thromboxane-a2 and Acidosis

Mild to moderate hypothermia (32-35 degrees C) is the first treatment with proven efficacy for postischemic neurological injury. In recent years important insights have been gained into the mechanisms underlying hypothermia's protective effects; in addition, physiological and pathophysiological changes associated with cooling have become better understood.. To discuss hypothermia's mechanisms of action, to review (patho)physiological changes associated with cooling, and to discuss potential side effects.. Review article.. None.. A myriad of destructive processes unfold in injured tissue following ischemia-reperfusion. These include excitotoxicty, neuroinflammation, apoptosis, free radical production, seizure activity, blood-brain barrier disruption, blood vessel leakage, cerebral thermopooling, and numerous others. The severity of this destructive cascade determines whether injured cells will survive or die. Hypothermia can inhibit or mitigate all of these mechanisms, while stimulating protective systems such as early gene activation. Hypothermia is also effective in mitigating intracranial hypertension and reducing brain edema. Side effects include immunosuppression with increased infection risk, cold diuresis and hypovolemia, electrolyte disorders, insulin resistance, impaired drug clearance, and mild coagulopathy. Targeted interventions are required to effectively manage these side effects. Hypothermia does not decrease myocardial contractility or induce hypotension if hypovolemia is corrected, and preliminary evidence suggests that it can be safely used in patients with cardiac shock. Cardiac output will decrease due to hypothermia-induced bradycardia, but given that metabolic rate also decreases the balance between supply and demand, is usually maintained or improved. In contrast to deep hypothermia (

Topics: Acidosis; Apoptosis; Body Temperature Regulation; Brain Edema; Brain Ischemia; Calpain; Critical Care; Epilepsy; Free Radicals; Genes, Immediate-Early; Humans; Hypothermia, Induced; Infections; Inflammation; Ion Pumps; Mitochondria; Reperfusion Injury; Thrombosis; Thromboxane A2

Previous studies concerning ischemic priapism revealed that hypoxia alters the erectile and contractile responses of penis. But the effects of accompanying acidosis on those responses have not been fully evaluated or understood yet. We performed this study to elucidate the role of acidosis on the trabecular smooth muscle contractility like in ischemic priapism. Under the general anesthesia, 55 mature male cats were conditioned to systemic metabolic acidosis by hypoventilation by animal ventilator. The changes of intracavernous pressure (ICP) to erectogenic agents (acetylcholine, L-arginine, prostaglandin E1: PGE1), erectolytic agents (epinephrine, thromboxane A2; TXA2), K channel-related drugs (pinacidil, 4-aminopyridine, tetraethylammonium; TEA, glibenclamide) and calcium ionophore were monitored at Set 1 (PO2 > 60 mmHg, pH > 7.25), Set 2 (PO2 < 30 mmHg, 7.25 > pH > 7.0), Set 3 (PO2 < 30 mmHg, pH < 7.0), and Set 4 (PO2 > 60 mmHg, pH < 7.0) in vivo. At Set 1 and Set 2, epinephrine, TXA2, and ionomycin decreased the ICP by acetylcholine or PGE1 (n = 9, P < 0.01). The decrease of ICP was in order of epinephrine, TXA2 and ionomycin. Acidosis reduced the increase of ICP to acetylcholine or PGE1 (n = 8, P < 0.01), TXA2 or ionomycin did not affect ICP under severe acidosis but epinephrine decreased ICP even under severe acidosis (n = 7, P < 0.05). Pretreatment of potassium channel blockers did not suppress the increase of ICP by erectogenic agents under acidosis (n = 6, P < 0.05). Pinacidil did not affect ICP under acidosis (n = 6, P < 0.01). These results suggest that acidosis impairs the contractile response of cavernous smooth muscle to erectolytic agents. It may be the results of the interference by [H+] with the intra and extracellular mechanisms that regulate the homeostasis of [Ca2]. Conclusively, besides hypoxia, acidosis is another limiting factor of trabecular smooth muscle contractility like in ischemic priapism.

Topics: Acetylcholine; Acidosis; Alprostadil; Animals; Arginine; Cats; Epinephrine; Hypoxia; Ionomycin; Male; Muscle Contraction; Muscle, Smooth; Penile Erection; Penis; Potassium Channel Blockers; Pressure; Thromboxane A2

Using an isolated rat heart preparation and 31P magnetic resonance spectroscopy, we studied the effects of endothelin-1 (ET-1) and U-46619, a thromboxane-A2 analogue, on coronary flow (CF), left ventricular developed pressure (LVP), and high-energy phosphate metabolism under control conditions (normal myocardium) and during postischemic reperfusion (reperfused myocardium). The selected doses of ET-1 and U-46619 reduced CF in the normal myocardium to a similar extent (47.8 +/- 1.5% and 48.7 +/- 4.6%, respectively). In contrast to ET-1, U-46619 induced a depression of LVP (20.2 +/- 6.9% versus 6.8 +/- 4.7%; p < 0.05) which was accompanied by an intracellular acidosis, indicating that a low-flow ischemia occurred. In reperfused hearts, the ET-1-induced decrease in CF was more pronounced compared to U-46619 (79.5 +/- 1.6% versus 59.0 +/- 5.9%; p < 0.05) and to ET-1-induced decrease in CF in the normal myocardium (74.0 +/- 7.9% versus 32.4 +/- 6.3%; p < 0.05). This was accompanied by a large decrease in LVP and in levels of high-energy phosphate compounds. Therefore, the effects of ET-1 but not of U-46619 are enhanced in reperfused hearts. This may contribute to the delayed recovery of the postischemic reperfused myocardium.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Acidosis; Adenosine Triphosphate; Animals; Coronary Circulation; Endothelins; Heart; Hydrogen-Ion Concentration; In Vitro Techniques; Magnetic Resonance Spectroscopy; Myocardial Reperfusion Injury; Myocardium; Prostaglandin Endoperoxides, Synthetic; Rats; Rats, Sprague-Dawley; Thromboxane A2; Vasoconstrictor Agents; Ventricular Function, Left

Thromboxane A2 (TXA2) is a proaggregatory vasoconstrictor that is synthesized and released during reperfusion of ischaemic brain. We administered a TXA2 receptor antagonist, SQ29,548, and a thromboxane A synthase inhibitor, 1-benzylimidazole (1-BI), to rats subjected to 30 min of reversible forebrain ischaemia. Cerebral thromboxane B2 (TXB2), the stable metabolite of TXA2, measured after 60 min of reperfusion was 0.37 +/- 0.08 ng/mg brain protein in animals treated with SQ29,548/1-BI compared with 1.20 +/- 0.16 in ischaemic controls (p < 0.05). Cerebral pH determined by 31P magnetic resonance spectroscopy was higher in treated animals, 7.06 +/- 0.04, than in ischaemic controls, 6.5 +/- 0.01, after 20 min of reperfusion (p < or = 0.01). The significant elevation of cerebral pH in treated animals persisted at 30 (7.17 +/- 0.05 vs. 6.5 +/- 0.01; p < or = 0.01), 35 (7.17 +/- 0.05 vs. 6.44 +/- 0.04; p < or = 0.01), and 40 min of reperfusion (7.06 +/- 0.06 vs. 6.37 +/- 0.01; p < or = 0.05). We conclude that SQ29,548/1-BI reduces thromboxane levels and promotes resolution of tissue acidosis in ischaemic brain. The combination of a TXA2 receptor antagonist with a thromboxane A synthase inhibitor deserves further study as a potential treatment for acute cerebral infarction.

Topics: Acidosis; Animals; Brain Ischemia; Bridged Bicyclo Compounds, Heterocyclic; Drug Therapy, Combination; Fatty Acids, Unsaturated; Hydrazines; Hydrogen-Ion Concentration; Imidazoles; Magnetic Resonance Imaging; Male; Prosencephalon; Rats; Rats, Wistar; Receptors, Thromboxane; Reperfusion Injury; Thromboxane A2; Thromboxane-A Synthase

Rumen acidosis was induced experimentally with 70 g barley/kg b.w. in 2 rumen fistulated cows. The cows were followed for 80 h after the grain engorgement. Endotoxin was monitored in cell-free ruminal fluid and peripheral plasma together with inflammation mediators TXA2, PGI2 and PGE2 and several clinical and clinical-chemical parameters. The results do not support the theory of systemical endotoxemia due to a large increase in rumen endotoxin concentration in cattle suffering from rumen acidosis. However, both clinical and clinical-chemical data suggest that an endotoxicosis developed, but the levels of inflammation mediators TXB2, FGI2 and PGE2 were not significantly elevated in the peripheral circulation. An absorbtion of endotoxins and synthesis of inflammation mediators are therefore suggested to take place prehepatically.

Topics: Acidosis; Animals; Cattle; Cattle Diseases; Dinoprostone; Endotoxins; Epoprostenol; Female; Rumen; Stomach Diseases; Thromboxane A2