Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Mar 1996
Antifibrillatory effect of esmolol alone and in combination with lidocaine.
The primary objective of this study was to determine the effect of esmolol, administered alone and in combination with lidocaine, on ventricular fibrillation threshold (VFT) in pigs. A secondary objective was to determine the relationship between blood esmolol concentrations and VFT. We determined VFT using a train of electrical stimuli delivered to the right ventricle after eight paced beats at a basic cycle length of 285 ms. ⋯ The relationship between blood esmolol concentrations and VFT was described by a counterclockwise hysteresis curve, suggesting delay in equilibration of esmolol between blood and site of effect. The antifibrillatory efficacy of esmolol is significantly greater than that of lidocaine in this model. Administration of the two agents in combination resulted in significantly greater antifibrillatory efficacy than that associated with either drug administered alone.
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J. Cardiovasc. Pharmacol. · Jan 1996
ReviewRestoration of the normal coagulation process: advances in therapies to antagonize heparin.
A number of naturally occurring anticoagulants exist that preserve normal blood fluidity and limit blood clot formation to vascular injury sites, thus acting as regulators of hemostasis. The protein C/protein S pathway is one system that acts to modulate thrombin formation. The activation of protein C by thrombin is accelerated more than 1,000-fold at the endothelial surface by thrombomodulin localized on the endothelial cell. ⋯ The first human open-label phase 1 trial of rPF4 reported no serious side effects and no important hemodynamic effects. Doses of 2.5 and 5.0 mg/kg were uniformly effective in reversing the anticoagulant effect of heparin and reducing the ACT to <200 s by 5 min after administration. Repeated monitoring of the ACT did not detect a rebound effect of heparin.
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J. Cardiovasc. Pharmacol. · Jan 1996
ReviewLeft ventricular dysfunction due to the new ischemic outcomes: stunning and hibernation.
Several potential manifestations and outcomes are associated with myocardial ischemia and reperfusion. When ischemia is severe and prolonged, irreversible damage occurs and there is no recovery of contractile function. When ischemia is less severe or shorter in duration, recovery of contraction may occur instantaneously or more commonly, after considerable delay, which is the condition recognized as "stunned myocardium." Stunning is defined as a transient left ventricular dysfunction that persists after reperfusion despite the absence of irreversible damage and restoration of normal or near-normal coronary flow. ⋯ A number of methods are available to access the hibernating myocardium. These include cardiac imaging techniques that evaluate myocardial viability, such as positron emission tomography and thallium myocardial imaging, or methods that evaluate contractile reserve, such as low-dose dobutamine echocardiography. Interestingly, reperfusion of patients with end-stage ischemic cardiomyopathy and hibernating myocardium can be considered an alternative to transplantation.
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J. Cardiovasc. Pharmacol. · Jan 1996
ReviewAmplification of the inflammatory response: adhesion molecules associated with platelet/white cell responses.
Cardiopulmonary bypass (CPB) causes leukocyte and platelet activation, resulting in upregulation of the adhesion receptor CD11b/CD18 on leukocytes and upregulation of P-selectin, the adhesion receptor that binds the activated platelet to polymorphonuclear neutrophils (PMNs) and monocytes. Our laboratory has studied the expression of activation-dependent adhesion receptors during in vivo CPB. Both PMN and monocyte CD11b were upregulated during CPB but with differing time courses. ⋯ Generation of the complement fragments C5a and the C5b-9 membrane-attack complex may contribute to platelet P-selectin expression and formation of leukocyte-platelet conjugates during CPB. The in vitro model has been used to test the cellular effects of complement inhibition employing a monoclonal antibody that blocks cleavage of C5 into C5a and C5b to determine the role of early vs. late complement components in the cellular activation induced by CPB. Preliminary results demonstrate that blockage of the formation of C5a and the C5b-9 membrane-attack complex during simulated extracorporeal circulation effectively inhibits platelet and PMN activation and the formation of leukocyte-platelet conjugates.
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J. Cardiovasc. Pharmacol. · Jan 1996
ReviewReducing thrombin formation during cardiopulmonary bypass: is there a benefit of the additional anticoagulant action of aprotinin?
During cardiopulmonary bypass (CPB), contact-phase activation of factor XII, prekallikrein, and high molecular weight kininogen initiates the intrinsic pathway of coagulation. To prevent gross clot formation during CPB, heparin is commonly used as an anticoagulant. There is a wide variability in the sensitivity of individual patients to the actions of heparin. ⋯ Despite lower plasma concentrations of heparin, aprotinin-treated patients had significantly lower concentrations of the markers of coagulation activation (thrombin-antithrombin III complex, fibrin monomers, and antiplasmin-plasmin complex). We have also investigated the role of aprotinin in contact-phase [correction of contact phase] activation of fibrinolysis. Patients treated with aprotinin showed higher concentrations of single-chain urinary type plasminogen activator (scuPA) at the end of CPB compared with control patients, indicating reduced contact- phase [correction of contact phase] activation.