Biomedical subjects

K S Kilgore

Publications and source records attributed to K S Kilgore.

40 records · Page 3Linked to original sources

PubMed1993

Soluble complement receptor type 1 prevents human complement-mediated damage of the rabbit isolated heart.

The purpose of this study was to determine if recombinant human soluble CR1 (sCR1) could prevent tissue damage associated with the activation of human complement. Directly mediated human complement-dependent myocardial injury was induced in the rabbit isolated heart perfused with a Krebs-Henseleit buffer containing 6% human plasma. There were three study groups: 1) 6% heat-inactivated human plasma (control); 2) 6% normal human plasma (NHP); or 3) 6% normal human plasma + 20 nM sCR1 (NHP + sCR1). Recorded functional parameters of the control group remained stable throughout the duration of the 70-min protocol. Complement activation in hearts perfused with 6% NHP increased the diastolic pressure; decreased developed pressure; and increased coronary perfusion pressure. These alterations were accompanied by a decrease in the maximum positive and negative dP/dt. Complement activation also increased cardiac muscle lymphatic fluid flow rate. The changes were greatest between 20 and 40 min, but persisted for the duration of the protocol. sCR1 (20 nM) in the perfusate containing 6% NHP prevented the complement-mediated alterations in the systolic, developed, and coronary perfusion pressures. sCR1 prevented the decrement in the positive and negative dP/dt, and the increase in the lymphatic fluid flow rate. Values for each of these parameters in hearts perfused with 6% NHP + sCR1 were not altered from those of controls at any time point in the protocol. Ultrastructural changes were present in tissues perfused with 6% NHP along with immunohistochemical evidence for presence of the terminal C5b-9 complex. sCR1 prevented the ultrastructural changes and the formation of the terminal complex. sCR1 offers significant protection against the cytolytic effects resulting from activation of the human complement system.

Animals↗

PubMed1993

Reperfusion injury after myocardial infarction: the role of free radicals and the inflammatory response.

Development of thrombolytic therapy as a treatment for myocardial infarction has focused attention on the events that occur upon reperfusion of ischemic myocardial tissue. Although it is well documented that salvage of the ischemic myocardium is dependent upon timely reperfusion, it is likely that the very events critical for survival may, in fact, lead to further tissue injury. A widely recognized source of reperfusion injury is the generation of oxygen-derived free radicals. These reactive oxygen species, which are formed within the first moments of reperfusion, are known to be cytotoxic to surrounding cells. In addition, strong support exists for the involvement of the inflammatory system in mediating tissue damage upon reperfusion. Coincident with the recruitment of neutrophils and activation of the complement system is an increase in the loss of viable cells. Although a number of mechanisms are likely to be involved in reperfusion injury, this discussion focuses on the roles that oxygen-derived free radicals and the inflammatory system play in mediating reperfusion injury.

Cell Adhesion↗

PubMed1993

Platelet GPIIb/IIIa receptor inhibition by SC-49992 prevents thrombosis and rethrombosis in the canine carotid artery.

OBJECTIVE: Platelet glycoprotein IIb/IIIa (GPIIb/IIIa) receptors represent the final common pathway for aggregation. GPIIb/IIIa inhibition with antibodies or RGD peptides prevents arterial thrombosis. The present study examined the ability of SC-49992 (SC), a GPIIb/IIIa receptor antagonist, to prevent thrombosis in a canine model of carotid artery thrombosis. METHODS: Both carotid arteries of anaesthetised dogs were instrumented with Doppler probes. A 300 microA current was applied to the intimal surface of the right carotid artery via an intraluminal electrode; time to occlusive thrombus formation was noted. SC (30 and 60 micrograms/.kg-1 x min-1, intravenously) or saline was infused for 240 min. The procedure for thrombus formation was repeated after 60 min of drug infusion for the left carotid artery. RESULTS: SC did not alter heart rate or blood pressure. Frequency of occlusive thrombus formation was reduced or prevented in a dose dependent manner (control = 100%, n = 12; SC 30 micrograms = 50%, n = 6; SC 60 micrograms = 0%, n = 6; p < 0.05). SC resulted in a reduction in thrombus weight (p < 0.05) v control. Ex vivo platelet aggregation to ADP and arachidonic acid was inhibited. Platelet reactivity remained inhibited 60 min after cessation of SC infusion. In a second group of animals, a carotid artery thrombus was formed and lysed with administration of anisoylated plasminogen streptokinase activator complex (0.05 U.kg-1). SC (60 micrograms.kg-1 x min-1, intravenously, n = 6) or saline (n = 6) was infused for 240 min. In dogs receiving saline there was an 83% rate of rethrombosis; none of the SC treated animals had reocclusion after recanalisation (p < 0.05). CONCLUSIONS: SC-49992 inhibits ex vivo platelet aggregation, prevents occlusive thrombus formation in a canine model of arterial thrombosis, and prevents rethrombosis after thrombolysis. The data are consistent with results obtained with murine monoclonal antibodies directed against the platelet GPIIb/IIIa receptor.

Animals↗

PubMed1993

Effect of hypoxia and reoxygenation on the isolated rabbit heart determined by monoclonal antimyosin antibody uptake.

OBJECTIVE: The aim was to examine the effect of hypoxia and reoxygenation upon the isolated rabbit heart, and to determine whether or not irreversible tissue injury develops in association with the reintroduction of molecular oxygen to the previously hypoxic heart. METHODS: Isolated rabbit hearts suspended on a Langendorff apparatus and perfused with a modified Krebs-Henseleit buffer were subjected to either 5 or 30 min hypoxia and, when applicable, followed by 45 min reoxygenation. The effect of hypoxia and reoxygenation upon the isolated heart was determined with a 125labelled monoclonal antibody to the intracellular protein myosin. Determination of tissue creatine kinase release and morphological analysis, using lanthanum chloride as a marker of vessel damage, were also performed to document the uptake of antimyosin with myocardial tissue injury. RESULTS: Hearts subjected to 30 min hypoxia followed by 45 min reoxygenation showed a significant increase in antimyosin uptake when compared to hearts exposed to 30 min hypoxia. Creatine kinase release and morphological analysis showed an increase in intracellular damage in hearts receiving 30 min hypoxia and 45 min reoxygenation when compared to hearts receiving 30 min hypoxia without subsequent reoxygenation. Hearts subjected to 5 min hypoxia followed by reoxygenation did not show a significant increase in antimyosin uptake as compared to continuously oxygenated control hearts or hearts made hypoxic for 5 min without subsequent reoxygenation. CONCLUSIONS: Antimyosin antibody binding increased in hearts subjected to hypoxia and reoxygenation compared to hearts subjected to hypoxia without reoxygenation. The data provide compelling evidence that reoxygenation of hypoxic tissue exacerbates the extension of cellular damage. The ability of superoxide dismutase and catalase to decrease antimyosin uptake suggests that reactive oxygen species play a role in reoxygenation induced myocardial damage. This study also provides evidence that the labelled antimyosin antibody provides a convenient approach to quantitate the extent of damage induced by hypoxia with and without subsequent reoxygenation.

Animals↗