and PGH2-induced PGI2 synthesis is found. Incubation of HUVEC or BAEC with a physiologic concentration of plasminogen (180 micrograms/mL) and recombinant tissue plasminogen activator (tPA) generates tPA dose-dependent plasmin activity that exceeds that generated in the absence of EC. In the presence of plasminogen, tPA also causes a tPA dose-dependent inhibition of thrombin- and ionophore A23187-stimulated PGI2 production. PGI2 inhibitory plasmin activity is generated within the concentration range of tPA achieved in plasma during pharmacologic therapy with tPA. These findings suggest that vascular endothelial cells not only regulate activation of the fibrinolytic system but may also be targets of plasmin action on PGI2 synthesis in the modulation of hemostasis and thrombosis.

show abstract

Intracoronary Administration of Streptokinase in a Canine Model: Disturbances in Thromboxane A2-Prostacyclin Balance

Cited by 3 publications

References 0 publications

Potentiation of myocardial salvage by tissue type plasminogen activator in combination with a thromboxane synthetase inhibitor in ischemic cat myocardium.

Potentiation of myocardial salvage by tissue type plasminogen activator in combination with a thromboxane synthetase inhibitor in ischemic cat myocardium.

The proton-controlled fluorescence of aminomethyltetraphenylporphyrin–tin(IV) derivatives

Inhibition of vascular endothelial cell prostacyclin synthesis by plasmin

Contact Info

Product

Resources

About