The American journal of physiology
-
Comparative Study
Dissociation between anti-infarct effect and anti-edema effect of ischemic preconditioning.
This study tested the hypothesis that preconditioning, by reducing catabolite accumulation during ischemia, reduces osmotic swelling and myocardial necrosis during subsequent reperfusion. Farm pigs were randomly allocated to one of three groups of treatment: a control group undergoing a 48-min coronary occlusion (CO) of the middle left anterior descending artery, a preconditioned group (2 cycles of 5-min CO and 5-min reperfusion before the 48-min CO), or an intracoronary perfusion group receiving a substrate-free anoxic buffer perfusion into the area at risk between minutes 5 and 10 of the prolonged CO. Animals were killed after 30 min (n = 23) or 6 h (n = 31) of reperfusion. ⋯ Myocardial lactate content before reperfusion, measured in an additional series of 12 experiments, was reduced by 35% in animals receiving preconditioning or intracoronary perfusion. Thus ischemic preconditioning has a marked protective effect against reperfusion edema, and this effect can be explained by reduced catabolite accumulation during ischemia. However, there is no evidence from this study indicating that reduced catabolite accumulation and limited reperfusion edema explain the important anti-infarct effect of ischemic preconditioning.
-
Comparative Study
Limitation of reperfusion injury by a monoclonal antibody to C5a during myocardial infarction in pigs.
The complement system has been implicated in reperfusion injury during acute myocardial infarction. We therefore attempted to reduce reperfusion injury with a monoclonal antibody (MAb) to the complement component, C5a. In 13 control pigs and 9 pigs pretreated with this MAb, ischemia was induced by a 50-min occlusion of the left anterior descending coronary artery, followed by 3 h of reperfusion. ⋯ In conclusion, myocardial infarction-reperfusion is associated with activation of the alternative complement pathway. Furthermore, a MAb to C5a that inhibits neutrophil cytotoxic activity, but neither the membrane attack complex nor myocardial neutrophil accumulation, decreases infarct size in pigs. These data suggest an important role of the alternative complement pathway and C5a in the propagation of ischemia cardiac damage during reperfusion.
-
The effects of SR-49059, a new nonpeptide and selective arginine vasopressin (AVP) V1a antagonist, were investigated in binding and functional studies on cultured human aortic vascular smooth muscle cells (VSMC). Characterization of human vascular V1a receptors, using a specific V1a radioiodinated ligand, showed that [125I]-linear AVP antagonist binding to human VSMC membranes was time dependent, reversible, and saturable. A single population of high-affinity binding sites (apparent equilibrium dissociation constant = 15 +/- 6 pM; maximum binding density = 36 +/- 5 fmol/mg protein, i.e., approximately 3,000 sites/cell) with the expected V1a profile was identified. ⋯ SR-49059 strongly and stereospecifically inhibited [125I]-linear AVP antagonist binding to VSMC V1a receptors [inhibition constant (Ki) = 1.4 +/- 0.3 nM], AVP-evoked Ca2+ increase [concentration of inhibitor required to obtain 50% inhibition of specific binding (IC50) = 0.41 +/- 0.06 nM], and the mitogenic effects induced by 100 nM AVP (IC50 = 0.83 +/- 0.04 nM). OPC-21268, another nonpeptide V1a antagonist, was more than two orders of magnitude less potent than SR-49059 in these models. However, the consistent affinity (Ki = 138 +/- 21 nM) and activity found with OPC-21268 on human VSMC in comparison with the inactivity already observed for other human V1a receptors (liver, platelets, adrenals, and uterus) strongly suggested the existence of human AVP V1a-receptor subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)
-
We tested the hypothesis that attenuation of the hyperemia at the margin of acetic acid-induced gastric ulcer in rats by tobacco cigarette smoke will increase the size of the ulcer in the acute and the healing stages. Compared with the adjacent mucosa, blood flow measured by hydrogen gas clearance at the ulcer margin was significantly higher (ulcer margin hyperemia). Tobacco cigarette smoke and subcutaneous nicotine but not nicotine-free smoke from non-tobacco cigarettes significantly attenuated the ulcer margin hyperemia in a dose-related fashion. ⋯ Subcutaneous nicotine but not nicotine-free smoke also increased the size of ulcers in the acute stage. These results indicate that the nicotine in tobacco cigarette smoke may be responsible in part for its adverse effects. We conclude that attenuation of the hyperemia at the ulcer margin is a plausible explanation for the mechanism of the adverse effect of the tobacco cigarette smoke on experimental gastric ulcers in rats.